Share this article on:

General Poster Display

doi: 10.1097/01.PAT.0000412609.83437.b2
Back to Top | Article Outline


Iain Abbott, Adam Jenney, Denis Spelman

Department of Microbiology, The Alfred Hospital, Melbourne, Vic, Australia

Background: Patients with unrecognised colonisation with multidrug resistant Gram-negative bacteria (MDRGNB) constitute a reservoir of organisms that can precede invasive disease and potentially be transmitted to other patients. A large percentage of patients colonised with these resistant bacteria are not recognised by clinical cultures but are only detected by performing surveillance cultures.1

Aims: To validate an active surveillance screening method to detect MDRGNB.

Methods: An agar-based method was trialled to detect MDRGNB. The media was tested against known susceptible and resistant organisms, mixed cultures, and clinical urine and rectal swab specimens. A low-risk ethics application was obtained.

Results: A selection of different media was used with each testing isolate: MacConkey agar (MCA) with gentamicin 8 mg/L, MCA with ciprofloxacin 2 mg/L, MCA with ceftazidime 2 mg/L and ESBL CHROMagar®. MCA without antibiotic addition was used as a control. The media was tested across 50 different specimens.

Discussion: We have demonstrated a reliable and practical method to screen for MDRGNB. This methodology can be utilised for an active surveillance study to establish colonisation rates with MDRGNB.


1. Maragakis LL. Recognition and prevention of multidrug-resistant Gram-negative bacteria in the intensive care unit. Crit Care Med 2010; 38 (8 Suppl): S345–51.

Back to Top | Article Outline


Sanaz Ainechi1, Buge Oz1, Sebnem Batur1, Mehmet Y. Kaynar2, Bernd W. Scheithauer3

1Department of Pathology, CerrahPasa Medical Faculty, Istanbul University,2Department of Neurosurgery, CerrahPasa Medical Faculty, Istanbul University, Turkey, and3Department of Pathology, Mayo Clinic, Rochester, MN, US

Introduction: Pilocytic astrocytoma (PA), a grade I glioma, rarely occurs in adults sporadically. Presenting anaplastic features within PA are uncommon and we report such a patient.

Case report: A 57-year-old woman presented with headache and ataxia. Magnetic resonance imaging (MRI) of the brain showed a 3 cm heterogeneous-enhancing mass harbouring cystic component in the right cerebellar hemisphere. Histological examination of the tumour exhibited that it was mostly composed of compact piloid astrocytes and microcystic changes typical of PA with scattered eosinophilic granular bodies and Rosenthal fibres. Presence of coagulative necrosis, marked pleomorphism, focal vascular endothelial proliferation and multiple mitosis was consistent with anaplastic features. Ki-67 was 5% and p53 stained in >50% of cells. She received post-operative radiation therapy and the tumour relapsed 8 months later.

Discussion: The rarity of pilocytic astrocytoma in adults accounts for difficulties in diagnosing anaplastic features and distinguishing it from glioblastoma and degenerative PA. There are specific histological criteria for diagnosis of PA with anaplastic features including presence of coagulative/pseudopalisading necrosis, hypercellularity, cytological atypia and brisk mitotic activity in addition to typical features of PA. Studies show that such tumours, specifically when necrosis presents, behave in a more aggressive manner, analogous to grade III astrocytoma, but with better behaviour than grade IV astrocytoma.

Back to Top | Article Outline


Abdul Rahman Al-Azri1, Richard M. Logan1,2

1Discipline of Oral Pathology, Oral Diagnostic Sciences, School of Dentistry, Faculty of Health Sciences, The University of Adelaide, and2Division of Surgical Pathology, SA Pathology, Adelaide, SA, Australia

Mucoepidermoid carcinoma (MEC) is one of the most common malignant salivary gland tumours. It mainly affects the parotid gland and the minor salivary glands of the palate. It is classically characterised by three main cellular components: epidermoid, intermediate, and mucus-producing cells, and is graded according to its histological features.

Some histological variants of MEC have been described, such as the clear cell, spindle cell, sclerosing, oncocytic and sebaceous subtypes. Calcification has also been reported in MEC, however it is a rare occurrence. There are few reported cases of calcification in MEC in the literature.

A case report of a clear cell subtype of MEC with calcifications in the soft palate is presented. A description of the histopathological features and the immunoprofile used to confirm the diagnosis is outlined. A brief literature review of this subtype of MEC and the significance of the presence of calcifications are also discussed in this case report.

Back to Top | Article Outline


Janet Anderson1, Richard B Fulton1, Michael Rose2, Sarah Green2, Suran L. Fernando1

1PaLMS Immunorheumatology, Royal North Shore Hospital, Sydney, and2Department of Anaesthesia, Royal North Shore Hospital, Sydney, NSW, Australia

Background: Neuromuscular blocking agents (NMBAs) are the most frequently reported causative agents in cases of anaesthetic related anaphylaxis. Assays for specific IgE (sIgE) to morphine and pholcodine are available as indicators of sIgE to the substituted ammonium groups on NMBAs. Chlorhexidine is an antiseptic also implicated in perioperative anaphylaxis.

Aim: To evaluate laboratory tests for sIgE to morphine, pholcodine and chlorhexidine in the investigation of perioperative anaphylaxis.

Method: This study included 140 patients referred to the Anaesthesia Allergy and Adverse Events clinic at Royal North Shore Hospital. Standardised skin tests were performed with all suspected agents to which patients had been exposed. Testing for sIgE to morphine, pholcodine and chlorhexidine was performed via the Phadia ImmunoCAP system.

Results: Using the recommended cut-off value sIgE tests for morphine, pholcodine and chlorhexidine all showed good sensitivity and specificity with reference to skin test results. ROC analysis suggested an alternative positive cut-off. Application of this lower threshold allowed for increased sensitivity without adversely affecting specificity.

Conclusion: Specific IgE testing to morphine, pholcodine and chlorhexidine is a reliable adjunct to skin testing in determining diagnosis of allergy to NMBAs and/or chlorhexidine. Additionally, adjustment of cut-off thresholds is able to increase test sensitivity.

Back to Top | Article Outline


A. Andreou

Pathology Queensland, Nambour Base Hospital, Sunshine Coast, Qld, Australia

Case summary: A 70-year-old ex-smoker, with a history of left pyeloplasty and hydronephrosis, underwent nephrouretectomy following discovery of an incidental 44 mm left renal mass on CT scan during investigation for bladder outlet obstruction. Two well circumscribed, cortical-based, yellow tumours, measuring 22 mm and 40 mm, and situated 3 mm apart, were identified macroscopically. Histological examination confirmed Type 1 papillary renal cell carcinoma (RCC) and Fuhrman grade 1 conventional (clear cell) RCC, respectively. Attempts at molecular evaluation were unsuccessful.

Discussion: Multiple ipsilateral synchronous RCC of different histological subtypes are rarely documented in the absence of familial syndromes. Therefore with each RCC subtype thought to represent a separate genetically distinct neoplasm, their sporadic occurrence in a single kidney poses interesting questions regarding their pathogenesis. Currently hypotheses describe evolution of one type of neoplasm into another or the presence of cancer stem cells from which multiple RCC develop. Furthermore, the prognostic significance of multiple ipsilateral synchronous RCC has not been established.

Conclusion: Through increased evaluation and reporting of the coexistence of multiple different renal neoplasms within a single kidney, we hope to gain further insight into the pathogenesis and molecular relationship between RCC subtypes, including the effects of multiple concurrent RCC on biological behaviour and prognosis.

Back to Top | Article Outline


A. Andreou1, J. Perry-Keane2, P. Burke3, I. Brown4

1Sullivan and Nicolaides Pathology, Taringa,2Pathology Queensland, Royal Brisbane and Women's Hospital, Herston,3Brisbane Urology Clinic, Wickham Terrace, and4Envoi Pathology, Herston, Qld, Australia

Case summary: An 82-year-old female underwent biopsy and subsequent right partial cystectomy of a bladder mass showing extension into the pelvis. Macroscopically the resection specimen showed ulcerated urothelium overlying a relatively circumscribed heterogenous and haemorrhagic mass within the bladder wall. Histology of both the biopsy and the resection specimen were concordant, demonstrating the morphological and immunohistochemical profile of a PEComa.

Discussion: The PEComa family of neoplasms may arise anywhere within the body, and typically display spindled, epithelioid or an admixture of these patterns microscopically. PEComa of the urinary bladder is rare, with only nine cases having been previously reported. Accordingly the more common benign and malignant differential diagnoses should first be excluded, as they show different biological behaviour. Criteria describing pathological features that may predict malignant behaviour in these neoplasms have been proposed. However their significance in PEComas of the urinary bladder is unknown and the little available evidence suggests they behave indolently in this location. Consequently precise recommendations regarding follow-up have not yet been established.

Conclusion: In order to better understand the pathogenesis, biological behaviour and prognosis of PEComas, further evaluation of the PEComa family of neoplasms needs to be undertaken, including long-term follow-up.

Back to Top | Article Outline


S. C. Aw1, H. Y. Lee1, C. M. E. Wang2, S. H. Chew3, C. F. Wong1, W. M. Yap1, K. L. Chuah1

1Department of Pathology, Tan Tock Seng Hospital,2Department of Neurosurgery, National Neuroscience Institute, and3Department of Pathology and Laboratory Medicine, Kandang Kerbau Women and Children's Hospital, Singapore

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumour composed of varying proportions of spindle and epithelioid cell components associated with HMB45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. A primary bone PEComa is extremely rare, with less than 15 cases reported in the literature. In this report, we detail yet another instance of a primary bone PEComa with malignant histological features which affected the L4 vertebral bone in a 46-year-old Chinese lady. Significantly, she had a past medical history of uterine leiomyosarcoma. Histology of the bone biopsy disclosed a proliferation of epithelioid cells with clear to eosinophilic cells associated with an arborising vascular network resembling a clear renal cell carcinoma but associated with HMB45 expression. Review of the uterine tumour disclosed a neoplasm with a different morphology not associated with HMB45 expression. The differential diagnoses of a PEComa affecting the bone, criteria for predicting its biological behaviour and its relationship with uterine leiomyosarcoma are presented. Awareness of the histological appearance and immunohistochemistry characteristics of PEComa are pivotal in achieving the correct diagnosis.

Back to Top | Article Outline


Anastasia Backhouse, Harold Lukse

Central West Pathology Services, Orange Health Service, Orange, NSW, Australia

Annular pancreas is a rare congenital anomaly consisting of a partial or complete ring of pancreatic tissue encircling the second part of the duodenum. The encircling tissue is continuous with the head of the pancreas and may include a pancreatic duct. The true incidence is not well established and is estimated to be 3 in 20 000. Annular pancreas is diagnosed equally in children and adults. The diagnosis in children is often suggested prenatally by neonatal ultrasound and confirmed within the first 1–2 days of life. Adults present with pain and gastrointestinal symptoms including nausea, vomiting and abdominal bloating. Childhood cases are frequently associated with congenital anomalies whereas adults show an increased risk of pancreatobiliary neoplasia. We present a Whipple's resection of an annular pancreas associated with duodenal adenocarcinoma in a 63-year-old male, a rarely reported combination. The second part of the duodenum was thickened by not only the circumferential tumour mass but also a variably thick rim of pancreatic tissue containing an aberrant pancreatic duct. The macroscopic evaluation of this specimen was challenging and in the absence of a cancer, the duodenum thickened by an annular pancreas could potentially be mistaken for a tumour mass.

Back to Top | Article Outline


S. Badman1, D. Byers1, R. Widjaja1, S. Ali1, Y. S. Lim1, R. Devarajo1, W. Rawlinson1,2

1RCPA Serology QAP, and2Virology Division, SEALS Microbiology, Prince of Wales Hospital, NSW, Australia

Aims: External quality assurance programs provide samples on a regular basis, for which the expected or target result is unknown to the participants enrolled in the scheme. This enables participants to evaluate their performance compared to their peers in the pre-analytical, analytical and post-analytical phases of sample analysis. The Royal College of Pathologist of Australasia (RCPA) Serology Quality Assurance Program (QAP) evaluated how a laboratory can assess their accuracy simply by reviewing their individualised Participant Assessment Report.

Methods: The RCPA Serology QAP uses the consensus of qualitative results, as the assigned value to which participant performance is evaluated, whilst robust statistics are used to evaluate (not score) quantitative serological results returned by participants.

Results: An analysis of 2011 survey results highlighted issues with participant accuracy when compared with their peers.

Conclusion: Quality assurance is a means of evaluating overall laboratory performance. A laboratory can record reproducible daily quality control, indicating that their assays are precise, but QA gives an indicator of accuracy. The RCPA Serology QAP individualised Participant Assessment Reports provide a ‘score’ for the qualitative data but apply robust statistics to evaluate quantitative data to provide participants with an indication of a bias in their operating system and an overall assessment of their accuracy compared with their peers.

Back to Top | Article Outline


Russell Barker, Patricia Lehmann, Sean O’Neill, Catherine Toong

Liverpool Hospital, Liverpool, NSW, Australia

Aims: Anti-dsDNA antibody measurement by radioimmunoassay has traditionally had better performance characteristics for the diagnosis of systemic lupus erythematosus (SLE) than ELISA methods. However, a new anti-dsDNA ELISA in which the dsDNA is attached to the plate by nucleosomes (dsDNA-NcX) has recently been reported to be equivalent. This study is a case-control validation comparing the two assays.

Methods: Consecutive samples sent for anti-dsDNA testing were measured by the Farr radioimmunoassay (Amerlex) and the anti-dsDNA-NcX ELISA (Euroimmun). Performance characteristics and correlation with disease activity were assessed.

Results: There were 26 patients with SLE and 26 controls with no connective tissue disease. The sensitivity and specificity for the Farr was 85% and 85% versus 77% and 96%, respectively, for the ELISA. There was no statistical difference between these results. The ELISA showed a better correlation with disease activity.

Conclusion: Our preliminary data also suggest that the performance of the Anti-dsDNA-NcX ELISA is comparable to the Farr radioimmunoassay, with lower sensitivity but better specificity at the manufacturer cut-offs. Correlation with disease activity appears to be better by ELISA. Further evaluations on a larger sample size are now to be performed.

Back to Top | Article Outline


Simone Birch, Jenny Grew

Queensland Medical Laboratory, Buderim, QLD, Australia

Aim: To illustrate an important potential diagnostic pitfall in salivary gland cytology. In particular, to demonstrate that acinic cell carcinoma can have an appearance indistinguishable from Warthin's tumour, and should be considered in the differential diagnosis.

Methods: Corresponding cytology and histology findings are presented for a case of acinic cell carcinoma.

Results: A 78-year-old male presented with a right parotid swelling. Fine needle aspiration (FNA) showed features typical of a Warthin's tumour with clusters of oncocytes in a background of small lymphocytes and granular debris. However, histological examination of the excision specimen showed an acinic cell carcinoma invading into surrounding fat and normal parotid. It had very prominent lymphoid stroma with germinal centres.

Conclusions: Acinic cell carcinomas often have very bland appearing nuclei and may have abundant granular or foamy cytoplasm. These features combined with the prominent lymphoid stroma that may be present in acinic cell carcinomas can easily be misdiagnosed as Warthin's tumour on FNA and should therefore be considered in the differential diagnosis. It should be remembered that there are numerous neoplastic and non-neoplastic lesions that can give a similar cytological appearance to Warthin's tumour. FNA results for salivary gland neoplasms should always be interpreted in conjunction with clinical and radiological features.

Back to Top | Article Outline


Mona Botros, Abdulhadi Bima, Zhong Lu, Craig Redden, Ken Sikaris

Melbourne Pathology, Collingwood, Vic, Australia

Aims: Vitamin B12 deficiency is usually due to dietary factors, however clinicians always consider the possibility of autoimmune pernicious anaemia. The Schillings test is no longer routinely available and therefore diagnosis often includes the specific intrinsic factor auto-antibodies (IFAb) +/– parietal cell auto-antibodies (PCAb). Holo-transcobalamin (HoloTC), also known as active B12, has proved to be a more reliable indicator of B12 deficiency than measuring total B12 (TB12). We therefore reviewed our experience with this test to see if HoloTC was more closely associated with pernicious anaemia testing.

Methods: We reviewed 1359 patients where HoloTC +/– TB12 was measured as well as one or more of IFAb and PCAb. We used each patient's first B12 result(s) for the analysis. HoloTC was measured by Abbott AxSym and total B12 was measured by Abbott Architect. PCAb antibodies are detected by immunofluorescence whereas IFAb are measured by Alegria automated ELISA.

Results: When HoloTC was very low (<10 pmol/L), 21% of patients had positive IFAb and 42% had positive PCAb. When HoloTC was mildly low (10–22 pmol/L), 8% had positive IFAb and 18% had positive PCAb. For very low TB12 (<100 pmol/L), 8% had positive IFAb and 24% had positive PCAb. When TB12 was mildly low (100–149 pmol/L), 4% had positive IFAb and 11% had positive PCAb.

Conclusions: PCAb were more likely to be positive at any B12 level consistent with its known poor specificity. The more specific IFAb positivity is more likely to be associated with low HoloTC levels than low TB12 levels.

Back to Top | Article Outline


Travis Brown

Royal Melbourne Hospital, Melbourne, Vic, Australia

Ever since the division of surgery from pathology in the mid to late 19th century, the anatomical pathology report has been the primary link between pathologists and clinicians. In earlier times, the pathology report was significantly shorter and rarely longer than a few sentences in total. Nowadays, the pathology report includes five sections (patient data and history, macroscopic description, microscopic description, diagnosis and comments), ranges from paragraphs to pages and contains so much jargon that few, if any, outside the pathology field fully understand it. To add to the confusion, a single clinician can receive a multitude of reporting formats and styles for identical diagnoses simply because they were reported by different pathologists. In an effort to address these issues, the Royal College of Pathologists of Australasia have developed a series of structured reporting protocols that provides guidance as to the content and presentation for cancer reports. Using these protocols, I have written a computer program that generates standardised pathology reports for pathologists to use in everyday practice. This application greatly reduces the time spent on reporting while providing important and consistent information to clinicians in accordance these recommendations.

Back to Top | Article Outline


C. Li1,3, M. Lee1,2, S. Flanagan1,2, R. Gupta1,2, C. M. Suter3, M. E. Buckland1,2

1Discipline of Pathology, Sydney Medical School, University of Sydney,2Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, and3Victor Chang Cardiac Research Institute, Sydney, NSW, Australia

O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme which is commonly hypermethylated in glioblastomas. Methylation of the MGMT promoter is associated with an improved response to alkylating agent chemotherapy and patient survival. Hence MGMT promoter methylation is often assessed as a prognostic marker for determining the course of treatment. Cytosine hydroxymethylation is another DNA modification whose significance is only now becoming clear, and in mammals it is known to occur at high levels in the brain and pluripotent stem cells. Importantly, 5’hydroxymethylcytosine is indistinguishable from 5’methylcytosine by bisulphite-based techniques. We hypothesised that hydroxymethylation may confound MGMT methylation assessment in a subset of glioblastomas, and may account in part for those glioblastomas that are classified as having MGMT hypermethylation but who fail to respond to chemotherapy. In this study the levels of both hydroxymethylcytosine and methylcytosine were assessed in a cohort of gliomas. Hydroxymethylation was found to be present in most samples, and ranged from 0.7% to 80% of the total ‘methylation’ signature of this region. These results demonstrate that hydroxymethylation can comprise a substantial amount of the ‘methylation’ levels detected at the MGMT promoter in glioblastomas, and may potentially confound the classification of patients for treatment with alkylating agents.

Back to Top | Article Outline


Carol E. Buchner, Cassandra C. Bryant, Pieter A. Baker, Rachel A. Rosenblum, Gabriella Lakos, Rufus W. Burlingame

INOVA Diagnostics Inc., San Diego, CA, USA

Objectives: Evaluate the precision of the NOVA View® automated digital image analysis system for anti-nuclear antibody (ANA) testing on HEp-2 cells, and compare the NOVA View interpretation of positive/negative to human interpretation.

Methods: For assessing intra-assay precision, four specimens were assayed in 12 replicates. For inter-assay precision, five serum samples were tested in 25 runs. Endpoint titres of four sera were established in 25 separate runs. To evaluate positive/negative agreement, 204 clinically defined sera were processed on HEp-2 cells and analysed manually and on the NOVA View.

Results: The intra-assay and inter-assay variability were <20%. The same endpoint was found by titration on average 15 out of 25 runs, and was one dilution lower or higher in the rest of the cases. The total agreement for positive and negative interpretation between the automated system and the human was 92%.

Conclusion: The high precision of the NOVA View, and the good agreement of results on 204 clinically defined sera demonstrate the capability of the NOVA View to reliably discriminate between positive and negative specimens. In addition, the archived images can be stored, which provides a basis for objective ANA interpretation, and may facilitate the establishment of ANA testing standardisation.

Back to Top | Article Outline


Michael Mahler1, Andrea Seaman1, Elena Csernok2, Jan Damoiseaux3, Renato A. Sinico4, Antonella Radice5, Zhao Cui6, Alenka Vizjak7, Rufus W. Burlingame1

1INOVA Diagnostics, Inc, San Diego, CA, USA,2Department of Rheumatology, University of Lübeck and Klinikum Bad Bramstedt, Germany,3Laboratory of Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands,4Nephrology and Clinical Immunology, San Carlo Borromeo Hospital, Milan,5Microbiology Inst, San Carlo Borromeo Hospital, Milan, Italy,6Renal Division, Department of Medicine, Peking University First Hospital, Institute of Nephrology, Peking University, Beijing, China, and7Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia

Introduction: Anti-proteinase 3 (PR3), anti-myeloperoxidase (MPO) and anti-glomerular basement membrane (GBM) autoantibodies are hallmarks in diagnosing the ANCA-associated vasculitides, granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), as well as Goodpasture's syndrome, respectively. The objective was to analyse three novel chemiluminescence immunoassays (CIA) on a random access chemiluminescent auto-analyser (BIO-FLASH) for the detection of anti-PR3-, anti-MPO- and anti-GBM autoantibodies.

Methods: Sera from patients with GPA (n = 81), MPA (n = 70) and GPS (n = 90) and from various healthy and disease controls were tested for anti-PR3 (n = 990), anti-MPO (n = 920) and anti-GBM (n = 797). Randomly selected samples were also tested by ELISA (INOVA Diagnostics).

Results: Sensitivities/specificities were: 70.4%/98.2% for PR3, 79.5%/98.7% for MPO and 95.6%/99.6% for anti-GBM antibodies. The areas under the curves were 0.868 (95% CI 0.805–0.931) for PR3, 0.948 (0.914–0.982) for MPO and 0.980 (0.958–1.00) for GBM. Positive and negative likelihood ratios were 38.7/0.30 (PR3), 60.91/0.21 (MPO) and 253.86/0.04 (GBM). Good agreements were observed between ELISA and CIA. The positive, negative and total agreements were 98.2%/96.0%/96.7% for anti-PR3 (n = 181), 100.0%/87.0%/91.0% for anti-MPO (n = 167) and 98.8%/97.1%/98.3% for anti-GBM antibodies (n = 120).

Conclusion: The novel CIAs showed valuable test characteristics for the diagnosis of ANCA-associated vasculitis and Goodpasture's syndrome.

Back to Top | Article Outline


Peter Martis, Priscilla Carrion, Kitty Li, Rufus W. Burlingame, Gabriella Lakos

INOVA Diagnostics Inc., San Diego, CA, USA

Objective: Evaluate the analytical and clinical performances of four new chemiluminescent immunoassays developed for the random-access, automated BIO-FLASH® instrument for the diagnosis of coeliac disease (CD): IgA and IgG anti-human tissue transglutaminase (h-tTG) and anti-deamidated gliadin peptide (DGP).

Methods: The precision, limits of detection and linearity were determined following Clinical Laboratory and Standards Institute (CLSI) guidelines. Clinical sensitivities and specificities were determined using more than 700 subjects consisting of CD patients, healthy subjects, and patients with other diseases.

Results: The QUANTA Flash assays have larger dynamic ranges than ELISAs. The entire reportable range shows linearity for all four antibodies. The within-run, between-run and total % CVs in all four CD assays were less than 12.2%. The clinical sensitivities were 93%, 50%, 68% and 81% for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively. The clinical specificities ranged from 98.0% to 99.6%. All tests have high diagnostic efficiency, characterised by areas under the curve values of 0.99, 0.93, 0.92, and 0.93 for h-tTG IgA, h-tTG IgG, DGP IgA and DGP IgG, respectively.

Conclusion: The new assays show excellent analytical performance characteristics. Their high clinical sensitivity and specificity make these tests invaluable for the diagnosis and management of coeliac disease patients.

Back to Top | Article Outline


W. L. Binder, R.W Burlingame, S. Lewis

INOVA Diagnostics Inc., San Diego, CA, USA

Objective: Determine the performance characteristics and clinical utility of an ELISA for detecting autoantibodies against a complex of phosphatidylserine and prothrombin (PS/PT).

Method: 71 patients with anti-phospholipid syndrome (APS), 24 with lupus anticoagulant (LAC), 167 normal blood donors and 52 disease controls were tested for IgG and IgM antibodies to PS/PT. The new assays were compared to traditional anti-B2GPI and LAC assays. Matched serum and citrated plasma samples were tested.

Results: All LAC positive patients were found to be positive for either IgG or IgM PS/PT antibodies, or both. Forty-eight of the 71 APS patients (68%) were PS/PT positive, and many of these individuals were negative for anti-B2GPI and LAC. Only three of 167 blood donors and one of 52 disease controls were positive on either assay, for a combined specificity of 98% (4/219). The assays had high inter- and intra-run precision. Equivalent results are obtained with serum or citrated plasma.

Conclusion: IgG and IgM autoantibodies that react with a complex of PS/PT are sensitive markers for APS. Unlike LAC, these antibodies can be detected in people treated with anticoagulants, and anti-PS/PT antibodies should be considered as additional new markers for diagnosing patients with APS.

Back to Top | Article Outline


Keith Byron1, Lisa Paiman1, Richard Tothill2, Evangeline Beula1, Fan Shi3, Adam Kowalczyk3, Robert Klupacs4, David Bowtell2

1Healthscope Advanced Pathology, Clayton,2Peter MacCallum Cancer Centre, Melbourne,3National (ICT) Australia, Parkville, and4Circadian Technologies Limited, Toorak, Vic, Australia

Aim: Carcinomas of unknown primary (CUP) account for 3–5% of all malignancies. Although the prognosis for patients with CUP is poor, identifying the primary site of the tumour can allow for more specific treatment selection and may prolong survival. We aimed to develop a gene expression based assay to determine the origin of metastatic carcinomas of unknown primary.

Methods: RNA was extracted from formalin fixed, paraffin embedded (FFPE) samples containing known metastatic tumours of various classes. Whole genome expression analysis was performed and a binary support vector machine was used as the classification method.

Results: 405 tumours of 16 classes were analysed. Following a cross validation strategy, we demonstrated an assay accuracy of 82% (93% within top three primary site predictions). Accuracies for individual tumour classes ranged from 72% to 93% for single site predictions, and between 83% and 100% for top three primary predictions.

Conclusion: Although further assay refinement and validation using an independent test cohort of known metastatic and CUP tumours is required, our preliminary data suggest that a gene expression-based diagnostic could aid in identifying the tumour of origin in patients with CUP.

Back to Top | Article Outline


A. D. Cala

Newcastle Department of Forensic Medicine, Newcastle, NSW, Australia

Aims: To investigate blood carboxyhaemoglobin saturation levels in coronial deaths where carbon monoxide (CO) is supected of playing a causative or contributary role in the death of a person.

Methods: Retrospective analysis of all departmental cases (around 100) from 2009 to 2011 in which CO levels have been performed.

Results: Blood CO levels in cases of suspected car exhaust gassing, house fire deaths, motor vehicle and other types of trauma with incineration are summarised.

Conclusions: ‘Normal’ blood CO levels range from 1% to around 10%, depending on smoking habits. Blood CO levels in house fire deaths range from around 11% to 75%. Blood CO levels in deaths from car exhaust fumes range from around 52% to over 80%.

Back to Top | Article Outline


A. D. Cala

Newcastle Department of Forensic Medicine, Newcastle, NSW, Australia

A 19-year-old female had a lifetime history of alternating diarrhoea and constipation. After developing acute lower abdominal pain for several days, she was taken to hospital but died soon after admission. A coronial autopsy showed massive distension and infarction of the descending colon and rectum, which were loaded with faeces. Microscopic features of the distal colon were indicative of Hirschprung's disease.

A diagnosis of Hirschprung's disease is usually made in early infancy, however this can be delayed for many reasons. In this unusual case, no medical investigation of this debilitating condition was ever performed, despite its near 20 year course.

Back to Top | Article Outline


Rachael Chambers1, Jane Armes1, Alejandro Arbelaez2, Rohan Lourie1

1Anatomical Pathology, Mater Pathology Services, South Brisbane, and2Mater Health Services, South Brisbane, Qld, Australia

Maternal intercurrent illness is an uncommon cause of perinatal death. We present a case of thrombotic thrombocytopenic purpura (TTP), with characteristic placental abnormalities, leading to fetal death, and review the literature concerning the onset of the rare condition during pregnancy.

A 25-year-old G1P0 woman presented at 20 weeks gestation with a one day history of headaches, dark urine and decreased fetal movements. Initial assessment showed fetal heart activity present. Concurrent investigation revealed thrombocytopenia, and haemolytic anaemia consistent with TTP. A fetal morphology scan was performed several days after admission which revealed fetal death.

Placental examination revealed large areas of acute infarction with widespread maternal vascular thrombosis. Some maternal vessels showed the characteristic finding of alternating zones of vascular dilatation and constriction (the ‘snowman sign’) consistent with aneurysmal dilatation of maternal spiral arteries with segmental intramural hyaline deposits. The placental findings directly link the TTP to the fetal death.

TTP is characterised by absence or inactivation of the plasma protease (ADAMTS13) which breaks down von Willebrand factor multimers. Deficiency leads to platelet aggregation and thrombus formation. In the placenta these changes are seen in conjunction with the effects of trophoblast on the spiral arterioles producing the characteristic histological appearance. TTP rarely occurs during pregnancy, but is associated with a high rate of perinatal death.

Back to Top | Article Outline


Long Chen1, Jane E. Dahlstrom1,2,3, Danny Rangasamy1

1The John Curtin School of Medical Research,2ANU Medical School, The Australian National University, Canberra, and3Department of Anatomical Pathology, ACT Pathology, The Canberra Hospital, Garran, ACT, Australia

Activation of long interspersed elements, type 1 (LINE-1 or L1) retrotransposons may be one of the mechanisms facilitating genomic instability of breast carcinomas.

Aim: To determine whether the expression of L1 proteins can serve as a useful biomarker in breast cancers.

Methods: L1 expression was evaluated in breast cancer cell lines and breast tissues by Western blot, immunofluorescence and immunohistochemistry. The expression of L1 proteins was determined in non-neoplastic breast tissue, fibroadenomas, ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC), and was correlated with pathological parameters and patient prognosis.

Results: L1 protein expression was higher in non-invasive compared with highly metastatic breast cell lines. DCIS showed greater immunoreactivity for L1 proteins than IDC. Normal breast tissue did not express L1 protein while fibroadenomas showed low L1 expression. L1 immunostaining positively correlated with the tumour's expression of oestrogen and progesterone receptors (p < 0.05). Patients with IDC showing high levels of nuclear L1 protein expression had a poor patient prognosis.

Discussion: L1 protein expression is highest in DCIS supporting the notion that genomic instability occurs at an early stage of cancer development. Nuclear L1 protein overexpression in invasive cancers appears to be a predictor of poor prognosis.

Back to Top | Article Outline


Srilakshmi Chennapragada1, Mahtab Farzin2, Anthony J. Gill2

1 PaLMS, Gosford Hospital, Gosford, and2Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia

Background: IMP3 (insulin like growth factor II mRNA binding protein 3) is an oncofoetal protein expressed in many malignancies.

Aim: To analyse IMP3 expression in lung cancer.

Methods: Immunohistochemistry for IMP3 was performed on a tissue microarray (TMA) containing 61 pulmonary squamous carcinomas, 155 adenocarcinomas and nine neuroendocrine tumours.

Results: IMP3 was positive in 124/225 (55%), comprising 52/61 (85.2%) squamous cell carcinomas, 67/155 (43.2%) adenocarcinomas and 5/9 (55%) neuroendocrine tumours. Positive staining was more common in aggressive subtypes of adenocarcinoma (solid, sarcomatoid and micropapillary) compared to acinar and lepidic subtypes. Among the neuroendocrine tumours, carcinoids were consistently negative whereas small cell carcinomas were all positive. Strongly positive staining was more frequently observed with higher clinical stage and with lymph node metastasis (58/90; 64.4%).

Conclusion: IMP3 expression is frequently observed in pulmonary squamous cell and small cell carcinomas and less commonly in adenocarcinomas. IMP3 expression correlates with lymph node metastasis and pathological stage of lung cancer, and therefore shows promise as a marker of aggressive behaviour. IMP3 expression may be useful in the differential diagnosis of carcinoid (negative) versus small cell carcinoma (positive).

Back to Top | Article Outline


Wayne Chou, David Challis

Department of Anatomical Pathology, Royal Hobart Hospital, Tas, Australia

A 52-year-old female with background of non-Hodgkin's lymphoma and polymyositis presented with a 4 year history of slow growing, left parotid mass. There were no other associated symptoms. Fine needle aspirate of the mass was performed and the diagnosis of an atypical primary salivary gland neoplasm was made. Subsequent left parotidectomy was performed and the diagnosis of parotid basal cell adenoma, membranous type was made.

Basal cell adenoma is a benign epithelial neoplasm of the salivary gland which is characterised by uniform proliferation of basaloid cells. Basal cell adenoma often occurs in the parotid gland followed by the submandibular gland and the upper lip region. Basal cell adenoma accounts for 1–3% of all benign parotid tumours, and the peak incidence is in the 6th to 7th decades of life. There are various subtypes based on morphological features which include solid, trabecular, tubular, and membranous types. The membranous subtype has been associated with the dermal cyclindromas which have similar incidence of chromosomal alteration at 16q12–13. The membranous subtype is characterised by tumour cells arranged in a jig-saw like pattern with prominent PAS+ eosinophilic, basement-membrane type material.

The main differential diagnosis is basal cell adenocarcinoma, and it can be difficult to distinguish between the two. Basal cell adenocarcinoma is characterised by increased number of mitotic figures, increased nuclear pleomorphism, infiltrative growth, and perineural and intravascular invasion. In our case, the proliferative index Ki-67 is low, and there is no significant nuclear pleomorphism, infiltrative growth pattern, or perineural invasion. However, the lesion extends to the diathermied margin, which is associated with a higher rate of recurrence of approximately 25%.

Back to Top | Article Outline


Steve Clark, Wendy Pryor, Sarah Halawani

Royal College of Pathologists of Australasia, Sydney, NSW, Australia

Aim: Development of eLearning resources is a vital element for any successful eLearning environment. We present a study of RCPA Trainees’ preferences for online modalities to support study and preparation for pathology exams.

Methods: In March 2011, the RCPA Education Portal ( was implemented to offer RCPA Trainees access to a range of eLearning resources. In an online survey distributed to 657 RCPA Trainees in November 2011, we sought opinions about the helpfulness of 15 different eLearning resources.

Results: 195 Trainees responded. The seven most popular eLearning resources, based on percentages who rated them as very helpful, were: case-based mock exams (72.5%), journal access (70.3%), multiple choice questionnaire (MCQ) mock exams (69.1%), online textbooks (68.2%), printable documents and articles (61.9%), case-based teaching modules (52.3%) and information-based teaching modules (51%). Open-ended comments highlighted needs for: improved accessibility, exam specific content, online journals and opportunities to engage with subject experts online.

Conclusion: Providing support for RCPA Trainees’ study and exam preparation will be enhanced by development of eLearning resources that firstly, build knowledge using easily accessible, searchable and printable online documents including journals and textbooks; and secondly, enable assessment of knowledge using formative MCQ and case-based mock exams.

Back to Top | Article Outline


Nanise Cuthers, Sanjay Sinha

Waikato Hospital, Hamilton, New Zealand

Idiopathic diffuse pulmonary ossification is a rare condition characterised by widespread osseous metaplasia within the lungs. It is usually asymptomatic and often diagnosed at autopsy. There have been a limited number of case reports in the literature. This report presents a case of idiopathic diffuse pulmonary ossification diagnosed at autopsy in a 76-year-old gentleman who died of a ruptured myocardial infarct. Macroscopically the lungs appeared to show extensive parenchymal ossification. The presence of heterotopic bone was confirmed histologically. A review of published literature on this unusual entity is presented.

Back to Top | Article Outline


Nanise Cuthers, Michael Arendse

Waikato Hospital, Hamilton, New Zealand

Intravascular large B-cell lymphoma (IVLBCL), a subtype of diffuse large B-cell lymphoma, is a rare entity characterised by proliferation of malignant lymphocytes within the intravascular compartment usually without involvement of lymph nodes. It has a heterogeneous clinical presentation and aggressive, often fatal, clinical course. As such the diagnosis is often made at autopsy. This case report presents a 46-year-old male in whom the diagnosis of IVLBCL affecting multiple organs was established at autopsy. The variable presenting and clinical features of this entity are discussed with the aim of heightening the awareness of this aggressive disease.

Back to Top | Article Outline


Joanna Czerwinski1, Kim M. Griggs1, Douglas W. Henderson1,2, Andrea J. Yool3, Sonja Klebe1,2

1Department of Anatomical Pathology, Flinders University, Bedford Park,2SA Pathology, Flinders Medical Centre, Bedford Park, and3Department of Physiology, Adelaide University, Adelaide, SA, Australia

Background: Malignant mesothelioma (MM) is an aggressive tumour of serosal membranes with a poor prognosis. We have identified aquaporin 1 (AQP1) as a significant prognostic marker.

Aims: To investigate if expression levels of AQP1 correlate with proliferation of MM cells and if alteration of AQP1 function by pharmacological blockers and siRNA cell inhibits cell proliferation in vitro.

Methods: MM cell lines (H28, H2052, 211H, H226 and H2452) and normal mesothelial cells (MET5A) obtained from the ATCC and primary MM cells harvested from malignant pleural effusions were used. AQP1 expression was determined by immunohistochemistry (IHC) and mesothelial phenotype confirmed. Cell proliferation was measured with and without altered AQP1 channel function using the MTS assay.

Results: AQP1-positive cell lines (H226 and H28) and patient-derived MM cells with high AQP1 expression had overall higher proliferation rates than the AQP1 negative cells (H2052, 211H, H2452 and Met5A). AQP1 modulation by pharmacological agents from a custom synthetic chemical library can decrease cell proliferation without inducing cytotoxicity or increasing apoptosis.

Conclusions: AQP1 is a prognostic marker for MM and modulation of AQP1 function can alter MM cell proliferation. This has treatment potential. AQP1 inhibition by siRNA will further clarify the molecular mechanism leading to specific AQP1 modulation.

Back to Top | Article Outline


A. L. Kent1,2, L. Brown3, M. Broom1, A. Broomfield3, J. E. Dahlstrom2,3

1Department of Neonatology, Canberra Hospital, Woden,2Australian National University Medical School, Canberra, and3Department of Anatomical Pathology, Canberra Hospital, Woden, ACT, Australia

Preterm infants are delivered while glomerulogenesis is ongoing and thus may be exposed to a number of insults including medications that may affect renal development. Podocytes detected in the urine are an indicator of glomerular injury in a number of renal conditions.

Aims: To determine whether preterm and term infants excrete podocytes in their urine and if exposure to gentamicin and indomethacin increased podocyte excretion in their urine.

Methods: Preterm infants less than 33 weeks gestation had urine collected each day while receiving either gentamicin or indomethacin and the number of casts and podocytes present in the urine were compared with preterm and term control infants urine who did not receive gentamicin or indomethacin.

Results and conclusions: Forty-two neonates were included in the study. Podocytes were present in small numbers (<2) in the urine of both preterm and term control neonates. There were increased numbers of podocytes in the urine of preterm neonates receiving indomethacin (p = 0.02). The increased number of podocytes in preterm neonates receiving indomethacin suggests that glomerular injury is occurring. It is unknown whether injury to glomeruli during glomerulogenesis in preterm neonates has long-term sequelae for renal development and function into adulthood.

Back to Top | Article Outline


Dariush Daneshvar1, Jeanne Tomlinson1, Ross Boadle2

1Department of Tissue Pathology and Diagnostic Oncology, and2Electron Microscopy Unit, Institute of Clinical Pathology and Medical Research, Westmead Hospital, NSW, Australia

Membranoproliferative glomerulonephritis (MPGN) type III, Strife variant is very rare. Although the actual incidence of this variant is unclear, it is thought to account for less than 1% of glomerulonephritis diagnoses. It commonly affects young people, who usually present with nephrotic syndrome. There are some recognised secondary associations, namely Sjögren syndrome, cirrhosis, human immunodeficiency virus infection, and systemic lupus erythematosus.

Here, we report a case of membranoproliferative glomerulonephritis, Strife variant. The light microscopic, immunofluorescence and electron microscopic findings that facilitate its diagnosis will be presented and discussed.


1. Mathieson PW. Mesangiocapillary glomerulonephritis. In: Pusey CD, editor. The Treatment of Glomerulonephritis. Boston: Kluwer Academic Publishers, 1999; 81–92.

2. Strife CF, McEnery PT, McAdams AJ, West CD. Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol 1977; 7: 65–72.

Back to Top | Article Outline


Dariush Daneshvar, Shaun Chou, Jeanne Tomlinson, Anita Achan, Winny Varikatt, Raghwa Sharma

Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia

Vascular tumours are very uncommon in the kidney and most of these have been described in single case reports. Some of these can be diagnosed radiologically so the histological features of many of these tumours are not well recognised. We report a case of a haemangioma arising from within the renal vein in a patient with chronic renal failure and bilateral adrenal cortical hyperplasia. The tumour has an unusual sinusoidal architecture and focal extramedullary haematopoiesis reminiscent of the spleen. As expected, the endothelial cells stain positively for CD31 and CD34 but negative for CD8. We will also briefly discuss the clinical and histological features of this unusual tumour based on literature reviews.


1. Brown JG, Folpe AL, Rao P, et al. Primary vascular tumors and tumor-like lesions of the kidney: a clinicopathologic analysis of 25 cases. Am J Surg Pathol 2010; 34: 942–9.

2. Montgomery E, Epstein JI. Anastomosing hemangioma of the genitourinary tract: a previously undescribed lesion mimicking angiosarcoma. Mod Pathol 2009; 22: 184–5A.

3. Zhao X, Zhang J, Zhong Z, et al. Large renal cavernous hemangioma with renal vein thrombosis: case report and review of literature. Urology 2009; 73: e441–3.

Back to Top | Article Outline


Dariush Daneshvar1, John Uther2, Rajesh Puranik3, Raghwa Sharma1

1Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead,2Department of Cardiology, Westmead Hospital, Westmead, and3Department of Nuclear Medical Science, Royal Prince Alfred Hospital, Camperdown, NSW, Australia

Isolated ventricular noncompaction, also known as left ventricular noncompaction (LVNC), isolated noncompaction of the ventricular myocardium (INVM), noncompaction of the left ventricular myocardium (INLVM), left ventricular hypertrabeculation, and spongy myocardium, is a rare and recently described cardiomyopathy with characteristic gross morphological abnormalities. It can present in paediatric and adult patients. Currently, the diagnosis can be made by echocardiography or magnetic resonance imaging (MRI). To the best of our knowledge, so far, there is no histopathology description of this entity in the English literature. Although aetiology, pathogenesis and histopathological features of IVNC are not clear, there is evidence for genetic basis in at least some cases, with subsequent implication of genetic counselling for family members of the patients. Here, we report a case of isolated ventricular noncompaction cardiomyopathy, and discuss its clinical, imaging and histopathology features.


1. Botto LD. Left ventricular noncompaction. Orphanet Encyclopedia. September 2004 (cited December 2011).

2. Stanton C, Bruce C, Connolly H, et al. Isolated left ventricular noncompaction syndrome. Am J Cardiol 2009; 104: 1135–8.

3. Roberts WC, Karia SJ, Ko JM, et al. Examination of isolated ventricular noncompaction (hypertrabeculation) as a distinct entity in adults. Am J Cardiol 2011; 108: 747–52.

4. Belanger AR, Miller MA, Donthireddi UR, et al. New classification scheme of left ventricular noncompaction and correlation with ventricular performance. Am J Cardiol 2008; 102: 92–6.

Back to Top | Article Outline


Dariush Daneshvar, Anita Achan, Raghwa Sharma

Department of Anatomical Pathology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia

To the best of our knowledge, there has been no report of primary small cell carcinoma (pulmonary type) of the fallopian tube in the English literature. Our case is a 60-year-old woman who presented with profuse brownish PV (per vagina) discharge over several months. The patient underwent hysterectomy and bilateral salpingo-oophorectomy, after which the diagnosis of small cell carcinoma (pulmonary type) of the right fallopian tube was made. On immunohistochemistry, the carcinoma revealed positivity for chromogranin, CD56, synaptophysin, TTF-1, CK-7 and EMA, and negativity for WT-1, P53, inhibin, CD-31, S100, HMB-45, CA-125, SMA, desmin, CK-20, Oestrogen, Napsin-A and CD-99. Here, for the first time, we present a case of small cell carcinoma (pulmonary-type) of the fallopian tube, and discuss its clinical presentation, imaging findings and histopathological features.


1. Eichhorn JH, Young RH. Neuroendocrine tumors of the genital tract. Am J Clin Pathol 2001; 115 (Suppl 1): S94–S112.

2. Singh V, Singh H, Leong C, et al. Vaginal small cell carcinoma: case report and review of literature. New York Medical Journal. 2008 (cited December 2011).

3. Miller B, Dockter M, el Torky M, Photopulos G. Small cell carcinoma of the cervix: a clinical and flow-cytometric study. Gynecol Oncol 1991; 42: 27–33.

4. Conner MG, Richter H, Moran CA, et al. Small cell carcinoma of the cervix: a clinicopathologic and immunohistochemical study of 23 cases. Ann Diagn Pathol 2002; 6: 345–8.

5. Campo E, Brunier MN, Merino M. Small cell carcinoma of the endometrium with associated ocular paraneoplastic syndrome. Cancer 1992; 69: 2283–8.

6. Tsujioka H, Eguchi F, Emoto M, et al. Small cellcarcinoma of the endometrium: an immunohistochemical and ultrastructural analysis. J Obstet Gynaecol Res 1997; 23: 9–16.

7. Eichorn JH, Young RH, Scully RE. Primary ovarian small cell carcinoma of pulmonary type: aclinicopathologic, immunohistologic, and flow cytometric analysis of 11 cases. Am J Surg Pathol 1992; 16: 926–38.

8. Kaminski M, Anderson PR, Han AC, et al. Primary small cell carcinoma of the vagina. Gynecol Oncol 2003; 88: 451–5.

9. Prasad CJ, Ray JA, Kessler S. Primary small cell carcinoma of the vagina arising in abackground of atypical adenosis. Cancer 1992; 70: 2484–7.

10. Cliby W, Soisson AP, Berchuck A, Clarke-Pearson DL. Stage I small cell carcinoma of the vulva treated with vutvectomy, lymphadenectomy, and adjuvant chemotherapy. Cancer.1991; 67: 2415–7.

Back to Top | Article Outline


B. Devanapalli, K. Sim, K. H. Carpenter

NSW Biochemical Genetics Service, The Children's Hospital at Westmead, NSW, Australia

Amino acid analysis is an essential service for the diagnosis and management of inborn errors of metabolism (IEM). For over 50 years the gold standard technique has been lithium ion exchange chromatography (IEC) with post-column ninhydrin derivatisation and photometric detection. This technique is laborious and expensive with typical run times over 120 minutes and requires dedicated instrumentation.

Reverse phase chromatography with pre-column derivatisation and either fluorimetric or photometric detection reduces runs times but can suffer from interference. Many biochemical genetics laboratories already have tandem mass spectrometry (MS/MS) equipment which can be linked to ultra performance liquid chromatography (UPLC). The combination of these two techniques gives the opportunity to produce highly specific quantitative assays with high throughput and we report on our experience with a UPLC-MS/MS system for amino acid analysis in physiological fluids.

Twenty-three physiological amino acids and 13 stable isotope internal standards, using 34 mass pairs are analysed within a 20 minute run utilising a simple acetonitrile/water gradient with tridecafluoroheptanoic acid ion pairing reagent. Sample preparation is limited to ultrafiltration to remove protein and dilution with internal standard mixture in mobile phase.

The method correlates well with IEC results and gives comparable precision and external QAP performance.

Back to Top | Article Outline


N. Doshi, G. Damant, J. Shatwell, R. Amelan, M. Taylor, S. Maxwell, J. Catania

Department of Microbiology and Infection Prevention and Control, Stepping Hill Hospital, Stockport NHS Foundation Trust, Manchester, United Kingdom

Aim: Sub-optimal usage of antimicrobials is associated with rise in antimicrobial resistance across the globe. Antimicrobial stewardship has been advocated by Department of Health (DH) UK to achieve prudent antibiotic prescribing. Our study aims to highlight the 858 bed UK NHS hospital's antimicrobial prescribing practises, to promote appropriate choices and to educate the prescribers. This can add to hospital cost savings and control HCAI like Clostridium difficile or multi-resistant infections.

Methods: A multidisciplinary team visited adult in-patients for different specialities and filled a proforma based on the ‘Antimicrobial care bundle’ within the Health and Social Care Act, UK 2010. Inappropriate antibiotic choices were changed and documented after discussing with the clinicians. Data were presented to raise awareness within prescribers and the board members.

Results: During March 2010–May 2011, the hospital antibiotic prescribing prevalence was around 22% of which 75% was appropriate and 25–50% needed intervention. Stopping or de-escalating antibiotics were the major changes. Overall documentation of antibiotic usage, clinical indication and culture sensitivity was good in the drug charts. Around 75% antibiotics were prescribed in line with local antibiotic guidelines and were reviewed by the clinical team within 72 hours. Piperacillin, tazobactam and co-amoxi clavulanate acid were the commonly used intravenous antibiotics. This was reflected in quarterly antibiotic and other clinical audits.

Conclusions: A rolling antimicrobial stewardship programme with several elements was introduced engaging clinician and hospital executive ownership. Real time education, daily review of antibiotics, and robust antibiotic policies with patient involvement are the mainstay of this challenging health care surveillance tool.


1. UK Department of Health. The Health and Social Care Act 2008. Code of Practice for the NHS on the Prevention and Control of Health Care Associated Infections and Related Guidance. London: Department of Health, December 2009.

2. Cooke J, Alexander K, Charani E, et al. Antimicrobial stewardship: an evidence-based, antimicrobial self-assessment toolkit (ASAT) for acute hospitals. J Antimicrob Chemother 2010; 65: 2669–73.

3. Department of Health Steering Group on Healthcare-Associated Infection and Health Protection Agency. Clostridium difficile Infection: How to Deal with the Problem. London: Department of Health, December 2008.

4. Davey P, Brown E, Fenelon L, et al. Systematic review of antimicrobial drug prescribing in hospitals. Emerg Infect Dis 2006; 12: 211–6.

5. Cooke FJ, Holmes AH. The missing care bundle; antibiotic prescribing in hospitals. Int J Antimicrob Agents 2007; 30: 25–9.

6. Miliani K, L’Hériteau F, Alfandari S, et al. Speci&filig;c control measures for antibiotic prescription are related to lower consumption in hospitals: results from a French multicentre pilot study. J Antimicrob Chemother 2008; 62: 823–9.

7. Dellit TH, Owens RC, McGowan JE, et al. Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship. Clin Infect Dis 2007; 44: 159–77.

8. Stone S, Kibbler C, How A, et al. Feedback is necessary in strategies to reduce hospital acquired infection. BMJ 2000; 321: 302–3.

9. Ansari F, Gray K, Nathwani D, et al. Outcomes of an intervention to improve hospital antibiotic prescribing: interrupted time series with segmented regression analysis. J Antimicrob Chemother 2003; 52: 842–8.

10. Gould LM. European Study Group on Antibiotic Policies. Minimum antibiotic stewardship measures. Clin Microbiol Infect 2001; 7 (Suppl 6): 22.

11. Paterson DL. ’Collateral damage’ from cephalosporin or quinolone antibiotictherapy. Clin Infect Dis 2004; 38 (Suppl 4): S341–5.

Back to Top | Article Outline


Mahtab Farzin, Loretta Sioson, Adele Clarkson, K. T. George, Anthony Gill

Department of Anatomical Pathology, Royal North Shore Hospital, Sydney, NSW, Australia

Aim: The availability of more targeted therapies has created a need for more precise subtyping of non-small cell lung carcinomas (NSCLCs), particularly to separate adenocarcinoma (AC) from squamous cell carcinoma (SCC). The aim of this study was to assess the utility of immunohistochemical markers performed on small biopsies to predict the final histology in excision specimens.

Methods: De facto small biopsies were made by creating a TMA from consecutive cases of resected lung cancer. Immunohistochemistry was performed on these biopsies and compared to the final histology from the excision specimens.

Results: TTF-1 stained 129 of 151 ACs (85.4%) and 12 of 70 (17.1%) SCCs. Napsin A stained 124 of 151 ACs (82.1%) and 9 of 70 (12.9%) SCCs. P63 stained 5 of 151 ACs (3.3%) and 58 of 70 SCCs (82.9%). CK5/6 stained 7 of 151 ACs (4.6%) and 62 of 70 SCCs (88.6%). The presence of one or both of the adenocarcinoma or squamous markers resulted in accurate classification in 183 of 223 (82.1%) cases. Thirty-seven cases showed positive staining for both adenocarcinoma and squamous carcinoma markers. Slides were unavailable for three cases.

Conclusion: We conclude that immunohistochemistry may assist subclassification of poorly differentiated NSCLCs in small biopsies, but is not always definitive.

Back to Top | Article Outline


Mahtab Farzin1, Loretta Sioson1, Adele Clarkson1, Bing Yu2, Ronald Trent2, Chiu Chin Ng2, Christina Selinger2, K. T. George1, Wendy Cooper3, Sandra O’Toole3*, Anthony Gill1*

1Department of Anatomical Pathology, Royal North Shore Hospital,2Department of Molecular and Clinical Genetics, Royal Prince Alfred Hospital,3Departments of Tissue Oncology and Pathology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; *these authors contributed equally

Activating mutations of EGFR and the EML4-ALK translocation predict sensitivity to specific targeted therapies for lung cancer. Currently testing is generally performed by direct sequencing and fluorescence in situ hybridisation (FISH) respectively.

We trialled immunohistochemistry with mutation-specific antibodies for EGFR exon 19 (Cell Signalling catalogue 2085S) and EGFR EXON 21 (Cell Signalling catalogue 3197S) and ALK (Novacastra, clone 5A4) as screening tests for these targets.

Staining was performed on a TMA containing 231 resected non-small cell carcinomas including 151 adenocarcinomas. Six showed positive staining for EGFR exon 19 mutation, six for EGFR exon 21 and four for ALK. All 16 demonstrated adenocarcinoma histology and were subsequently shown to harbour the predicted activating mutation or translocation by sequencing and FISH.

Although our study was not intended or designed to assess the sensitivity of immunohistochemistry, we conclude that immunohistochemistry is highly specific for these targets. We propose that immunohistochemistry may be used to triage all patients (including low risk patients) for formal sequencing or FISH analysis. If our results are confirmed by others, it may be appropriate to offer targeted therapies to those with positive immunohistochemistry and reserve sequencing/FISH for those cases negative by immunohistochemistry but considered to have a high clinical probability of these abnormalities.

Back to Top | Article Outline


Peter Ferguson, Richard Tilley, Brett Delahunt, Ian Hermans

Malaghan Institute of Medical Research and MacDiarmid Institute of Advanced Materials and Nanotechnology, Wellington, New Zealand

Despite advances in non-invasive medical imaging, accurate nodal staging of malignancy continues to rely on surgical pathology. Superparamagnetic iron oxide nanoparticles (FeOx NPs) have shown some promise as contrast agents for magnetic resonance imaging (MRI) of the lymph nodes, but recent large-scale studies failed to show consistent detection of tumours below 5 mm, and raised issues of high inter-reader variability. Here we describe imaging of lymphoid tissue using iron/iron oxide core/shell nanoparticles (Fe NPs) that have superior magnetic qualities to FeOx NPs, producing improved negative contrast in T2-weighted MRI. To provide an in vivo model of lymphoid metastases, breast cancer cells were injected into the spleens of mice, providing localised areas of tumour growth. MR images of tumour-bearing and sham-treated animals were generated using a 1.5 T imaging system and analysed by two independent, blinded radiologists. The superior contrast with Fe NPs improved the sensitivity and specificity of detection of tumours when compared to FeOx NPs, allowing detection of tumours as small as 1–3 mm. Importantly, the image analysis was performed by radiologists without prior training. The use of Fe NPs as contrast agents could improve diagnostic accuracy of MRI in cancer patients, leading to more rapid staging and effective treatment.

Back to Top | Article Outline


Lisa Marie Fiorentino

Department of Anatomical Pathology, Royal Hobart Hospital, Tas, Australia

Central neurocytomas are rare benign tumours of the central nervous system, first described by Hassoun et al. in 1982. Typically patients with central neurocytomas have a favourable prognosis, but some subsets of this tumour are associated with a more aggressive clinical course.

In our case, a 41-year-old lady presented with right frontal headaches of recent onset. A magnetic resonance imaging (MRI) scan of the brain showed a large right-sided intraventricular tumour causing midline shift to the left and obstructive hydrocephalus at the level of the third ventricle. The patient underwent stereotactic craniotomy and excision of the lesion. The diagnosis of a central neurocytoma was made intraoperatively, on the basis of cytology smears and a frozen section. A definite diagnosis of central neurocytoma with atypical features was subsequently issued, following the examination of paraffin-embedded sections and performance of an immunoperoxidase panel.

As cumulative data outlines a wider range of clinical, radiological and biological variations of this tumour entity, the MIB-1 proliferation index currently remains the most reliable and readily quantifiable parameter which correlates with recurrence rate and clinical outcome.

Back to Top | Article Outline


Robert Flower, Jesse Fryk, Melanie Dunford, Catherine Hyland, Helen Faddy

Research and Development, Australian Red Cross Blood Service, Kelvin Grove, Qld, Australia

Aim: Insect-transmitted viral infections remain a significant public health concern in Australia. The positive predictive value (PPV) for detection of anti-viral antibodies in donors was assessed using commercially-available kits.

Methods: Blood samples collected from Australian blood donors were tested by ELISA for IgM or IgG specific for either Dengue virus (DENV), Ross River virus (RRV) or Barmah Forest virus (BFV). The PPV was determined by comparison with results from reference laboratories.

Results: For the commercially-available kits: anti-DENV IgG, 225 kit-positive, 213 confirmed, PPV 94.7%; anti-RRV IgG, 315 kit-positive, 239 confirmed, PPV 75.9%; anti-BFV IgG, 127 kit-positive, 47 confirmed, PPV 37.0%; anti-DENV IgM, 118 kit-positive, 7 confirmed, PPV 5.9%; anti-RRV IgM, 138 kit-positive, 45 confirmed, PPV 32.6%; anti-BFV IgM, 142 kit-positive, 71 confirmed, PPV 50.0%. Some potential sources of unexpected kit-positives were investigated, however, these contributed minimally to the unacceptable PPVs.

Conclusions: These kits are designed for diagnostic testing of symptomatic patients, however, it would be expected that reliability for investigation of sub-clinical infection would be equal. PPVs, with the exception of 94.7% for IgG anti-DENV, were less than 80%. To measure rates of subclinical infection an investigation algorithm including exploration of unexpected positives and reliable confirmatory testing is required.

Back to Top | Article Outline


M. Gera, A. Gill

Royal North Shore Hospital, Sydney, NSW, Australia

Case reports: Case 1 was a 54-year-old female who presented with a right upper lobe lung lesion. Macroscopic examination showed a 20 mm nodular tumour. Microscopically, a mitotically active, monophasic spindle cell tumour extended into the lung and infiltrated the pleura. Immunohistochemistry was positive for CD99 and BCL2 and negative for CD34.

Case 2 was a 49-year-old female who presented with groin, lung and mediastinal lesions. Macroscopically there was a 45 mm lung tumour with a 10 mm subpleural lesion. Microscopic examination showed a mitotically active spindle cell tumour. Immunohistochemistry was positive for CD99, BCL2, and β-catenin and negative for CD10, ER and PR.

Case 3 was a 37-year-old female who presented with a left-sided pleural mass. Macroscopic examination showed a 135 mm nodular tumour and microscopically a mitotically active spindle cell tumour. Immunohistochemistry was negative for CD34, cytokeratins and S100.

Case 4 was a 43-year-old female who presented with a left lung mass and pleural effusion. There was a 95 mm cystic necrotic lung tumour macroscopically. Microscopy showed closely packed sheets of spindle cells. Immunohistochemistry was positive for CD99 and BCL2 and negative for cytokeratins and S100. Fluorescence in situ hybridisation (FISH) showed t(X; 18) (p11; 911) translocation in all four cases.

Diagnosis: Synovial sarcoma.

Discussion: Synovia sarcoma is commonly found in soft tissue. Histologically it is classified into four subtypes: biphasic, monophasic, monophasic epithelial and poorly differentiated. Synovial sarcoma occurs predominantly in the extremities. Primary synovial sarcoma arising in lung is rare.


1. Dennison S, Weppler E, Giacoppe G. Primary pulmonary synovial sarcoma: A case report and review of current diagnostic and therapeutic standards. Oncologist 2004; 9: 339–42.

Back to Top | Article Outline


M. Gera, A. Kaufman

Royal North Shore Hospital, Sydney, NSW, Australia

Case report: A 39-year-old male presented with unexplained fever, hepatosplenomegaly, jaundice and encephalopathy. Liver biopsy was performed as a last diagnostic tool. Macroscopic examination showed 5–15 mm of multiple fragments of liver cores. Microscopically there was inflammatory infiltrate in both liver lobules and portal tracts composed primarily of histiocytic granulomas. The granulomas had a distinct ring form with central clearing and a ring of fibrin. Immunohistochemistry was positive for CD68 and negative for CMV, ZN and fite.

Diagnosis: Granulomatous hepatitis with ring granulomas (Q fever).

Discussion: Q fever, due to Coxiella burnetti is a ubiquitous zoonosis. In humans, infection results from inhalation of contaminated aerosols from amniotic fluid or placenta or contaminated wool.

Diagnosis can be confirmed by serology and/or DNA amplification from blood, cerebrospinal fluid, bone marrow, bone biopsy, liver biopsy and fetal specimens. The immune response results in the formation of granulomatous lesions most commonly involving the lungs, liver, and bone marrow.

Prognosis: Q-fever present as acute or illness which can be treated by oral doxycycline.


1. Fournier P-E, Marrie TJ, Raoult D. The diagnosis of Q fever. J Clin Microbiol 1998; 36: 1823.

2. Parker NR, Barralet JH, Bell AM. Q fever. Lancet 2006; 367: 679–88.

Back to Top | Article Outline


M. Gera, B. Atmore

PaLMS, Royal North Shore Hospital, Sydney, NSW, Australia

Case report: A 38-year-old female presented with an exophytic right kidney mass. Macroscopic examination showed a 25 mm myxoid, nodular lesion within the perinephric fat. Microscopically, thre was a well circumscribed, uniformly mildly cellular, unencapsulated, myxoid spindle cell lesion present in the perinephric fat, immediately adjacent to the renal capsule. There was no involvement of the kidney. Immunohistochemistry was positive for EMA, SMA, Vimentin, BCL2, WT-1 and negative for MDM2, CDK4, claudin, CD34, S100, Desmin, HMB45, melan A, B-catenin, and AE1/AE3. Fluorescence in situ hybridisation (FISH) showed a normal signal pattern for probe for FUS/CREB3L2 fusion transcript between chromosomes 7 and 16 (excluding low grade fibromyxoid sarcoma).

Diagnosis: Myxoid soft tissue perineurioma.

Discussion: Perineuriomas are uncommon benign peripheral nerve sheath tumours. Location in the perinephric fat has not been previously reported in the literature, and therefore it is important to be aware of the possibility of occurrence at this site. The tumours typically show a morphological spectrum ranging from a hypercellular with collagenous stroma to hypocellular with myxoid stroma. In our case, the lesional cells are notable for having delicate elongated nuclei and numerous very attenuated bipolar cytoplasmic processes, which are highlighted by EMA.

Prognosis: Generally benign with rare local recurrence.

Acknowledgement: Professor CDM Fletcher, Brigham and Women's Hospital, USA (consultation diagnosis).

Back to Top | Article Outline


S. G. H. Goh, Y. H. Ho, C. Y. P. Chau, W. M. Yap, K. L. Chuah

Department of Pathology, Tan Tock Seng Hospital, Singapore

The rectal tonsil is a term originally coined to describe a structure composed of dense lymphoid tissue primarily in rodents. Subsequently, this term is applied to prominent lymphoid tissue located in the rectum in human beings as well. When the lymphoid proliferation becomes exuberant, separation from a lymphoma can be problematic, particularly for those who are not aware of this rather uncommon entity. The simultaneous occurrence of rectal tonsil and adenocarcinoma has not been previously documented to the best of our knowledge. In this report, we detail an instance when an exaggerated proliferation of such lymphoid tissue occurred in association with rectal adenocarcinoma in an 82-year-old lady who underwent a rectal biopsy during sigmoidoscopy for dyspepsia. On histology, there was a marked lymphoid proliferation expanding the lamina propria accompanying malignant glands. Lymphoepithelial complexes were noted. A subsequent anterior resection was performed. The differential diagnoses and criteria for separating benign from malignant lymphoid proliferations as well as the significance of the occurrence of rectal tonsil in association with an adenocarcinoma are presented.

Back to Top | Article Outline


Goh Chin Hong Ronald1, Avery Khoo1, Steven Messenas2, Damien Tan2, Lim Kiat Hon Tony1

1Department of Pathology, and2Department of Gastroenterology, Singapore General Hospital, Singapore

Aim: To study the prevalence and distribution of IgG4-positive plasma cells in pancreatic and ampullary carcinoma.

Method: 29 cases of primary pancreatic and ampullary carcinoma between 2008 and 2011 were retrieved from archive. IgG4 staining by immunohistochemistry was performed on sections of the tumour with surrounding pancreas and pancreatic ducts. The pattern of distribution and the mean numbers of IgG4-positive plasma cells were obtained.

Results: 19 of 29 (66%) cases showed the presence IgG4-positive plasma and eight cases (28%) featured >30 positive cells/HPF. Six cases (21%) showed a periductal distribution of IgG4 positive plasma cell with three cases (10%) displaying >10 positive cells/HPF. Two cases (7%) showed a diffuse distribution of IgG4-positive plasma cells.

Conclusion: IgG4-positive plasma cells are not infrequently found in association with pancreatic and ampullary adenocarcinoma. Our study highlights the presence of both peritumoural and periductal IgG4-positive plasma cells, which may rarely be diffusely distributed, in a significant minority of pancreatic and ampullary carcinomas. It is important that clinical, radiological and pathological correlation be used in the diagnosis of autoimmune pancreatitis as IgG4-positive cells may be seen in a proportion of carcinomas.

Back to Top | Article Outline


Abha Malik, Mahdieh Gorji

Douglass Hanly Moir Pathology, Sydney, NSW, Australia

Introduction: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver malignancy. It is classifiable into mass forming, periductal infiltrating and intraductal growth types grossly. Recognition of these patterns is important as they can be related to different prognosis. Until recently, the staging system for hepatocellular carcinomas was also applied to these tumours, however, important changes have been made on the basis of retrospective analysis of data in a multi-institutional analysis, and a new separate staging system for ICC has been introduced in the 7th edition of AJCC classification and staging.

Case report: An 83-year-old man who presented with malaise, weight loss and abnormal liver test, was found to have an ill-defined mass in his liver by imaging. Excisional biopsy showed a stellate pink solid mass 47 mm in maximum dimension with some infiltrative linear thickening at the periphery. Microscopically, the lesion was confirmed to be a moderate to poorly differentiated ICC with mixed mass forming and periductal pattern. Foci of vascular and perineural invasion were noted. The tumour was staged pT4 in view of the periductal pattern.

Conclusion: According to the 7th edition of TNM staging, having features of periductal pattern takes the tumour into stage pT4. In contrast to hepatocellular carcinoma staging, size is not considered relevant for prognostication and has therefore been excluded from staging criteria of ICC in the recent AJCC classification, 7th edition.

Back to Top | Article Outline


D. N. Gunawardane1, A. Ruszkiewicz2, J. K. Brealey3, T. J. Dodd1

1Department of Surgical Pathology, IMVS/SA Pathology, Lyell McEwin Hospital, Elizabeth Vale,2Department of Surgical Pathology, IMVS/SA Pathology, Royal Adelaide Hospital, Adelaide,3The Centre for Ultrastructural Pathology, SA Pathology, Royal Adelaide Hospital, Adelaide, SA, Australia

A 52-year-old female presented with gastrointestinal bleeding caused by a polypoid tumour of the ampulla of Vater which clinically was suspected to be a carcinoma. A CT guided biopsy showed a tumour with morphology and immunophenotype in keeping with a ‘neuroendocrine tumour’. Subsequent pancreatico-duodenectomy revealed a large 35 mm periampulary polyp.

Histological and ultrastructural examination of the polyp showed features of a gangliocytic paraganglioma. The ganglion cells were present focally in a nested arrangement resembling a pattern of paragangliomas.

Gangliocytic paragangliomas are rare solitary, periampullary tumours of the duodenum usually not exceeding 20 mm in diameter, which occur without age or sex predilection. Histologically, they consist of three cell types, namely epithelioid, ganglion cells and spindle cells admixed in various proportions with immunohistochemical and ultrastructural evidence of neuroendocrine differentiation.

Gangliocytic paragangliomas may pose diagnostic difficulties in small endoscopic biopsies, as not all three components may be sampled. The ganglion and epithelioid cells can appear cytologically atypical which, combined with disorganised growth pattern, inflammation and necrotic debris, may lead to erroneous diagnosis of malignancy. It is of paramount importance to notice that desmoplasia and mitoses are absent. Demonstration of dual expression of epithelial and neuroendocrine markers assists to arrive at correct diagnosis.

Back to Top | Article Outline


R. Gupta1,2, S. Flanagan1,2, M. Lee1,2, R. Stankovic1,2, M. E. Buckland1,2

1Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, and2Discipline of Pathology, Sydney Medical School, University of Sydney, Australia

Isocitrate dehydrogenase (IDH) gene mutations are the earliest known molecular defects in the majority of low grade diffuse gliomas, and secondary glioblastomas. All reported mutations are heterozygous missense mutations which affect arginine residues in the substrate binding site of IDH1, or less commonly, IDH2. The IDH mutation status of a glioma is a strong predictor of tumour behaviour and patient outcome. Here we report our experience with IDH mutation testing of over 130 neurosurgical specimens. In this cohort the demographic and clinical characteristics of patients with IDH-mutant tumours are similar to those described from a variety of centres across the globe. Kaplan-Meier survival analyses showed significantly improved progression-free survival in IDH mutant astrocytomas compared to IDH wildtype astrocytomas. We also identified rare and novel IDH1 mutations: these include the first identified homozygous loss of wildtype IDH1, an IDH1 (p.R100Q) mutation, and several instances of IDH1 (p.R132S) caused by a previously undescribed dinucleotide mutation. Our experience indicates that the spectrum of IDH1 defects in adult gliomas in Australia is more diverse than would be expected from the current literature, and that genetic screening should not be restricted to common IDH1 variants.

Back to Top | Article Outline


Ruta Gupta1,2, Bill O’Brien3, John Parratt4,5, Michael Buckland1,2

1Department of Neuropathology, Royal Prince Alfred Hospital, Sydney,2Discipline of Pathology, Sydney Medical School, University of Sydney,3Department of Neurology, John Hunter Hospital, Newcastle,4Department of Clinical Neuroscience, University of Sydney, and5Department of Neurology, Royal North Shore Hospital, Sydney, NSW, Australia

Susac syndrome is an under-recognised disease characterised by the clinical triad of encephalopathy, retinal artery occlusion and sensorineural hearing loss. It is thought to be due to a microangiopathy of uncertain aetiology. Only limited histopathological descriptions are available. We aimed to better characterise the neuropathological features of Susac syndrome and to define the vascular pathology present. Neurosurgical biopsies from three cases of Susac syndrome were examined morphologically, histochemically and immunohistochemically. Controls included cerebral and cerebellar tissue from six age matched cases. In addition, patient serum was assessed in a direct immunofluorescence assay. All three cases had cortical microinfarcts of varying ages. Acute cases showed perivascular CD8 positive lymphocytic cuffs with endothelial swelling and subtle micro-infarcts. Older cases showed thick walled, non-congophilic, hyalinised blood vessels. Intravascular fibrin thrombi, disrupted elastic lamina or complement activation was not seen. Serology testing revealed IgG binding to the internal elastic lamina in one case, a non-specific finding. We conclude that the neuropathology of Susac syndrome is relatively non-specific, and that vascular damage is T-cell-mediated rather than due to humoral responses. Awareness of the clinical, radiological and neuropathological features will aid the pathologist in alerting clinicians to the possibility of this treatable disorder.

Back to Top | Article Outline


M. S. Elliott1, R. Gupta2, K. Gao3, E. L. Chua4, A. Gargya4, J. R. Clark1

1Head and Neck Surgery, Royal Prince Alfred Hospital,2Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital,3Sydney Head and Neck Cancer Institute, and4Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Background: The incidence of papillary thyroid cancer is increasing, largely due to an increase in the number of incidentally discovered tumours. A significant number are 10 mm or less in size [papillary thyroid microcarcinomas (PTMC)]. There is controversy in the literature regarding optimal management of these tumours.

Aim: Review our institution's experience with the presentation and management of PTMC.

Methods: Retrospective analysis of prospectively collected data at the Sydney Head and Neck Cancer Institute from 1987 to 2009.

Results: The analysis includes 228 PTMC patients with 41 males and 187 females with a median age of 56.1 and 49.3 years, respectively. PTMC were discovered incidentally in 116 (50.9%) patients and non-incidentally in 112 (49.1%) patients. Amongst the non-incidental group, 11.6% patients presented with lateral cervical lymph node involvement. Non-incidental tumours were significantly associated with younger age (<45 years) (p = 0.007), and larger tumours (0.5–10 mm) (p < 0.001), when compared with incidental tumours. Amongst the non-incidental group, four patients developed recurrence as compared to none in the incidental group. None of the patients developed distant metastases or died of disease. None of the patients in the incidental group required additional surgery, or radioactive iodine.

Conclusions: PTMC presents equally both incidentally and non-incidentally. PTMC has a variable presentation and treatment should be dictated by the extent of disease.

Back to Top | Article Outline


P. Guzman-Barrera1, C. S. Selinger1, S. A. O’Toole1,4, J. F. Thompson2,4, M. H. N. Tattersall3,4, R. A. Scolyer1,4, R. Gupta1,4

Departments of1Tissue Pathology and Diagnostic Oncology,2Melanoma and Surgical Oncology, and3Medcial Oncology, Royal Prince Alfred Hospital, Sydney,4The University of Sydney, Sydney, NSW, Australia

Myxoid liposarcoma (MLS) characterised by chromosomal t(12;16)(q13;p11) resulting in FUS-DDIT3 fusion account for approximately 35% of liposarcomas. MLS occurs in young adults. Serosal and retroperitoneal metastases refractory to surgery, chemotherapy and radiotherapy are common, portending poor prognosis. Trabectedin, a marine derived alkaloid, has shown clinical responses in MLS in early phase clinical trials. Limited information is available regarding trabectedin-induced histopathological changes and residual disease assessment. We present a case of trabectedin-treated MLS and discuss histomorphological changes in the context of relevant drug mechanisms.

A 40-year-old female with MLS of the thigh developed multiple intra-abdominal metastases over 14 years. Trabectedin was commenced in 2008 after several relapses following conventional therapy. Imaging showed decreased tumour burden in 2011. In contrast to the typical histological features of MLS in previous biopsies, post-trabectedin debulking specimens showed marked reduction in tumour cellularity with myxoid change in <1% of tumour. Nodules of well differentiated adipocytes with size variation, lacking characteristic plexiform vascularity were seen amidst unusual hyaline sclerosis. FISH demonstrated persistent FUS-DDIT3 fusion in the absence of classical histopathological features.

Trabectedin treatment results in morphological changes that could be misdiagnosed as well differentiated liposarcoma or reactive changes. Knowledge of therapy and treatment-related effects prevents misdiagnosis.

Back to Top | Article Outline


Leah Ha1, W. Chiu1, R. Boswell1, J. Scott2

1Clinical Biochemistry Laboratory, and2Clinical Haematology Laboratory, Middlemore Hospital, Auckland, New Zealand

Introduction: Sitosterolaemia is a rare autosomal recessive disorder caused by mutations of ABCG5 and ABCG8, which leads to progressive accumulation of plant sterols within the body. We describe a patient with sitosterolaemia who presented with stomatocytosis and macrothrombocytopenia.

Case report: A pre-operative full blood count was checked on a 30-year-old Turkish woman (from parents as first degree cousin) with known history of idiopathic thrombocytopenia. Review of this blood film together with those from the past 2 years revealed a persistent picture of stomatocytosis and macrothrombocytopenia. Literature suggests these features can be from sitosterolaemia. There was history of migraine, oral contraceptive pill related acute hepatocellular hepatitis and hyperlipidaemia (total cholesterol 6.1 mmol/L, LDL-C 4.0 mmol/L, triglyceride 0.9 mmol/L - not on OC pills). There was no history of statin therapy and no family history of sitosterolaemia or premature cardiovascular diseases. Examination only revealed bilateral xanthelasma.

Results: Total plasma plant sterol was markedly raised (1.3 mmol/L; NR <0.02 mmol/L), consistent with sitosterolaemia. Secondary sitosterolaemia has been observed in TPN recipients but that is not the case here. Oral cholestyramine was instituted, with a view to add ezetimibe afterwards. The patient was planning to bear children from a blood related partner (cousin). Genetic analysis is pending.

Conclusions: Sitosterolaemia can present exclusively with stomatocytosis and macrothrombocytopenia.1 Whether they represent a subgroup with a different prognosis is unknown.


1. Wang G, Wang Z, Liang J, et al. A phytosterolemia patient presenting exclusively with macrothrombocytopenia and stomatocytic hemolysis. Acta Haematol 2011; 126: 95–98.

Back to Top | Article Outline


C. Hemmings1,2, N. Zeps2,3, C. Platell2,3

1ACT Pathology, Canberra, ACT,2School of Surgery, University of Western Australia, and3St John of God Healthcare, Subiaco, WA, Australia

Aims: Patients with locally advanced rectal cancer are generally offered neoadjuvant chemoradiotherapy in an effort to downstage the tumour prior to surgery; however, the degree of tumour regression achieved is highly variable and is difficult to predict. We postulated that tumour regression and the degree of post-radiation fibrosis would be causally related.

Methods: 133 patients undergoing neoadjuvant chemoradiotherapy were classified as ‘good responders’ (Dworak regression grade 3 or 4), ‘intermediate’ (grade 2), or ‘non-responders’ (grade 0 or 1). A semiquantitative three-step fibrosis score was developed and applied to all cases.

Results: There was no correlation between tumour regression score and fibrosis score, with each response group showing similar per centages of fibrosis (15–20% score 1, 30–35% score 2 and approximately 50% score 3).

Conclusions: Post-radiation fibrosis does not correlate with tumour regression. Rather the degree of fibrosis may correlate with differences in fibroblast gene expression signatures, and this is the subject of further study. The fibrotic response may be patient-dependent rather than tumour-dependent, and this may have predictive value in terms of subsequent complications of radiotherapy.

Back to Top | Article Outline


Choon Yan Ho, Lai Meng Looi

Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia

Pregnancy associated with malignancy and placental metastasis is uncommon. Seventy-three cases of placental metastases have been reported in the English literature. The most common placental metastases are from melanoma, followed by haematological malignancies. We report a case of maternal breast malignancy with placental micrometastasis despite an unremarkable gross placental appearance in a 42-year-old Chinese lady. She was diagnosed with infiltrating ductal carcinoma grade 3 in 2007 and underwent surgery and chemoradiation. She presented recently with an unplanned pregnancy and opted for termination of pregnancy. The placenta was grossly normal. However, microscopy revealed infiltration of chorionic villi by malignant epithelial cells which were immunopositive for ER and PR; negative for β-hCG, S-100 protein and HMB-45. The amniotic membranes, umbilical cord and major fetal organs were unremarkable. This case highlights the importance of examination of the placenta in maternal malignancies, as findings have a bearing on management of the patient and newborn (in the case of term pregnancy). Other than microscopy for the presence of malignant cells in the intervillous space, one needs to scrutinise for malignant villous invasion which is associated with fetal metastasis. This warrants closer and longer follow-up for the infant to detect systemic involvement by malignancy.

Back to Top | Article Outline


Melissa Holmes, Sophie Bittinger

Royal Women's Hospital, Melbourne, Vic, Australia

Primary ovarian non-Hodgkin's lymphoma (NHL) is rare. B-cell and T-cell NHL can arise in the ovary but B-cell tumours are most common.1 We present a case of a 76-year-old woman who presented with lower abdominal pain for one month and a complex 15 cm left ovarian mass, for which she underwent a laparotomy and removal of the mass. She had no lymphadenopathy or masses on MRI. A frozen section was performed intra-operatively which showed a discohesive tumour, favouring lymphoma. Paraffin H&E sections showed a tumour composed of sheets of discohesive cells with angular, hyperchromatic nuclei and scant cytoplasm, frequent mitoses and necrosis. The tumour extended into adherent fat on the surface of the tumour. Immunohistochemical studies were positive for CD45 and CD20, and negative for CK (AE1/AE3), CD30 and CD10. Ki-67 stained 90% of tumour cells. Flow cytometry was suggestive of large B-cell lymphoma. The overall features were of an ovarian diffuse large B-cell lymphoma. Although rare, primary ovarian lymphoma should be considered in the differential diagnosis of a pelvic mass.


1. Vang R, Medeiros J, Warnke R, et al. Ovarian non-Hodgkin's lymphoma: a clinicopathologic study of eight primary cases. Mod Pathol 2001; 14: 1093–9.

Back to Top | Article Outline


Michelle Houang, Loretta Siosin, Nicole Watson, Adele Clarkson, Anthony Gill

Royal North Shore Hospital, St Leonards, Sydney, NSW, Australia

Aims: Immunohistochemistry for ERG has been reported to be highly sensitive and specific for the TMPRSS2-ERG fusion oncogene. This fusion oncogene has been found in 50–70% of prostate cancers in screened populations but rarely to never in benign disease. We sought to assess the sensitivity and specificity of immunohistochemistry for ERG for the diagnosis of prostate carcinoma in an Australian population.

Methods: A TMA was constructed containing material from 283 consecutive prostatic adenocarcinomas from radical prostatectomies. Immunohistochemistry was performed with a mouse monoclonal antibody directed against ERG (clone 9FY Biocare Medical, USA).

Results: ERG staining was positive in 146 adenocarcinomas (51.5%). There was no staining of benign glands (specificity 100%). Commonly high grade PIN (HGPIN) adjacent to adenocarcinoma showed positive staining, but in only two cases was there positive staining in PIN without there being ERG positive carcinoma present in the same TMA core.

Conclusions: ERG shows a sensitivity of 51.5% and a remarkable specificity of 100% for the diagnosis of prostatic adenocarcinoma versus benign glands. ERG positive PIN is almost always associated with invasive adenocarcinoma in the same core biopsy. Immunohistochemistry for ERG may therefore have significant role in the pathological differential diagnosis of difficult prostate biopsies.

Back to Top | Article Outline


Kuang-Chih Hsiao1, Francoise Mechinaud2, Chris Czajko1, Marilyn Clark1, Sharon Choo1

1Immunology Laboratory, Royal Children's Hospital, Melbourne, and2Children's Cancer Centre, Royal Children's Hospital, Melbourne, Vic, Australia

Haemophagocytic lymphohistiocytosis (HLH) is characterised by lymphocyte and macrophage activation, resulting in fever, hepatosplenomegaly, coagulopathy, cytopenias and other features of inflammation. Diagnosis of HLH can be established when five of eight criteria, one of which is elevated soluble IL2-receptor-alpha (sIL2-Ra), are fulfilled.1 Mortality is high, despite HLH04 chemotherapy, prompting the search for better biomarkers of disease activity.

Aims: To assess the utility of sIL2-Ra in diagnosis of patients with suspected HLH and in disease activity monitoring.

Method: sIL2-Ra was measured by ELISA (R&D Systems) in stored serum, collected at presentation, from eight patients with known HLH (5 of 7 criteria, excluding sIL2-Ra). In two of the eight patients (Patients A and B), serial sIL2-Ra were measured and compared with serum ferritin and clinical disease activity (CDA), retrospectively assessed by the lead clinician, who was blinded to the sIL2-Ra results.

Results: All eight patients had elevated sIL2-Ra levels. Patient A's sIL2-Ra and ferritin levels correlated with CDA. Serial sIL2-Ra/ferritin/CDA results were 39518/14987/severe, >50000/6146/moderate, 13013/2315/mild, 10167/5038/moderate, 8446/2745/moderate, 5184/1772/inactive. Patient B's sIL2-Ra levels correlated better with CDA than ferritin levels. Serial sIL2-Ra/ferritin/CDA results were 47021/2948/severe, 18188/1173/moderate, 33870/1246/severe, 17147/5277/severe, 9806/20429/severe, 11333/3851/severe.

Conclusion: This study demonstrates the diagnostic sensitivity of sIL2-Ra and its value in complementing traditional disease activity markers in HLH.


1. Henter J-I, Horne A, Aricó M, et al. HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer 2007; 48: 124–31.

Back to Top | Article Outline


C. Hughes, N. Herrmann

RCPA Transfusion QAP, Qld, Australia

Aim: In 2012, the RCPA Transfusion QAP will be introducing a pilot for Performance Monitoring in the General Compatibility module.

Method: After each survey, the Transfusion Advisory Committee review laboratory results and points are allocated for each assessable element. This allows participants to be placed into a performance level based on the final score obtained.

From the survey levels, a cumulative performance level (CPL) is calculated. Performance levels are weighted and the CPL is calculated from the sum of individual survey performance levels divided by the last six surveys regardless of year/cycle.

Performance levels: Reference 100, loss of 0 points, weighting = 1; Reference 99, loss of 1–19 points (minor errors), weighting = 2; Operational, loss of 20–49 points (minor errors), weighting = 3; Review, loss of 50–99 points (1 critical error) weighting = 4; Unsatisfactory, loss of >100 points (2 or more critical errors) weighting = 5.

Exceptions: Unsatisfactory survey performance level defaults to unsatisfactory CPL; Review survey performance level defaults to review CPL; 3rd consecutive Reference 100 survey performance level resets the CPL to Reference 100.

Conclusions/outcomes: Participants results falling outside the criteria will be referred to the Advisory Committee for review. A letter of notification and committee report will be issued to the participant, supervisor(s) and Director of Pathology as below.

Criteria for letter of notification: Letter 1: two critical errors – letter and report sent to participant and supervisor(s); Letter 2: three critical errors – letter and report sent to participant and supervisor(s); Letter 3: four critical errors – letter and report sent to participant, supervisor(s) and Director of Pathology.

Back to Top | Article Outline


Doris Ip Hee Wai, Simon Nazaretian

The Royal Women's Hospital Anatomical Pathology, Melbourne, Vic, Australia

Ovarian Sertoli-Leydig cell tumour (SLCT) is a rare sex cord stromal tumour. Some SLCT, usually of intermediate or poor differentiation show heterologous elements such as gastrointestinal type epithelium, immature cartilage or skeletal muscle. However, SLCT with serous epithelium and immature neural tissue as heterologous elements have not been documented.

We describe a rare ovarian SLCT with heterologous elements in a 25-year-old woman with post-partum abdominal swelling and pain. Heterologous elements included cystic locules lined by a benign epithelium of serous and mucinous cells and a small foci of immature neural tissue.

SCLT with heterologous mucinous elements should be distinguished from pure mucinous cystic ovarian tumours which may appear similar macroscopically and present with virilising symptoms. Heterologous elements may present in a variable proportion from microscopic foci to predominant tumour masking the SLCT. This case highlights the importance of extensive sampling because of common and overlapping morphological features with other ovarian tumours.

Back to Top | Article Outline


P. Irandoost, L. Siosson, A. Clarkson, A. J. Gill

Royal North Shore Hospital, Sydney, NSW, Australia

Aims: It has recently been postulated that goblet cells in the oesophagus eventually develop from a field of metaplastic columnar cells with MUC2 positivity. The aim of our study was to assess whether MUC2 positivity in columnar cells predicts subsequent identification of goblet cells.

Methods: Twenty-two study cases were found (over 1998–2011) with intestinal metaplasia that had initial negative biopsies. MUC2 staining was performed on a positive and a negative biopsy from every case and compared with 29 control cases that never had goblet cells on multiple subsequent biopsies.

Results: All goblet cells and the majority of columnar cells directly in the vicinity of goblet cells (17/22 cases) showed MUC2 staining. This was less significant in the columnar cells away from goblet cells with only 6/22 cases showing positive staining. Fifteen of 22 (68%) cases with intestinal metaplasia showed some positive MUC2 staining on their earlier negative biopsies. Fourteen of 29 (48%) individuals who never had goblet cells on subsequent biopsies showed positive MUC2 staining.

Conclusion: Although the rate of MUC2 positivity was slightly higher on initial negative biopsies of individuals with intestinal metaplasia, our findings do not suggest that routine staining for MUC2 will be useful to predict subsequent diagnosis of intestinal metaplasia in columnar lined oesophagus.


1. McIntire M, Soucy G, Vaughan T, et al. MUC2 is a highly specific marker of goblet cell metaplasia in the distal oesophagus and the gastrooesophageal junction. Am J Surg Pathol 2011; 35: 1007–13.

2. Hahn H, Blount PL, Ayub K, et al. Intestinal differentiation in metaplastic, non-goblet columnar epithelium in the oesophagus. Am J Surg Pathol 2009; 33: 1006–15.

3. Chandrasoma P, Wijetunge S, DeMeester S, et al. Columnar-lined oesophagus without intestinal metaplasia has no proven risk of adenocarcinoma. Am J Surg Pathol 2012; 36: 1–7.

4. Niv Y, Fass R. The role of mucin in GERD and its complications. Nat Rev Gastroenterol Hepatol 2011; 9: 55–9.

Back to Top | Article Outline


P. Irandoost, K. De Silva

Royal North Shore Hospital, Sydney, NSW, Australia

Case presentation: An 85-year-old female presented with intestinal obstruction. Imaging revealed a mesenteric mass suspicious for a neuroendocrine tumour.

Macroscopic examination showed a convoluted segment of small bowel with a 50 mm mesenteric mass causing adhesion of adjacent bowel loops at multiple points. The cut surface was solid yellow with areas of calcification.

Microscopically there was a variable combination of fat necrosis, fibrosis, sclerosis, chronic inflammation and focal calcification. There was no cytological atypia or mitotic activity.

Immunohistochemistry was negative for β-catenin, Alk1 and CD34 and positive for SMA. There was no increase in IgG4 positive plasma cells.

Diagnosis: Sclerosing mesenteritis.

Discussion: This is a rare benign disease of unknown aetiology, characterised by tumour-like mass composed of chronic inflammation, fat necrosis and fibrosis. Patients may present with abdominal pain, obstruction, fever, chylous ascites or changed bowel habbits. Although various causes have been suggested including infection, trauma or ischaemia, the exact aetiology cannot be affirmed. Diagnosis is hard to make clinically and radiologically and needs pathological assessment of the excision biopsy.

Treatment and prognosis: It has a favourable prognosis and may be self-limiting. Asymptomatic cases may be observed. Some suggest immunosuppressive therapy for cases with mild symptoms to prevent progression. Surgical resection is reserved for cases with complications (bowel obstruction or perforation).


1. Okumu W, Schmidt CM, LeBlanc JK. Fat necrosis, fibrosis, chronic inflammation, abdominal pain, and a small bowel mass in a 65 year old man. Practical Gastroenterol 2008; July: 44–46.

2. Guo-Li G, Shi-Lin W, Xue-Ming W, et al. Sclerosing mesenteritis as a rare casue of abdominal pain and intraabdominal mass; a case report. Cases Journal 2008; 1: 242.

3. Akram S, Pardi DS, Schaffner JA, Smyrk TC. Sclerosing mesenteritis; clinical features, treatment, and outcome in ninety-two patients. Clin Gastroenterol Hepatol 2007; 5: 589–96.

4. Lim CS, Singh Tanger G, Tibrewal S, et al. Sclerosing mesenteritis presenting with small bowel obstruction and subsequent retroperitoneal fibrosis. Eur J Gasteroenterol Hepatol 2006; 18: 1285–7.

Back to Top | Article Outline


P. Irandoost, R. Eckstein, S. McCarthy, R. Scolyer

Royal North Shore Hospital, and Royal Prince Alfred Hospital, Sydney, NSW, Australia

Case presentation: A 38-year-old female presented with a soft tissue lesion beneath the nail bed of the right middle finger. Imaging showed a lucent lesion involving the medial aspect of the shaft of distal phalanx with some bone erosion.

Macroscopic examination showed a 12 mm transparent myxoid nodule.

Microscopically there was a uniformly moderately cellular myxoid lesion with a pushing margin, composed of spindled and stellate cells. No cytological atypia, mitosis or necrosis was observed. Thin-walled, curvilinear blood vessels and scattered mast cells were also present throughout.

Immunohistochemistry was negative for NF, S100, EMA and SMA, and positive for CD34.

Fluorescence in situ hybridisation (FISH) was negative for FUS translocation, specific for low-grade fibromyxoid sarcoma.

Diagnosis: Superficial acral fibromyxoma.

Discussion: These lesions are typically located in the dermis or subcutis of fingers and toes, with a tendency to involve the nail bed. They are composed of spindled and stellate cells in a myxoid background with accentuated vasculartiy and increased mast cells. They are typically CD34, EMA and CD99 positive and need to be differentiated from low-grade fibromyxoid sarcoma (MUC4–, CD34–, FISH showing FUS translocation), myxoid neurofibroma (S100+), superficial angiomyxoma (CD34–) and myxoid DFSP [also CD34+ but has subcutaneous fat infiltration and typically shows t(17;22)].

Prognosis: Generally benign with 10% recurrence rate and therefore needing complete excision and follow-up.


1. Al-Daraji W, Miettinen M. Superficial acral fibromyxoma: a clinicopathological analysis of 32 tumors including 4 in the heel. J Cutan Pathol 2007; 35: 1020–6.

2. Fetsch JF, Laskin WB, Miettinen M. Superficial acral fibromyxoma: a clinicopathologic and immunohistochemical analysis of 37 cases of a distinctive soft tissue tumor with a predilection for the fingers and toes. Hum Pathol 2001; 32: 704

3. Abou-Nukta F, Fiedler P, Parkash V, et al. Superficial acral fibromyxoma of the distal phalanx of the thumb. J Hand Surg (Br) 2006; 31: 619.

4. Quaba O, Evans A, Al-Nafussi AA, et al. Superficial acral fibromyxoma. Br J Plast Surg 2005; 58: 561.

Back to Top | Article Outline


Kambin Jafari Nejad

Prince of Wales Hospital, Sydney, NSW, Australia

Mixed adenocarcinoma and neuroendocrine carcinomas (MANEC) of the ampulla of Vater are extremely rare with only ten reported cases in the literature. This is a report of a rare case of mixed adenocarcinoma and neuroendocrine carcinoma which was centered in the ampullary region. A 53-year-old male presented with an ampullary tumour causing pancreatobiliary obstruction and a pancreaticoduodenectomy was performed. Macroscopic examination of the specimen revealed a 22 × 17 × 11 mm tumour involving the ampulla of Vater. Microscopically, the tumour was diagnosed as a mixed tumour predominantly consisting of high grade neuroendocrine carcinoma with juxtaposed area of conventional adenocarcinoma arising in an intestinal type adenoma. The diagnosis was supported by immunohistochemistry studies. The tumour was classified according to the WHO classification of tumours of the digestive tract and staged by the AJCC guidelines. These tumours are generally treated by pancreatico-duodenectomy followed by adjuvant chemotherapy. However, the clinical behaviour appears to be highly aggressive, with early metastases and fatal outcome.

Back to Top | Article Outline


Kambin Jafari Nejad

Douglass Hanly Moir Pathology, Sydney, NSW, Australia

Whilst haemangiomas are one of the most common benign tumours of the head and neck region, primary haemangioma of the thyroid gland is an extremely rare entity with only 15 cases reported in the literature so far. This is a report of thyroid haemangioma in a 49-year-old female who presented with multinodular goitre. Fine needle aspiration (FNA) of the left thyroid lobe revealed a benign follicular pattern; however, two consecutive FNAs of the right thyroid nodule were heavily blood stained and reported as insufficient for diagnosis. Subsequently, a thyroidectomy was performed. Macroscopic examination of the specimen revealed a well circumscribed 11 mm haemorrhagic nodule in the right lobe. Microscopically, the nodule was diagnosed as a lobular capillary haemangioma unassociated with reparative fibrosis or haemosiderin deposition. A CD31 immunostain confirmed the vascular nature of the lesion. Most vascular lesions of the thyroid are reparative in nature, related to the organisation of haematoma after FNA or a biopsy related procedure. This case report highlights the importance of including primary vascular tumours such as haemangiomas in the list of differential diagnosis of thyroid nodules.

Back to Top | Article Outline


Alexandra Jolley, Jillian Nicholl, Yee Khong, Nick Manton, Jill Lipsett, Wendy Waters, Janice Fletcher, Lynette Moore, Christopher Barnett, Sui Yu

SA Pathology, Women's and Children's Hospital, 72 King William Road, North Adelaide, SA, Australia

Aim: To evaluate the usefulness of microarray in fetal autopsy cases with or without malformations.

Introduction: Microarrays were performed as part of autopsy investigation on 90 cases, including stillbirths, fetuses that died in utero or were terminated due to abnormal ultrasound findings between February 2009 and September 2011.

Methods: Microarray was performed using the BlueGnome Cytochip oligo ISCA 60K array platform. Microarray results and autopsy reports of all cases were reviewed to determine the presence of any fetal malformations and to categorise the positive microarray findings as causative, of unknown clinical significance or not causative. The number of causative findings identified by microarray in cases with at least one malformation was compared to the number of causative findings identified in cases without any malformations.

Results: Five microarrays failed. Of the remaining 85 cases with microarray results, 53 cases had at least one malformation and 32 cases had no malformation. Four cases (7.5%) with one or more malformations had a causative finding on microarray, compared to no cases without any malformations.

Conclusions: Microarray is a valuable investigation in fetal autopsy cases with at least one malformation, but not for those without any malformation.

Back to Top | Article Outline


D. Joshi, R. Spokes

Pathcare/St John of God Pathology, Geelong, Vic, Australia

There has been a rise in gastrointestinal tuberculosis incidence among immigrants and HIV patients, both in Europe and the United States. However, abdominal tuberculosis is very uncommon in Australia. The diagnosis of tuberculosis may be overlooked due to lack of experience and the fact that one type of tuberculosis, hypertrophic tuberculous colitis (HTC), can mimic Crohn's disease colonoscopically and radiologically. The ileocaecal region and peritoneum are the most likely sites of infection. Pulmonary tuberculosis is evident in less than half of patients. We present a case of HTC in a 29-year-old Indian man presenting with right iliac fossa pain. Appendicectomy was embarked upon but was converted to right hemicolectomy on intraoperative suspicion of pathology – Crohn's disease or tuberculosis. Macroscopically there were severe cobblestone skip lesions in the colonic mucosa, with fissures penetrating into the muscularis propria. Necrotising granulomatous inflammation on microscopic examination and positive mycobacterium species nucleic acid amplification test (PCR) confirmed the tuberculous colitis. This case emphasises the significance of histopathological examination in guiding and validating the management, as the administration of corticosteroids (for the treatment of the Crohn's disease) to a patient with colonic tuberculosis may have disastrous results.

Back to Top | Article Outline


D. Joshi, R. Spokes

Pathcare/St John of God Pathology, Geelong, Vic, Australia

Primary non-Hodgkin's lymphoma (NHL) of the breast is rare (1.7–2.2% of extra-nodal NHL) and predominantly of B-cell phenotype. Anaplastic large cell lymphoma (ALCL) is a T-cell lymphoma accounting for only 3% of all NHLs. In its report of January 2011, the US Food and Drug Administration stated that it was aware of approximately only 60 case reports of ALCL in women with breast implants worldwide. Data are insufficient to determine whether a specific type of implant (silicone versus saline) or reason for implant (reconstruction versus aesthetic augmentation) is associated with lower or higher risk of ALCL. We present a rare case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of silicone breast implant in a 54-year-old female. The patient had undergone mastectomy for breast carcinoma 13 years ago. She presented with a ruptured breast implant with masses on medial and lateral sides. Histology, immunohistochemistry, and T-cell gene rearrangement studies were supportive of a diagnosis of CD30-positive ALK-1-negative anaplastic large cell lymphoma. This rare case highlights the importance of histological examination of breast implant capsule specimens.

Back to Top | Article Outline


R. C. Junckerstorff1, C. Ly1, P. Bannan3, P. Glendenning2, V. A. Fabian1

1PathWest Neuropathology,2PathWest Biochemistry, Royal Perth Hospital, and3The Mount Hospital, Perth, WA, Australia

Suprasellar ganglion cell tumours are infrequent with few cases reported in the literature. We report a rare case of a suprasellar prolactin secreting pituitary macroadenoma and gangliocytoma.

Hyopthalamic gangliocytomas may be hormonally active, producing regulatory peptides resulting in endocrinopathies mediated by the pituitary gland. Hypothalamic gangliocytomas may be intermingled with adenohypophysis and occasionally admixed in a pituitary adenoma. A review of 50 reported cases in the literature, which includes a mixture of functional hypothalamic gangliocytomas and hypothalamic gangliocytomas with pituitary adenomas, indicates the clinical phenotype is usually characterised by either growth hormone (acromegaly) or cortisol hypersecretion (Cushing's disease), the combination of a prolactinoma and hypothalamic gangliocytoma being extremely rare. The adenohypophysis and neurohypophysis do not contain neurons. Gangliocytomas are more common in women and their association with pituitary adenomas suggests a common causative mechanism. Sellar gangliocytomas may arise from abnormal cellular differentiation during neoplastic proliferation of the adenohypophyseal cells whilst others consider these tumours are of hypothalamic origin.

Our case, a 67-year-old female, presented with visual field failure, hyperprolactinaemia and cranial magnetic resonance imaging (MRI) showing a complex suprasellar mass extending into the pituitary fossa. Initial transphenoidal resection was successful but subsequent transcranial resection was required within 6 months due to residual tumour growth with compression of the right optic nerve and chiasm. Immunohistology demonstrated a prolactinoma admixed with a gangliocytoma.


1. Serri O, Berthelet F, Belair M, et al. An unusual association of a sellar gangliocytoma with a prolactinoma. Pituitary 2008; 11: 85–7.

2. Asa SL. Tumours of the Pituitary Gland. AFIP Atlas of Tumour Pathology. Series 4, Fascicle 15. Washington, DC: AFIP, 2011; 181–6.

Back to Top | Article Outline


Jennifer Kim1, Tamazin Leecy1, Annabelle Mahar1, Rooshdiya Karim1, Christina Brown2, Wendy Cooper1

1Department of Tissue Pathology and Diagnostic Oncology, and2Department of Haematology, Royal Prince Alfred Hospital, Sydney, NSW, Australia

Castleman disease, also known as angiofollicular lymph node hyperplasia is a rare lymphoproliferative disorder of unknown aetiology that was first desribed by Castleman in 1954. It is clinically classified into unicentric or multicentric variants according to its localisation and is histologically classified into hyaline vascular, plasma cell or mixed type.

We present a rare and unusual case of unicentric plasma cell variant of Castleman disease involving a mesenteric mass of an 18-year-old previously well woman who presented with a 1 year history of constitutional symptoms.

The core biopsy in conjunction with a fine needle aspiration biopsy showed no diagnostic evidence of malignancy. Subsequent excisional resection specimen confirmed the diagnosis, which was HHV-8 negative.

We discuss the cytological and histological features of this rare lesion and its pathogenesis and differential diagnosis. Exact sub-classification of Castleman disease is vital as it has significant implication in terms of management and clinical behaviour.

Back to Top | Article Outline


I. Koh1, D. Giron1, A. Ammar2, W. M. Yap1, K. L. Chuah1

1Department of Pathology, Tan Tock Seng Hospital, and2Laboratory Medicine Department, Khoo Teck Puat Hospital, Singapore

A primary thyroid teratoma is uncommon, the disease being more prevalent in infants. In adults, the tumour is even less common with less than 40 cases documented in the English literature. The neoplasm is usually malignant in such a setting in contrast to the usual benign tumour in infancy. In this report, we describe the cytological findings of an immature teratoma affecting the thyroid gland of a 33-year-old Chinese woman who presented with a right sided thyroid lump for 4 months. The fine needle aspiration material disclosed single and clusters of medium-sized, primitive appearing cells with stippled chromatin. In addition, there were rosettes identified, suggesting neuroepithelial differentiation. The excised specimen revealed immature teratoma (encapsulated follicular tumour with immature teratoma) with primitive neuroectodermal, mesodermal and endodermal tissue derivatives. The neuroectodermal component corresponded to the tumour cells identified on the cytology sample. As the description of this thyroid neoplasm on cytology is very rare, this report serves to increase awareness of this entity. A summary of the reported cases of immature (malignant) thyroid teratoma as well as the cytological and histological features are presented. The problems in diagnosing this neoplasm on cytology are also highlighted.

Back to Top | Article Outline


Mary-Ann Koh, Lakshmy Nandakumar

Royal Brisbane and Women's Hospital, Qld, Australia

Littoral cell angioma is a rare splenic lesion that was described in 1991. It demonstrates both endothelial and histiocytic differentiation. We present a case of a 55-year-old gentleman with a 3.5 cm splenic lesion found on staging CT scan following excision of a level 1 malignant melanoma. There was no other significant medical history. The main differential diagnoses considered included a splenic haemangioma or metastatic melanoma. Due to the uncertain nature of the lesion, it was surgically excised. The histological and immunohistochemical profile were consistent with a littoral cell angioma. Within the current literature, there are several cases describing patients with synchronous visceral malignancies and lymphomas. There are also rare cases showing malignant potential while most cases were discovered incidentally. A dysfunction in the immune system has been postulated as possible underlying pathogenesis and may explain its association with other cancers. This case occurred in a patient with recently diagnosed melanoma. A possible association with malignancy has yet to be confirmed and further studies are required to determine this.


1. Falk S, Sutte HJ, Frizzera G. Littoral cell angioma. A novel splenic vascular lesion demonstrating histiocytic differentiation. Am J Surg Pathol 1991; 15: 1023–33.

2. Hanna T, Friedman TM, Baumgarten D. Littoral-cell angioma: A case and a review of the literature. Radiology Case Reports 2011; 6: 324.

3. Tee M, Vos P, Zetler P, Wiseman SM. Incidental littoral cell angioma of the spleen. World J Surg Oncol 2008; 6: 87.

Back to Top | Article Outline


N. W. C. Koh, C. F. Wong, C. H. Y. Teo

Department of Pathology, Tan Tock Seng Hospital, Singapore

Extramedullary haematopoiesis is rarely seen in the breast parenchyma and axillary lymph nodes in the setting of neoadjuvant chemotherapy, with intrinsic and extrinsic factors hypothesised as causes for this phenomenon. Documenting the response of the invasive carcinoma to the preceding chemotherapy is an important part of the pathological examination, which has implications to the prognosis and treatment algorithms of these patients. An increased awareness of this uncommon and yet important phenomenon of extramedullary haematopoiesis in such a setting is pivotal in avoiding a misdiagnosis. Here we report the occurrence of extramedullary haematopoiesis in the axillary lymph nodes and breast parenchyma of a 45-year-old female patient who had undergone neoadjuvant chemotherapy for locally advanced breast cancer, which was previously reported as an invasive ductal carcinoma. On histology, there was no residual carcinoma; however, subtle foci of tri-lineage haematopoiesis were seen both within the breast parenchyma and multiple lymph nodes, especially within the capsule and sinuses of the latter. Although rare, this phenomenon may potentially mimic a primary breast carcinoma, particularly an invasive lobular carcinoma as well as residual breast cancer. The histological criteria and use of immunohistochemistry stains as an adjunct in separating extramedullary haematopoiesis from malignancy is presented.

Back to Top | Article Outline


Rina Leonetti, Craig Curtin, Andrea Rita Horvath

SEALS Department of Clinical Chemistry, Prince of Wales Hospital, Sydney, NSW, Australia

Aim: Interferences with creatinine measurements may result in inaccurate estimations of the glomerular filtration rate, particularly in children and neonates. We investigated the impact of common interferences on three creatinine methods.

Methods: Pooled serum samples at three creatinine concentrations were spiked with HbA, HbF, unconjugated bilirubin and Intralipid and measured in duplicates with Roche's compensated, rate-blanked, kinetic Jaffe and enzymatic methods and on Radiometer's ABL827 analyser. Absolute and relative differences between spiked and unspiked specimens were compared to interference indices recommended by manufacturers. Our interference criterion was ±8% recovery of unspiked samples, based on the Royal College of Pathologists of Australasia Quality Assurance Program's (RCPA QAP) allowable limits of performance.

Results: The degree of HbA and HbF interference in the Roche Jaffe and enzymatic methods depended on creatinine concentration. The manufacturer's single HbA haemolysis index (1000 Jaffe; 800 enzymatic) was only applicable when creatinine was >95 μmol/L. When creatinine was <95 μmol/L the interference criterion was met at lower indices (200 Jaffe; 500 enzymatic). HbF interference makes the Jaffe test unsuitable in neonatal specimens and the enzymatic method, up to HbF ≤6 g/L, is recommended. However, in neonates the enzymatic assay already underestimated creatinine by 20% when HbF was 3–4 g/L. Unconjugated bilirubin did not interfere up to 700 μmol/L (Jaffe) and 300 μmol/L (enzymatic; manufacturer's recommendation 171 and 342, respectively). The Radiometer ABL 827 creatinine method was not affected by any interference.

Conclusion: Creatinine method interference by haemolysis and bilirubin can be additive, therefore we found the Radiometer ABL 827 enzymatic method the most reliable for such specimens. Interference indices provided by manufacturers should be critically evaluated at different analyte concentrations, and single cut-off values cannot be universally applied to all specimens without verification.

Back to Top | Article Outline


J. Li, A. Mahar

Royal Prince Alfred Hospital, Sydney, NSW, Australia

Rhodococcus equi is a Gram positive coccibacilli that can infect immunocompromised individuals and cause necrotising pneumonia. Histologically, it often produces an unusual malakoplakia-like appearance in the lung. We present a case of a 57-year-old immunosuppressed man with renal transplant who presented with right upper lobe cavitating pneumonia. Blood and tissue cultures grew Rhodococcus equi. The patient was treated with surgical lobectomy and histology showed a malakoplakia-like appearance in the pulmonary abscess. A review of recent literature is also presented.

Back to Top | Article Outline


K. Limarporn, L. Shen

Department of Anatomical Pathology, Princess Alexandra Hospital, Pathology Queensland, Woolongabba, Qld, Australia

Aim: To describe and review the literature for aggressive digital papillary adenocarcinoma, a rare tumour of eccrine sweat gland, and to discuss the differentials and potential diagnostic pitfalls.

Method and result: An excision from a 45-year-old Caucasian man presenting with a lump on his left finger was routinely processed and examined. The tumour was composed of cystic spaces displaying tubulo-alveolar growth and some papillary projections protruding into the cystic lumina, outlined by thick fibrous tissue. The cells displayed a relatively even nuclear chromatin pattern, smooth nuclear outlines, with occasional nucleoli and abundant mitoses with focal squamous metaplasia. A diagnosis of aggressive digital papillary adenocarcinoma was made.

Discussion: This entity is a rare neoplasm of eccrine sweat gland origin which typically presents as a mass on a finger. The majority of these cases occur in males in their 5th–7th decade, and less than 100 cases have been reported.

Back to Top | Article Outline


K. Limarporn, R. Lourie, L. Pool, D. Wong

Pathology Department Princess Alexandra Hospital, Pathology Queensland, Woolongabba, Qld, Australia

Aim: To describe and review literatures for malignant melanocytic matricoma and, to discuss the differentials and potential diagnostic pitfalls.

Method: A skin excision from an 81-year-old man presenting with a skin lesion was processed routinely and examined, including several immunohistochemical studies, namely AE1/AE3, S-100, and MelanA.

Result: The tumour was characterised by an exophytic nodular growth with ulceration displaying biphasic features, and composed of both basaloid cells and larger pigmented melanocytic cells. Pigmentation was variable, with dendritic cells noted. Up to 20 mitoses/10 HPF were observed. The small basaloid tumour cells were positive for AE1/AE3, and the larger tumour cells were positive for S-100 and MelanA.

Discussion: This entity is a malignant neoplasm with hair matrix and hair differentiation. The histological criteria in favour of malignancy include infiltrative growth, numerous mitotic figures, abnormal mitoses, nuclear atypia, loss of ghost cells at the advancing edge, lymphatic and blood vessel invasion, perineural invasion, local recurrence and lymph node or visceral metastases.

Back to Top | Article Outline


Grace Liu, Nicholas Fleming, Lara Lipton, Oliver Sieber

Ludwig Colon Cancer Initiative, Ludwig Institute for Cancer Research, Royal Melbourne Hospital, and Cabrini Health, Malvern, Vic, Australia

Aim: The TGF-β signalling pathway is principally composed of the TGF-β receptors (including TGFBR2) and the SMAD family signalling factors, and is implicated in the control of epithelial mesenchymal transition (EMT). In colorectal cancer, SMAD4 and TGFBR2 are mutated in approximately 15% and 10%, respectively. We hypothesised that cancers harbouring these gene mutations would differ in their biology and perhaps thus clinical progression.

Methods: Ten cancers with biallelic mutation of TGFBR2, ten with biallelic mutation of SMAD4 and ten wildtype for the two genes were assessed for tumour budding and E-cadherin expression. Tumour sections were stained with H&E, AE1/3 and immunohistochemistry for E-cadherin. Staining intensity and percentage of cell positivity were scored and compared between the three groups.

Results: Tumour budding was lower in TGFBR2 mutant cancers than the SMAD4 and WT groups when stained by H&E (p < 0.05). The percentage of cells staining positive for E-cadherin was significantly higher in the SMAD4 mutant cancers than the TGFBR2 mutant set (p < 0.028), but the difference in intensity was not significant.

Conclusions: These data suggest that the mutation status of the TGF-β pathway may correlate with colorectal tumour biology and is potentially relevant to clinical progression and metastatic spread. These results warrant further investigation.

Back to Top | Article Outline


Michaela Lucas1,3, Silvana Gaudieri2,3,4, Andrew Lucas3, Elizabeth McKinnon3, Hiba Albloushi4, Andri Rauch5, Julia di Iulio6, David Martino7, Susan L. Prescott7, Meri K. Tulic7

1Department of Immunology, PathWest, Fremantle Hospital, WA,2School of Anatomy and Human Biology, University of Western Australia, WA,3Institute for Immunology and Infectious Diseases (IIID), Murdoch University, WA,4Centre for Forensic Science, University of Western Australia, WA, Australia,5University Clinic of Infectious Diseases, University Hospital Bern and University of Bern, Switzerland,6Institute of Microbiology, University Hospital Centre and University of Lausanne, Switzerland, and7School of Paediatrics and Child Health, University of Western Australia, WA, Australia; the majority of the work was performed at IIID, Murdoch University

Background: Environmental changes influencing the interaction between the maturing immune system and pathogen exposure are implicated in the rising rates of allergic disease. There is emerging evidence that differences in innate immune function contribute to the development of allergy. Consequently, associated genetic factors may be critical for the difference in immune ontogeny, seen in allergic children.

Aims: We examined if genetic variation associated with the IL28B gene, encoding for the potent immune modulator IFN lambda 3, contributes to the divergent immune response in selected children who were followed from birth to 5 years of age (35 allergic and 35 non-allergic children).

Results: We found that carriage of the T allele of the SNP rs12979860, tagging the IL28B gene, is significantly associated with allergy (p = 0.004; OR 4.56). This association increases with age and is particularly evident in girls (OR 16). In addition, variation at rs12979860 correlates with differences in the pro-inflammatory profile (IL1B production) at birth after TLR stimulation of cord blood cells.

Conclusion: In the context of rising rates of disease, the genetic variation described may contribute to key differences in innate immune development of allergic children and points towards a role of IFN lambda III in allergic disease pathogenesis.

Back to Top | Article Outline


H. M. Manuchehri, A. Clarkson, L. Siosson, A. J. Gill

Royal North Shore Hospital, Sydney, NSW, Australia

Adrenocortical carcinoma (ACC) is a rare tumour with challenging pathological diagnosis. The Weiss scoring system which is based on the recognition of at least three of nine morphological parameters is the most widely used criteria. However the Weiss system is not entirely sensitive or specific, and some of the criteria are subjective and potentially problematic. As an alternative to the morphological approach, a wide array of chromosomal, genetic, molecular and immunohistochemical markers have been tested in ACC. Alterations of the insulin-like growth factor-II (IGF-2) molecule seem to be promising particularly when used in conjunction with Ki67 index. The insulin-like growth factor-II mRNA-binding protein (IMP3) has been shown to be a useful marker of malignancy in multiple organs. We investigated IMP3 expression by immunohistochemistry in TMAs of 35 ACCs and 161 adrenal cortical adenomas. IMP3 immunoreactivity was seen in two (6%) ACC and in none of the adrenal cortical adenomas. We conclude that despite its high specificity for the diagnosis of malignancy in adrenal cortical neoplasms, its very low sensitivity means IMP3 overexpression is unlikely to be useful in the diagnostic setting.


1. Findeis-Hosey JJ, H Xu H. The use of insulin like-growth factor II messenger RNA binding protein–3 in diagnostic pathology. Hum Pathol 2011; 42: 303–14.

2. Volante M, Buttigliero C,Greco E, et al. Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 2008; 61: 787–93.

3. Soon PS, Gill AJ, Clarkson, et al. Microarray gene expression and immunohistochemistry analyses of adrenocortical tumors identify IGF2 and Ki-67 as useful in differentiating carcinomas from adenomas. Endocr Relat Cancer 2009; 16: 573–83.

Back to Top | Article Outline


Ellen Maxwell on behalf of the Blood Matters Serious Transfusion Incident Reporting Expert Group, Blood Matters Program, Department of Health Victoria and the Australian Red Cross Blood Service

Background/aim: Serious Transfusion Incident Reporting system (STIR) is the voluntary haemovigilance framework developed by Blood Matters program for Victoria, on behalf of the Department of Health and the Blood Service. It was developed in 2005 to capture serious transfusion incidents, including near misses. It provides a central system for reporting events related to administration and handling of fresh blood components and pre-transfusion samples.

Method: Health services submit initial notifications and the STIR office provides follow-up forms relevant to the event type (e.g., incorrect blood component transfused, IBCT) for completion. Information (de-identified) regarding the case is returned for data entry and review, including attribution of causality and severity, by an expert clinical group. STIR links with the Victorian Department of Health sentinel event program, where it is mandatory to report ABO incompatible transfusion events.

Results: Participation to date is 71 public and private hospitals and laboratories, across four jurisdictions (Victoria, Tasmania, Australian Capital Territory and Northern Territory). To date there have been 946 transfusion adverse events in 939 patients (both adults and children) notified.

Conclusion: STIR continues to evolve in its processes for transfusion data reporting while ensuring it provides ongoing feedback to those reporting and derives recommendations for better, safer transfusion practice.

Back to Top | Article Outline


Mikkaela McCormack, Catriona McLean

Department of Anatomical Pathology, The Alfred Hospital, Prahran, Vic, Australia

We present a unique autopsy case of a 61-year-old female with concurrent renal and multi-focal pulmonary angiomyolipomata (AML) in the setting of pulmonary lymphangioleiomyomatosis (LAM), and in the absence of documented tuberous sclerosis. There are no previously reported cases of pulmonary AML in the setting of LAM.

The patient had undergone single lung transplantation 12 months prior to presenting with severe acute fibrinoid organising pneumonia in her donor lung. Despite full treatment she died 3 months following admission. Imaging revealed multiple tumours in the right kidney and left retroperitoneum, consistent with large angiomyolipomata. A left nephrectomy for a ‘benign tumour’ was performed 45 years previously.

Limited post-mortem examination of the native lung revealed marked cystic change and two 3 mm homogenous yellow parenchymal nodules. Histological examination showed cystic dilatation and a patchy proliferation of interstitial human melanoma black 45 (HMB45)-positive spindled cells consistent with LAM. The nodules were well-circumscribed, composed of mature adipocytes, small blood vessels and bland spindled cells with occasional epithelioid forms exhibiting positive staining with HMB45, smooth muscle actin and myosin, consistent with a diagnosis of AML.

On review, these lesions were not seen on repeated antemortem imaging.

This case illustrates that pulmonary lesions morphologically and immunohistochemically identical to AML can rarely co-exist with LAM and renal AML, and that they may be small, multiple and undetectable by imaging. We recommend that all lungs with known or suspected LAM be carefully examined for such lesions.

Back to Top | Article Outline


Julianne Bayliss1, Catherine L. Cherry1,2,3, Catriona A. McLean1,4

1Department of Medicine, Monash University, Alfred Hospital, Melbourne,2Centre for Virology, MacFarlane Burnet Institute, Melbourne,3Infectious Diseases Unit, Alfred Hospital, Melbourne, and4Anatomical Pathology, Alfred Hospital, Melbourne, Vic, Australia

Background: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by JC virus (JCV) reactivation with a high mortality and no definitive treatment. HIV-1 infection represents the most common underlying immunosuppressive condition associated with PML.

Methods: Nested PCR (nPCR) and real time PCR (qPCR) for JCV DNA was performed on serial plasma samples obtained from 14 HIV patients with a clinical diagnosis of PML and 27 controls (HIV patients without PML matched to cases on CD4 count, viral load, and treatment status).

Results: nPCR detected JCV LT DNA in 4/14 (29%) PML cases at disease onset but no controls (p = 0.003). JCV LT DNA was detected via qPCR in 11/14 (78%) PML patients at disease onset and 4/27 (15%) controls (p < 0.001). The availability of plasma samples collected prior to PML diagnosis allowed a preliminary evaluation of the predictive utility of JCV LT qPCR. Logistic regression analysis revealed proximity to PML diagnosis, duration of known HIV infection, absence of a prior AIDS defining illness and absence of cART to be independently associated with a positive qPCR result (p < 0.001; R2 = 0.35). Overall, JCV LT qPCR was more likely to be positive in the 8 months prior to PML diagnosis compared with earlier samples (p = 0.01).

Conclusions: qPCR is more sensitive for detecting JCV DNA than nPCR. Detection of JCV DNA in plasma of HIV infected patients via qPCR may represent a valuable test for diagnosing patients at increased risk of developing PML.

Back to Top | Article Outline


Namita Mittal1, Raghwa Sharma2, Melissa Robbie1

1Capital Pathology, Canberra, ACT, and2Tissue Pathology and Diagnostic Oncology, Westmead Hospital, Sydney, NSW, Australia

Aim: A case report of amyloidosis with Schnitzler syndrome. Ninety-four cases of this syndrome have been reported. This is the fourth report of amyloidosis in Schnitzler syndrome.

Method: Gastric and duodenal biopsies of a patient were stained with haematoxylin and eosin, Congo red and kappa and lambda immunostains.

Results: The patient initially presented 10 years ago with ‘urticaria’ and bone pain. Since then leucocytosis, altered liver function tests and markedly raised ESR have persisted. He has a low level IgM paraprotein. One year ago, the patient developed irritable bowel symptoms, and iron deficiency anaemia was noted. He had unremarkable gastric and duodenal biopsies. Due to persistent symptoms, repeat biopsies were performed, which showed hyaline deposits in the lamina propria and around the vessels, with apple green birefringence on Congo red staining. Kappa and lambda immunostains were negative. The patient also has hepatomegaly. Amyloid A, amylpoid P, transthyretin, lysosome and fibrinogen stains are pending.

Conclusion: Regular follow-up in Schnitzler syndrome is necessary due to occurrence of amyloidosis and lymphoproliferative disorders. The three previous cases had AA amyloid. Distinction from AL amyloid is necessary to guide treatment. In our case the gastrointestinal amyloidosis may have caused occult blood loss.

Back to Top | Article Outline


Ali Moghimi, Simon Nazaretian

Anatomical Pathology Department, The Royal Women's Hospital, Parkville, Vic, Australia

The most frequent type of cervical cancer is squamous-cell carcinoma which develops from cervical intraepithelial neoplasia (CIN) / squamous intraepithelial lesion (SIL). Its tumorigenesis is related to human papillomavirus (HPV). High-risk HPV is integrated into the genome and leads to tumour progression. Cytological screening leads to detection of precursors and their mimics. P16INK4a and Ki-67 immunohistochemistry assists in the histological differential diagnosis of precursors to reactive and metaplastic epithelium. P16INK4a has emerged as a valuable surrogate marker for high-risk HPV infection and shows increased immunoexpression with worsening grades of CIN. Numerous studies have supported its role in the detection of high-grade dysplasia and have lead to the use of p16INK4a immunohistochemistry in many laboratories. However, only a few studies have examined the possible predictive or prognostic value of p16INK4a in CIN or cervical cancer. This review addresses some of the practical issues in the application of p16INK4a in everyday practice, including the problems in the interpretation of the patterns of immunostaining and standardisation of the p16INK4a scoring.

Back to Top | Article Outline


Ali Moghimi, Jan Pyman

Anatomical Pathology Department, The Royal Women's Hospital, Parkville, Vic, Australia

Introduction: Inflammatory myofibroblastic tumour (IMT) is a histologically low-grade neoplasm of myofibroblasts and is most commonly seen in lung. Uterine IMT is a rare entity with limited number of cases reported in the literature.

Case report: We report a case of uterine IMT in a 65-year-old woman presenting with menorrhagia. Her ultrasound showed an intramural ‘fibroid’ 18 mm in diameter. Macroscopic examination of the uterus identified a well defined intramural pale tan rubbery lesion consistent with the ‘fibroid’ described by the ultrasound. In histological examination, this was a spindle cell lesion with bland nuclear features, rare mitoses and scattered small aggregates of mononuclear chronic inflammatory cells. The tumour cells exhibited strong widespread cytoplasmic staining with ALK-1 as well as patchy strong cytoplasmic staining with smooth muscle actin and desmin. CD34 staining was negative. The findings were consistent with an IMT.

Discussion: Uterine IMTs appear to behave in an indolent fashion. A constellation of morphologic and immunohistochemical features, including ALK expression, distinguishes this entity from its malignant mimics and allows for a more conservative management than dictated by uterine sarcomas. This case emphasises the significance of considering IMT as a possible differential diagnosis in a uterine lesion.

Back to Top | Article Outline


Rebecca Morrow, Leonardo Santos

Liverpool Hospital Department of Anatomical Pathology, Sydney South West Pathology Services, NSW, Australia

A 63-year-old male presented with a pharaphimosis, a constricting ring and a firm depressed ulcer of his foreskin. The histopathology of the foreskin specimen revealed a basaloid squamous cell carcinoma (BC) arising in the mucosa with peri-neural and lymphovascular invasion. The tumour cells were p16, p63, 34BE12, CD34 and CD31 positive. Ultrastructurally there were a few intracytoplasmic tonofilaments and desmosomes, however neurosecretory dense core granules were absent. Three years earlier the patient underwent a total laryngectomy and neck dissection for a large supraglottic moderately differentiated squamous cell carcinoma (T3N2B).

Basaloid carcinoma is a recognised unusual variant of squamous cell carcinoma of the penis. It usually occurs in the glans, and is frequently associated with human papilloma virus. To our knowledge there have been no reported cases of BC arising in the foreskin. Given the unusual location of this BC, the discussion as to whether this foreskin lesion represents a metachronous primary BC or an unfortunate metastasis of the laryngeal SCC arises. We favour this lesion to be a primary BC of the foreskin.

Back to Top | Article Outline


Enders K. O. Ng1, Candy P. H. Leung1, Vivian Y. Shin1, Hong Chuan Jin3, Kent-Man Chu1, Chris L. P. Wong2, Edmond S. K. Ma2, Ava Kwong1

1Department of Surgery, The University of Hong Kong,2Biomedical Research Center, Sir Runrun Shaw Hospital, Medical School of Zhejiang University, Hangzhou, and3Department of Molecular Pathology, Hong Kong Sanatorium and Hospital, Hong Kong, China

Aims: We aimed to develop plasma-based microRNA (miRNA) assay for breast cancer (BC) detection.

Methods: PCR-based miRNA profiling was performed in tumour, adjacent non-tumour, corresponding plasma from five BC patients, and plasma from five matched controls. All putative markers identified were verified in a training set of plasma by real-time quantitative PCR. Selected markers were validated in a case-control cohort of 120 BC patients, 100 controls, and 95 other types of cancers and then blindly validated in an independent set.

Results: Profiling results showed eight miRNAs were concordantly up-regulated in both plasma and tumours. Of the eight miRNAs, three were significantly elevated (p > 0.0001) before surgery and reduced after surgery in the training set. Marker validation showed that a combination of miR-145 and miR-451 was the best biomarker (p < 0.0001) in discriminating BC from controls and all other types of cancers. In blind validation, these plasma markers yielded ROC curve area of 0.923. The positive predictive value was 87% and the negative predictive value was 92%. Plasma elevation has been detected not only in advanced stages but also early stages of tumours.

Conclusions: These results suggest that such plasma miRNAs could be a potential molecular marker for BC screening.


1. Ng EKO, Yu J, Kwong A Sung JJY. Systemic microRNAs: novel biomarkers for colorectal and other cancers? Response. Gut 2010: 59: 1004.

2. Ng EK, Chong WW, Jin H, et al. Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009; 58: 1375–81.

Back to Top | Article Outline


Bing Yu1,7, Po Yee Yip2,4, Wendy Cooper3,5, Chiu Chin Ng1, Belinda Mercorella1, Huong Le1, Ronald Trent1,7, Maija Kohonen-Corish4,5,8, Catherine Kennedy6,7, Brian McCaughan6,7, James Kench2,4,7, Michael Boyer2,7, Lisa Horvath2,4,7, Sandra O’Toole3,4,7,8

Departments of1Molecular and Clinical Genetics,2Medical Oncology, Sydney Cancer Centre and3Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown,4Garvan Institute of Medical Research, Darlinghurst,5School of Medicine, University of Western Sydney,6Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown,7Sydney Medical School, University of Sydney, and8Faculty of Medicine, University of NSW, Sydney, NSW, Australia

Introduction: Inhibitors of the epidermal growth factor receptor (EGFR) show impressive response rates in selected lung cancer patients with activating EGFR gene mutations. Newer targeted agents are also in development with a pressing need to accurately identify the presence of ‘actionable’ mutations in patients with this poor prognosis cancer. We describe our experience with a sensitive, high throughput mass spectrometry based assay which detects a panel of 238 specific mutations in 19 oncogenes identified as biologically significant through literature review including KRAS, EGFR, BRAF, PIK3CA, MET, AKT1 and ERBB2.

Methods: DNA was extracted from resected tumours of 160 patients with lung adenocarcinoma, prepared using the Oncocarta v1.0 kit and processed on the Sequenom compact MassARRAY platform.

Results: We identified 101 mutations in 160 patients, with eight patients (5%) showing a mutation in two different genes concurrently. KRAS gene mutations were the most prevalent, seen in 40.6% of patients while EGFR mutations were seen in 13.1%. Rarer mutations were detected in PIK3CA (3.8%), MET (3.1%) and AKT1 (1 case only).

Conclusions: We detected at least one potentially clinically relevant mutation in the tumours of over half of our patients. We suggest this accurate and high throughput method may offer significant advantages over traditional Sanger sequencing.

Back to Top | Article Outline


David H. Owen1, Jill Bell2, Jennifer Stapleton2, James D’Rozario1,2

1Australian National University Medical School, Clinical School, Garran, and2Capital Region Cancer Service/ACT Pathology – Bone Marrow Transplant Unit and Laboratory, Woden, ACT, Australia

Introduction: Autologous peripheral blood stem cell (PBSC) transplantation has an established role in the treatment of some haematological and non-haematological malignancies. The safety and efficacy of this procedure are dependent on the fact that haematopoietic stem cells can be mobilised, harvested, cryopreserved and accurately enumerated prior to transplantation. The effect of the cryopreservation procedure on the PBSC product is evaluated.

Methods: We analysed the number of CD34+ peripheral blood cell progenitors obtained by aphaeresis pre- and post-cryopreservation to determine if there is significant loss of CD34+ cells during freezing, processing and thawing. We then further correlated CD34+ cell degradation and its effect on neutrophil or platelet engraftment.

Results: Twenty-eight CD34 products from 28 individual patients, most undergoing treatment for haematological malignancy, were analysed for viable CD34 number using the standard ISHAGE single platform enumeration assay immediately post-harvest and pre-infusion. CD34 numbers were then calculated and expressed in the standard form of CD34+ cells/kg body weight.

Mean pre-cryopreservation CD34+ cell product numbers were 4.04 ± 2.17 × 106/kg (mean+SD). Mean post-cryopreservation CD34+ cell product numbers were 2.80 ± 1.39 × 106/ kg. Mean CD34+ ‘loss’ with cryopreservation = 1.24 ± 106/kg. Mean time to neutrophil and platelet engraftment was 10.6 ± 0.04 and 13.52 ± 0.13 days, respectively. There was no significant difference in CD34+ cell loss in products stored for >100 days compared with those stored for <100 days, with no change seen in engraftment potential.

Conclusion: Despite a documented decrease in viable CD 34 numbers arising form the cryopreservation and processing process, generally adequate CD34 numbers are preserved and no effect is seen on either neutrophil or platelet engraftment. The length of cryopreservation appears to have no effect on viable CD 34+ cell numbers inferring that cell loss, when it occurs, is during the initial processing of CD34+ products.

Back to Top | Article Outline


Jia-Min Pang1, Annabelle Mahar1, Kerwin Shannon2, James Kench1, Charles Chan3, Ruta Gupta1

1Tissue Pathology and Diagnostic Oncology,2Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Camperdown, and3Electron Microscopy Unit, Anatomical Pathology, Concord Hospital, Concord, NSW, Australia

Background: Microcystic/reticular variant of schwannoma is a rare, distinctive variant of schwannoma with predilection for visceral sites. Fewer than 20 cases are described in the literature and involvement of head and neck has not previously been reported. Microcystic/reticular variant of schwannoma demonstrates similar biological behaviour to usual schwannoma and should be distinguished from parotid gland tumours that may recur aggressively if incompletely excised.

Aim: To present a case of microcystic/reticular variant of schwannoma in the parotid gland with literature review and discuss pertinent differential diagnoses.

Case report: A 59-year-old female presented with a preauricular swelling. FNA showed cytologically bland spindle shaped cells amidst myxoid stroma. At operation, the tumour was found to be closely associated with facial nerve and was resected with nerve preservation. Histopathological examination showed a well circumscribed, unencapsulated lesion composed of slender, spindle shaped cells with intracytoplasmic vacuoles amidst myxoid stroma. Areas with accordion-like linear cellular arrays, reticular pattern and microcysts were present. Features of typical schwannoma, atypia, mitoses, or necrosis were absent. Diffuse immunoreactivity with S100 was noted. Immunohistochemistry helped exclude differential diagnoses like myoepithelioma, pleomorphic adenoma, perineuroma, parachordoma, and epithelioid haemangioendothelioma.

Conclusion: We present a case of microcystic/reticular variant of schwannoma in the head and neck, to our knowledge the first report of this entity in this location.

Back to Top | Article Outline


Felik Paulus

Prince of Wales Hospital, Sydney, NSW, Australia

Kimura's disease is a rare chronic inflammatory condition which affects predominantly males of Asian descent. This is a case report of this condition. A 45-year-old male presented with a subdermal lesion posterior to the left ear with associated peripheral eosinophilia. The specimen excised consists of five irregular pieces of firm, grey-white tissue ranging from 5 × 3 × 2 mm to 10 × 8 × 5 mm. Microscopically, the tissue fragments show aggregates of lymphoid tissue set within a dense, sclerotic background. There is prominent lymphoid hyperplasia with many of the follicles broken up by small lymphoid cells. The infiltrate consists of small lymphocytes and is accompanied by prominent post-capillary venules as well as large numbers of eosinophils and fewer numbers of histiocytes and Langerhans cells. The lymphoid infiltrate is a mixture of B cells (CD20 positive) and small numbers of T cells (CD3 positive). No atypical cells are seen within the infiltrate. The appearances are consistent with so called Kimura's disease which presents as a head and neck lymphadenopathy with associated soft tissue mass, late stage sclerosis and peripheral eosinophilia. The aetiology is unknown. The lesions are benign although recurrence may occur after surgical excision.

Back to Top | Article Outline


M. Peck

Anatomical Pathology RCPA QAP, Burwood, Vic, Australia

In 2012, the Royal College of Pathologists of Australasia (RCPA) Anatomical Pathology Quality Assurance Program (QAP) will introduce a pilot for performance monitoring in the General and Breast Diagnostic Modules.

The Anatomical Pathology Performance Review Committee has developed a set of criteria for Diagnostic Pathology assessment.

If any of the following criteria apply, a participant will be considered to be outside criteria for satisfactory performance:

Participation: 1 × survey non-participation.

Performance of test: ≥3 × in the bottom 10% survey rank, over 3 years; thereafter, if in bottom 10% rank subsequently. Average survey rank ≤10%, over 3 years; thereafter, if average survey rank is < the average survey rank on the previous survey; thereafter reset scoring if >10% 3 × consecutively. If average discordant sum is ≥1.50 AND number of surveys completed is ≥2 (in rolling 12 month period); thereafter, if ≥1.50 AND ≥2 surveys completed AND survey contains discordant result. ≥5 non-concordant results per survey.

Notification: RCPA QAP response to notifiable unsatisfactory performance will initially take the form of letter to participants; subsequent deviations from the outlined criteria may result in copies of notifications forwarded also to National Association of Testing Authorities (NATA).

Back to Top | Article Outline


Roisin Reynolds, Veli Marjoniemi, Ewan Millar

Department of Anatomical Pathology, SEALS St George Hospital, Kogarah, NSW, Australia

We present two separate cases of unusual renal neoplasms, one an adult neuroblastoma, the second a smooth muscle tumour.

Neuroblastoma is a relatively common childhood neoplasm but exceedingly rare in adults. The disease in adults differs from children in that it is less likely to have n-MYC gene amplification or secrete catecholamines and has a worse prognosis. We describe the case of a 77-year-old woman who underwent left sided total nephrectomy for a 70 mm lesion. Histology showed a small round blue cell tumour which was diagnosed as adult neuroblastoma. Immunohistochemistry was positive for synaptophysin, neurofilament, CD56 and chromogranin. Muscle markers, vimentin, WT1 and CD99 were negative. FISH studies for n-MYC were negative.

Benign renal smooth muscle tumours are rare and most found incidentally. They resemble their counterparts in other organs, both in histological appearance and clinical behaviour. Most are less than 3 mm in diameter and are usually asymptomatic. We present a case of a 42-year-old woman who underwent partial left sided nephrectomy for a 40 mm lesion in the upper pole. Subsequent histology showed a benign smooth muscle tumour with positive smooth muscle immunohistochemical markers. A diagnosis of renal leiomyoma is complicated by the lack of specific diagnostic criteria to distinguish it from leiomyosarcoma.

Back to Top | Article Outline


Tanya Robb, Gordon Wright

Pathology Queensland: Gold Coast Hospital, Qld, Australia

The condition of women with uterine leiomyomas and concurrent erythrocytosis, with restoration and maintenance of normal haematological values after hysterectomy, has been classified as ‘myomatous erythrocytosis syndrome’. The first case was described in 1953 by Thomson and Marson,1 and according to LevGur and Levie,2 fewer than 40 cases have been reported in the literature since.

The exact pathophysiology of myomatous erythrocytosis syndrome is uncertain. Substantial myoma size has been noted as a common denominator in this condition, and recent evidence has confirmed Epo production by the myoma cells themselves.3

We present a case which likely documents another example of myomatous erythrocytosis syndrome, occurring in a patient with a large uterine leiomyoma.


1. Thomson AP, Marson FGW. Polycythemia associated with uterine myomas. Lancet 1953; 2: 759–60.

2. LevGur M, Levie MD. The myomatous erythrocytosis syndrome: a review. Obstet Gynecol 1995; 86: 1026–30.

3. Pollio F, Staibano S, Mansueto G, et al. Erythropoietin and erythropoietin receptor system in a large uterine myoma of a patient with myomatous erythrocytosis syndrome: possible relationship with the pathogenesis of unusual tumour size. Hum Pathol 2005; 36: 120–7.

Back to Top | Article Outline


Kathy Robinson, Wendy Pryor, Steve Clark

Royal College of Pathologists of Australasia, Sydney, NSW, Australia

Aims: Supervisor proficiency, enthusiasm and commitment are considered necessary for effective learning. At the same time, the willingness of Trainees to utilise proffered learning opportunities is imperative. We explored differing expectations and perceptions of Supervisors and Trainees.

Methods: Face-to-face workshops were conducted with over 400 RCPA Supervisors and Trainees in Australia, New Zealand and South East Asia. Additional data relating to teaching and supervision, personal study, and work/life balance was obtained from a survey distributed to all RCPA Fellows and Trainees in November 2011.

Results: Although the survey results indicated that the majority of responding Supervisors (93%) and Trainees (84.5%) agreed with the adequacy of teaching and feedback opportunities, workload caused dissatisfaction with work/life balance for 27% of Trainees. Supervisors and Trainees reported divergent perceptions both in the survey, and in open discussion. Supervisors highlighted that some trainees focussed on textbooks and teaching materials rather than engaging effectively in service work. Trainees preferred to study in the context of work as indicated by 39% studying four or fewer hours per week out of work time.

Conclusions: Tensions may arise in the context of expectations of Supervisors, and Trainees’ perceptions of the requirements to fulfil service commitments, study and prepare for examinations.

Back to Top | Article Outline


Jennifer Ross1, Vanessa Thomson2

1RCPA Cytopathology QAP, Kelvin Grove, Brisbane, Qld, and2Performance Monitoring Project, RCPA QAP, Surry Hills, Sydney, NSW, Australia

Aim: The aim of the Royal College of Pathologists of Australia Quality Assurance Program (RCPA QAP) Performance Monitoring Project is to develop key performance criteria across all disciplines which can be used to identify suboptimal laboratory performance earlier than the usual 3 year NATA accreditation cycle. In Cytopathology, a review of retrospective data from both gynaecological slide surveys and Performance Measures was undertaken to assist in developing criteria relating to gynaecological cytopathology. The aim of the review was to determine any relationship between results from QAP gynaecological slide surveys and Performance Measures data.

Method: Seven years of Australian participant data from conventional gynaecological surveys (GYN), liquid-based gynaecological surveys (LBC) and Performance Measures (PM) were extracted from the Cytopathology QAP database (2004–2010). Results from participants with one or more major error in any year in GYN or LBC surveys were compared with their PM data. Results from participants with one or more Performance Measure outside the National Standard in any year were compared with their GYN and LBC survey results.

Results: Participants with one or more major error in any year in the GYN or LBC surveys had more Performance Measures outside the national standard compared to those with no major errors (GYN 36% vs 26%; LBC 39% vs 23%). Participants with one or more Performance Measure outside the standard in any year returned twice as many GYN major errors compared to those with no Performance Measures outside the standard (1% vs 0.5%). There were twice as many major errors for LBC than for GYN survey results (1.27% vs 0.7%). While there is a tendency for participants with one or more major errors or Performance Measures outside the standard to do more poorly in all indicators, it did not preclude participants in the better performing group from returning major errors or having Performance Measures outside the standard.

Conclusion: This retrospective study showed a relationship between results from routine gynaecological slide surveys and Performance Measures data. The RCPA Cytopathology Performance Monitoring Committee proposes to establish performance monitoring criteria using results from both gynaecological slide surveys and Performance Measures data. These results will be utilised in the pilot phase of the project planned for 2012. The outcomes of the pilot phase will help determine the effectiveness of these criteria in assisting NATA to identify laboratories that may require early review.

Conflict of interest statement: This research was supported by the Department of Health and Ageing. The Department had no role in analysing the data or preparing this abstract.

Back to Top | Article Outline


Jennifer Ross

RCPA Cytopathology QAP, Kelvin Grove, Brisbane, Qld, Australia

Following the establishment of the Cytopathology Performance Review Committee this year, criteria for monitoring laboratory performance have been developed and a pilot phase will be undertaken in 2012. Criteria are based on both results from routine gynaecological Quality Assurance Program (QAP) surveys and Performance Measure data. The pilot phase will help determine the effectiveness of these criteria in assisting the National Association of Testing Authorities (NATA) to identify laboratories that may require early review.

Criteria for the pilot are: one Performance Measure outside the National Standard set by NPAAC; non-submission of results for Performance Measures; one major error in a conventional gynaecological (GYN) survey; three unacceptable responses in any GYN survey in any 12 month period; non-submission of results for any GYN survey.

Results will be reviewed within a rolling 12 month cycle. When a laboratory's results have fallen outside these established criteria, the laboratory's results will be forwarded to the Cytopathology Peer Review Committee for review. If results are assessed as unacceptable, notification letters will be sent to the laboratory in accordance with the framework developed by the Royal College of Pathologists of Australasia (RCPA) QAP.

It is hoped the outcomes of the pilot phase of the Cytopathology Performance Monitoring Project will assist in evaluating criteria for unacceptable performance in Cytopathology. As the project progresses results will be monitored by the Cytopathology PRC and these criteria may be reviewed.

Back to Top | Article Outline


Safoorah Sagheer, Akash Kalro, Merriane Wardle, Ferenc Szabo

Pathology Department, Royal Darwin Hospital, NT, Australia

Aims: To compare the extent of correction of prolonged activated partial thromboplastin time (APTT) on patients’ samples using protamine sulphate and heparin resistant calcium chloride.

Methods: Citrated blood samples from inpatients with APTT >40 seconds were tested for correction of APTT using the two reagents. Results were then correlated with clinical details and history of use of any anticoagulants. Reagents were also compared after in vitro spiking of normal plasma with varying concentrations of unfractionated heparin.

Results: Testing with spiked samples demonstrated that the procedure is effective at <2 U/mL heparin for both the reagents. Regarding patients’ samples, 37 samples with prolonged APTT were run and 17 (45.9%) of these showed complete correction of APTT with either of the reagents. Review of the clinical details revealed that all the patients were on heparin. Four patients (10.8%) were on warfarin and heparin and showed partial correction only. No correction was observed in 16 samples (43.2%) and the cause of prolonged APTT was liver disease, warfarin therapy or disseminated intravascular coagulation.

Conclusion: Protamine sulphate and heparin resistant calcium chloride have comparable results in correction of APTT for samples contaminated with heparin. The degree of correction of APTT was found to be the same for both reagents.


1. Dade Actin FSL Activated PTT Reagent: Product Insert. Dade, June 2006.

2. Dade CiTrol Heparin Controls, Low and High: Product Insert. Dade, May 2008.

3. Sysmex. Instructions for Use, Automated Blood Coagulation Analyser CA 500 Series, Operator's Manual. Sysmex, 2003.

4. NCCLS. H21-A3 Collection, Transport and Processing of Blood Specimens for Coagulation Testing and General Performance of Coagulation Assays: Approved Guideline. Third edition, Volume 18, No 20. Wayne, PA: NCCLS, 1998.

5. Sysmex CA 540/ 560 Activated Partial Thromboplastin Time (QHPS). Brisbane, Queensland Health.

Back to Top | Article Outline


Alaa A. Salim1, Peter J. Wilson2, Ravi K. Cherukuri2, Sandra McKenzie3, Michael E. Buckland1

1Department of Neuropathology, Royal Prince Alfred Hospital, Sydney, Departments of2Neurosurgery and3Anatomical Pathology, Wollongong Hospital, NSW, Australia

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare tumours that can occur anywhere in the central nervous system. The aetiology and natural history of these lesions is unclear. We report an unusual case of intraparenchymal CAPNON that occurred in association with interhemispheric lipoma and agenesis of the corpus callosum. The patient was a 47-year-old woman with known congenital absence of corpus callosum who presented with a progressive 6-month history of worsening headache, ataxic gait, blurred vision and poor memory. Magnetic resonance imaging (MRI) revealed complete agenesis of the corpus callosum with associated interhemispheric lipoma and an unusual calcified intraparenchymal mass, largely hypointense on T2 with intermediate signal centrally on T1, surrounded by an ill-defined vasogenic oedema. Histologically, the first lesion was confirmed as lipoma. The second lesion consisted of multiple nodules of chondromyxoid matrix partially rimmed by a single layer of palisading spindled to epithelioid cells and focal osseous metaplasia including mature lamellar bone. The final diagnosis was CAPNON associated with interhemispheric lipoma and agenesis of the corpus callosum. To our knowledge, this is the first reported association between these uncommon lesions. CAPNON have relatively non-specific radiological features with a broad differential diagnosis, but have distinctive histological features. Accurate identification of CAPNON will help avoid misdiagnoses and unnecessary therapeutic procedures since wide local excision is curative.

Back to Top | Article Outline


H. T. Samarasekara, J. Branley, R. Vaz

Department of Microbiology, Orange Hospital, Orange, NSW, Australia

Aim: Analysis of positive bacteriology specimens performed over one year to determine local epidemiology data and to improve methods and reporting procedure.

Methods: The study was performed at a regional microbiology laboratory servicing a large number of rural health facilities.

All positive bacteriology cultures for 7467 organisms were extracted from the laboratory information system and analysed using Microsoft Excel. This included 354 positive blood cultures, 1696 wound swabs, 2293 urine cultures and 512 sputum samples. Susceptibility data were analysed for Staphylococcus aureus, Enterococci, ESCPPM and non-ESCPPM groups of Enterobacteriaceae and Pseudmonas aeruginosa. Observations were made regarding current methodology and opportunities for improvements with ongoing support of supervising laboratory were identified.

Results: Direct susceptibility data for urine specimens for ampicillin, amoxycillin-clavulanate, cephalothin, gentamicin and trimethoprim for non-ESCPPM organisms were 43%, 76%, 45%, 98% and 80%, respectively; the ESCPPM group of organisms showed susceptibilities of 93% for gentamicin and 78% for trimethoprim and 88% for norfloxacin. The single anti-Pseudomonal drug tested, gentamicin, showed 99% susceptibility. Eighty percent of Enterococci remained susceptible to ampicillin. Forty percent of urinary S. aureus were methicillin-resistant Staphylococcus aureus (MRSA) with the majority community (CMRSA).

Susceptibilities for bacteraemic S. aureus isolates included 88% of methicillin-sensitive Staphylococcus aureus (MSSA), 10% of CMRSA and 2% of nosocomial MRSA. Non-ESCPPM organisms showed susceptibilities of 48%, 67%, 92%, 92% 98% and 100% for ampicillin, amoxycillin-clavulanate, gentamicin, cefotaxime, ciprofloxacin and meropenem, respectively. Susceptibilities of bacteraemic ESCAPPM isolates for gentamicin, ciprofloxacin and meropenem were 100%, 88% and 100%. Sixty-two percent of Enterococci remained susceptible to ampicillin.

Conclusions: A number of analytical and post-analytical factors were identified with potential improvements to be done in view of upgrading the quality of services.

Back to Top | Article Outline


Gagandeep Sandhu, Mark Formby

Department of Anatomical Pathology, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia

Background: Juvenile granulosa cell tumour (JGCT) is a rare benign neoplasm of testicular stroma that accounts for 1–5% of tumours arising in prepubertal testis. JGCT is uncommon in older children and adults. Occasional JGCT have occurred in undescended testis of infants with intersex disorders.

Case report: We present a case of 9-week-old infant with a mass in the right testis for which right orchidectomy was performed. Macroscopically, there was a 1 cm cystic lesion confined to the testis. Microscopically, the lesion was multicystic with a follicular pattern. Follicles were lined by single to multiple layers of large cells with oval nuclei, inconspicuous nucleoli and abundant pale eosinophilic to clear cytoplasm. Follicles contained basophilic secretions which were PAS and mucicarmine positive. There were frequent mitoses. The tumour showed positive staining for inhibin and S100. There was no staining for AFP and PLAP.

Discussion: JGCT usually presents in the first 6 months of life. Common differential diagnosis is yolk sac tumour, particularly when the tumour has a reticular pattern with brisk mitotic activity. AFP and alpha-inhibin immunostains are helpful in distinguishing these entities. JGCT follows a benign clinical course with no reports of metastasis. Some case series have advocated partial orchiectomy in management of these tumours.

Back to Top | Article Outline


Gagandeep Sandhu, Debra Hean, Barbara Young

Department of Anatomical Pathology, Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia

Background: Metanephric stromal tumour (MST) is a purely stromal neoplasm at the benign end of the spectrum of metanephric tumours of kidney with a mean age at presentation of 2 years.

Case report: A 3-year-old girl presented with haematuria. Imaging revealed a non-enhancing mass in the right kidney with no evidence of distant spread. Right nephrectomy was performed. Macroscopically, a 45 mm, pale, white, tumour was present in the kidney. Microscopically, the lesion was a non-encapsulated, circumscribed, bland spindle cell tumour with vaguely nodular appearance on low power. Condensation of spindled cells was seen around entrapped tubules. Arterioles within the mass showed features of angiodysplasia. Epithelial component, heterologous tissue, necrosis and mitoses were absent. Spindle cells were positive for CD34. There was focal weak nuclear positivity for WT-1. Epithelial markers were negative.

Discussion: Patients with MST can present with hypertension resulting from juxtaglomerular cell hyperplasia. Rarely, morbidity has been reported due to extrarenal angiodysplasia. None of these features were present in our case.

MST has a benign course and surgical resection is curative. Hence, it is importance to differentiate it from other tumours like congenital mesoblastic nephroma, clear cell sarcoma of kidney and synovial sarcoma, all of which are different histologically and do not stain for CD34.

Back to Top | Article Outline


Sanaz Sasani1, John Quin2, Christopher Henderson1,3, C. Soon Lee1,3, Joo-Shik Shin1,3

Departments of1Anatomical Pathology,2HIV Medicine/Sexual Health and Clinical Immunology, Liverpool Hospital, and3Discipline of Pathology, School of Medicine, University of Western Sydney, NSW, Australia

Toxoplasmosis caused by Toxoplasma gondii is one the most frequent opportunistic infections among the immunocompromised patients and commonly affects the brain of those individuals with advanced human immunodeficiency virus (HIV) infection with acquired immune deficiency syndrome (AIDS). Cerebral toxoplasmosis can be a challenging histopathological diagnosis when it presents as the early sequela of clinically unsuspected immunosuppression.

We report a case with problematic histopathological diagnosis of cerebral toxoplasmosis because of the patient's unsuspected HIV status, the clinico-radiological impression of metastatic malignancy, and the compounded difficulty of identifying the typical T. gondii organisms in frozen section material. However, this case highlights the need to always contemplate a non-neoplastic infective cause as the basis for observed necrosis in brain biopsies, regardless of the clinical suspicion under which the histopathological examination has been requested.

Back to Top | Article Outline


Christina I. Selinger1, Toni-Maree Rogers2, Prue Russell3, PoYee Yip4,5, Sandra O’Toole1,5,6, Lisa Horvath4,5,6, Michael Boyer4,5, Brian McCaughan7, Maija Kohonen-Corish6,8, Stephen Fox2, Wendy Cooper1,9, Ben Solomon10

1 Department of Anatomical Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW,2Department of Pathology, Peter MacCallum Cancer Centre, East Melbourne,3Anatomical Pathology, St Vincent's Hospital, Fitzroy, Vic,4Sydney Medical School, University of Sydney, Camperdown,5Sydney Cancer Centre, Royal Prince Alfred Hospital, Camperdown,6Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst,7Department of Cardiothoracic Surgery, Royal Prince Alfred Hospital, Camperdown,8Faculty of Medicine, University of NSW, Sydney,9Discipline of Pathology, School of Medicine, University of Western Sydney, Campbelltown, NSW, and10Department of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Vic, Australia

Aims: Non-small cell lung cancer (NSCLC) has the highest cancer-related mortality globally. Rearrangements of ALK in NSCLCs define a subgroup of patients with specific clinical, pathological and molecular characteristics and are associated with sensitivity to an ALK/MET inhibitor, with promising response rates. We aimed to assess the clinical utility of ALK translocation screening and to identify the frequency and clinicopathological features of lung adenocarcinomas harbouring ALK translocations, using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH).

Methods: NSCLC tissue was obtained from patients treated at the Royal Prince Alfred Hospital and Concord Repatriation Hospital, Sydney, and St Vincent's Hospital and Peter MacCallum Cancer Centre, Melbourne, with a total of 666 cases evaluated. Tissue microarrays were screened using ALK IHC (Clone ALK-1, Dako; Clone 5A4, Novocastra) and ALK break-apart translocation FISH (Abbott Molecular).

Results:ALK rearrangements were found in six cases (1%) by FISH, which is comparatively lower than other reported frequencies. The 5A4 ALK antibody identified all six ALK positive cases (100% sensitivity). One false negative resulted from the ALK-1 antibody (86% sensitivity).

Conclusions: We believe ALK IHC represents an effective means of routinely screening selected NSCLC patients for ALK rearrangement testing using FISH.

Back to Top | Article Outline


Mahsa Seyed Ahadi, Kirstin Johnson, Jeffery Donlon

Department of Pathology, Wagga Wagga Hospital, Wagga Wagga, NSW, Australia

Background: Extraskeletal osteosarcoma (ESOS) is a rare soft tissue tumour which accounts for approximately 1% of soft tissue sarcomas. In particular, subcutaneous osteosarcoma is extremely rare, occurring in less than 10% of ESOS cases.1

Case report: The case of a 71-year-old-woman with a 30-mm mass arising in the subcutaneous tissue of the thigh is presented. Radiological investigations showed spotty calcification in the mass without any attachment to the underlying bone. Wide surgical excision was performed. Microscopic examination revealed a pleomorphic spindle cell neoplasia with abnormal osteoid, some with ossification. It confirmed the diagnosis of subcutaneous ESOS with extension to the dermis and one lateral subcutaneous margin. Radiotherapy was commenced after a wide re-excision. Five months after the primary surgery, she developed metastases to the ipsilateral inguinal and pelvic lymph nodes and 5 months later she was diagnosed with inoperable pulmonary metastasis. Unfortunately she died 25 months after her first presentation.

Discussion: ESOS has been most often described in the deep soft tissues of the extremities. Subcutaneous tissue as a primary site is rare. This case emphasises the poor prognosis in patients with ESOS and the importance of aggressive treatment even in the cases with smaller size and more superficial location.


1. Bane BL, Evans HL, Ro JY, et al. Extraskeletal osteosarcoma, a clinicopathologic review of 26 cases. Cancer 1990; 65: 2762–70.

Back to Top | Article Outline


S. Sim1, D. James1, G. Phillips1, N. Mellick2

1Department of Anatomical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, and2Sullivan and Nicolaides Pathology, Taringa, Qld, Australia

An 82-year-old man underwent investigations for a right perihilar mass in November 2011. He had a previous history of malignant fibrous histiocytoma (pleomorphic sarcoma) of the scalp which was excised in October 2009.

TBFNA cytology showed single, multinucleated, large pleomorphic malignant cells that were positive for Vimentin and CD10. Review of the histology showed a dermal spindle cell tumour displaying morphology reminiscent of an atypical fibroxanthoma but which was invading the subcutis and abutting the deep fascia. The tumour was CD10+ and negative for cytokeratins, melanocytic and other markers including SMA, CD99 and Desmin. The morphology and immunoprofile was that of a malignant fibrous histiocytoma, as previously reported. There was no lymphovascular space invasion or perineural invasion. Although peripheral margins were well clear, the clearance from the deep margin was only 0.3 mm.

Pleomorphic sarcomas account for a large proportion of sarcomas in late adulthood, with a local recurrence rate of 19–31%, a metastatic rate of 31–35% (lungs 90%) and a 5-year survival of 65–70%.

This case highlights the cytological criteria for the diagnosis of pleomorphic sarcoma and also confirms that deeply invasive AFX-like dermal tumours are best classified as pleomorphic sarcomas to better indicate their metastatic potential.

Back to Top | Article Outline


Shivani Singh1, Nerida Steele2, Felicity Frost1

1Department of Cytopathology, PathWest Laboratory Medicine WA, QEII Medical Centre, Nedlands, and2WA Cervical Cytology Registry, Perth, WA, Australia

Background: Australian laboratories must show a biopsy proven high grade (HG) rate of >33% in ‘possible HGSL’ (pHGSL) Paps. For coding and education our laboratory divides pHGSL into three groups: INCS1 (crowded sheets, indeterminate cell type), INCS2 (atypical squamous cells, high N:C ratio), INCS3 (at least LSIL, ?HSIL).

Aims: (1) To determine the HG biopsy rate in pHGSL Paps according to cytological pattern, age and HPV status. (2) To review 87 INCS1 slides.

Methods: All pHGSL Paps during 2008 were retrieved. The Western Australian Cervical Cytology Registry (WACCR) provided follow-up data. The highest biopsy abnormality was recorded. All INCS1 slides were reviewed.

Results: Of 295 women, 229 had biopsy follow-up. For INCS1 the HG rate was 29% while for INCS2 and INCS3 the HG rate was 43% each. Review of 87 INCS1 Paps resulted in fewer pHGSL reports (53, HG biopsy rate 32%). However, seven with HG biopsies were missed. In women >50 years, HG biopsy rate was 19%. The sensitivity of HPV testing in 84 women was 86% for a HG abnormality.

Conclusions: Crowded sheets of uncertain cell type gives the lowest HG biopsy rate but cytological review gives no better results. Human papillomavirus (HPV) testing especially in older age groups would improve accuracy.

Back to Top | Article Outline


Jonathan Smiles, Lavinia Hallam

Department of Anatomical Pathology, ACT Pathology, The Canberra Hospital, Woden, ACT, Australia

A 36-year-old man presented with obstructive lower urinary tract symptoms. Prostatic enlargement was confirmed radiologically. Prostate biopsies were obtained, and a radical prostatectomy performed.

The prostatectomy specimen weighed 175 g. Macroscopically there was a circumscribed tumour expanding the left lobe of the prostate. Histologically the tumour was composed of spindle cells in storiform and fascicular arrangements. The bulk of the tumour had cellular morphology consistent with stromal tumour of uncertain malignant potential (STUMP). At one edge of the tumour there was a secondary area showing a distinct increase in cellularity and mitotic activity that met the criteria for low grade prostatic stromal sarcoma. Tumour cells within each component were positive for CD34, progesterone receptor, Bcl-2, vimentin and CD99; and negative for smooth muscle and skeletal muscle markers as well as CD117 and ALK-1.

Primary tumours of the specialised prostatic stroma are rare. They are classified based on accepted criteria into (1) STUMP and (2) prostatic sarcoma (low/high grade). STUMP can dedifferentiate into, or occur concurrently with prostatic sarcoma. Patients may be young (as in our case) making accurate diagnosis essential, given the potential for long-term morbidity. The differential diagnosis and immunohistochemistry will be discussed.

Back to Top | Article Outline


Wan Li Soh, Daniel D. Wong, Jeremy Parry

Department of Anatomical Pathology, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, WA, Australia

Aims: To assess predictive factors for lymph node yield and metastases in resections for colorectal carcinoma at a single, tertiary level hospital. To determine the lymph node size most predictive of nodal metastases.

Methods: Consecutive cases between 2008 and 2010 were identified from our database. Clinical and pathological data were obtained from medical records and pathology reports. The size of nodes recovered and any metastases were measured from paraffin sections. Age, sex, surgery type, tumour site, size, grade, neoadjuvant treatment and lymphovascular invasion were entered into a multivariate regression model to determine independent predictors of nodal yield and metastases. Nodal size most predictive of metastases was determined using receiver operating characteristic curves.

Results: 94 cases were analysed including 1398 lymph nodes. Median number of nodes recovered was 14 (range 2–35). Mean number of positive nodes was 1 (±2.8). Tumour size independently predicted for increased nodal yield (p = 0.04). Neoadjuvant treatment reduced the nodal yield (p = 0.03). The most predictive factors for metastases were tumour grade (p < 0.001) and lymphovascular invasion (p < 0.001). A nodal size of 5.4 mm (long axis) was the most sensitive (62%) and specific (77%) for metastases.

Conclusion: A reduced lymph node yield should reasonably be expected in patients treated with neoadjuvant therapy. A nodal size of 5.4 mm in the long axis represents the best compromise between sensitivity and specificity for detection of metastases.

Back to Top | Article Outline


Suzanne Danieletto1, Heejin (Jinny) Song2

1San Pathology, Sydney, and2St George Hospital, Sydney, NSW, Australia

This is a case report of a localised amyloidosis at a site of insulin injection in a 66-year-old man, clinically mimicking lipohypertrophy. The patient has been insulin dependent diabetic since 1963, and was initially treated with bovine insulin followed by porcine insulin until switching to recombinant in the 1990s. Whilst on bovine and porcine insulin treatment, he had noticed three lumps at his regular injection sites over his right and left thigh. These sites had not been used for insulin injection since the 1990s but the lumps gradually enlarged. The microscopic examination showed masses predominantly composed of eosinophilic and partly yellow-brown, non-birefringent amorphous material that is associated with a foreign body reaction, occasional calcification, fibrosis and chronic inflammation. This stained positively with Congo red stain and displayed green birefringence of the eosinophilic material by polarised microscopy, consistent with amyloid. It is known that full-length insulin molecules are found in fibrillar form at the site of frequent insulin injections. These insulin fibrils formed in vivo display the defining characteristics of amyloid aggregates. This amyloid deposition interferes with insulin absorption, leading to suboptimal glucose control. This phenomenon is seen with both porcine and humanised insulin.

Back to Top | Article Outline


Vishnu Subramanian1, Anita Achan1, Russell Hogg2

1Department of Tissue Pathology and Diagnostic Oncology, ICPMR Westmead Hospital, Westmead, and2Department of Obstetrics and Gynaecology, Westmead Hospital, Westmead, NSW, Australia

The ovaries are common sites for intra-abdominal metastasis. About 6% of ovarian cancers found at laparotomy are secondary tumours from other sites.1 However, metastatic transitional cell carcinoma (TCC) involving the ovary from the urinary bladder or elsewhere within the urinary tract is extremely rare. Primary TCC accounts for 1–2% of all ovarian tumours.2 TCC of the ovary is a recently recognised subtype of ovarian surface epithelial-stromal cancer. Microscopically, metastatic urothelial carcinoma of ovary is very similar to a primary ovarian TCC. The presence of a component of benign or borderline Brenner tumour confirms an ovarian primary.3 The distinction between metastatic TCC of urothelial origin and a borderline or malignant Brenner tumour and a primary ovarian TCC can be difficult or sometimes impossible.

We present a case of ovarian metastasis from urothelial carcinoma of the bladder. The patient developed bilateral bulky ovarian metastases 7 years after the diagnosis of the primary bladder tumour. The history of primary tumour was not available initially. We favoured metastatic ovarian tumours for the following reasons: (a) definite histological evidence of a primary bladder tumour, (b) bilateral ovarian involvement, and (c) lack of residual Brenner tumour.

Although rare, possibility of metastasis from urothelial carcinoma should be considered as a differential diagnosis in cases of transitional cell carcinoma of ovary. Relevant clinical information is vital for accurate diagnosis. Careful histological and histochemical analysis may help to differentiate between the two.


1. Petru E, Pickel H, Heydarfadai M, et al. Nongenital cancers metastatic to the ovary. Gynecol Oncol 1992; 44: 83–6.

2. Young RH, Scully RE. Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature. Int J Gynecol Pathol 1988; 7: 197–211.

3. Eichhorn JH, Young RH. Transitional cell carcinoma of the ovary: a morphologic study of 100 cases with emphasis on differential diagnosis. Am J Surg Pathol 2004; 28: 453–63.

4. Logani S, Oliva E, Amin MB, et al. Immunoprofile of ovarian tumors with putative transitional cell (urothelial) differentiation using novel urothelial markers: histogenetic and diagnostic implications. Am J Surg Pathol 2003; 27: 1434–41.

Back to Top | Article Outline


Katrina Tang, Leonardo Santos

Department of Anatomical Pathology, SSWAPS Liverpool, NSW, Australia

A 30-year-old primigravid woman underwent an emergency caesarean section for delivery of twins at 34 weeks gestation, with an incidental intra-operative finding of a 70 mm right ovarian cyst and a 45 mm left ovarian cyst. Both cysts contained abundant hair and oily sebaceous material.

Microscopic examination confirmed both ovarian cysts were dermoid cysts (mature cystic teratomas) composed of skin with adnexal structures, adipose tissue, cartilage, glial tissue, thyroid and gastrointestinal glands. In addition, the right dermoid cyst showed a focus of glandular tissue resembling lactational breast tissue. PASD highlighted the intraluminal secretions, while the glandular epithelium stained positively with CK7 and 34βE12. A surrounding layer of myoepithelial cells was seen with p63 and CD10. Ultrastructurally, abundant secretory material was apparent. The organelle-rich acinar cells contained lipid droplets and a few electron-dense secretory granules. Myoepithelial cells were flattened and attenuated.

Breast tissue and lactational breast tissue are not commonly seen within dermoid cysts. Only three cases have been reported in the literature, all occurring in pregnant women. The response of the breast tissue to the endogenous systemic hormones in pregnancy illustrates the potential functional capability of the differentiated tissue found within dermoid cysts.

Back to Top | Article Outline


Y. L. Tang, C. Y.P Chau, W. M. Yap, K. L. Chuah

Department of Pathology, Tan Tock Seng Hospital, Singapore

Epithelial misplacement or ‘pseudoinvasion’ is a known phenomenon occurring in the gastrointestinal tract that may potentially result in the misdiagnosis of a malignancy, particularly to the uninitiated. Recent papers indicated that similar diagnostic dilemmas occur in the breast and thyroid tissues, usually following a biopsy procedure. In the gastrointestinal tract, the epithelial displacement is thought to result from herniation of the mucosa through defects of the muscularis mucosae and propria secondary to trauma from medical procedures or due to the inherent peristaltic action.

We detail an instance where epithelial misplacement in a hamartomatous polyp in the ileum affecting a 17-year-old Malay man with Peutz-Jeghers syndrome raised the concern for malignancy. The patient had undergone a subtotal colectomy with extended ileal resection following intussusception. The resected specimen revealed multiple hamartomatous polyps in the small bowel and caecum. On histology, one polyp disclosed the presence of mucosa and mucinous pools in the adipose tissue of the serosal layer which abut the peritoneal surface, mimicking an adenocarcinoma with mucinous features. The criteria and immunohistochemical stains acting as adjuncts for separating ‘pseudoinvasion’ occurring in the various types of gastrointestinal polyp including those with dysplasia from an adenocarcinoma are presented.

Back to Top | Article Outline


Hui Sien Tay, Alan E. Mills

Department of Anatomical Pathology, Bendigo Health Pathology Services, Bendigo, Vic, Australia

Capnocytophaga canimorsus, formally known as Dysgonic fermenter 2 (DF-2), is a commensal bacteria of dog and cat saliva. It can be transmitted to humans by bite, scratch, or mere exposure to animals by licking. It is a Gram negative rod that typically causes septicaemia and disseminated intravascular coagulopathy. Dermatological lesions and gangrene are common. The reported mortality rate is up to 30%. Most of the patients affected have compromised immunity, secondary to splenectomy or alcoholism. However, in one of the review articles, up to 40% of septicaemia occurred in patients with no predisposing factors. We described a 60-year-old female who presented with septicaemia secondary to Capnocytophaga canimorsus, following a minor bite by a dog. Her medical history included splenectomy for idiopathic thrombocytopenic purpura 24 years ago, with normal blood count since the splenectomy. The diagnosis was strongly suspected on peripheral blood film, which was later confirmed on blood cultures. Despite maximal therapy and surgical intervention, the patient succumbed to the infection. In view of the severity of this infection, clinicians should be aware of the possibility of Capnocytophaga canimorsus infection in the management of animal bites, especially in patients with predisposing factors.

Back to Top | Article Outline


Hui Sien Tay1, Alan E. Mills1

Department of Anatomical Pathology, Bendigo Health Pathology Services, Bendigo, Vic, Australia

The differential diagnosis of stromal tumours of the appendix includes leiomyoma, gastrointestinal stromal tumour and neurogenic lesions. Terminology of neurogenic tumours is confusing in the literature. The term ‘neuroma’ of the appendix includes the common obliterative fibrosis of the appendix. However, true neuroma of the appendix occurring as a circumscribed nodular tumour, like all appendiceal stroma tumours is extremely uncommon. We report a true neuroma of appendix in a healthy 3 year old boy, who presented with symptoms of appendicitis.

Back to Top | Article Outline


Carla Thomas1, Benhur Amanuel1, Jill Finlayson2, Fabienne G. Iacopetta1, Dominic V. Spagnolo1, Wendy N. Erber2,3

1Department of Anatomical Pathology,2Department of Haematology, PathWest Laboratory Medicine, Nedlands, and3School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands, WA Australia

Introduction: Hairy cell leukaemia (HCL) is a rare, indolent chronic B-cell leukaemia accounting for approximately 2% of all adult leukaemias. The recent association of the V600E BRAF mutation in HCL makes it a valuable molecular diagnostic marker.

Objective: To compare the ability of Sanger sequencing (SS), fluorescent single-strand conformational analysis (F-SSCA) and high resolution melting (HRM) analysis to detect BRAF mutations in HCL with DNA extracted predominantly from archival material.

Methodology: 20 cases of HCL consisting of four archival Romanovsky stained air-dried peripheral blood and bone marrow aspirate smears, 12 mercury fixed decalcified bone marrow trephine biopsies, three formalin fixed, paraffin embedded (FFPE) splenectomy samples and one fresh peripheral blood sample were reviewed. DNA was amplified by PCR and BRAF mutation status determined by the three methods above.

Results: V600E mutation was identified in 95%, 87% and 76% of HCL cases by F-SSCA, HRM and SS, respectively. In one HCL case, in addition to the V600E mutation, a K601T mutation was identified. One of the Romanowsky stained samples was negative for mutation by all three methods. Three mercury fixed cases were negative for mutation by sequencing but positive for the mutation using F-SSCA and HRM. This discrepancy could be due to mutations below the limit of sensitivity of SS.

Conclusion: DNA from archival slide scrapings, mercury-fixed and FFPE tissue can be used to identify BRAF mutations with high sensitivity especially using HRM/F-SSCA. The V600E mutation can be used as a supplementary molecular marker to aid in the diagnosis of HCL. The presence of the mutation may provide a target for therapy.

Back to Top | Article Outline


Vanessa Thomson

RCPA Quality Assurance Programs, Sydney, NSW, Australia

Aim: In 2010 the Royal College of Pathologists of Australasia Quality Assurance Programs (RCPA QAP), received Quality Use of Pathology Program funding to determine if regular external quality assurance that laboratories perform could be used to identify unacceptable performance earlier than the usual 3 year NATA accreditation cycle, to help minimise risk to patients.

Method: Criteria for unacceptable performance have been established to identify laboratories that maybe underperforming in external quality assurance (EQA). New frameworks have also been developed that outline the process of actions to be taken by the RCPA QAP when participant results and IVDs fall outside levels of acceptable performance. The frameworks proactively notify participants or manufacturers or their sponsors to assist them early.

Results: When unacceptable performance is identified, according to the set criteria, a letter will be sent to the participant outlining the result(s) falling outside the criteria for acceptable performance and offer assistance to review the QAP results. Persisting unacceptable performance will be referred to a Committee for review and results referred to the National Association of Testing Authorities (NATA) or Therapuetic Goods Administration (TGA) for follow-up.

Conclusion: The RCPA QAP has established a performance monitoring system using the EQA results. The early warning system will identify laboratories of concern and assist them to obtain their accreditation.

Conflict of interest statement: This research was supported by the Department of Health and Ageing. The Department had no role in analysing the data or preparing the abstract.

Back to Top | Article Outline


Clinton Turner, Jessica Matich, Chris van Vliet

LabPlus, Auckland City Hospital, Auckland, New Zealand

NUT (nuclear protein in testis) midline carcinoma (NMC) is a rare highly aggressive tumour characterised by chromosomal rearrangements of NUT on 15q14. Initially described in paediatric and adolescent populations, NMC is now known to occur over a wide age range. In adults, a common site of occurrence is the upper aerodigestive tract. We describe the case of a 54-year-old male presenting with 3 months of epistaxis. Examination revealed a mass in the right middle meatus. Biopsy showed a small round blue cell tumour without differentiating histological features. Immunohistochemically, the tumour was positive for cytokeratins (MNF-116, HMWCK, CK7, CK5), p63, CD99 and CD34. FISH studies for Ewing/PNET and synovial sarcoma translocations were negative. FISH analysis confirmed the presence of the BRD4-NUT rearrangement typical of NMC. The patient underwent cranio-facial resection and post-operative radiotherapy. Follow-up to date has shown no recurrence. NMC is not commonly included in the differential diagnosis of upper aerodigestive tract carcinomas. However, NMC should be considered in any poorly differentiated carcinoma of the upper aerodigestive tract, particularly those co-expressing cytokeratin and CD34. FISH testing for the characteristic translocation confirms the diagnosis. Aggressive therapy has resulted in no evidence of recurrence 18 months after original diagnosis.

Back to Top | Article Outline


Ricardo E. Vilain1,2, Stephen G. Braye1, Rodney J. Scott1,2

1Hunter Area Pathology Service, Hunter New England Health Service, Newcastle, and2School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia

The evolution in the understanding of kinase oncogene addiction as the driver of melanomagenic MAPK cascade activation has encouraged the molecular characterisation of melanoma on the basis of potentially druggable kinase mutations. Currently, the three best-characterised targets are BRAF, KIT and NRAS. Mutations in these genes largely occur in a mutually exclusive manner, with the former two kinases offering tantalising therapeutic opportunities, and are currently the subject of phase II and III trials. Notwithstanding the potential therapeutic opportunities offered by some of these mutations, there are conflicting data on the potential prognostic information conferred by the knowledge of the NRAS and BRAF mutational status. In this study, we have genotyped 192 cases of thick and/or metastatic melanoma, arising in a population exposed to a high degree of ambient UV radiation, and analysed the mutations in relation to the degree of cutaneous sun damage, and to clinical outcome. We report BRAF and NRAS mutations are associated with impaired and enhanced survival outcomes, respectively. Furthermore, this effect is mediated by a differential metastatic rate to locoregional sites, and subsequently upon distant sites.

Back to Top | Article Outline


Vipul Vyas, Kris Kerr

Department of Anatomical Pathology, Sullivan Nicolaides Pathology Brisbane, Qld, Australia

We present here a case of mucinous adenocarcinoma of urinary bladder type, arising from the prostatic urethra in a 78-year-old man who also had a previous history of prostatic adenocarcinoma of acinar type treated with radiotherapy. The patient presented to the clinic with haematuria. A biopsy from the prostatic urethra showed poorly differentiated mucinous adenocarcinoma favouring primary mucinous urothelial adenocarcinoma. The subsequent transurethral resection of prostate revealed poorly differentiated (signet-ring) malignant cells floating in pools of extracellular mucin within the prostatic stroma. The overlying urothelium exhibited intestinal metaplasia and glandular dysplasia. The tumour was positive for cytokeratin 20, villin, CEA and CDX2 but was negative for prostate specific antigen (PSA), Alpha methylacyl co-A racemase (AMACR) and cytokeratin 7. Beta catenin showed positive membrane staining. Mucinous adenocarcinoma arising from the prostatic urethra is a rare and aggressive tumour which must be differentiated from prostatic mucinous adenocarcinoma, metastatic colonic adenocarcinoma and metastatic adenocarcinoma from urinary bladder. These tumours share morphological and immunohistochemical features with enteric adenocarcinoma, and the presence of surface intestinal metaplasia and glandular dysplasia in this case favours a urothelial origin.

Back to Top | Article Outline


Karen Whale1, Narada Hapangama2, Jane E. Dahlstrom1,3

1Department of Anatomical Pathology, ACT Pathology,2Department of Oral Maxillofacial, Canberra Hospital, Woden, and3Australian National University Medical School, Canberra, ACT, Australia

A 15-year-old male presented with an incidentally discovered radiopacity above an unerupted wisdom tooth of the right mandible. A biopsy 2 years prior was inconclusive.

Light microscopy of the biopsy revealed proliferating cords of odontogenic epithelium with a moderately cellular mesenchymal matrix enclosing loose stellate reticulum-like areas. There was associated new enamel and dentine formation with the structure of a complex odontoma. These features are of an ameloblastic fibro-odontoma.

Ameloblastic fibro-odontoma is a rare, slowing growing, mixed odontogenic neoplasm which is usually diagnosed before the age of 20. They involve the posterior mandible or maxilla and can be associated with unerupted teeth. Radiographically the ameloblastic fibroma component appears as a well defined radiolucent area with the odontomatous component appearing as irregular radiopacities. Radiological differential diagnoses include calcifying odontogenic cyst and odontoma. Ameloblastic fibro-odontomas are generally not aggressive and can be treated with surgical curettage without removal of adjacent teeth. Recurrences have been reported. The risk of developing an amelobastic fibrosarcinoma is less than for an ameloblastic fibroma. However, follow-up is recommended.

Back to Top | Article Outline


L. Wienholt, S. Adelstein

Clinical Immunology, Royal Prince Alfred Hospital, Sydney Australia

The identification of antibodies to extractable nuclear antigens (ENA) is important in the diagnosis of connective tissue diseases. Traditional gel based methods of detection such as counterimmunoelectrophoresis (CIEP) have been replaced in recent years by more automated semi-quantitative systems such as ELISA and multiplex based assays. However the sensitivity and specificity of these assays have been shown to be variable.

A review of 3000 patient samples showed that by decreasing the cut-off for positive confirmation by 25% on the Euroimmun screening ELISA [ANA Screen 11-ELISA (IgG)], an additional 28 patients (0.9%) were referred for confirmatory testing by the Euroimmun line blot [Euroline ANA Proflie 3 (IgG)]. Of these 20 (71%) showed positivity to a variety of nuclear antigens while 8/28 (29%) were negative.

Clinical information was available on 14/20 (70%); the identification of an ENA was consistent with a connective tissue disease in 8/14 (57%) of patients, while 10/14 (71%) patients were already on immunosuppressive therapy.

Decreasing the threshold value for confirmatory testing to 75% of the kit calibrator, reflective of the uncertainty of measurement (UOM) of the assay, increased the diagnostic sensitivity of the assay in detecting true positive samples that would not have had additional testing using the threshold recommended by the manufacturer.

Back to Top | Article Outline


M. H. Yilmaz, S. Arbuckle, N. Graf

Department of Histopathology, The Children's Hospital at Westmead, Sydney, NSW, Australia

Aims: An umbilical artery aneurysm is a rare vascular anomaly, associated with significant fetal morbidity and mortality. We report a case seen in our institution and review the literature on this entity.

Methods: A 30-year-old lady, with a background of factor V Leiden deficiency, delivered a live healthy baby at 39 weeks gestation. There were no peripartum complications. Macroscopic examination of the placenta showed a large, blood-filled cyst arising from the umbilical cord, located near the disc insertion. The umbilical cord was thin, mildly overcoiled, and had a furcate insertion.

Results: Microscopically, the cyst was a markedly enlarged blood vessel lined by endothelium, with smooth muscle in the wall. Subchorionic fibrin was present at the cord insertion site. No infarction, villitis or fetal thrombotic vasculopathy was identified.

Conclusions: Umbilical artery aneurysms are rare and associated with fetal morbidity and mortality. In this case, there were no significant fetal complications. The furcate nature of insertion of the umbilical cord may have been a contributory factor in the development of the aneurysm.

Back to Top | Article Outline


F. Ziad1, D. Ninin1, L. Graham2

1Department of Pathology, Waikato Hospital, Hamilton, and2Department of Electron Microscopy, Lab Plus, Auckland, New Zealand

Background: Embolic tubular epithelial cells in the lumina of glomerular capillary loops have been described following percutaneous biopsy as a rare artifact.

Method: A 37-year-old male underwent a percutaneous renal biopsy as a part of investigation for proteinuria.

Result: Epithelial cells with abundant mitochondria and surface villification similar in morphology to proximal tubular epithelial cells were discernible in the glomerular capillary loops on electron microscopy in a percutaneous needle biopsy sample.

Conclusion: Tubular epithelial cell emboli is a rare artifact of the needle biopsy in which tubular cells or fragments are detached from the tubule by the needle and pushed into the glomeruli through arterioles. Awareness of this artifact is important to avoid misinterpretation as focal proliferative lesion or metastasis.

© 2012 Royal College of Pathologists of Australasia