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Abstract

Oral Abstracts Presented at the 24th Virtual Joint Meeting of the International Society of Dermatopathology, April 12–16, 2021

The American Journal of Dermatopathology: August 2021 - Volume 43 - Issue - p 15-21
doi: 10.1097/DAD.0000000000002029
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“Oral Abstract Presentations”, Monday, April 12, 2021, 10:30 AM

Low Expression of Galectin-3 Around Blisters in Pemphigus Vulgaris

Maryam Aghighi, MD,*,1 and Bruce Smoller, MD†

*Department of Pathology, RWJ Barnabas Health, Livingston, NJ; and †Department of Pathology, University of Rochester Medical Center, Rochester, NY.

1Presenter

Background: Pemphigus vulgaris (PV) is an autoimmune bullous dermal condition associated with IgG autoantibodies against desmoglein-3. It involves with blistering and erosion of the skin due to intraepidermal separation of keratinocytes. Galectin-3 is one of the main elements of the IgE group which is essential in the cell-cell adhesion. Here, we evaluated the expression of galectin-3 in PV.

Methods: Thirty PV cases were stained with galectin-3 antibody. The percentages of nuclear and cytoplasmic expression were evaluated semi-quantitatively around blisters and normal skin.

Results: We observed a significant decrease in galectin-3 cytoplasmic expression around blisters (mean = 5.20% ± 0.46%) compared to normal skin (mean = 63.50% ± 2.19%, P < 0.0001) and nuclear expression (mean = 1.07% ± 0.05%) compared to normal skin (mean = 45.17% ± 1.54%, P < 0.0001).

Conclusions: Presence of autoantibodies against desmogleins lead to the blister development. However, lack of galectin-3 around the blisters may influence the extension of blisters due to its role in cell-cell adhesion at intercellular keratinocyte. We showed galectin-3 diminishes around the blisters which may be related to the pathogenesis of the skin condition in PV.

p75 Nerve Growth Factor Receptor is a Useful Marker in the Differential Diagnosis of Dermatofibrosarcoma Protuberans and Dermatofibroma

Albert Alhatem, MD

Rutgers University.

Background: The histologic distinction between dermatofibrosarcoma protuberans (DFSP) and dermatofibroma (DF) may pose a diagnostic challenge. Immunohistochemical stains are usually used to aid in the differential diagnosis. p75 nerve growth factor receptor (NGF-R) is a 75kd glycoprotein cell surface receptor and a member of the tumor necrosis receptor family. It is expressed on a variety of cells derived from the neural crest. Expression of this marker has also been demonstrated in non-neural mesenchymal tumors.

Objective: Our goal was to evaluate the utility of p75 NGF-R in distinguishing between DFSP and DF.

Methods: A total of 52 cases including 14 DFSPs, 20 cellular DFs, and 18 DFs were analyzed with antibodies against p75 NGF-R, CD34, and Factor XIIIa.

Results: p75 NGF-R and CD34 were strongly expressed by all 14/14 (100%) cases of DFSP. p75 NGF-R was negative in all DFs. CD34 positivity was noted in 6/38 (16%) DFs, 4 of which were DFs staining diffusely (n = 2) and focally (n = 2) with the marker. Two cases of cellular DF also labeled with CD34. None of the DFSPs expressed Factor XIIIa; whereas, 100% of DFs revealed expression of this marker.

Conclusions: p75 NGF-R is a useful adjunct in the differential diagnosis between DFSP and DF. It is particularly helpful in distinguishing cases of DFSP from DFs, which show CD34 positivity but do not express p75 NGF-R. We propose adding this marker to the current available repertoire in order to increase diagnostic accuracy.

Pathology Report Format and Pictures…Does it Matter?

Mahtab Fakhari, MD,* Eric Ollila, MD,* Monica Henderson, MSHI,* and Peter Pavlidakey, MD†

Departments of *Pathology, and †Dermatology, University of Alabama at Birmingham.

Pathology report formats and inclusions of images has been a debate for years. The question is do pictures, color or alert banners really do anything, at least from a pathology perspective? A questionnaire was distributed to all pathology attendings and residents at UAB to help identify an optimal format for pathology reports. Thirty-one individuals participated consisting of 18 attendings and 13 residents. Four different reports were included: a standard hospital report, an enhanced layout, an enhanced layout with an image, and an enhanced layout with an image and a red stripe on the side labeled malignant. Thirty-nine percent choose the detailed report with images and no border. Twenty-three percent preferred the detailed reports without images. Nineteen percent chose the report with diagnoses only. Nineteen percent chose the detailed report with images and a border. In total, 58% preferred the images on the report. Sixty-six percent felt the images add no medical legal liability. Does the extra time for a photo add value?

Superficial Vs Deep Pleomorphic Sarcomas: Do They Have Different Mutation Profiles?

Yasmin Hambaroush, MD, Jennifer Stocks-Candelaria, PhD, Shulin Zhang, MD, PhD, and Shadi Qasem, MD

Department of Pathology, University of Kentucky.

Background: Soft tissue tumors are rare and present a variety of histological subtypes with unique molecular abnormalities and varied outcomes. However pleomorphic sarcomas have complex, non-recurrent, genetic abnormalities and is morphologically diverse. These tumors are erratic in their behavior and often have poor prognosis. They may involve superficial or deep anatomic locations in the body, and this has significant implications on their behavior and prognosis. This is presumed to be due to loco-regional factors. Molecular categorization based on location has not been thoroughly studied. The main objective of this pilot study is to investigate the mutation profiles for superficial and deep pleomorphic sarcomas, and correlate that with their clinical behavior.

Design: A laboratory-developed next generation sequencing (NGS) panel of 198 cancer gene panel was utilized to interrogate the molecular make up of 17 PS cases with adequate amplifiable material. Samples were sequenced on the Illumina HiSeq 2500 (Illumina, Inc, CA). A custom bioinformatics pipeline aligned the data to human reference genome GRCh37 to call variants. Results were correlated with location.

Results: Seven superficial and 10 deep tumors represented 17 patients with average age of 69.3 (52-80) and a male to female ratio of 2.4 to 1. All deep tumors were located in the extremities; 5 superficial tumors were located in the head and 2 in the extremities. TP53 was detected in 5/7 (71%) of superficial sarcomas and 6/10 (60%) deep sarcomas. CDKN2A was detected in 3/7 (42%) of superficial sarcomas, and none in deep sarcomas. 6/10 Deep sarcoma patients had pulmonary metastases, and 1/10 had only local recurrence. One of 3 superficial sarcomas with follow up had local recurrence, but none had metastasis.

Conclusions: In this study, TP53 is the most prevalent mutation in pleomorphic sarcoma 64%, and is prevalent in both superficial and deep locations. CDKN2A is uniquely over represented in this limited sample of superficial sarcomas. Further studies are needed to explore the significance of CDKN2A in superficial sarcomas and any possible correlation with prognosis.

Lentigo Maligna/Lentigo Maligna melanoma

Annia Henning, MD

Summa Health System, Akron, OH.

Lentigo maligna/lentigo maligna melanoma (LM/LMM) is a subtype of melanoma that arises on sun-exposed surfaces secondary to chronic UV exposure. Histologically, LM/LMM are characterized by an atypical lentiginous proliferation of melanocytes with or without dermal involvement. A wide-excision with 1 cm clinical margins is currently recommended due to the poorly circumscribed and subclinical extensive nature of the process to ensure complete removal. However, there is no defined minimal histologic margin needed to declare complete excision. We hypothesize that the interobserver reproducibility of the peripheral borders of the LM/LMM is poor given the morphologic overlap with sun-induced melanocytic hyperplasia, skip lesions, and often subtle growth pattern and therefore would result in difficulties objectively measuring and defining the margins. To test our theory, we gathered 90 LM/LMM wide excision specimens and asked pathologists to determine the peripheral limit of the disease process by marking where the LM/LMM stopped on selected H&E slides. The measurements from the marked boundary of the LM/LMM and margin were then recorded and compared. Statistical intraclass correlation (ICC) was 0.506 with a 95% confidence interval which indicates that the pathologists did not reliably agree where the lesions stopped. In conclusion the poor interobserver reproducibility of the peripheral borders of LM/LMM further account for the wide-excision margins needed for complete excision and further provide suggestion for close clinical follow-up with consideration for re-excision if the margins are close.

Performance of 35-Gene Expression Profile Test in Desmoplastic Melanoma

Gregory A. Hosler, MD, PhD* and Matthew S. Goldberg, MD†,‡

*ProPath, Dallas, TX; †Castle Biosciences, Friendswood, TX; and ‡Icahn School of Medicine at Mount Sinai, NY.

Desmoplastic melanoma remains a diagnostic challenge despite availability of immunohistochemical stains and other ancillary testing. Consensus recommendations of FISH and gene expression profile (GEP) testing for differentiation of desmoplastic melanomas from benign nevi are lacking. The recently developed and validated diagnostic 35-GEP test for difficult-to-diagnose primary cutaneous melanocytic neoplasms evaluates a lesion's transcriptomic profile providing an objective test result of benign, intermediate-risk or malignant. The 35-GEP has reported 99.1% sensitivity in the independent validation cohort of 503 cases. Here, we report performance of the 35-GEP test in 48 desmoplastic melanoma lesions. The 35-GEP accurately assigned a malignant GEP result for 45 lesions, which represents 93.8% sensitivity. Although this is lower than accuracy reported for the overall validation cohort, it indicates a high sensitivity for desmoplastic melanoma classification. These data suggest that the 35-GEP can be used as an objective tool for diagnostic differentiation of benign nevus and desmoplastic melanoma, potentially leading to improved patient management decisions. This study was sponsored by Castle Biosciences.

Reflectance Confocal Microscopy-Guided Biopsy as A Novel Technique for Diagnosis of Mycosis Fungoides

Banu Farabi MD,* Marielle Jamgochian MBS,* Aamir Hussain MD, MAPP,† and Babar Rao MD, FAAD*

*Dermatology Department, Rutgers University, Robert Wood Johnson Medical Center, NJ; †MedStar Washington Hospital Center/Georgetown University, Dermatology Residency Program, Washington, DC.

Background: Reflectance confocal microscopy (RCM) may help diagnose mycosis fungoides (MF) through high-resolution in-vivo visualization of skin. We present a case of plaque-stage MF that was diagnosed through a combination of RCM and histopathologic analysis.

Patient History: An 87-year-old female presented with many erythematous, scaly papules and plaques including on the scalp. Three lesions with high clinical suspicion for MF were imaged with RCM and biopsied.

Results: Vesicle-like dark spaces with round cells correlating to Pautrier microabscesses were visualized on RCM. Biopsies showed atypical band-like lymphocytic infiltrate at the dermo-epidermal junction with epidermotropism and Pautrier microabscessess in the epidermis, and immunohistochemical pattern consistent with MF.

Conclusions: Pautrier microabscesses, pathognomonic histologic markers of mycosis fungoides, can be visualized through RCM. RCM is useful in determining biopsy sites and diagnosing mycosis fungoides.

Eosinophil Predominance Underscores the Range of Histopathology in Linear IGA Bullous Dermatosis

Calvin Knapp III, Kevin White, Lynne Morrison, and Jesse Keller

Department of Dermatology, Oregon Health and Science University, Portland, OR.

A 67 year old female who had not previously seen a physician and carried no diagnoses presented to dermatology clinic with 2 months of an asymptomatic bullous eruption. On exam were grouped, tense, annular bullae on her arms and trunk. Biopsy demonstrated subepidermal vesicles and dense eosinophilic infiltrate with rare neutrophils spanning the entire specimen on light microscopy, typical of bullous pemphigoid. However, DIF demonstrated a confluent linear band of IgA at the basement membrane zone with absence of other immunoreactants. Given the DIF findings, linear IgA bullous dermatosis (LABD) was diagnosed.

LABD is an immunologic disorder classically characterized by subepidermal bullae with dense neutrophilic infiltrate, vacuolar change in the dermal papillae, with only occasional eosinophils, particularly in later stage lesions. Though an eosinophilic predominant infiltrate has been reported previously, cases are frequently attributed to drug associated LABD and do not report this degree of eosinophil involvement. This case illustrates that although uncommon, eosinophilic predominant LABD exists, and confirmatory DIF is essential to differentiate from other subepidermal immunobullous conditions.

Rowell Syndrome Induced By Terbinafine

Almeera Lateef, John Metcalf, MD, and Joni Mazza-McCrann, MD

Medical University of South Carolina

Drug-induced Rowell Syndrome presents as an overlap syndrome of lupus erythematosus and erythema multiforme. The oral antifungal medication terbinafine has been observed to induce Rowell Syndrome [1,2]. A 64 year old woman with previously known cutaneous lupus erythematosus on Plaquenil presented with worsening rash that had began about 5 weeks prior, soon after starting terbinafine for onychomycosis. A biopsy showed interface dermatitis superficial and deep perivascular and periadnexal inflammation with necrotic keratinocytes, as well as an increase in dermal mucin. DIF showed linear deposition of IgG, IgA, C3, kappa and lambda compatible with lupus erythematosus. The combination of these finding is consistent with a diagnosis of Rowell's syndrome. There have been 2 previous cases of a Rowell syndrome after the use of terbinafine. Hopefully this additional case will bring continued awareness of this rare but important syndrome when observing both features of lupus and erythema multiforme on path. Additionally, this case suggests that dermatologists should use caution or even avoid the use of terbinafine in patients with known cutaneous lupus.

Spheroid Amyloid Deposition Mimicking Panniculitis

Dan R. Lopez, MD, Cathy Massoud, MD, Laura S. Winterfield, MD, MPH, and Jessica A. Forcucci, MD

Medical University of South Carolina, Charleston, SC.

Spheroid-type amyloid deposition is a very unusual morphologic variant. It has not been previously described in the skin within the English literature. An 82 year old woman developed focal painful induration of her right thigh. Her past medical history included systemic amyloidosis, papular elastorrhexis on her neck, and stable bilateral pulmonary nodules. A punch biopsy was performed. The specimen consisted of epidermal, dermal, and subcutaneous fragments. Prominent spheroid - ovoid, eosinophilic, concentrically laminated deposits, reminiscent of Liesegang rings, were identified in the reticular dermis and subcutis. Congo Red confirmed the presence of amyloid within the deposits, and demonstrated apple green birefringence under polarization. Spheroid (corpora amylacea-like/Liesegang ring-like/salmon roe-like) amyloid deposition has been previously described in pituitary adenomas, localized bronchial amyloidosis, squamous cell carcinoma of the uterus, amyloidomas of colon, bone, and jejunum, and colonic adenocarcinoma. These depositions are thought by some to represent an inadequately understood process of intermittent accumulation of amyloid via macrophage giant cell reaction due to either a deranged inflammatory process or chronic tissue damage.

Reducing Dermatopathology Review Time Using A Deep Learning Algorithm

Kiran Motaparthi,* Diana Braswell,* Coleman C. Stavish,† Theresa A. Feeser,† Ramachandra Vikas Chamarthi,† Julianna D. Ianni,† Rajath E. Soans,† Pratik Patel,† Rachana Kotapalli,† and Michael J. Bonham†

*Department of Dermatology, University of Florida College of Medicine, Gainesville, FL; †Proscia, Inc., Philadelphia, PA.

Objective: To quantify the efficiency gain when a deep learning (DL) algorithm capable of multivariate classification is introduced into the dermatopathology workflow.

Methods: In this 4-week, prospective blinded study, a board-certified dermatopathologist reviewed and recorded diagnoses for 1150 whole slide images (WSIs). Fifty percent of the WSIs were pre-classified by a DL algorithm into 1 of 5 categories: Basaloid, Squamoid, Melanocytic, Other, or Uncertain. Review time, measured as the time between opening successive cases, was recorded by the image management system. Efficiency gain was calculated as mean review time without pre-classification minus mean review time with classification, divided by review time without pre-classification.

Results: After excluding cases that were opened multiple times or nonconsecutively, 535 WSIs generated from 255 specimens and containing 78 distinct diagnoses were pre-classified and sorted by the DL algorithm and included in statistical analysis for comparison to 233 specimens reviewed without pre-classification. The algorithm yielded an efficiency gain of 15 percent overall; excluding an initial training period of 3 days, the efficiency gain was 28 percent.

Conclusions: Pre-classification of routine diagnoses by a DL algorithm may reduce dermatopathologist review time and increase efficiency.

Signet-Ring Cells Cutaneous Metastasis as a Debut of Metastathic Lung Adenocarcinoma

Reculé F,* Fajre X,* Whittle C,† and Castro A‡

*Department of Surgery, Dermatology Service, Universidad del Desarrollo - Clínica Alemana, Santiago, Chile; †Department of Radiology, Universidad del Desarrollo—Clínica Alemana, Santiago, Chile; and ‡Department of Pathology, Universidad del Desarrollo - Clínica Alemana, Santiago, Chile.

A 61-year-old male presents with acute lymphedema of both upper arms and multiple firm nodules. An ultrasound (US) showed soft tissue lymphedema and avascular suspicious nodules. Biopsy revealed normal epidermis and dermis with multiple discohesive cells of round nuclei, prominent nucleoli and abundant eosinophilic granular cytoplasm. Many of the cells had intracytoplasmic vacuoles forming signet-ring cells. Immunohistochemistry; Pancytokeratin (AE1/AE3) positive for neoplastic cells, CK7 positive, CK20 positive in neoplastic cells, CDX2 negative in neoplastic cells, TTF-1 negative, SATB2 negative (Signet-Ring Cell Carcinoma). The study of digestive and pulmonary neoplasia: PET-CT with pleural effusion without other alterations. Lung biopsy: Signet-ring cell carcinoma with multiple lymph permeations. Signet-ring cell carcinoma -a subtype of adenocarcinoma- is a very rare variant of primary lung cancer (incidence 0.14%–1.9%).1,2 Almost 10% of visceral malignancies develop cutaneous metastasis (CM); which represent near 2% of all skin cancers.3 After digestive origin, pulmonary is the second most common.4 There are 43 reports of signet-ring cell carcinoma CM and only one of pulmonary origin.4 To our knowledge, until 2017, CM arising from a pulmonary signet-ring cell adenocarcinoma has not been reported.4 CM may mimic contact dermatitis, erysipela or erythema annulare centrifugum.5–8 One report with signet-ring cell adenocarcinoma with chylothorax (gastric).9 This case illustrates how CM may be the clinical debut of a clinically silent visceral cancer. We must be aware of this entity with a high clinical suspicion in order to achieve an optimal diagnosis and prompt treatment.

The Role of Skin Biopsy in Diagnosis of Lafora Disease

Krasimira Rozenova, Julia Lehman, Joseph Grande, Anthony Fine, and Carilyn Wieland

Mayo Clinic, Rochester.

Lafora Disease (LD), a rare but devastating disease, presents as myoclonus epilepsy with onset in late childhood or early adolescence. An autosomal recessive disorder, LD is caused by mutations in laforin or malin, enzymes involved in glycogen metabolism. We present a patient with LD, for whom skin biopsy played a crucial role in confirming diagnosis. A 16-year-old female presented for evaluation of progressive worsening epilepsy and cognitive decline. The patient continued to experience increasingly frequent myoclonic seizures despite treatment with antiepileptic medications. Axillary skin biopsy demonstrated eosinophilic, PAS-positive, diastase-resistant intracellular oval inclusions located close to the basement membrane in apocrine and eccrine glands. Lafora bodies (polyglucosan inclusions) were also visualized by electron microscopy. Whole exome sequencing identified a homozygous mutation in the NHLCR1 gene, c.98T>C (p.F33S), further supporting a diagnosis of Lafora disease. While intracellular inclusions can be seen in multiple organ systems, accessibility to the skin and abundance of sweat glands in the axilla allows for skin biopsy to be instrumental for diagnosis.

Unusual Case of Visual “Floaters” With Yellow Papules on The Neck

Shiyanbola O,* Okun M,† Bell J‡, Shah K§

*Department of Pathology, University of Wisconsin-Madison, and the Departments of †Dermatology, ‡Ophthalmology and §Pathology, St Mary's Hospital, Madison WI.

We present a case of pseudoxanthoma elasticum (PXE) in a 39-year-old woman with rheumatoid arthritis. This autosomal dominant disorder of elastic tissues can involve multiple organs, such as the skin, eye and the cardiovascular system. Hence, non-dermatology physicians encountering patients with PXE symptoms should have a high index of suspicion, and refer such patients to the dermatologists for assessment of suspected skin lesions. This approach will lead to accurate identification and diagnosis of PXE. The patient was evaluated for “floaters” in her visual field, with eye examination revealing macular hemorrhage and angioid streaks. Her young age and the presence of skin lesions prompted a dermatology clinic referral. Skin examination revealed yellow papules, with axillary skin laxity. Histologic findings demonstrated distortion of reticular dermal collagen with clumping and calcification of dermal elastin fibers, highlighted with Elastin and Von Kossa stains. This case underscores the correlation of demographic, clinical and histologic findings in accurately diagnosing complex connective tissue disorders such as PXE.

Granulomatosis With Polyangiitis: Important Histopathological Clues to Early Diagnosis

Pooja Srivastava,* Jonhan Ho,† Viktoryia Kazlouskaya,† Sonal Choudhary,† and Arivarasan Karunamurthy†

*Department of Pathology, †Department of Dermatology, University of Pittsburgh Medical Center.

Introduction: An early and accurate diagnosis of Granulomatosis with polyangiitis (GPA) remains very critical as it rapidly progresses to life threatening disease. We discuss histopathological clues which are useful in timely diagnosis.

Case Report: Seventy-year-old female presented with 1-month history of diffuse painful erythematous rash. Laboratory work up showed elevated antinuclear antibody (ANA) and negative Antineutrophil cytoplasmic antibody. Biopsy of skin lesions at 0, 1- and 2-months intervals revealed perivascular and interstitial granulomatous and mixed inflammation. Initial biopsies also showed extravasated erythrocytes (0 & 1 month) and rare fibrin foci (1 month). Biopsy at 2-month showed characteristic fibrinoid necrosis of the vessel walls and hemorrhage. Granulomatous inflammatory process with differential including GPA was suggested. Patient progressed to develop multiple lung nodules which revealed similar histopathology.

Conclusions: Early cutaneous GPA may not reveal the characteristic findings. Important clues such as extravasated erythrocytes and/or fibrin type material in a background of granulomatous inflammation may be extremely useful in suspecting diagnosis of GPA especially in patients lacking other systemic symptoms of the disease.

Aberrant Melan-A Expression In Extramammary Paget's Disease

Gillian K. Weston MD,* and Michael M. Murphy MD†

*The Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine, New York, NY; and †UConn Health, Department of Dermatology, Farmington, CT.

A 50-year-old Caucasian male was diagnosed with invasive extramammary Paget's disease (EMPD) on the left inguinal fold. Excisional biopsy revealed an intraepithelial (in situ) and subjacent intradermal/subcutaneous neoplasm composed of single, nests and cords of cells containing abundant pale staining cytoplasm and large vesicular nuclei. By immunohistochemistry, tumor cells were strongly reactive for AE1/AE3, Cam 5.2, CK7, CEA and GATA-3; with focal nuclear reactivity for estrogen receptor and strong (3+) membranous expression for Her-2. Tumor cells were negative for p63, D2-40, CK20, villin, CDX2, TTF-1, prostatic specific antigen and progesterone receptor, in addition to S-100, HMB-45, SOX10, and MITF. The tumor showed diffuse intracytoplasmic grainy positivity for Melan-A (A103 clone). Melan-A (A103 clone) and MART-1 (melanoma antigen recognized by T cells) (M2-7C10 clone) antibodies recognize the same gene product, a melanosome-associated protein that is involved in melanosome biogenesis and are expressed by normal melanocytes, nevi, and melanoma. Both are well-known to be observed in non-melanocytic tumors of the skin as well, possibly as a result of cross reactivity with an unrecognized epitope within tumor cells. A recent case report has highlighted aberrant Melan-A expression in the pagetoid (in situ) cells in EMPD. Our case of EMPD demonstrated diffuse reactivity for Melan-A in both intraepithelial and invasive tumor cells. Inappropriate or aberrant melanocyte related protein expression in EMPD and other human non-melanocytic tumors demonstrates the need for caution in microscopic interpretation and for employing multiple immunohistochemical stains to corroborate clinical-histopathological features and ensure accurate diagnosis.

“Dermatopathology Trainee World Cup”Wednesday, April 14, 2021, 10:30 AM

A Case of Degos-Like Lesions in Systemic Lupus Erythematosus

Julia Dai, MD and Oluwakemi Onajin, MD

Section of Dermatology, University of Chicago, Chicago, IL.

Degos disease (DD), or malignant atrophic papulosis, is a rare vaso-occlusive disorder that can present with systemic or skin-limited disease. DD is often associated with connective tissue diseases including systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). We report a case of a 48-year-old woman with a history of SLE and APS who presented with multiple stellate, atrophic white papules with surrounding erythema on the scalp and chest. Skin biopsy demonstrated hyperkeratotic and atrophic epidermis with vacuolar interface dermatitis, wedge-shaped area of ischemic dermis, and increased mucin. Lymphocytic infiltration of the vessel wall with occlusive thrombus and fibrinoid necrosis was also identified in the deep dermis. Based on the clinical and histopathologic findings, a diagnosis of SLE with Degos-like lesions was made. Degos-like lesions can occur in systemic and cutaneous lupus erythematosus. Clinicopathologic correlation is necessary to distinguish lupus-related pathology from true DD given the striking differences in prognosis and treatment. We present this case to highlight the myriad cutaneous morphologic and histologic findings associated with SLE, which is commonly referred to as the “great imitator.”

Inner Thigh Hyerpigmentation: Key to Diagnosis of H Syndrome

Maged Daruish,* Ahmed El Sabagh,† Nada Ibrahim,* Ayman Gameel,† and Mahmoud Abdallah*

*Department of Dermatology, Andrology and Venereology, Ain Shams University, Cairo, Egypt; †Department of Internal Medicine, Ain Shams University, Cairo, Egypt.

A 50 years old male patient was admitted to the internal medicine department of our hospital for investigating a rapidly enlarging scrotal swelling. The patient was born to consanguineous parents and suffered from hearing impairment. He also suffered from inner thigh hyperpigmentation, for which our dermatology department was consulted. The hyperpigmented skin was found to be indurated on palpation. A punch 3 mm was taken from his skin lesions, and histopathological examination revealed basilar hyperpigmentation, marked thickening of the dermis, mixed inflammatory infiltrate, thickened collagen fibers and focal calcium deposits. The diagnosis of H syndrome was reached by clinico-pathological correlation.

Discussion: H syndrome is a rare autosomal recessive genodermatosis caused by mutations in SLC29A3. The described clinical findings include hyperpigmentation, hypertrichosis, sclerodermoid skin changes, flexion contractures, hearing loss, and short stature. Other reported systemic features include Insulin-dependent diabetes mellitus, lymphadenopathy, heart anomalies, pancytopenia, hypogonadism and organomegaly.

Utility of CD123 For Evaluation of Cutaneous Myeloid Sarcoma

Carlo De la Sancha,* Simon Warren,* and Mehdi Nassiri*

Indiana University School of Medicine.

Evaluation of the leukemic infiltrate in extramedullary locations is often challenging. CD123 has diagnostic utility for hairy cell leukemia and plasmacytoid dendritic cell tumors. In addition, new therapeutic agents against CD123 are being evaluated in clinical trials. Cases diagnosed as myeloid sarcoma or leukemia cutis during 2000-2014 were evaluated, including any bone marrows performed before or after the diagnosis. All samples were evaluated for CD123 by immunohistochemistry. Cases of plasmacytoid dendritic cells tumors were excluded. Thirty cases of cutaneous myeloid sarcoma were amenable for evaluation. CD123 was positive in 10 cases. In 4 of these cases bone marrow blasts were negative for CD123. CD123 is expressed in myeloid sarcoma, which can be incongruent with bone marrow blast immunophenotype. In work-up of cutaneous lesions, evaluation of CD123 should be interpreted with regard to rest of the myeloid antigens. Myeloid sarcoma positive for CD123 might benefit from specific targeted therapy.

Primary Axillary Signet Ring Cell/Histiocytoid Carcinoma With CDH1, PIK3CA, And EP300 Mutations

Koorosh Haghayeghi,* Gladys Telang,† Leslie Robinson-Bostom,† Peter Reilly,† and Christopher R. Elco*

Departments of *Pathology and †Dermatology. Brown University, Rhode Island Hospital, Providence, RI.

Primary signet-ring cell/histiocytoid carcinoma (PSRCHC) is a very rare tumor with histopathologic resemblance to histiocytoid variant of mammary lobular carcinoma. PSRCHC arises most commonly in the eyelid with few primary axillary cases described to date. We report a 52-year-old man with 3 year history of gradually enlarging left axillary lesion. Physical exam revealed a 2.5 × 1.5 cm erythematous nodule. Complete radiologic work-up showed neither primary mammary nor metastatic disease. Biopsy showed a diffuse interstitial infiltrate of histiocytoid cells many with vacuolated cytoplasm extending into subcutis. An in-situ component was present. No breast parenchyma was identified. Lesional cells were positive for GCDFP-15, CK7, P120, and negative for ER, PR, HER2, p63, CD68, and S-100. The tumor cells were weakly/partially positive for Gata-3 and mammaglobin. Patient underwent surgical excision. Molecular studies showed somatic mutations in CDH1, PIK3CA and EP300 which are also described in mammary lobular carcinoma. This is the first case drawing further genetic equivalence between 2 distinct but histopathologically similar neoplasms.

A Fatal Case of Hemophagocytic Lymphohistiocytosis With Cutaneous Involvement: A Rare Phenomenon

Shaymaa Hegazy, MD, UPMC, John Moesch, DO, UPMC, Arivarasan Karunamurthy, MD, UPMC, and Johan Ho, MD, UPMC

Pittsburgh, Pennsylvania.

Hemophagocytic Lymphohistiocytosis (HLH) is a rare, life-threatening syndrome, characterized by aberrant activation of T lymphocytes and macrophages leading to hypercytokinemia. HLH can be familial or a result of numerous secondary etiologies.

We present a case of a 46-year-old female with a past medical history of multiple sclerosis on Rituximab who presented as a transfer from an outside hospital with numerous clinical abnormalities including hypertriglyceridemia, steatohepatitis, persistent leukocytosis, and recurrent fevers of unknown origin for 3 weeks. Due to the uncertain nature of her illness, she underwent a punch biopsy of normal abdominal skin to exclude malignancy.

Histopathology revealed a brisk superficial dermal infiltrate rich in histiocytes accompanied by a perivascular lymphocytic infiltrate. The histiocytes were large and exhibited focal areas of hemophagocytosis. The histiocytes were positive for CD4, muraminadase, and CD68.

According to HLH-2004 protocol, our patient met the diagnostic criteria of HLH. Concurrent bone marrow biopsy showed similar rare hemophagocytosis. Cytogenetics and molecular studies were negative, supporting a secondary nature of HLH.

A CIC-DUX4 t(4:19)(q34;q13.1) Ewing-Like Sarcoma Masquerading as a Subcutaneous Cyst

Megan Kachur, MD, Samantha Bartling, DO, and Sarah Heaton, MD

Walter Reed National Military Medical Center, Bethesda, MD.

CIC-DUX4 sarcomas are rare aggressive tumors usually occurring in the trunk and extremity deep soft tissues. To our knowledge, this is the first case presenting as strictly subcutaneous. A 16 years old male presented with a subcutaneous back mass which was clinically and radiographically consistent with an epidermal inclusion cyst. When the mass tripled in size in the subsequent 4 months, an incisional biopsy was performed. The tumor was composed of poorly differentiated round blue cells with >20 mitoses/HPF. A broad immunohistochemical work-up was performed and revealed DUX4 and ERG positivity with CD99 positivity in a subset of cells. Fluorescence In-situ Hybridization revealed CIC (19q13) rearrangement and was negative for EWSR1 and FLI1 rearrangements. The patient subsequently underwent 6 cycles of neoadjuvant chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide before a wide local excision, which revealed a partial therapeutic response. CIC-DUX4 sarcoma is a rare aggressive tumor, only described within the last decade, which should be considered in the differential diagnosis of a rapidly growing subcutaneous mass.

Vulvar Mammary-Type Apocrine Ductal Carcinoma in Situ With Focal Suspicious Invasion Arising in Hidradenoma Papilliferum—A Case Report

Grace Kim, Malvika Solanki, and Ruifeng Guo

Department of Dermatology, Mayo Clinic, Rochester, MN; and Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN

Hidradenoma papilliferum is a benign adnexal neoplasm of the vulva that typically presents as a unilateral, flesh-colored papule. Malignant transformation of vulvar hidradenoma papilliferum is an extremely rare finding by applying strict histological criteria. We present a 51-year-old female who presented with a several year history of a “cyst” clinically that recently became tender and enlarged. Excisional biopsy of the lesion demonstrated a complex glandular proliferation including tubular and papillary structures. The peripheral portion of the tumor showed typical features of a hidradenoma papilliferum, which, however, abruptly transitioned into expansile growth of tumor nests and strands with prominent cytological atypia and noticeable mitoses. Immunostains with calponin and p63 confirmed the presence of myoepithelial layer in the periphery of tumor nests. The tumor cells had large nuclei, prominent nucleoli and abundant lightly eosinophilic cytoplasm, features identical to that of mammary apocrine ductal carcinoma in situ (DCIS), confirmed by immunostains (negative ER and positive AR). In addition, focal area with infiltrative growth pattern and stromal desmoplasia is noted, concerning for invasion. In spite of the unusual pathological findings, this lesion was completely excised with negative surgical margins. There was no recurrence or metastasis with over 10-year follow-up.

Angiolymphoid Hyperplasia With Eosinophilia Involving Large Arteries

Janina Markidan* and Linglei Ma†

*University of Maryland Medical Center, Baltimore, MD; and †Anne Arundel Dermatology, Glen Burnie, MD.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a benign vascular lesion, which usually consists of small vascular channels lined with epithelioid endothelial cells and surrounded by lymphocytes and eosinophils. Here, we report a rare case of ALHE involving large arteries in the skin. The patient presented with a 9 month history of an asymptomatic nodule on the forehead, which was thought to be an epidermal inclusion cyst. Skin biopsy revealed areas of small vessels lined by prominent endothelial cells, associated with a dense lymphoid infiltrate with eosinophils. Additionally, there were adjacent large arteries with clusters of epithelioid cells in the lumen and scattered eosinophils in the vascular walls. No significant cytologic atypia was noted. Given the presence of small vessel involvement, along with CD31 reactivity for the large intravascular epithelioid cells, the findings are best regarded as ALHE involving large arteries. There have been only a handful of reported cases of ALHE involving large arteries in the literature, while such occurrence in skin, as seen in our patient, is extremely rare.

Rupioid Psoriasis in an HIV Seropositive Patient With Skin of Colour: A Case Report

Josiah Masuka, MBChB, Zamambo Mkhize, FCDerm(SA), and Ncova Dlova, FCDerm(SA)

Department of Dermatology, Nelson R Mandela School of Medicine, Congella, Durban.

Background: Psoriasis is a common dermatological condition which may present atypically especially in HIV sero-positive individuals.

Case Presentation: We present a newly diagnosed HIV sero-positive 37 years old, male patient, with a CD4 count of 20 cells/mm3 who exhibited hyperpigmented, hyperkeratotic plaques on the face, trunk and extremities. He had also recently been diagnosed with a computed tomography scan confirmed brain space occupying lesion, possibly a tuberculoma and was currently on highly active antiretroviral therapy and anti-tubercular medications. Our differential diagnoses included rupioid syphilis, rupioid psoriasis and the systemic fungal infections—histoplasmosis and emergomyesis. Initial histology findings indicated eosinophilic folliculitis, but a re-biopsy of the lesions showed psoriasiform hyperplasia and Munro abscesses in keeping with a diagnosis of psoriasis.

Conclusions: This case presented both clinical and histologic diagnostic dilemmas given the atypical, rare clinical presentation and the eosinophilic infiltration in the rupioid psoriatic plaques. Thorough histologic examination should assist in avoiding missing atypical presentations of common pathology.

A Rare Case of Cutanous Solitary Fibrous Tumor

Sara Moradi, MD, Srinivas Mandavilli, MD, and Torsten Ehrig, MD

Department of Pathology and Laboratory Medicine, Hartford Hospital, Hartford, CT.

Introduction: Most extrathoracic soft tissue solitary fibrous tumors (SFT) occur in a deep location and only rarely in the subcutis or dermis. Herein we report a SFT in the subcutis on the forehead of a 65 y/o male.

Case Report: The patient presented with a 3 cm left upper forehead, tan, lobulated lesion. Microscopically it consisted of a well-circumscribed nodule that was variably cellular with uniform spindle cells and focal dilated blood vessels. Only rare mitotic figures were seen. There was no cytologic atypia or necrosis. On immunohistochemistry, the tumor cells were positive for CD34 and STAT6.

Discussion: A problematic question regarding SFTs relates to their metastatic potential which is generally low, but it cannot be accurately predicted which tumors will metastasize based on histopathologic and/or clinical criteria. A number of risk stratification models have been proposed based on parameters such as mitotic activity, tumor size, patient age and extent of necrosis; using one such model, our tumor falls in the low-risk category indicating an excellent prognosis.

Cutaneous Findings of Sporadic, Adult-Onset Neuronal Intranuclear Inclusion Disease

Jakob M. T. Moran, MD,* Katharina Eikermann-Haerter, MD,† Otto Rapalino, MD,† Timothy M. Dang, MD,‡ Robert K. Holmes,* Steven T. Chen, MD,‡ and Mai P. Hoang, MD*

Departments of *Pathology, †Radiology and ‡Dermatology, Massachusetts General Hospital, Boston, MA.

Introduction: Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disease with heterogeneous clinical manifestations. The characteristic pathological finding is ubiquitin-positive intranuclear inclusions in neuronal and non-neuronal cells. The magnetic resonance imaging (MRI) findings of NIID include high signals along the cortico-medullary junction on diffusion-weighted imaging (DWI).

Case Report: A 61-year old male with a complex medical history presented with altered mental status, stimulus-induced myoclonus and hallucinations. A brain MRI revealed bilateral hyperintensities along the corticomedullary junctions in the frontal lobes on DWI, extensive FLAIR hyperintense areas in the supratentorial white matter and characteristic symmetric T2-FLAIR hyperintensities within the cerebellar paravermal areas. Histologic sections of skin biopsy revealed rare intranuclear inclusions in eccrine epithelium that were positive for ubiquitin immunohistochemistry. Electron microscopy demonstrated intranuclear whorls of filamentous material without limiting membrane within the sweat gland epithelium as well as in dermal fibroblasts.

Discussion: The intranuclear inclusions found in neuronal and non-neuronal cells in NIID are thought to be composed of excess, accumulated proteins. However, the complete pathogenesis of NIID is not completely elucidated. The ease of skin biopsy coupled with the clinical heterogeneity of NIID suggests NIID should be considered more often in the differential diagnosis of progressive neurodegenerative disorders.

Deep Penetrating Nevus (DPN)-Like Melanoma Arising Within a Combined Nevus

Heather M. O'Connor, DO and Jessica A. Forcucci, MD

Medical University of South Carolina - Charleston, South Carolina.

One-third of melanomas arise from nevi due to sequential mutation accumulation. We report a case of DPN-like melanoma with molecular features and clinical history supporting the evolution of a combined nevus into melanoma. A 68 year old man presented to dermatology when he noticed change in size and shape in an upper back pigmented lesion that had been present “for as long as he could remember”. A biopsy demonstrated 2 distinct cell populations, raising the possibility of an unusual combined nevus with components of banal (common acquired) nevus and DPN. Significant pagetoid scatter or confluence was not identified on SOX-10 immunostain, and MART-1/ki-67 demonstrated a low proliferative index (<5%). Beta-catenin stained a subset of the dermal melanocytes. Next generation sequencing revealed NRAS and APC mutations, supporting combined nevus; however, microarray revealed multiple losses (5q, 9q, 16q, 17, and Y), gain of 22, and loss of heterozygosity on 9p. A diagnosis of melanoma arising within a combined nevus was rendered and the patient underwent excision and sentinel lymph node biopsy with a final stage of pT4a pN0.

Malignant Proliferating Trichilemmal Tumor of The Scalp: A Systematic Review

Muhammad Osto, BS* Nathan Parry, BS† Rafey Rehman, BS† Uddin Ahmed, BS,‡ and Darius Mehregan, MD*

*Wayne State University School of Medicine, Detroit, MI; †Oakland University William Beaumont School of Medicine, Rochester, MI; and ‡University of Michigan-Dearborn, Dearborn, MI.

Objective: Our objective was to perform a systematic review evaluating clinical presentation, tumor characteristics, and treatment modalities used for Malignant proliferating trichilemmal tumors of the scalp (MPTT) to determine which treatment strategies had the best outcomes.

Methods: The databases PubMed, Embase, and Cochrane Library were searched. Patient demographics, imaging, treatments, and clinical characteristics were obtained. Results were reported using the Preferred Reporting Systems for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results: Thirty-nine studies with a total of 65 patients were identified. The most common presentation was a history of slow-growing, painless swollen mass on the scalp. In total, 10 patients (15.4%) presented with spread to the regional lymph nodes and 6 (9.2%) additional patients presented with metastasis to distinct locations. In total, 61 patients (93.8%) underwent surgery. Of the 45 cases that documented follow-up, 11 (24.4%) patients had one or multiple instances of local, lymph node or metastatic tumor recurrence.

Conclusions: Surgery is favored, and the exact approach should be based on clinical judgement. However, Mohs micrographic surgery should be considered due to its superior margin control against such an invasive tumor. Radiotherapy and chemotherapy have been used as adjuvant therapy in aggressive cases or recurrence. Patients should be followed closely and examined often to frequently assess recurrence or metastasis.

Shiitake Flagellate Dermatitis in a Young Woman

Gabriella Santa Lucia, Jessica Forcucci, and Joni Mazza-McCrann

Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina, Charleston, South Carolina.

Shiitake mushroom flagellate dermatitis is an uncommon rash distinguished by its edematous, erythematous, pruritic, linear whiplash-like plaques following ingestion of raw or undercooked shiitake mushrooms (SM). Characteristically the plaques arise on the trunk and to a lesser degree on the extremities. A 34-year-old female with Addison's disease presented with a progressive erythematous, pruritic, burning rash for 2 days. She endorsed eating mushrooms frequently including shiitake mushrooms in a salad on the day prior to onset. A biopsy showed spongiotic dermatitis with interface injury and mixed superficial and deep perivascular inflammation including eosinophils, consistent with flagellate dermatitis secondary to mushrooms; however, the differential also included drug eruption, arthropod assault and other eczematous processes. The pathogenesis may be attributed to the toxicity of lentinan, a polysaccharide in the cell wall of SM, stimulating an overexpression of interleukin-1 and vasodilatory factors. Cooked SM are less likely to cause this reaction as heat may play a role in denaturing lentinan. SM-induced dermatitis is a rare cause of flagellate dermatitis with only 35 cases reported. Bleomycin-induced dermatitis, dermatomyositis and adult-onset Still's disease can also present with flagellate erythema making history a key component of diagnosis.

Common Melanocytic Nevi: Age And Body Location Distribution

Jose Candido Xavier-Junior,* Juliana P Ocanha-Xavier,† Solange CGP D'Ávilla,‡ and Mariangela EA Marques§

*Unisalesiano, Araçatuba, Brazil; †Private Clinic, Araçatuba, Brazil; ‡FAMERP, São José do Rio Preto, Brazil; and §UNESP, Botucatu, Brazil.

Object: To describe the age distribution and frequency at body sites presenting common melanocytic nevi (junctional, compound and intradermal).

Methods: Observational and cross-sectional study which analyzed all common nevi during a period of 54 months in a Brazilian medium sized Laboratory. Clinical information was collected from medical reports. Histopathological diagnoses were based on WHO classification. Melanocytic lesions from mucosal sites and lesions without site information were excluded.

Results: In total, there were 3,471 patients and 6,802 lesions. Intradermal nevi were most frequent (70.2%), followed by junctional (9.7%) and compound (20.1%) ones. The mean age among patients with intradermal, junctional and compound were 41, 42, and 32 year olds respectively. Intradermal nevi were more frequent in head and neck (52.4%) while junctional and compound nevi were more frequent in the trunk (62.8% and 62.5% respectively). In all groups, the limbs were the less frequently affected sites.

Conclusions: In our population, considering common melanocytic nevi, trunk is the preferential anatomical site and patients with compound nevi showed younger age.

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