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Abstracts Presented at the 21st Joint Meeting of the International Society of Dermatopathology, February 14–15, 2018, the Westin San Diego, San Diego, California, USA

The American Journal of Dermatopathology: May 2018 - Volume 40 - Issue 5 - p e66–e73
doi: 10.1097/DAD.0000000000001162
Abstracts

Oral Abstract Presentations, Wednesday, February 14, 2018, 8:00–10:00 AM

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Basal Cell Carcinoma Induced by Therapeutic Radiation for Tinea Capitis—Clinical Pathological Study

A. Barzilai,* S. Oshinsky,* S. Baum,* A. Debby,* and M. Huszar†

*Departments of Dermatology and Pathology, Sheba Medical Center, Tel Hashomer, Sackler Faculty of Medicine; and †Kaplan Medical Center, Rehovot, Israel.

An increased prevalence of aggressive histological subtypes has been described, irrespective of the clinical course, in BCC following irradiation for tinea capitis. In this retrospective study we assessed the histopathological features of these BCCs and correlate them with the clinical course. Thirty-one patients (17 male, 14 female) were included. The average age at time of first biopsy was 56 years. The total number of lesions was 185, with 80% of subjects showing multiple lesions. Nodular subtype was the most prevalent, followed by superficial, micronodular, and mixed tumours. Histologically aggressive tumours comprised ∼ third of the tumours. Stromal fibroplasia and melanin deposits were common. There was no mortality related to BCC. None of the 17 patients who completed a telephone survey had evidence of local invasiveness or metastases. BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort.

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Development of Dermatopathological Expertise in Africa

Helmut Beltraminelli

Dermatology, Inselspital Bern University Hospital, Switzerland.

Background: The most important steps in dermatological diagnosis are a competent clinical evaluation supported by a dermatopathological analysis when necessary. In subsaharan Africa dermatopathologists and laboratory services are extremely rare. Therefore a precise dermatological diagnosis is frequently missing, affecting the health of numerous African patients.

The Project: Our goal is to spread dermatopathology expertize in Africa starting from the Regional Dermatology Training Centre (RDTC), Tanzania. Since 2009 we are training dermatopathology skills to several African specialists (dermatologists or pathologists) as preparation for the International Board Examination in Dermatopathology (IBED) in Germany. These experts are now spreading their knowledges to other African colleagues, which ensures the sustainability of the project. We have a collaboration with some European experts and received an initial financial support from the EADV, ISD, IFD, and some private persons.

Achieved goals: We are training 13 African pathologists/dermatologists, 4 fellows successfully passed the IBED, we ensured the dermatopathology activities at the RDTC, since 2015 we organize yearly an “African Dermatopathology Conference” (ADPC) at the RDTC, in 2016 we founded the “African Dermatopathology Society” (ADPS), we support African dermatopathology research.

All project participants are enormous enriched from this experience.

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Cyclin D1 Is Useful to Differentiate Neoplastic Langerhans Cell From Reactive Langerhans Cell Proliferation

Debajyoti Chatterjee, Vikarn, Uma Nahar Saikia, Dipankar De, and Bishan Radotra

Department of Histopathology and *Dermatology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Langerhans cell (LC) proliferation can be seen in different reactive dermatosis. This study aimed to evaluate the role of CyclinD1 to differentiate reactive LC proliferation from Langerhans cell histiocytosis (LCH).

Methods: Ten cases of cutaneous LCH were stained with CD1a, S-100 and cyclin D1. Five cases each of discoid lupus erythematosus (DLE) and lichen planus (LP) were taken as control. Presence of CD1a, S-100 and cyclinD1 positive LCs were compared in epidermis and dermis.

Results: Intraepidrmal LCs in all cases (LCH, DLE, LP) were highlighted by S-100 and CD1a, while they were negative for cyclin D1. In all LCH cases, dermal neoplastic LCs showed diffuse CD1a, S-100 and variable (30%–70%) cyclin D1 positivity. In controls, there was variable LC proliferation in the dermis which showed positivity for CD1a and S-100, but was negative for cyclin D1.

Conclusions: Cyclin D1 is an efficient marker to differentiate neoplastic from reactive LC proliferation, and can be used as a surrogate marker in LCH.

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Clinicopathologic Spectrum of Dermal Hypersensitivity Reactions (DHRs)

Thinh Chau, and Maxwell A. Fung

University of California Davis School of Medicine, Sacramento, CA.

DHR is defined as superficial and mid perivascular dermatitis with eosinophils and minimal/absent epidermal changes. The range of clinicopathologic diagnoses associated with DHR remains under-characterized. We documented clinical features, diagnosis, and outcomes in a large DHR series. Cases were identified (2007–2017) based on wording of the pathology report and confirmed microscopically. Clinical features, treatment, and outcomes were documented. One hundred twenty-two biopsies from 112 patients (36M:76F, median age 55) were reviewed. Frequently affected sites included the upper and lower extremities and trunk with symmetric involvement (78%); clinical morphology was predominantly papules (65%) and plaques (38%) with pruritus (83%). Associations included atopy (38%) and systemic malignancy (9%). The top final diagnoses were arthropod bite, itchy red bump disease, urticaria, eczematous dermatitis NOS, and atopic dermatitis. Patients required systemic corticosteroids, oral doxepin, and narrowband UVB phototherapy. Roughly 70% of patients were symptom-free within weeks to months, while one-fifth had persistent disease for >1 year. In conclusion, DHR represents a sparse histologic expression of a variety of disorders and may represent the fullest expression of so-called itchy red bump disease and urticarial dermatitis.

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Clinicopathological Characteristics of Cutaneous Carcinosarcomas: A Single Institution Experience of 16 Cases

Jarish Cohen, Timothy McCalmont, and Philip LeBoit

University of California, San Francisco.

Cutaneous carcinosarcomas are rare tumors composed of malignant epithelial and mesenchymal components, and have the potential for local recurrence and distant spread. Given the paucity of cases reported, we retrieved 16 cases from the UCSF Dermatopathology archives (2007–2017). Tumors mainly arose in the elderly (median: 82, range: 50–101), with a male predilection (4:1). The most common site was the head (56%), followed by extremities (19%) and trunk (19%). Tumors consisted of 6 basal cell carcinosarcomas (38%), one of which had osteosarcomatous differentiation, 5 squamous cell carcinosarcomas (31%), 2 adnexal carcinosarcomas (13%), one carcinosarcoma with trichoblastic differentiation (6%), and one with matrical differentiation (6%), and one with indeterminate differentiation (6%). In each case, the epithelial component had unequivocal morphology or was positive for an epithelial marker (pan-keratin, HMWK903, CEA, BerEP4, CK5/6, p63), and the mesenchymal components were negative for epithelial markers and demonstrated immunoreactivity for procollagen I, CD10, and vimentin in select cases. p53 imunohistochemistry, performed in 8 cases, either showed diffuse strong positivity in both components (5/8) or diffuse absence of staining in both components (3/8). Collectively, these cases highlight the diverse epithelial lineages that can give rise to cutaneous carcinosarcomas.

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Cutaneous Cysts: What Lies Beneath

M.T. Fernández-Figueras, N. Pérez, E. Musulen, A. Quer *, I. Koptseva, and M.A. Carrasco

Hospitals Universitaris General de Catalunya and Germans Trias i Pujol. Universitat Internacional de Catalunya.

Cutaneous cysts are often benign lesions, easily recognizable under the microscope, that are removed for cosmetic reasons. However, it is important to be aware of possible pitfalls that can cause serious misdiagnosis. We will review 10 case scenarios that should always be considered when facing a cystic lesion: (1) Solid-cystic tumors incompletely excised. (2) Artifacts due to detachment of an epithelial nodule leaving a cavity or a cell monolayer, simulating a hydrocystoma. A relatively common phenomenon in tricholemmal cysts. (3) Reactive cysts due to foreign bodies, epidermal inclusions and others. (4) Cystic lesions hiding parasitic or infectious processes. (5) Cysts with peculiar features such as adenodermatofibromas or some perianal and genital cysts (tailgut, mammary-like and others). (6) Epidermal cysts with unusual changes, such as melanin pigmentation, acantholytic dyskeratosis or verrucous apperance. (7) Cystic malignant tumors. (8) Cystic metastases. (9) Malignant tumors developed in the wall of pre-existing cysts. (10) Cysts as markers of systemic diseases.

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Contiguous Verrucous Proliferations in Syringocystadenoma Papilliferum: A Retrospective Analysis With Additional Evaluation via Mutation-Specific BRAF V600E Immunohistochemistry

Ben J. Friedman, * and Jason B. Lee†

*Henry Ford Medical Center, Departments of Dermatology and Pathology, Detroit, MI; and †Sidney Kimmel Medical College at Thomas Jefferson University, Department of Dermatology and Cutaneous Biology, Philadelphia, PA.

There have been several reports describing collision lesions of syringocystadenoma papilliferum (SCAP) and verruca, although little is known about the frequency of this association. Molecular testing has revealed the BRAFV600E mutation in a large proportion SCAP cases, although its expression pattern has not been previously evaluated. In a retrospective analysis, we explored the potential histopathological association between verruca and SCAP. We also evaluated mutation-specific BRAF V600E expression in these lesions by immunohistochemistry. Cases of SCAP diagnosed over a 7-year period were closely reviewed for the presence of contiguous verrucous proliferations. Additional sections were cut and stained using the BRAF V600E specific clone VE1 antibody. Contiguous verrucous proliferations were identified in 9 out of 12 identified cases. Expression of the BRAF V600E mutation was identified in 7 out of 12 cases. Interestingly, in SCAP associated with endophytic verrucous proliferations, expression of BRAF V600E was found in both the glandular and the contiguous hyperplastic squamous epithelium. Overall, these findings suggest that contiguous verrucous proliferations in SCAP are common. Both components of the neoplasm may express the BRAFV600E mutation, which implicates a common origin.

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Next Generation Sequencing for Spindle Cell Melanomas

Eva George, Kimberly Newsom, Ruifeng Guo, and Kiran Motaparthi

Department of Dermatology, University of Florida, Gainesville, FL; Mayo Clinic, Rochester, MN.

Winner Best Oral Abstract

Melanomas with spindle cell morphology are often negative for all melanocytic markers except S-100 and SOX-10. Within the spectrum of spindle cell melanomas (SCM), desmoplastic melanoma (DM), hypercellular spindle cell melanoma (HSCM), and melanoma with undifferentiated pleomorphic sarcoma-like features (MUPS) form a continuum. Precise definition of these tumors as distinct pathologic subtypes, based on morphology and/or immunohistochemistry, is often ambiguous. Additionally, the biology and clinical behavior of SCM variants compared to each other is poorly understood. Herein, we compare 4 cases of DM, 4 cases of HSCM, 2 cases of MUPS, and 4 cases of conventional melanoma, based on histopathologic parameters, immunohistochemical profiles, and a 76-cancer gene mutation next generation sequencing (NGS) panel to improve the definition of these variants of SCM. Our results suggest that DM, HSCM and UPS likely represent different stages of malignant progression, resulting in loss of morphologic and immunohistochemical differentiation but retention of a characteristic molecular profile. NGS may be helpful distinguishing SCM variants from other poorly-differentiated spindle cell neoplasms.

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Muse (Microscopy With UV Surface Excitation) for Slide-Free Rapid Dermatopathology

Amir Ghorbani-Aghbolaghi, MD, Farzad Fereidouni, PhD, Richard Levenson, MD, and Maxwell Fung, MD

Dermatopathology Departement, University of California Davis, Sacramento, CA.

Aim: MUSE is a slide-free microscopy technique that employs ultraviolet excitation of common fluorescent tissue dyes within about 10 μm of the surface of fresh or fixed specimens (fresh or fixed). The method requires about 2 minutes of sample preparation and generates full-color, high-resolution images in 200 ms, which can be color-converted to resemble H&E. The aim of this study was to evaluate MUSE on a wide range of dermatopathology cases.

Methods: One hundred twenty skin samples of from 30 different cases across 5 categories (epidermal, melanocytic, adnexal, cystic, elastin) by 3 dermatopathologists, and one pathology resident. For each case, diagnostic and comparison scores were determined by comparing the MUSE images with the corresponding conventional FFPE-H&E images. Results indicate that MUSE is a promising modality for diagnosing skin lesions, particularly epidermal ones, with a diagnostic score of 95% and a comparison score of 0.9.

Conclusions: MUSE represents a fast, reliable and inexpensive approach for evaluating dermatology specimens. Going forward, we will evaluate MUSE for intraoperative evaluation, especially in Mohs surgeries.

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Clinicopathologic Consistency of Dermatologic Diseases: A 5-Year Retrospective Study in A Philippine Tertiary Hospital

Bryan Edgar Guevara, MD, and Vicotria P. Guillano, MD

Southern Philippines Medical Center, Davao, Philippines.

Methodology: Retrospective review of 1183 records (2011–2015).

Results: Consistent clinicopathologic findings were mostly given a diagnosis of connective tissue diseases (100%), adnexal diseases (100%), inflammatory (90%) and malignant tumors (90%). In the group with inconsistent findings were mostly from pigmentary (49%), metabolic (38%) and infectious diseases (25%). Clinicopathologic rates were significantly different in reports according to biopsy type (P = 0.014), disease location (P = 0.03), use of special stain (0.037) and mean duration of reporting (0.031). Whereas, no effect on clinicopathologic consistency was noted observed in disease localization, adequacy of clinical report and number of clinical diagnosis. There was a negative correlation between clinicopathologic consistency and biopsy type, specifically wedge type (P-value = 0.0002). While, diseases located on the head/neck, trunk and extremities had positive correlations.

Conclusions: Our institution's clinicopathologic consistency was 76%, which was affected significantly by the type of biopsy, location, special stain use and the duration.

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Do Blaschkoid Dermatoses Show Distinctive Histopathologal mChanges?

Vishal Gupta, Sudheer Arava, Sujay Khandpur, and M. Ramam

All India Institute of Medical Sciences, New Delhi, India.

Introduction: Blaschkoid dermatoses can be recognised by their clinical pattern, however not much information is available on their histopathological pattern.

Objective: To study the histological features of blaschkoid dermatoses, and compare them with generalized disorders.

Methods: This was a retrospective case-series where biopsy slides of blaschkoid (n = 61) and generalized (n = 79) dermatoses were evaluated by 2 dermatopathologists blinded to the clinical information.

Results: Of the 53 biopsies of blaschkoid dermatoses with diagnostic histological changes, 20 (37.7%) showed alternating changes (focal changes with skipping of epidermis): ILVEN: 7/9 (77.8%), epidermolytic hyperkeratosis: 5/7 (71.4%), VEN: 2/5 (40%), linear porokeratosis: 1/4 (25%), linear Darier's disease: 1 (100%), linear psoriasis: 1 (100%) and hyperpigmentary blaschkoid disorders: 3 (100%). The alternating changes were those of the underlying disease in all cases except 2. In linear porokeratosis, compact hyperkeratosis alternated with basket weave hyperkeratosis while in VEN, agranulosis alternated with a normal granular layer. None of the biopsies of nevus sebaceous, lichen striatus, nevus comedonicus, linear lichen planus or linear lichen planus pigmentosus showed alternating changes. Alternating histological changes were seen in only 3/68 (4.41%) non-mosaic cases (Darier's disease, n = 1; Dowling-Degos disease n = 2). Overall, alternating pattern was seen significantly more frequently in blaschkoid dermatoses (37.7% vs. 4.41%, P < 0.001).

Conclusions: Alternating histological pattern of changes could be a histopathological clue to blaschkoid dermatoses.

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Intralymphatic and Intravascular Histiocytosis

Benjamin F. Kelley, MD, Siavash Toosi, MD, and Laurence E. Gibson, MD

Department of Dermatology, Mayo Clinic, Rochester MN.

Intralymphatic and intravascular histiocytosis (IV/IVH) is a rare disorder thought to be associated with systemic inflammatory conditions, in particular, rheumatoid arthritis. Recognition of this benign process is essential to help distinguish it from metastatic carcinoma and intravascular lymphoma. Three cases of IV/IVH were seen in our department. All patients had previous orthopedic surgery in the affected area. Two had a history of inflammatory arthritis, and 2 of breast carcinoma. The clinical differential included carcinoma, lupus panniculitis, erythema nodosum, vasculitis, morphea and infection. On microscopy, all 3 showed dilated vessels with intravascular aggregates of large histiocytes, positive for CD68. Five years after the initial presentation, one case resolved after surgical joint revision. Another spontaneously resolved after 3 months. The third case has been stable and asymptomatic without treatment with a 7 month follow-up. Since it was originally described by O'Grady in 1994, approximately 50 cases of IV/IVH have been described. We believe this may be underreported. Follow-up information is scarce. We present 3 new cases, with an emphasis on the clinical and histopathologic differential as well as follow-up information.

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GATA-3 Staining in Primary Cutaneous Apocrine Cribriform Carcinoma

M. Llamas-Velasco, MD,* Y. C. Pérez-Gónzalez, MD,† E. Daudén, MD,* and A. Rütten, MD‡

*Department of Dermatology, Instituto de Investigación Sanitaria (IIS-IP) Hospital Universitario de La Princesa, Madrid, Spain; †Pathology Department. Fundación Jimenez Diaz, Madrid, Spain. Centro Médico Voth, Madrid, Spain; and ‡Dermatopathologie Friedrichshafen, Friedrichshafen Germany.

Background: Primary cutaneous apocrine cribriform carcinoma (PCACC) is a rare tumor, clinically appearing as a solitary nodule, mostly involving extremities of females and this lesion usually raise a differential diagnosis with metastatic cribriform carcinomas, especially breast cancer.

Design: To study GATA3 expression in a series of 14 primary cutaneous cribriform carcinomas and to test this immunostaining usefulness to differentiate this tumor from metastatic breast cancer.

Results: No primary cutaneous apocrine cribriform carcinoma express GATA3. Breast cancer metastasis express GATA3 in 100% of our studied cases.

Conclusions: Even when GATA3 expression has been reported in many benign and malignant adnexal tumors, mostly the sebaceous, follicular and apocrine ones, as well as in many other neoplasms, GATA3 staining to differentiate PCACC from skin breast cancer metastasis has a high negative predictive value. A positive GATA3 staining in this context should led to rule out PCACC with a high level of confidence.

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Leishmaniasis: An Endemic Human Disease in the United States

Bridget McIlwee, DO, and Gregory Hosler, MD

ProPath; Dallas, TX.

Leishmaniasis is a chronic disease endemic in Africa, Asia, and South America. Most medical providers in the United States consider leishmaniasis a disease of immigrants, travelers, or military personnel; thus clinical suspicion for the disease remains low. Currently, medical textbooks do not recognize leishmaniasis as an endemic human disease in the Americas, and leishmaniasis remains federally non-reportable. We reviewed deidentified, pathologically-confirmed diagnoses of leishmaniasis from our archives. We identified a total of 69 cases of leishmaniasis, of which 41 (59.4%) were autochthonous—occurring without any history of travel outside the US. This stands in stark contrast to prior reports of only “small numbers of autochthonous leishmaniasis” occurring in the United States. Our data support reclassification of leishmaniasis as an endemic human disease in the US and argue in favor of making leishmaniasis a federally-reportable disease. Climate models predict the number of American citizens exposed to leishmaniasis will double by 2080. Thus, proper classification of leishmaniasis as an endemic disease will impact public health initiatives throughout the US and Canada and hopefully increase awareness of the disease among dermatologists, dermatopathologists, and other physicians.

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Histopathological Spectrum of Skin Tumours: A Retrospective Study at A Cancer Centre in Nepal

Pandey G, Shrestha S

B.P.Koirala Memorial Cancer Hospital (BPKMCH), Bharatpur, Nepal.

Background: Skin cancers are not so common in South Asia. Hence, limited data is available on the spectrum of skin neoplasms in Nepal. BPKMCH being government cancer centre; cases are referred from all over Nepal; thus the result represents data of Nepalese population.

Aim: To evaluate the frequency of skin tumors and give an outlook of skin cancers in Nepal.

Material and methods: A retrospective study of skin biopsies received from January 2016 to October 2017 at department of Pathology of BPKMCH. All skin tumors except soft tissue tumors were included. The neoplasms were classified as per WHO classification of skin tumors.

Results: Out of 110 cases, 31.8% were benign and 68.2% were malignant neoplasms; basal cell carcinoma being the commonest. F: M ratio was 1:0.89. Malignant neoplasm was common in 51–75 years age group. Head and neck was the most frequent location.

Conclusions: Incidence of keratinocytic tumour was highest followed by melanocytic and adnexal tumours. This study shows that prevalence of skin cancers are more than expected and is on increasing trend.

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Meta-Analysis Reveals Role of Inflammatory and Hyperproliferation Pathways in the Pathogenesis of Actinic Keratosis

Laraib Z. Safeer,* Jihad Aljabban,† Maryam Panahiazar,‡ Isaac Neuhaus,§ and dexter hadley‡

*Baylor College of Medicine, Houston, TX; †Ohio State University College of Medicine, Columbus, OH; ‡Institute for Computational Health Sciences, University of California, San Francisco, CA; and §Department of Dermatology, University of California San Francisco, California.

Objective: Define the pathogenesis of actinic keratosis using crowd-sourced meta-analysis.

Methods: We analyzed 30 skin samples of actinic keratosis against healthy controls using our STARGEO platform. We then analyzed the signature in IPA Ingenuity.

Results: From skin analysis, we found IL-17A in psoriasis and granulocyte and agranulocyte adhesion and diapedesis as top canonical pathways. OSM (part of the IL-6 cytokine family) was the top upstream regulator. We noted upregulation of hyperproliferation genes SERPINB3/B4 (serpin peptidase inhibitors) and S100A8/A9 (upregulated in cutaneous squamous cell carcinoma and other epithelial malignancies). Additionally, we noted upregulated of inflammatory peptides DEFB4A/DEFB4B defensins, and of keratin 6A/6B.

Conclusions: Our analysis emphasized the role of hyperproliferation and IL-17A mediated inflammation in the pathogenesis of actinic keratosis.

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Tipping Point: Re-Evaluation of Gross Examination of Skin Specimens to Improve Workload Efficiencies

Carolyn J. Shiau, MD,*,† Janet Tunnicliffe, MLT, ART,‡ and Richard I. Crawford†

*Royal Columbian Hospital, New Westminster; †University of British Columbia Departments of Pathology and Dermatology; and ‡BC's Agency for Pathology and Laboratory Medicine, Vancouver, BC, Canada.

Background: Standardized grossing processes advocate embedding of excision tips in a separate block. Clinical value of multiple upfront levels, deeper levels, and separate tips block is re-evaluated.

Design: Three strategies were implemented: 1- discussion of value of deeper levels of tips to clear margins; 2- revision of grossing processes; 3- alteration of default microtomy to one slide/block. Five hundred consecutive skin specimens from 3 years were evaluated: 2012 pre-implementation; 2015 following implementation of 1, and 2017 following implementation of 2 and 3. Results: Re-evaluation of pathologist practice reduced the proportion of cases requiring deeper sections (18.4%–11.2%). Revised grossing processes yielded 34.8% decrease in number of blocks. Adjustment of slide level defaults yielded 32.5% decrease in H&E slides required for diagnosis. Overall improved technical workload ratios of blocks/case (2.10 vs. 1.27), routine slides/case (2.50 vs. 1.69), and routine slides/block (1.39 vs. 1.23) are noted. Conclusions: Skin specimens less than 20 mm in size can be embedded in a single block and diagnosed based on a single representative slide level. Embedding skin tips and central sections in the same block yields tangible workload efficiencies.

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Management of Atypical Junctional Melanocytic Proliferations

Jessica Terrell, BA,* Jiahui Bao,† Lihong Qi, PhD,* and Maija Kiuru, MD, PhD*

*UC Davis, Sacramento, CA; and †Zhejiang University, Zhejiang, China.

Background: Atypical junctional melanocytic proliferation (AJMP) is a histopathologic diagnosis used for proliferations that do not fully meet criteria of melanoma in situ. Their malignant potential is uncertain, posing a problem for management by clinicians. Currently, there are no standard guidelines for treatment.

Objective: To identify clinical and histopathological factors that influence management strategies of AJMPs.

Methods: We performed a cross-sectional study of 256 AJMPs from academic and private practices diagnosed by board-certified dermatopathologists at UC Davis. Correlation with management and histopathological and clinical features was performed.

Results: Two hundred fifty-six cases were identified and reports and clinical data, when available, was reviewed. The lesions were managed with shave biopsy, shave removal or shave excision, punch biopsy, punch excision, excision, or Mohs with frequencies of 6.64, 1.95, 5.08, 1.95, 54.3, and 2.73%, respectively. We did not find statistically significant correlations with the histopathological features recorded and management, possibly due to a small sample size.

Conclusion: Further studies are needed to establish standardized guidelines to AJMPs by clinicians.

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Reassessment of Histological Features of Cutaneous Sebaceous Neoplasms With Special Emphasis on Cytological Grading

Mariantonieta Tirado, MD,* and Almut Böer-Auer, MD†

*Baylor Scott & White Health, Pathology, Texas; and †Dermatologikum Hamburg, Dermatology, Germany.

Both, architectural and cytologic characteristics are used to distinguish benign from malignant sebaceous neoplasms, however specific cytopathologic features of sebocytes have not been well defined. The authors assessed architectural and cytological features of 77 sebaceous neoplasms (15 Miescher nevi (control), 15 sebaceous hyperplasias, 12 sebaceomas,16 sebaceous adenomas,14 sebaceous carcinomas and 6 ocular sebaceous carcinomas) to investigate whether cytological grading may facilitate classification of lesions. Among other criteria, nuclear pleomorphism (size, nucleolar appearance, membrane irregularity, crowding, mitoses, chromatin pattern) was assessed and 3 nuclear grades established. Most sebaceous neoplasms, except ocular sebaceous carcinoma, showed a bland architectural silhouette. However, sebaceous adenomas, sebaceous carcinomas and ocular sebaceous carcinomas revealed larger nuclei (≥14 μm in ≥50% of cases), evident to multiple nucleoli, membrane irregularity, coarse to clumped chromatin and nuclear grade ≥2 (latter in ≥56% of cases); in contrast, Miescher nevi, sebaceous hyperplasia and sebaceomas showed smaller nuclei (≤10 μm in ≥50% of cases), smooth borders, inconspicuous nucleoli, fine chromatin and grade 1 nuclei (latter in 100% of cases). In conclusion, in the setting of a well circumscribed architecture, cytologic features gain importance in the classification of sebaceous neoplasms. Interestingly, cytologic similarities found in sebaceous adenomas and sebaceous carcinomas may indicate a close relationship of both neoplasms.

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Distinguishing Pustular Psoriasis and Acute Generalized Exanthematous Putulosis (AGEP) on the Basis of Plasmacytoic Dendritic Cells (PDCs) and MxA Protein

Nikki S. Vyas, MD,* Garrett T. Desman, MD,* and Jennifer M. McNiff, MD†

*Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY; and †Department of Dermatology, Yale University School of Medicine, New Haven, CT.

Background: Distinguishing acute generalized exanthematous pustulosis (AGEP) and pustular psoriasis (PS) histologically remains a challenge. Staining for plasmacytoid dendritic cells, or PDCs (producer of IFN-α/β),1 and MxA (an IFN-α/β inducible protein)2 may help discriminate these entities.

Methods: Forty-three cases of AGEP and PS were compiled from 2 academic institutions, stained with CD123, and examined for eosinophils and PDCs. A subset of 26 cases were stained for MxA.

Results: Eosinophils were identified in 10/18 (55.55%) AGEP cases and 2/25 (8%) PS cases. Intraepidermal PDCs were present in 11/25 (44%) PS cases versus 2/18 (11.11%) AGEP cases. Cases of PS were more likely to show at least 5 PDCs (24/25 or 96%), while cases of AGEP were more likely to not show PDCs (13/18 or 72.2%). M x A was positive in the epidermis of 15/16 cases of PS (93.75%) and 7/10 cases of AGEP (70%). M x A stained the endothelium of 14/16 (87.5%) of PS cases and 6/10 (60%) AGEP cases. The dermis stained with MxA in 16/16 (100%) of the PS cases and 6/10 (60%) of the AGEP cases.

Conclusions: The presence of eosinophils without PDCs favors AGEP while the presence of PDCs in the absence of eosinophils favors PS.

Farkas, L., et al, Plasmacytoid dendritic cells (natural interferon-alpha/beta-producing cells) accumlate in cutaneous lupus erythematosus lesions. Am J Pathol. 2001. 159:237–43.

Haller, O, and Kochs, G. Human MxA protein: an interferon-induced dynamin-like GTPase with broad antiviral activity. J Interferon Cytokine Res. 2011. 31:79–87.

“Dermatopathology Trainee World Cup,” Wednesday February 14, 2018, 10:36 AM–12:36 PM

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Report of A Case: Cutaneous Pseudosarcomatous Polyp in Pregnancy

Elizabeth Schell Bressler, MD, Sepehr Hamidi, MD, Jill Browning, MD, Helen Powell, BS, M. Angelica Selim, MD, and Kristen M. Paral, MD

Duke University Department of Pathology, Durham, NC.

A 22-year-old female presented with a recently discovered lesion on the vaginal mucosa at 15 weeks gestation. Physical examination revealed a solitary pedunculated nodule on the midline of the lower vaginal introitus measuring 1.3 cm. A biopsy was performed and demonstrated a polypoid lesion with marked hypercellularity, cytologic pleomorphism, greater than 10 mitoses per 10 high-power fields, and atypical mitoses. There was expression of CD10 but no significant expression of desmin, cytokeratin, S-100, or CD34, supporting the diagnosis of fibroepithelial stromal polyp (FSP). FSPs of the female genital tract may simulate sarcomas because of their worrisome histologic appearance. Lesions that develop during pregnancy (15% of cases) tend to have more sarcomatous features. Awareness of this entity is critical to avoid overdiagnosis of sarcoma.

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Pembrolizumab-Induced Exfoliative Dermatitis

Woo Cheal Cho,* Jette Hooper,† Frank Santoro,‡ Michael Murphy,§ Zendee Elaba,* and Frank H. Netter, MD

*Department of Pathology and Dermatology, Hartford Hospital, Hartford, CT; †School of Medicine, Quinnipiac University, North Haven, CT; ‡Department of Dermatology, Hartford Hospital, Hartford, CT; and §Department of Dermatology, University of Connecticut Health Center, Farmington, CT.

Programmed death-1 (PD-1) inhibitors, such as pembrolizumab, have been associated with the development of various cutaneous adverse events including lichenoid reactions, bullous pemphigoid, eruptive keratoacanthomas, and vitiligo. We describe a case of 63-year-old man with stage IV non-small cell lung cancer (NSCLC) who developed an exfoliative eruption 2 months following anti-PD-1 therapy. The patient's lung tumor showed no expression of PD-L1 and lacked mutations or gene re-arrangements in EGFR, ALK, and ROS-1. He received chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab. Following his third cycle of treatment, he developed a pruritic rash on the trunk which then spread to the extremities with blister formation. Physical examination showed diffuse erythroderma with overlying ichthyosiform scale. There were erosions and few tense vesicles with no mucosal membrane involvement. Biopsy revealed an erythema multiforme-like picture with basal vacuolation, dyskeratotic keratinocytes, focal full-thickness necrosis and background lichenoid infiltrate. Direct immunofluorescence studies were negative. The findings favored lichenoid interface dermatitis secondary to pembrolizumab. Dermatologic toxicities associated with immunotherapy are just beginning to be recognized and categorized. Awareness of the range of histopathologic patterns in anti-PD-1 therapy-related reactions is important for optimal clinical management.

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Comparison of TH2 and TH17 T-Cell Subsets and IL-36 and Beta-Defensin-2 in Psoriasis, Eczema, and Cases With Histologic Overlap

Jarish Cohen, Sarah Bowman, Zoltan Laszik, and Jeffrey North

University of California, San Francisco, CA.

Psoriasis and eczema are driven by “Th17” and “Th2” T-cells, respectively. Additionally, beta-defensin-2 (BD-2), and IL-36 are upregulated in psoriasis. Although the majority of psoriasis and eczema cases are discriminated on routine microscopy, a significant minority exhibit histologic overlap. Therefore, CD4/RORgt (Th17) and CD4/GATA3 (Th2), BD-2, and IL-36 immunohistochemistry was performed on 10 cases of psoriasis and spongiotic dermatitis, and 17 biopsies with histologic overlap in which the pathologist favored psoriasis or eczema. Compared to psoriasis, spongiotic dermatitis demonstrated a greater percentage of Th2 cells (66.9% vs. 57.0%) and a lower percentage of Th17 cells (15.9% vs. 26.8%). No differences were noted in Th2 and Th17 subsets in the overlap cases. Psoriasis and overlap cases in which psoriasis was favored demonstrated strong expression of BD-2 (10/10, 9/10) and IL-36 (9/10, 7/10). Spongiotic dermatitis and overlap cases in which spongiotic dermatitis was favored exhibited weak to negative expression of BD-2 (10/10, 4/7) and weak IL-36 immunoreactivity (10/10, 6/7). Collectively, these results highlight immunological markers that can discriminate between psoriasis, eczema, and cases with histological overlap.

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Mucin Deposition in Rheumatoid Nodules Masquerading as Deep Granuloma Annulare

Scott Diamond, MD,* and Brian Hinds, MD†

Departments of *Pathology; and †Dermatology, UC San Diego; San Diego, CA.

Background: Deep granuloma annulare (GA) is uncommon with microscopic distinction from rheumatoid nodule (RN) based upon more mucin, more histiocytes, and less fibrin. Mucin is considered a reproducible feature of deep GA. We examined mucin deposition in a series of RN to test this criterion.

Methods: RNs were collected from patients with known rheumatoid arthritis (n = 7). A block from each case was stained with colloidal iron. Mucin expression was graded for each case [0-absent; 1+scant; 2+moderate; 3+strong].

Results: All RNs showed varying degrees of mucin. The predominant pattern featured a localized cuff of mucin at the periphery of central fibrinoid necrosis embedded with neutrophils/basophilic debris [3+ (n = 3); 2+ (n = 3), and 1+ (n = 1)]. Dense mucin was present in 3 cases within peripheral cuffs of palisaded inflammation.

Conclusions: Variable amounts of mucin were identified in this series of RNs. In 43%, mucin pools and cuffs of mucin within palisaded granulomatous inflammation were reminiscent of deep GA. If history is lacking or the biopsy is small, dermatopathologists should be mindful of the lack of specificity of mucin before rendering an unequivocal diagnosis.

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The Natural Course of Recurring ALK-1 Positive, Translocation Variant Primary Cutaneous Anaplastic Large Cell Lymphoma; A Case With A 15 Year Follow-Up

Lacey Elwyn, DO,* Dwayne Montie, DO,† Carlos Ricotti, MD,‡ and Laszlo Karai, MD, PhD§

*Dermatopathology Fellow/Dermatologist, Larkin Community Hospital, Miami, FL; † Dermatologist, Waters Edge Dermatology, Palm Beach Gardens, FL; ‡Dermatopathologist/Dermatologist, Vitro Molecular Laboratory, Miami, FL; §Dermatopathologist, Aurora Diagnostics, Global Pathology Laboratory, Miami Lakes, FL.

We report an extraordinary case of recurring ALK-1 positive, translocation variant primary cutaneous anaplastic large cell lymphoma (PC-ALCL) with late systemic dissemination in a 62 year-old male. This patient had 15 years of recurrent nodules on his right upper arm with identical histology identified in all biopsies. The histology revealed a dermal nodular infiltrate with highly atypical cells strongly positive for CD30, cytoplasmic ALK-1, and EMA. The pattern of cytoplasmic ALK immunostaining is associated with those that lack the common t(2:5) translocation and therefore classifies this case as ALK-1 positive, translocation variant PC-ALCL. Against medical advice, this patient refused any additional systemic work-up or treatment other than excision. In due course, there was late systemic dissemination to his right rectus femoris and epigastrium. He responded well to standard CHOP chemotherapy and filgrastim with almost complete resolution of his right thigh tumor and 50% reduction of his gastric tumor in just 1 month. We report this exceptional case to illustrate the natural disease progression of these rare tumors which in all likelihood, eventually progress to systemic disease.

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Bullous and Blistering Lesions in Patients With Systemic Lupus Erythematosus

Emma Johnson,* David Wetter,* and Michael Camilleri1,†

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

Introduction: Bullous and blistering eruptions in patients with systemic lupus erythematosus (SLE) can be challenging to diagnose. Bullous lesions in patients with SLE can be related to the underlying SLE, as with bullous systemic lupus erythematosus (BSLE), or can be due to a second, primary blistering disorder.

Methods: A retrospective review was performed of clinical, laboratory, histopathologic and immunohistochemistry findings in patients with SLE, and the clinical finding of blistering or bullous skin lesions, seen at Mayo Clinic, Rochester, between 1997 and 2017.

Results: Eight patients were identified, ranging from 32 to 75 years (mean, 49 years). Sex distribution was equal. Bullous lupus erythematous was the diagnosis in 3 patients, while bullous lichen planus, bullous pemphigoid, pemphigus foliaceous, pemphigoid (Brunsting-Perry variant), and linear IgA bullous dermatosis were the diagnoses in one patient each. Clinical, laboratory and histopathologic findings are summarized for each patient.

Limitations: Small sample size and retrospective study design.

Discussion: Our results demonstrate the rarity and diversity of diagnoses of blistering eruptions in patients with SLE.

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Trichoblastic Carcinosarcoma—A Case Presentation and Review of A Rare Entity

Yuna Kang, MD,* Daniel Neil, MD,† Toru Ogawa, MD, PhD, MPM MBA,*,‡ George Peter Sarantopoulos, MD,* and Scott Binder MD*

*University of California Los Angeles, Los Angeles, CA; †Kansas University Medical Center, Kansas City, KS; and ‡Waseda University, Tokyo, Japan.

Trichoblastic carcinosarcomas are extremely rare biphasic tumors with malignant trichoblastic and mesenchymal cell populations. We describe a case of a trichoblastic carcinosarcoma presenting as a tibial mass in a 54-year-old woman. The tumor consisted of a predominantly encapsulated tumor involving the dermis and subcutis. The epithelial component was composed of mitotically active, atypical basaloid tumor cells, while the mesenchymal component was composed of markedly atypical stromal cells. The 2 components were sharply separated without transitions, and together formed structures resembling follicular papillae associated with hair germs. In addition, a probable benign trichoblastoma was seen in association with the carcinosarcoma. By immunohistochemistry, strong pankeratin and CD34 expressions were seen in the epithelial component, but not in the mesenchymal component. p53 showed strong nuclear expression in both components. Together, the features were diagnostic of a trichoblastic carcinosarcoma.

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A Case Report of an Acquired Medallion-Like Dermal Dendrocyte Hamartoma Presenting as A Dermal Nodule on the Left Shin

Mohammad S. Khan, DO, Joseph S. Frye, MD, Nima Gharavi, MD, and David Frishberg, MD

Cedars-Sinai, Los Angeles, CA 90048.

Plaque-like CD34-positive dermal fibromas, also known as medallion-like dermal dendrocyte hamartomas (MDDHs), are a rare group of congenital and acquired benign spindle cell neoplasms that may histologically and immunophenotypically resemble dermatofibrosarcoma protuberans (DFSP). Recognizing the clinical heterogeneity of this neoplasm, and subtle pathologic differences with its mimics are crucial to making the correct diagnosis and avoiding the aggressive surgical intervention required to treat DFSP. We present the case of a 29-year-old woman with MDDH presenting as a slowing growing dermal nodule on the left shin. FISH testing confirmed a lack of rearrangement of PDGFB characteristic of DFSP. Only 6 cases of acquired MDDHs have been reported to date, none located on the shin. Our case expands the anatomic spectrum where these lesions occur and highlights the heterogeneity of anatomic locations at presentation. Recognition of such heterogeneity, given this tumor' rarity and immuno-phenotypic overlap with DFSP (which commonly occurs on extremities), is important for avoiding misdiagnosis.

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Metastatic Basal Cell Carcinoma: Diagnostic Challenges Illustrated by 2 Cases

W. Phillip Moss, MD,* Ibrahim Zardawi, MD,† Zhaolin Xu, MD,† and Noreen M. G. Walsh, MD†

*Department of Pathology, Dalhousie University, Halifax, Nova Scotia Canada; and †Pathology Queensland, Australia.

The rarity of metastatic basal cell carcinoma (mBCC) and additional factors make it a diagnostic challenge. Case 1. A 57 year old Canadian man developed a right axillary nodal metastasis of basal cell carcinosarcoma (osteosarcomatous type) in 2014. The source of his disease was BCC (nodulo-infiltrative type) on the right scapular area, excised successively in 2007 and 2009. In 2017, in the setting of widespread pulmonary nodules, he expectorated a 1 cm mass comprising pure pleomorphic undifferentiated sarcoma with osteoclast-like giant cells. Case 2. A 68 year old Australian man developed a right axillary mass representing mBCC in 2014. Only in the following year was the primary BCC (nodulo-infiltrative type) removed from his trunk. He developed recurrent axillary mBCC in 2017. Immunohistochemical expression of CD56 and chromogranin A in the mBCC confounded investigation of the case. The rarity of mBCC, its phenotypic diversity, its under-recognized expression of neuroendocrine markers and its presentation prior to excision of the primary tumor render it a challenge in diagnosis.

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Function of Toll-Like Receptors in Psoriasis Pathogenesis

Liudmyla Naumova, Roman Stepanenko, and Victor Stepanenko

Bogomolets National Medical University, Kyiv, Ukraine.

The objective of our work was to study the mechanisms of development of local immune inflammation taking into consideration the changes in immunohistochemical expression of Toll-like receptor 2, 4 (TLR2, TLR4) in the skin of patients with psoriasis before and after performance of system immunosuppressive therapy. We performed the immunohistochemical research of biopsy from both psoriatic papules and intact skin of 62 patients with psoriasis in order to study the effect of immunosuppressive therapy. We applied the immunohistochemical methods with definition of marker for TLR2, TLR4 expression aiming to determine the character and distribution of local cellular immune and inflammatory reactions in the skin of patients with psoriasis. Studying the TLR2 immunohistochemistry, positive reaction with nuclear patterns of expression in epithelial and dendritic cells of basal epidermis was observed in skin of psoriatic patients before treatment. The intensity of TLR2 and TLR4 immunohistochemical reaction is a bit reduced after the treatment. Unlike normal skin, the positive background nuclear coloration of epithelial cells in the upper epidermis is observed in the skin of patients with psoriasis after treatment.

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A Case of Primary Cutaneous CD4 Positive Small/Medium-Sized T-Cell Lymphoproliferative Disorder

Oluwakemi Onajin, MD, Lindsay Strowd, MD, Michael W. Beaty, MD, and Omar P. Sangüeza, MD

Department of Pathology and Dermatology, Wake Forest School of Medicine, Winston-Salem, NC.

Primary cutaneous CD4+ small/medium-sized T-cell lymphoproliferative disorder (PCSM-TCLPD) is an indolent lymphoproliferative disorder with a favorable prognosis. Our patient is an otherwise healthy 30-year-old female who presented with a 2-month history of a tender, solitary nodule on the central forehead. Skin biopsy revealed a dense, diffuse dermal infiltrate of small to medium-sized lymphocytes and a few large pleomorphic cells, with focal epidermal and follicular involvement. The neoplastic cells were positive for CD3 and CD4, and negative for CD30. Small reactive CD8+ T cells, CD20 + B cells and rare Bcl6+ cells were also present. Molecular studies detected a clonal T-cell receptor gene rearrangement in the skin. Peripheral blood smear and bone marrow biopsy were normal. The patient was referred for local radiotherapy. PCSM-TCLPD is a lymphoproliferative disorder with a favorable prognosis. Careful clinicopathologic and immunophenotypic correlation is necessary for accurate diagnosis.

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The Morphologic Spectrum of Granuloma Annulare (GA): A Clinicopathological Study With Reevaluation of the Interstitial Variant

Shira Ronen,* David Suster†, and Saul Suster*

*Medical College of Wisconsin, WI; and †Beth Israel Deaconess Medical Center, Boston, MA.

The full-blown GA is characterized by necrobiotic granulomas with palisading of histiocytes and stromal mucin deposition. Cases in which the granulomatous features are not fully developed have been described and designated as the “interstitial” variant, however, there is no good consensus regarding the criteria for diagnosing of this variant. Thirty-four cases of “classical” GA and 62 cases of interstitial GA were reviewed. The cases of interstitial GA were characterized by a paucity of cells with only few scattered small mononuclear cells against a collagenized stroma, but lacking well-formed granulomas and multinucleated giant cells. Interstitial mucin was scant to absent in those cases. Immunohistochemical study showed that the conventional cases of GA stained strongly positive in the histiocytic cells for CD68 and CD163, whereas the small mononuclear cells in interstitial GA were strongly positive for CD163 only. Of interest, careful examination of cases of full-blown GA demonstrated areas identical to those seen in interstitial variant at the periphery of the lesions.

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An Old Enemy Returns: Subtle Signs of Syphilis and Non-Classical Histologic Findings

Rasleen Saluja, MD,* Jerad Gardner, MD,† Christopher Lum, MD,* and Jennifer Kaley, MD†

*University of Hawaii, Department of Pathology, Honolulu, HI; and †University of Arkansas, Department of Pathology Little Rock, AR.

As the incidence of syphilis in the US continues to rise at a surprising rate, it is critical for dermatopathologists to recognize potential non-classical histologic presentations. We present a series of 3 cases in which Treponemal organisms were identified despite subtle histologic clues. Clinical presentations included a pregnant woman with “contact dermatitis,” a young man with a maculopapular rash, and an elderly male admitted for neurosyphilis with a new macular rash. The histologic findings ranged from solely a sparse superficial perivascular lymphocytic infiltrate without plasma cells to a focal moderately-dense lymphoplasmacytic infiltrate. In all cases, epidermal changes were minimal; one case revealed a secondary finding of dermatophytosis. Anti-Treponemal immunohistochemical staining performed in each case revealed variable numbers of perivascular spirochetes, confirming the diagnoses. We highlight these cases across multiple institutions to illustrate variable and potentially subtle histologic findings encountered in cutaneous lesions of syphilis, a historic and re-emerging disease that maintains its reputation as the “great mimicker.”

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Erdheim-Chester Disease Associated With A Novel FLT3-MEF2C Fusion and Macular Cutaneous Lesions

Lisa M. Marinelli; Kabeer K. Shah, DO; Ronald S. Go, MD; Gaurav Goyal, MBBS, and Ruifeng Guo, MD

Mayo Clinic, Rochester, MN.

1st Place Winner DP Trainee World Cup

Case Description: A 35 year-old man presented with chest pain, edema, diarrhea, and flu-like symptoms. Initial diagnostic workup was equivocal. Three years later, the patient noted progressive tender brown-to-erythematous coalescing macules with ill-defined borders on his back and face. Biopsy revealed foamy cell histiocytes with fibrosis and touton giant cells. The histiocytes stained positively for CD163, patchy positive for S100, and negative for CD1A, Langerin, and BRAFV600E. The diagnosis of ECD was confirmed with PET-CT, revealing osteosclerotic femur lesions. Next-generation sequencing identified a FLT-MEF2C fusion. The patient is currently being treated with 4 cycles of cladribine.

Conclusions: This report identifies a novel FLT3-MEF2C fusion as an alternative means of activation of the RAS/ERK pathway in ECD. This is in contrast to the BRAFV600E mutation that is commonplace in ECD and therefore warrants the consideration of targeted FLT3 therapies in appropriate cases. Finally, this case highlights ECD's diverse skin manifestations that extend beyond the classical presentation with xanthelasma, and as such, may enable earlier diagnosis in future patients.

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Tumoral Melanosis Associated With Targeted Immunotherapy for Metastatic Melanoma

Andrea Jurgens, MD, Ruifeng Guo. MD, Jerry Brewer, MD, and Nneka Comfere, MD

Mayo Clinic Dermatology, Rochester, MN.

Tumoral melanosis clinically resembles metastatic melanoma, occurs in the context of regressed disease and requires evaluation for underlying melanoma and metastatic disease. Histology demonstrates a nodular infiltrate of melanophages in the dermis or subcutaneous tissue without melanocytes. Recent limited reports of tumoral melanosis in the context of immunotherapy with ipilimumab and most recently pembrolizumab (humanized monoclonal antibody against programmed death 1 receptor) highlight a unique presentation representative of tumor regression due to treatment and association with a favorable clinical response. We report a case of a 42-year-old woman with metastatic melanoma who presented for evaluation of multiple subcutaneous nodules after therapy with ipilimumab and pembrolizumab. Previous treatments included cranial stereotactic radiosurgeries, left lower lung thoracotomy, skin metastases excisions, vaccination against MART-1, intralesional interleukin-2 injections, dabrafenib and trametinib. Lesional skin biopsies demonstrated dermal and subcutaneous nodular collections of melanophages with rare to no viable melanocytes consistent with tumoral melanosis and regressed melanoma metastases. This patient is currently maintained on pembrolizumab without evidence of disease progression. The underlying pathomechanisms and prognostic implications of tumoral melanosis in this setting remain to be elucidated.

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Glomangiosarcoma Arising From A Precursor Glomangioma: A Case Report

Matthew Strausburg, MD,* Brittanya A. Limone, MA, BS,† and Simon Warren, MBBS*

*Indiana University School of Medicine, Department of Pathology, Division of Dermatopatholoy. Indianapolis, Indiana; and †Loma Linda University School of Medicine. Loma Linda, California.

Glomus tumors are common benign cutaneous neoplasms. Malignant glomus tumors are a rare variant, occurring in less than 1% of glomus tumors. In this case, we present a 69-year-old man presenting with a tumor on the right upper extremity. A biopsy revealed a tumor nodule consisting of large atypical cells with an increased mitotic activity arising from a precursor banal appearing glomus tumor remnant. The tumor stained positive with smooth muscle myosin and vimentin. A diagnosis of glomangiosarcoma arising from a glomus tumor remnant was rendered, of which only approximately 50 cases have previously been reported in the literature. The accurate diagnosis of glomangiosarcoma is imperative as they have shown a 40% metastatic rate and only ¼ of patients survive to the 3 years follow up point. The goal of this case presentation is to increase awareness amongst dermatopathologists of this rare diagnosis as it can display aggressive behavior.

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Utility of Cyclin-D1 Immunohistochemistry in Superficial Fibromatosis

Nicole Therrien, Jarish Cohen, and Timothy McCalmont

University of California, San Francisco, CA.

3rd Place Winner DP Trainee World Cup

Background: It is generally held that superficial fibromatosis represents a histomorphologic analogue to its deep counterpart, which harbors aberrations in the Wnt/β-catenin pathway and demonstrates nuclear β-catenin accumulation by immunohistochemistry. However, β-catenin staining in superficial fibromatosis is inconsistent and alternative markers have not been explored. Cyclin-D1 (bcl-1) constitutes a downstream target and has been shown to correlate with β-catenin activation in other tumors. However, this relationship has not been examined in fibromatoses.

Methods: Five cases of superficial fibromatosis were retrieved from the UCSF Dermatopathology Service archives. β-catenin and Cyclin-D1 immunohistochemistry was performed.

Results: All cases demonstrated cytoplasmic β-catenin immunoreactivity and focal to patchy nuclear Cyclin-D1 expression. Cyclin-D1 labeled nuclei in both hyper- and hypocellular areas.

Conclusions: Our results suggest that Cyclin-D1 immunohistochemistry may be a useful surrogate marker for activation of the Wnt/β-catenin pathway in superficial fibromatosis.

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Interstitial Granulomatous Dermatitis: A Novel Toxicity From Immune Checkpoint Blockade Therapy

Celestine M. Trinidad,*,† Kelly C Nelson,‡ Isabella C. Glitza Oliva,§ Carlos A. Torres-Cabala,* Jonathan L. Curry,*,‡ Priyadharsini Nagarajan,* Michael T. Tetzlaff,* Doina Ivan,*,‡ Wen-Jen Hwu,§ Victor G. Prieto,*,‡ and Phyu P. Aung*

*Departments of Pathology, University of Texas, MD Anderson Cancer Center, Houston, TX; †Department of Anatomic Pathology, University of Santo Tomas Hospital Benavides Cancer Institute, Manila, Philippines; ‡Dermatology; and §Melanoma Oncology, University of Texas, MD, Anderson Cancer Center, Houston, TX.

Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed significant therapeutic benefit in patients with clinically advanced solid malignancies, including melanoma. However, autoimmune adverse events are common, and novel dermatologic toxicities continue to emerge as more patients are treated with immunotherapy. Here we describe a patient treated with combination immunotherapy of ipilimumab and pembrolizumab, who developed asymptomatic erythematous patches on bilateral legs. Histopathologic examination revealed a cutaneous interstitial granulomatous dermatitis. Notably, our patient did not receive immunosuppressive therapy for these lesions. These subsequently remained stable, and the patient's cancer remained controlled. This case expands the dermatologic toxicity profile of immune checkpoint blockade, as recognition of such toxicities is critical to optimal patient management.

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Atypical Intraepidermal Melanocytic Proliferation: Classification and Significance

Shira Wieder, MD, Matthew Goldberg, MD, and Rajendra Singh, MD

Department of Dermatology and Pathology, Icahn School of Medicine at Mount Sinai, New York, NY.

Surveys of dermatopathologists across institutions yielded extensive variability in the definition of Atypical Intraepidermal Melanocytic Proliferation (AIMP). The object of this study was to better characterize this entity. In this retrospective study, a cohort of 529 AIMP cases were selected from the year 2008, of which 319 met inclusion criteria. Females outnumbered males 2:1. The majority of AIMP's were located on body areas with intermittent sun exposure (back, chest, arms, lower legs). The differential diagnosis given by the clinician was “atypical junctional nevus” (or variants that included the words “atypical” or “dysplastic”) in 64.7% of cases followed by “melanoma” in 7.5% of cases. Of the AIMP cases, 9 (2.81%) were reclassified as melanoma on re-excision. Clinicians included “melanoma” in their differential in 5/9 of these cases (55.6%). Importantly, of these cases, 8/9 (88.9%) were on maximally sun-exposed areas (face/scalp/ears). One of the most significant suggestions made by the data is that AIMP found on sun-exposed areas may warrant re-consideration as a lentigo maligna. This has important implications for patients and their care.

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Microrna-152 Targets Ribonucleotide Reductase Small Subunit 2B and Impacts Poor Outcome in Aggressive Melanoma

Lijun Xue, and Justin Kerstetter

Pathology Department, Loma Linda University, Loma Linda, CA.

Second Place Winner DP Trainee World Cup

The object was to investigate the roles of microRNA-152 (miR-152) in aggressive melanoma. We identified the eligible microRNAs targeting RRM2B, a DNA repair gene, through sequence predicting on www.microrna.org and coexpression analysis on GSE60904 gene expression dataset. Clinical analysis was performed on a high-throughput and population-based gene expression dataset GSE60904 (n = 214). It was indicated that hsa-miR-152 might potentially target RRM2B transcript at position 2260–2281 (mirSVR score = −0.4553; PhastCons score: 0.6119). A co-expression analysis showed that hsa-miR152 expression was negatively correlated with RRM2B (P = 0.024); Kaplan-Meier analysis revealed that hsa-miR-152 was significantly associated with poor overall (Log rank P < 0.001) and progression-free survival (Log rank P = 0.023) of melanoma. As miR-152 expression increases, the survival rate of melanoma decreases in a dose dependent manner. Further multivariate analysis demonstrated that miR-152 had the opposite prognostic significance of RRM2B. The hazard ratio of miR-152 and RRM2B were 2.34 (95% CI, 1.28–4.33) and 0.64 (95% CI, 0.42–0.97) respectively. The conclusion is that miR-152 might suppress the expression of RRM2B, predict poor survival, and would become a potential biomarker in invasive melanomas.

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