Genomic and Transcriptomic Underpinnings of Melanoma Genesis, Progression, and Metastasis.

Melanoma is a deadly skin cancer with rapidly increasing incidence worldwide. The discovery of the genetic drivers of melanomagenesis in the last decade has led the World Health Organization to reclassify melanoma subtypes by their molecular pathways rather than traditional clinical and histopathologic features. Despite this significant advance, the genomic and transcriptomic drivers of metastatic progression are less well characterized.

Cutaneous angiosarcoma clinically presenting as progressive solid facial edema in a 43-year-old male.

Cutaneous angiosarcoma of the head and neck is a rare, highly malignant neoplasm; prognosis is heavily influenced by tumor size, resectability, and stage at initial diagnosis. Most patients present with one to several erythematous to violaceous patches, plaques, or nodules. However, the clinical presentation is highly variable and leads to delayed diagnosis.

p63 expression in Merkel cell carcinoma predicts poorer survival yet may have limited clinical utility.

Objectives: To determine the clinical utility of p63 expression, which has been identified in several cohorts as a predictor of poorer prognosis in Merkel cell carcinoma (MCC).

Methods: Immunohistochemistry was used to determine p63 expression on MCC tumors from 128 patients.

Results: Of the patients, 33% had detectable p63 expression.

Langerhans cell sarcoma in a patient with hairy cell leukemia: common clonal origin indicated by identical immunoglobulin gene rearrangements.

Histiocytic/dendritic cell sarcomas are rare tumors, a few of which have been reported in association with B-cell lymphoma/leukemia. Isolated reports have documented identical immunoglobulin gene rearrangements suggesting a common clonal origin for both the sarcoma and the B-cell neoplasm from individual patients. We report a case of a 75-year-old male with hairy cell leukemia who subsequently developed Langerhans cell sarcoma 1 year after his primary diagnosis of leukemia.

Analysis of Tp53 codon 72 polymorphisms, Tp53 mutations, and HPV infection in cutaneous squamous cell carcinomas.

Background: Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers.

Keratinocyte dysplasia in hematopoietic stem cell transplantation recipients in the day-28-to-84 posttransplantation period.

Severe keratinocyte dysplasia (SKD) has been reported as a common event in the early posttransplantation period of hematopoietic stem cell transplantation patients. The purpose of our study is to determine the possible causes of SKD during the intermediate posttransplantation period and to ascertain its prevalence in skin biopsies. Skin biopsy slides, obtained from hematopoietic stem cell transplantation recipients who were days 28 to 84 posttransplantation, were evaluated for SKD.

Agminated cellular neurothekeoma.

Cellular neurothekeoma represents a benign, slow-growing neoplasm that typically occurs as a solitary lesion on the face, neck or arm. Reports of multiple lesions are rare. To our knowledge, multiple lesions occurring as eruptive clusters localized to a single anatomical site has not been previously reported.

Flow cytometric evaluation of skin biopsies for mycosis fungoides.

Multicolor flow cytometry (FC) is indispensable for lymphoma diagnosis and classification, but its utility in evaluating skin biopsies for mycosis fungoides (MF) is not well established. We describe the largest series to date of skin biopsies evaluated by FC for MF (n = 33), and we compare the flow cytometric results with the histologic, molecular, and clinical findings. Abnormal T-cell populations were identified by FC in 14 of 18 patients (78%) having histologically confirmed MF and in no patient whose histology was negative or indeterminate for MF (n = 14).

Transcriptome-wide studies of merkel cell carcinoma and validation of intratumoral CD8+ lymphocyte invasion as an independent predictor of survival.

Purpose: Merkel cell carcinoma (MCC) is a polyomavirus-associated skin cancer that is frequently lethal and lacks established prognostic biomarkers. This study sought to identify biomarkers that improve prognostic accuracy and provide insight into MCC biology.

Patients And Methods: Gene expression profiles of 35 MCC tumors were clustered based on prognosis.

Ancient melanocytic nevus: a simulator of malignant melanoma.

Ancient melanocytic nevus (AN) is an unusual but distinctive melanocytic neoplasm within the spectrum of simulators of malignant melanoma. This report describes 13 patients with AN where a long follow-up information was available. Histopathology is characterized by 2 populations of melanocytes, namely, one with large pleomorphic cells and the other with small melanocytes.

S100, HMB-45, and Melan-A negative primary melanoma.

The diagnosis of malignant melanoma can be challenging given the wide variation in morphologic features and immunohistochemical stains are often used to confirm the diagnosis. We report a case of melanoma with loss of staining for S100 protein, HMB-45, and Melan-A, with retained expression of tyrosinase. Regional lymph node metastases showed positive S100 protein staining.

Expanding the clinicopathologic spectrum of palisaded encapsulated neuroma.

Palisaded encapsulated neuroma (PEN; solitary circumscribed neuroma) is a benign, morphologically characteristic cutaneous or mucosal neuroma. Most are solitary lesions on the face, neck or oral mucosa. Histologically, the majority appears as dermal nodules of Schwann cell-rich fascicles, with or without distinctive encapsulation.

Diagnosis of mycosis fungoides with different algorithmic approaches.

Background: Algorithmic scoring approaches for evaluating early cases of mycosis fungoides (MF) provide a degree of diagnostic standardization. At the UWMC, biopsies from clinically concerning cases for MF are individually reviewed by a panel of pathologists and an average score is assigned to each biopsy reflecting the degree of suspicion for a diagnosis of MF; however, such an approach may not be practical outside of an academic center.

Methods: 78 cases characterized in our institution, with the diagnosis confirmed by clinicopathologic correlation/clinical follow-up were evaluated with two different algorithms, based entirely on histologic evaluation (Guitart algorithm) and partial implementation of the ISCL algorithm evaluating histology, immunohistochemistry and T-cell clonality.

Histiocyte-rich pleomorphic mastocytoma: an uncommon variant mimicking juvenile xanthogranuloma and Langerhans cell histiocytosis.

An 11-year old Caucasian female with a remote history of urticaria pigmentosa presented with a neck mass. A biopsy demonstrated a large intradermal nodule composed of unusually large epithelioid mast cells, including a prominent subset with bi-lobed and multi-lobed nuclei. By immunohistochemistry, the cells expressed CD117 (C-Kit), mast cell tryptase, CD68, and CD25, and were negative for CD163, CD1a, and S-100, confirming the diagnosis of mastocytoma.

Atypical neurofibroma of the skin and subcutaneous tissue: clinicopathologic analysis of 11 cases.

Background: Neurofibroma (NF) is a relatively common cutaneous tumor, which typically presents little diagnostic difficulty. Occasionally, however, pleomorphic cells may be present in NF raising consideration of other neoplasms like malignant peripheral nerve sheath tumor (MPNST).

Methods: This study examines the clinicopathologic and immunohistochemical features of 11 dermal and subcutaneous 'atypical' NF.

An infiltrative variant of non-neural granular cell tumor: a case report.

Dermal non-neural granular cell tumors are rare tumors of indeterminate lineage that typically present as well-circumscribed tumors with nuclear pleomorphism and mitotic activity. We describe a dermal non-neural granular cell tumor with a distinctive growth pattern with granular cells interspersed between collagen bundles. This asymptomatic papule arose on the scapula of a 46-year-old woman and consisted of a mixture of epithelioid and spindled granular cells.

Cutaneous ganglioneuroma associated with overlying hyperkeratotic epidermal changes: a report of 2 cases.

The occurrence of primary cutaneous ganglioneuroma is rare. We report 2 separate cases of primary cutaneous ganglioneuroma, both of which are associated with prominent overlying hyperkeratosis. The first case was in a 38-year-old woman with overlying verrucous keratosis.

Subungual Bowen disease in a patient with epidermodysplasia verruciformis presenting clinically as longitudinal melanonychia.

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive condition associated with a predisposition to infection with specific types of human papillomaviruses. A spectrum of wart-like lesions on the face, dorsa of the hands, and legs are characteristic clinical findings. Lesions usually develop in early childhood, persist, and may eventuate in cutaneous squamous cell carcinoma, usually in sun-exposed areas.

Unusual granulomatous variant of scleromyxedema.

Scleromyxedema is notable for significant morbidity and mortality. A generalized eruption of waxy papules in the absence of thyroid disease with histologic findings of mucin deposition, increased fibroblast proliferation, and fibrosis are the characteristic features of scleromyxedema. We report a case of scleromyxedema that, on histology, was associated with interstitial granuloma annulare-like features.

Collagen-rich variant of benign epithelioid peripheral nerve sheath tumor of the skin.

Schwannoma and neurofibroma account for the majority of cutaneous benign peripheral nerve sheath tumors and usually pose little diagnostic difficulty in their classic forms. In rare instances, however, benign peripheral nerve sheath tumors may display epithelioid morphology and lack otherwise usual features of schwannoma or neurofibroma, making classification difficult. These unusual changes may prompt consideration of other benign neoplasms or a malignancy.