Advances in the Genetic Characterization of Cutaneous Mesenchymal Neoplasms: Implications for Tumor Classification and Novel Diagnostic Markers

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Abstract

Cutaneous mesenchymal neoplasms often pose significant diagnostic challenges; many such entities are rare or show clinical and histologic overlap with both other mesenchymal and non-mesenchymal lesions. Recent advances in the genetic classification of many cutaneous mesenchymal neoplasms have not only helped define unique pathologic entities and increase our understanding of their biology, but have also provided new diagnostic markers. This review details these recent discoveries, with a focus on their implications for tumor classification and diagnosis.

Section snippets

Overview

Cutaneous mesenchymal neoplasms often pose significant diagnostic challenges; many such entities are rare or show clinical and histologic overlap with both other mesenchymal and nonmesenchymal lesions. Recent advances in the genetic classification of many cutaneous mesenchymal neoplasms have not only helped define unique pathologic entities and increase our understanding of their biology, but have also provided new diagnostic markers. Except for very difficult or unusual cases, molecular

Pseudomyogenic hemangioendothelioma

In 1992, Mirra and colleagues1 described a spindle-cell tumor thought to be a histologic variant of epithelioid sarcoma based on similarities in clinical features (arising on the extremities of young adults) and shared diffuse positivity for cytokeratin. A larger clinicopathologic study of 50 cases later defined this entity as pseudomyogenic hemangioendothelioma (PMHE), a tumor with distinct clinical, histologic, and immunohistochemical features showing endothelial differentiation.2 Subsequent

Epithelioid hemangioendothelioma

Epithelioid hemangioendothelioma (EHE) is a malignant tumor showing endothelial differentiation that occurs in the skin, soft tissue, viscera, and bone. Given the broad differential of epithelioid tumors at these various anatomic sites, these tumors can pose a significant diagnostic challenge. Fortunately, the recent identification of translocations associated with EHE have not only provided initial insights into their biology, but have also led to the identification of useful diagnostic

Hemosiderotic fibrolipomatous tumor

Originally designated hemosiderotic fibrohistiocytic lipomatous lesion and thought to be a reactive process associated with trauma,47 it is now known that hemosiderotic fibrolipomatous tumor (HFLT) is neoplastic48 and has overlapping molecular features with two other soft tissue neoplasms, myxoinflammatory fibroblastic sarcoma (MIFS) and pleomorphic hyalinizing angiectatic tumor (PHAT). HFLT typically presents as a mass on the ankle of middle-aged or elderly women,47 although it has been

Conventional fibrous histiocytoma

Fibrous histiocytoma (FH, also referred to as dermatofibroma) is the most commonly encountered cutaneous mesenchymal neoplasm. FH arises over a wide range of ages and anatomic sites but most commonly arises on the extremities of adult women in their third to fourth decade, as reddish-brown hyperpigmented papules or nodules. FH is dermal-based and consists of bland spindle cells with variable amounts of palely eosinophilic cytoplasm arranged in short fascicles or in a storiform pattern. There is

Epithelioid fibrous histiocytoma

Original descriptions of epithelioid fibrous histiocytoma (EFH) classified it as a type of FH due to similarities in clinical presentation and histologic appearances.68 However, a number of histologic features of EFH suggested it may be a distinct biologic entity, and this has been further supported by recent studies identifying recurrent ALK translocations in EFH.69, 70, 71 Similar to conventional FH, EFH most often arises on the lower extremities of young to middle-age adults, forming papular

Cutaneous myoepithelial tumors

Cutaneous myoepithelial tumors include chondroid syringoma, myoepithelioma, and myoepithelial carcinoma. Chondroid syringoma, also known as mixed tumor, is a benign neoplasm analogous to pleomorphic adenoma of the salivary gland. The typical presentation is a solitary, painless nodule on the head and neck area, usually in males. They arise in the dermis or subcutis, have a lobulated architecture and well-circumscribed borders. Epithelial and myoepithelial cells are present in varying

Clear cell sarcoma

The main role that molecular diagnostics plays in the evaluation of cutaneous mesenchymal neoplasms is in the diagnosis of clear cell sarcoma (CCS). CCS arises on the extremities (usually ankle or foot) of young to middle-age adults in association with tendons and aponeuroses and often involves superficial subcutis or dermis.93 Local recurrence is common and as many as 50% of patients will develop metastases, although distant spread tends to occur after many years.94, 95, 96, 97 Wide surgical

Summary

Over the past few years, insights into the genetic characterization of several different cutaneous mesenchymal neoplasms has allowed for the description of new tumor types, refinements in tumor classification, and the development of novel diagnostic markers, and therefore these insights have had significant diagnostic, therapeutic, and prognostic implications. Although the use of molecular diagnostic studies, such as FISH or RT-PCR, is relatively limited in the evaluation of cutaneous

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    The authors have no conflicts of interest to declare.

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