Myoepithelial neoplasms of soft tissue: an updated review of the clinicopathologic, immunophenotypic, and genetic features

Abstract

Myoepithelial tumors in skin and soft tissue are uncommon but have been increasingly characterized over the past decade. Men and women are equally affected across all age groups and lesions arise most frequently on the extremities and limb girdles. Approximately 20 % of cases occur in pediatric patients, in whom they are frequently malignant. Similar to their salivary gland counterparts, myoepithelial tumors of soft tissue demonstrate heterogeneous morphologic and immunophenotypic features. Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma; in soft tissue, tumors having at least moderate cytologic atypia are classified as malignant. Mixed tumor and myoepithelioma show a benign clinical course, with recurrence in up to 20 % (typically secondary to incomplete excision), and do not metastasize. In contrast, myoepithelial carcinoma shows more aggressive behavior with recurrence and metastasis in up to 40-50 % of cases. The majority of myoepithelial neoplasms typically coexpress epithelial antigens (cytokeratin and/or EMA) and S-100 protein; GFAP and p63 are frequently positive and a subset of malignant neoplasms lose INI1 expression. Up to 45 % of myoepitheliomas and myoepithelial carcinomas harbor EWSR1 gene rearrangements, unlike mixed tumor/chondroid syringoma which is characterized by PLAG1 gene rearrangement. While mixed tumor/chondroid syringoma are likely related to primary salivary myoepithelial tumors, soft tissue myoepithelioma and myoepithelial carcinoma appear to be pathologically distinct neoplasms.

Fig. 1

Myoepithelial neoplasms are frequently characterized by multinodular or lobular architecture (a) and consist of spindled, ovoid, or epithelioid cells arranged in variable growth patterns, namely reticular (b), trabecular or nested/solid (c), embedded in a variably myxoid, hyalinized or chondroid stroma. Cartilaginous and/or osseous metaplasia may be present (d)

Fig. 2

Mixed tumors/chondroid syringoma are similar to their salivary gland counterparts, with tubuloductal differentiation (a) and frequent immunopositivity for PLAG1 (b)

Fig. 3

Soft tissue myoepitheliomas are cytologically benign (a). Myoepithelial carcinoma is defined by cytologic/nuclear atypia, often with prominent nucleoli (b)

Fig. 4

A round cell, morphologically undifferentiated component is observed in up to 10 % of myoepithelial carcinomas that arise in pediatric patients

Fig. 5

Cutaneous syncytial myoepithelioma is characterized by syncytial growth of ovoid, spindled, or histiocytoid cells with eosinophilic cytoplasm (a and b)

Fig. 6

Myoepithelial neoplasms are frequently positive for epithelial markers cytokeratin (a, pan-keratin) and EMA. S-100 protein is frequently positive (b), while positivity for GFAP and p63 (c) is less frequent. SMARCB1/INI1 expression is lost in a subset of tumors (d)

Fig. 7

Distinctive morphologic features appear to be associated with certain fusion genes. Myoepithelial tumors with EWSR1-POU5F1 fusion are characterized by nested growth of epithelioid cells with clear cytoplasm