Myoepithelioma, Myoepithelial Carcinoma

Not clinically relevant

EWSR1 gene rearrangements are common in myoepithelial tumors of soft tissue (as well as in those of skin and bone). The largest study to date reported EWSR1 gene rearrangements in half of the soft tissue lesions tested, with the common fusion partners POU5F1 and PBX1 identified in 16% of cases each. Rare fusion partners include ZNF444, KLF17, ATF1, and PBX3, and occasional cases show alternative FUS gene rearrangements with similar partner genes. These studies have suggested some associations between genotype and phenotype. Most EWSR1-POU5F1–positive tumors present in deep soft tissues of the extremities in young patients and are composed of nests of epithelioid cells with clear cytoplasm; a subset of EWSR1-PBX1–positive tumors showed a deceptively bland and sclerotic appearance. A subset of myoepithelial carcinomas have homozygous deletions of SMARCB1. Mixed tumors with ductal differentiation have PLAG1 gene rearrangements (occasionally with LIFR as the fusion partner). The presence of rearrangements of PLAG1 and EWSR1, respectively, in salivary gland pleomorphic adenoma and myoepithelial carcinoma emphasizes that soft tissue myoepithelial neoplasms are genetically related to their salivary gland counterparts.

Most benign myoepithelial tumors are grossly well circumscribed and nodular, whereas malignant tumors typically have infiltrative margins. The cut surface ranges from gelatinous and glistening to firm or fleshy. Tumor size range is broad (1–20 cm in greatest dimension), with a mean size of 4–6 cm.

Myoepithelial tumors show a wide morphological spectrum of architectural and cytological heterogeneity, similar to their salivary gland and skin counterparts. Many show a predominantly reticular or trabecular growth pattern with prominent myxoid stroma; areas of more nested or solid growth and hyalinized stroma are commonly observed and occasionally predominate. Tumor cells range from spindled to epithelioid with uniform nuclei and eosinophilic to clear cytoplasm. Studies have suggested some associations between genotype and phenotype (see Pathogenesis). Some tumors have large epithelioid cells showing prominent cytoplasmic vacuolation (and were classified as parachordoma in the past), whereas others may show predominantly spindled morphology, including the cutaneous syncytial subtype. Plasmacytoid cells with hyaline cytoplasmic inclusions may be prominent. Osseous or cartilaginous differentiation is observed in 10–15% of cases, whereas squamous or adipocytic metaplasia is more rare. Mixed tumors show a ductal component and account for approximately 10% of all myoepithelial lesions. Myoepithelial carcinomas are defined as having nuclear atypia with easily discerned nucleoli, often together with a high mitotic count and necrosis. Some such tumors (especially in children) may show undifferentiated round cell morphology.

Immunohistochemistry is necessary to confirm myoepithelial differentiation, although expression of myoepithelial markers is often variable. More than 90% of tumors express broad-spectrum keratins and S100. Other frequently positive markers are EMA (~70%), GFAP (~50%), and SOX10 (~80%; lower in carcinomas). p63 is positive in a subset of tumors. Myogenic markers are more variable, with calponin being most frequent (90%), followed by SMA (60%) and desmin (0–20%). PLAG1 is positive in mixed tumors, correlating with PLAG1 gene rearrangement. Loss of expression of SMARCB1 (INI1) is observed in a subset of myoepithelial carcinomas.

Aspirate smears of myoepithelial tumors of soft tissue, similar to those of their salivary gland counterparts, show variably spindle, epithelioid, and plasmacytoid cells embedded within fibrillary myxoid stromal fragments. Rhabdoid morphology may be seen, and myoepithelial carcinoma shows appreciable cytological atypia.

Most myoepithelial tumors of soft tissue show benign or indolent behavior. The only reliable criterion for malignancy is the presence of moderate to severe nuclear atypia with discernible nucleoli. Histologically benign tumors have a 20% risk of recurrence, but they rarely metastasize, whereas myoepithelial carcinomas recur and metastasize in 40–50% of cases. Common sites of metastasis include lungs, lymph nodes, bone, and soft tissue.

Rearrangements of EWSR1, FUS, or PLAG1 (in mixed tumors) can be detected. EWSR1 FISH alone may not be sufficient for distinguishing myoepithelial neoplasms from other tumors with EWSR1 fusions.

Essential: trabecular, reticular, nested, and/or solid growth of variably spindled or epithelioid cells with a frequent myxoid or hyalinized stroma; mixed tumors in addition show ductal differentiation; myoepithelial carcinomas show increased cytological atypia and mitotic activity; positivity for EMA/keratin and S100, SOX10, or GFAP.

Desirable (in selected cases): EWSR1 rearrangements may be helpful.