EWSR1 gene rearrangement occurs in a subset of cutaneous myoepithelial tumors: a study of 18 cases

Abstract

Cutaneous myoepithelial tumors form a clinicopathological spectrum ranging from mixed tumor to myoepithelioma and myoepithelial carcinoma. Recently, EWSR1 rearrangement has been described in a subset of soft tissue myoepithelial tumors, whereas the cutaneous counterparts showed this aberration in a minority of cases. This raises the question whether cutaneous myoepithelial tumors have comparable genetic alterations. We examined 18 cases of cutaneous myoepithelial tumors arising in 7 female and 11 male patients (age range, 34-86 years; mean, 58 years). Eight mixed tumors occurred at the head, and one at the scrotum. Six myoepitheliomas arose at the extremities, and one case each at the back and head. One myoepithelial carcinoma occurred at the cheek. The tumor size ranged from 0.3 to 1.7 cm (mean, 1.0 cm). All mixed tumors and three myoepitheliomas were limited to the dermis. Four myoepitheliomas and the myoepithelial carcinoma involved the subcutis. Mixed tumors and myoepitheliomas were composed of myoepithelial cells with a variable cytomorphology, architecture and stromal background. Ductal structures were seen by definition in mixed tumors. The myoepithelial carcinoma represented an infiltrative dermal neoplasm consisting of atypical spindle cells. Immunohistochemically, all cases tested were positive for EMA and calponin, whereas S100, CK, ASMA and GFAP were expressed in 90%, 80%, 78% and 50% of the cases tested, respectively. By fluorescent in situ hybridization analysis, 7 out of 16 cases (44%) exhibited EWSR1 rearrangement. Four of them were mixed tumors, two were myoepitheliomas and one was a myoepithelial carcinoma, confirming that these lesions represent a spectrum of dermal myoepithelial tumors. Follow-up information, available for five patients (including the patient with a myoepithelial carcinoma), revealed no evidence of disease in all cases (range, 6-72 months). Our study provides a genetic relationship of myoepithelial tumors of the skin with their counterparts in soft tissue, bone and visceral localization by sharing EWSR1 rearrangement.

Cutaneous syncytial myoepithelioma: A case report with emphasis on the differential diagnosis of problematic dermal tumors

“…EWSR1 gene rearrangement occurs in a subset of cutaneous myoepithelial tumors (1,11), providing a genetic association between myoepithelial tumors of the skin and their counterparts in bone, soft tissue and visceral locations (11). The presence of EWSR1 gene rearrangement in the majority of cutaneous synovial myoepithelioma supports the concept of its close association to other subsets of myoepithelial tumors.…”

Myoepithelial Neoplasms of Soft Tissue: An Updated Review of the Clinicopathologic, Immunophenotypic, and Genetic Features

“…Documented fusion partners thus far include POU5F1 (6p21), PBX1 (1q23), ZNF444 (19q23), ATF1 (12q13) and PBX3 (9q33) [22,24,25]. Homozygous deletion of the SMARCB1 gene has recently been reported in 3/5 cases of myoepithelial carcinoma lacking EWSR1 gene rearrangement [26].…”

“…7). EWSR1-rearrangement occurs in up to 44 % of cutaneous myoepithelial tumors [25] (including cutaneous syncytial myoepithelioma [7]). While EWSR1 rearrangement is present in hyalinizing clear cell carcinoma [24], EWSR1 rearrangement has not been identified to date in other salivary neoplasms, including myoepithelial tumors [27,28] (see Addendum).…”

Myoepithelial Tumors

“…4-6,11-14,21,23,26 Documented fusion partners thus far include POU5F1 (6p21), PBX1 (1q23), ZNF444 (19q23), ATF1 (12q13), PBX3 (9q33), and KLF17 (1p34). 4,9,11,26 Homozygous deletions of the SMARCB1 gene have recently been reported in myoepithelial carcinomas lacking EWSR1 gene rearrangement. 27 Although the biologic significance of the fusion gene products is unknown, there may be some correlation between specific gene fusions and morphology based on preliminary observations.…”

“…[4][5][6] Cutaneous lesions are confined to the dermis and arise frequently in the extremities, trunk, and head and neck regions. [7][8][9] Tumors are classified as mixed tumor/chondroid syringoma, myoepithelioma, and myoepithelial carcinoma. Similar to their salivary gland counterparts, myoepithelial tumors of soft tissue, skin, and bone demonstrate heterogeneous morphologic and immunohistochemical features, but are notably distinct in their histologic criteria for malignancy.…”