Cutaneous soft tissue tumors: diagnostically disorienting epithelioid tumors that are not epithelial, and other perplexing mesenchymal lesions

Cutaneous metastasis of SMARCA4‐deficient thoracic sarcoma: A diagnostic dilemma with therapeutic implications

“…The morphologic findings of SMARCA4‐DTS are not distinct and overlap with several other cutaneous epithelioid neoplasms (Table ), which presents a significant diagnostic challenge, especially in the absence of classic clinical history. Fortunately, careful selection of an immunohistochemical panel and possible molecular testing will help delineate the majority of cases from SMARCA4‐DTS . Prior studies evaluating the immunohistochemical expression profile of SMARCA4‐DTS have showed that, in addition to nuclear loss of BRG1 ( SMARCA4 ) in all cases, useful markers for reaching the diagnosis included immunopositivity for EMA, CD34, SALL4, SOX2, and loss of nuclear expression of SMARCA2 .…”

“…Melanoma and clear cell sarcoma, although difficult to differentiate from each other, may be readily excluded from the differential diagnosis as all cases of SMARCA4‐DTS have been immunonegative for S‐100, Melan‐A, and HMB‐45 . SMARCA4 may also be readily distinguished from high‐grade lymphomas by a lack of immunopositivity of CD45 . Of the cutaneous soft tissue neoplasms, epithelioid sarcoma is the main differential diagnosis.…”

“…Although certainly not an exhaustive list of other cutaneous epithelioid neoplasms that enter the differential diagnosis, epithelioid malignant peripheral nerve sheath tumor, epithelioid angiosarcoma, and a recently described malignant epithelioid neoplasm with GLI1 fusions are near the top of the list. Epithelioid malignant peripheral nerve sheath tumor may be readily distinguishable from SMARCA4‐DTS by diffuse and strong immunopositivity for S‐100 and SOX10 with loss of nuclear expression of INI1 ( SMARCB1) and retention of nuclear expression of BRG1 ( SMARCA4) . Epithelioid angiosarcoma are also a diagnostic challenge, as they often show focal expression of EMA and low‐molecular‐weight cytokeratins similar to SMARCA4‐DTS, but they are immunopositive for CD31 and ERG which has not been reported in SMARCA4‐DTS .…”

“…Epithelioid malignant peripheral nerve sheath tumor may be readily distinguishable from SMARCA4‐DTS by diffuse and strong immunopositivity for S‐100 and SOX10 with loss of nuclear expression of INI1 ( SMARCB1) and retention of nuclear expression of BRG1 ( SMARCA4) . Epithelioid angiosarcoma are also a diagnostic challenge, as they often show focal expression of EMA and low‐molecular‐weight cytokeratins similar to SMARCA4‐DTS, but they are immunopositive for CD31 and ERG which has not been reported in SMARCA4‐DTS . Malignant epithelioid neoplasm with GLI1 fusions show strong and diffuse immunopositivity for S‐100 in most cases and are immunonegative for SOX10, SMA, and EMA.…”

“…One should always keep metastatic disease on the list of possibilities. Because the differential for cutaneous epithelioid neoplasms is so broad, it is crucial for the pathologist to be aware of the myriad of possibilities, not only because we want to reach the right diagnosis for our patients, but also because treatment algorithms in recent years and prognosis for these varied lesions differ significantly . Herein, we report a case of cutaneous involvement by the recently described entity SMARCA4‐deficient thoracic sarcoma (SMARCA4‐DTS), the identification of which carries significant prognostic and therapeutic implications.…”