Secretory Myoepithelial Carcinoma: A Histologic and Molecular Survey and a Proposed Nomenclature for Mucin Producing Signet Ring Tumors

Abstract

Signet ring cell (mucin producing) adenocarcinoma is a rare low grade salivary gland malignancy. While currently designated as an adenocarcinoma, myoepithelial differentiation has been implied in previously reported cases. We herein perform a survey of our cases of signet ring cell adenocarcinoma and review the literature in order to refine categorization of this rare tumor. Five cases were retrieved. One was reclassified as a mammary analogue secretory carcinoma, leaving four that fulfilled the criteria for signet ring cell adenocarcinoma: the presence of prominent signet ring or vacuolated cells arranged in islands, interconnecting strands, cords or sheets in a myxoid or hyaline stroma, or pools of mucin. An extensive panel of histochemical and immunohistochemical stains and fluorescence in situ hybridization (FISH) (modeled after common phenotypes and molecular alterations seen in signet ring and myoepithelial tumors at other sites) was performed. The male-to-female ratio was 3:1. The mean age was 56 years (range 18-81). Sites involved included buccal mucosa (2), soft palate (1) and deep parotid (1). Perineural and angiolymphatic invasion were present in three and two cases respectively. One patient was lost to follow up and the remainder were alive and without disease at time of last follow up (mean 38 months). All cases showed mucicarmine positive vacuolated/signet ring cells embedded in a myxoid stroma. Three cases showed at least focal p63 staining and two cases showed positivity for calponin. Membranous E-cadherin was retained in all cases. FISH was negative for ETV6, EWSR1, and ALK1 rearrangements in all four cases. Based on the current series and the previously reported cases, it is evident that signet ring adenocarcinomas have a dual secretory and myoepithelial phenotype and thus as a whole more appropriately designated as 'secretory myoepithelial carcinoma.' They behave in a fairly indolent fashion and do not share the major molecular alterations seen in other signet ring and myoepithelial tumor types.

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

“…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).…”

SalvGlandDx – a comprehensive salivary gland neoplasm specific next generation sequencing panel to facilitate diagnosis and identify therapeutic targets

“…The observed infiltrative growth pattern on the resection specimen, without a typical change of cell type or cell overgrowth rather represents a distinct clonal entity than a carcinoma ex pleomorphic adenoma in our view. Despite similarities to a myoepithelial-like immunophenotype [64] , the presence of abundant ductal structures did not admit diagnosis of a (secretory) myoepithelial carcinoma [ 65 , 66 ]. An uncommon variant of secretory carcinoma, involving commonly ETV6-NTRK3 fusions, could not be diagnosed due to a distinct morphology, molecular and immunohistochemical profile (e.g.…”

Salivary Mucinous Adenocarcinoma Is a Histologically Diverse Single Entity With Recurrent AKT1 E17K Mutations

“…Signet ring architecture has also been documented in the recently described variant of salivary duct carcinoma with rhabdoid features and secretory myoepithelial carcinomas-a significant subset of which were previously classified as signet ring carcinoma. 62 These tumors can also be differentiated by identification of AR positivity in salivary duct carcinoma with rhabdoid features 63 and myoepithelial markers including S100, calponin, p63, p40, and SMA in secretory myoepithelial carcinoma. 62,64,65 Of course, mucin-producing adenocarcinomas are currently classified as adenocarcinoma NOS-a heterogenous category regarded as a diagnosis of exclusion for tumors that do not meet criteria for more specific entities.…”