Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia: a clinicopathologic and molecular analysis of a distinct entity

Abstract

Sclerosing mucoepidermoid carcinoma with eosinophilia is a rare thyroid neoplasm of uncertain pathogenesis that resembles salivary gland mucoepidermoid carcinoma. This multi-institutional study characterizes the clinicopathologic and molecular features of this tumor by utilizing next-generation sequencing to assess common mutations and gene fusions involved in thyroid carcinogenesis as well as fluorescence in-situ hybridization for MAML2 translocations typical of salivary gland mucoepidermoid carcinoma. Nine cases (6 females and 3 males, mean age: 59 years, range 30–77 years) were identified. All cases were comprised of nests and strands of tumor cells with both squamous and mucinous differentiation embedded in a fibrohyaline stroma with an inflammatory infiltrate replete with eosinophils. All cases were p63 positive, thyroglobulin negative and showed variable expression of TTF-1. All nine cases were negative for MAML2 rearrangements. Five cases successfully tested by next-generation sequencing (ThyroSeq v.2 assay) were negative for mutations and translocations commonly involved in thyroid carcinogenesis. NTRK1 showed overexpression but no evidence of translocation. On follow-up, one patient died of persistent disease, whereas one of four remaining patients with available follow-up (mean: 7.3 years, range 4–11 years) demonstrated recurrence at 4 years. Thus, we show that sclerosing mucoepidermoid carcinoma with eosinophilia appears molecularly and morphologically distinct from follicular and C-cell-derived thyroid tumors as well as from salivary gland mucoepidermoid carcinoma. The overall and recurrence-free survival for these patients may be lower than for other well-differentiated thyroid cancers.

Thyroid sclerosing mucoepidermoid carcinoma with eosinophilia distinct from the salivary type

“…No recurrence or distant metastasis was detected during the follow-up period (20 years in case 1, 3 years in case 2, and 18 months in case 3). Shah et al concluded that the overall and recurrence-free survival of SMECE may be lower than those for other well-differentiated thyroid cancers [17], but we believe that outcomes are favorable when diagnosis is made at an early stage, such as in our cases. Ultrasound and FNAC of SMECE have not been well documented.…”

“…Microscopically, thyroid SMECE is characterized by a combination of nested epidermoid carcinoma cells, intermediate carcinoma cells, and mucous-secreting carcinoma cells, fibrohyaline stroma, and prominent eosinophilic and lymphoplasmacytic infiltrates [10][11][12][13][14][15][16][17][18][19]. All of our cases showed these features.…”

“…We believe that the formation of eosinophilic abscess in the tumor nests could be a novel characteristic finding of SMECE. According to previously reported cases, the immunohistochemical positive rates of thyroglobulin, p63, TTF-1, and PAX8 were 9%, 100%, 65%, and 11% in cases of SMECE, respectively [17]. The results probably show the reactivity of the epidermoid carcinoma cells, and do not include that of the mucus-secreting cells.…”

“…According to the review by Shah et al [17], thyroid SMECE has female predilection and typically occurs in the sixth decade. Almost all cases were associated with Hashimoto ' s thyroiditis.…”

“…Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an extremely rare variant of MEC that displays a sclerotic stroma with eosinophilic and lymphocytic infiltration [9]. Interestingly, we more frequently encountered cases with a sclerotic variant in the thyroid, in the literature [10][11][12][13][14][15][16][17][18][19].…”