title: 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.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Akeesha A
authors.initials: AA
authors.lastname: Shah
authors.affiliation: Department of Pathology and Laboratory Medicine, Indiana University Medical Center, Indianapolis, IN, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: La Fortune
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Caitlyn
authors.initials: C
authors.lastname: Miller
authors.affiliation: Department of Pathology, University of Virginia Health Science Center, Charlottesville, VA, USA.
authors.forename: Stacey E
authors.initials: SE
authors.lastname: Mills
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Zubair
authors.initials: Z
authors.lastname: Baloch
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: LiVolsi
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Alyssa L
authors.initials: AL
authors.lastname: Mahaffey
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Nikiforova
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
mesh_terms: D000328:Adult; D000368:Aged; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D004802:Eosinophilia / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D050939:Gene Fusion; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014178:Translocation, Genetic