Clinical Characteristics of Cribriform-Morular Variant of Papillary Thyroid Carcinoma
Mir Alikhan, Mojgan Hosseini, Jerome Taxy. University of Chicago, Chicago, IL
Background: The incidence of thyroid carcinomas in patients with Gardner Syndrome (GS) is uncommon. GS is an autosomal dominant disorder caused by APC gene mutation, leading to increased propensity of certain neoplasms. These include colonic adenomas/carcinomas, desmoid tumors, and thyroid cancers. The thyroid tumors often represent cribriform-morular variant of papillary carcinoma (C-MV). It is reported that most cases of C-MV take an indolent course. This study examines the relationship of C-MV to GS and familial adenomatous polyposis (FAP), with particular focus on the clinical characteristics of the thyroid cancers.
Design: Electronic medical records were searched for a 5 year period (2007-2012) for patients known to have GS or C-MV. Histologic and immunohistochemical studies as well as relevant serologic and molecular test reports were reviewed.
Results: Eight patients with GS and one patient with C-MV without GS were identified. Five were male and 4 female, ranging in age from 15 to 59 (average: 33). Seven patients presented with adenomatous polyposis, leading to total colectomy. Four patients also developed abdominal wall fibromatosis in addition to FAP. One patient had an initial presentation of a thyroid nodule. Three patients (all female) with thyroid lesions had C-MV, characterized by areas of cribriform architecture and squamous morules. Of these, one patient suffered a protracted course, with regional extension of the tumor, increased serologic β-hCG, and vaginal bleeding. After resection of the mass, the tumor cells were immunoreactive for β-hCG, indicating a paraneoplastic syndrome. APC mutation analysis was performed on the 3 patients with C-MV, 2 of whom were positive. Additionally, β-catenin immunostaining was positive in these two patients, in contrast to the one patient without APC mutation.
Conclusions: Most patients with GS present with polyposis and undergo total colectomy for prevention of carcinoma. In this series, patients with GS and thyroid lesions all had C-MV. In one case, C-MV was diagnosed in a patient without FAP; in this case, mutational analysis was negative, suggesting that C-MV is not restricted to patients with GS and FAP. Additionally, one case of C-MV had paraneoplastic secretion of β-hCG, a finding not reported in the literature. In most cases of C-MV, as shown here, there is a prior history of GS and/or FAP. Patients with C-MV are largely female, and the course, in general, is indolent. Rare paraneoplastic secretion may also occur. Immunoreactivity for β-catenin correlates well with mutational analysis and can be used to help identify patients with GS.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 80, Monday Morning