Background: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is a rare subtype of PTC, which occurrs predominantly in young women. This disease much more frequently presents in patients with familial adenomatous polyposis (FAP). FAP is an autosomal dominant inherited disease, which arises from germline mutations in the adenomatous polyposis coli (APC) gene. To clarify the distinctive clinical features of CMV-PTC, a comparison study was performed between familial types and sporadic types. Methods: Between 2007 and 2018, 15 CMV-PTC patients underwent thyroidectomy in Samsung Medical Center. The clinical features of these patients were retrospectively reviewed. Results: All patients were women with a median age of 26 years (range 17-46 years). The median maximum diameter was 1.0 cm (range 0.4-3.5 cm). All tumors underwent immunostaining and showed nuclear and/or cytoplasmic staining for β-catenin. On ultrasonography, most nodules had benign-looking features (well-defined, hypoechoic, and oval to round shapes without calcification), but a few nodules had capsular invasion and taller than wide shape. On preoperative fine-needle aspiration cytology, five patients (33%) were diagnosed as CMV-PTC, nine (60%) as PTC, but one (7%) as follicular neoplasm or PTC-follicular variant. Six patients (40%) had FAP, and four of them had total colectomy due to FAP. Five of them had a family history of FAP or colon cancer, or thyroid cancer. Germline mutations in the APC gene were found in all six patients with CMV-PTC associated with FAP, and five of them had de novo mutations. All patients with FAP-associated CMV-PTC had multiple tumors. All CMV-PTC patients had excellent response to initial therapy. Conclusions: Because of the association between FAP or colon cancer with multifocal CMV-PTC, we confirm that mutational analysis of the APC gene and colonoscopy should be carried out in these patients when multiple thyroid tumors are found.
Keywords: APC gene mutation; CMV–PTC; FAP; multifocality; β-catenin.