Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm

Abstract

Thyroid carcinoma has been described as occurring more frequently than expected in association with familial adenomatous polyposis. The histology of these cases has not been described in detail, although the reported cases were usually diagnosed as papillary carcinoma. We now report the pathological features of four cases of thyroid carcinoma associated with familial adenomatous polyposis, and review the findings in the literature. The tumours in these four cases were all of follicular cell origin as shown by thyroglobulin immunohistochemistry. In three they were multifocal. The tumours showed some features of papillary carcinoma--grooved nuclei and papillary architecture, but these were not consistent. They also showed features that were unusual for papillary carcinoma--a cribriform pattern and solid areas with spindle cell component. Commonly the tumours combined both patterns. A review of the reported cases of thyroid cancer associated with familial adenomatous polyposis showed that they also were commonly multifocal and occurred predominantly in young women. When the histology was adequately reported or illustrated it was, in most instances, consistent with the findings in our own cases. We therefore suggest that these thyroid tumours form a distinct type with some unusual features. Clearly it is likely that the APC gene is associated with their pathogenesis, and that other factors contribute to the predominantly female incidence in this as in sporadic tumours. Six of 63 reported cases showed metastasis or died from thyroid carcinoma. In a number of cases the tumours presented before the familial adenomatous polyposis was recognized. The findings of these unusual histological features in a thyroid tumour, and particularly of multicentricity, should alert the pathologist to the possibility of familial adenomatous polyposis with its implications for family screening. The tumours are often well demarcated but, because of the multicentricity, total thyroidectomy should be advocated.

Familial thyroid cancer: a review

“…The histological features are different from sporadic tumors 38 with the characteristic cribriform pattern having solid areas and a spindle cell component, most often associated with marked fibrosis. The cribriformmorular variant of PTC (CMv-PTC) described originally as FAP-associated thyroid carcinoma is a very rare subtype of PTC representing approximately 0.1-0.2% of all papillary carcinoma cases.…”

“…The characteristic morphological findings should alert the pathologist to the possibility of a familial cancer syndrome, 1 as the correct histological interpretation may lead to further molecular genetic evaluation of the patient and family members. [38][39][40] Young women with FAP are at particular risk of developing thyroid cancer, and their chance of being affected is approximately 160 times higher than that of normal individuals; PTC occurs with a frequency of about 10 times greater than that expected for sporadic PTC.…”

A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment

“…Attenuated FAP is characterized by 30-100 adenomatous polyps. Individuals with FAP are also at increased risk for duodenal (4-12%), pancreatic (~2%), and papillary thyroid (cribriform morular variant) 33,34 (1-2%) 29,30 cancers, as well as hepatoblastoma by age 5 (1-2%) 35,36 and medulloblastoma (<1%). 32 Extracolonic manifestations can include congenital hypertrophy of the retinal pigmented epithelium, osteomas, dental abnormalities, benign cutaneous lesions such as epidermoid cysts and fibromas, and desmoid tumors.…”

Aberrant Nuclear Localization and Gene Mutation of β-catenin in Low-Grade Adenocarcinoma of Fetal Lung Type: Up-Regulation of the Wnt Signaling Pathway May Be a Common Denominator for the Development of Tumors that Form Morules

“…Sporadic cases of thyroid papillary carcinomas with morules containing OCN have been termed to be cribriform-morular variant (14), and it has been recognized that an identical morphology also occurs in familial adenomatous polyposis (FAP)-associated thyroid carcinoma (15,16). The single lung cancer so far reported in association with FAP has been L-FLAC/WDFA (17).…”