Answer: Papillary carcinoma, cribriform variant

Histology: On cut section, the tumor was multifocal with five separate nodules separated by normal thyroid parenchyma. The nodules ranged in size from 1 to 4 cm. Microscopically the tumor exhibited a mixture of growth patterns. The predominant pattern was papillary. The cells lining these complex papillae had tall cytoplasm and elongated nuclei with crowding and stratification. The nuclei were more hyperchromatic than noted in most typical papillary thyroid carcinomas; that is, optical nuclear clearing was not a prominent features. In addition to the complex papillary component, a cribriform component was focally present. In these areas, follicular epithelial cells formed anastomosing bars and arches in the absence of an intervening fibrovascular stroma. Both components (papillary and cribriform) were found to be TTF-1 immunoreactive (not shown). Morule formations (i.e. solid whorls of spindled/squamoid cells) were not identified.

Discussion: The cribriform variant of papillary thyroid carcinoma is a distinct subtype of thyroid cancer that usually is affects young women (about 15 to 30 years in age). It is a variant that is important for the surgical pathologist to recognize as an indicator of familial adenomatous polyposis. For some FAP patients, development of this particular subtype will be the initial manifestation of the syndrome, even preceding the detection of colonic adenomas. In other patients, the development of the cribriform variant of PTC will occur as a result of a sporadic mutation of the APC gene and will be unassociated with the FAP syndrome. In any event, the recognition of the particular variant should prompt further investigation in any patient without a known history of FAP.

Histologically, the tumors often exhibit an admixture of cribriform, follicular, papillary, trabecular and solid patterns of growth with morular formations. The tumor cells themselves are sometimes tall with nuclear crowding and stratification. Although confusion with the aggressive columnar variant of PTC is a concern, the cribriform variant is morphologically more diverse (e.g. cribriforming and trabecular components), and it typically lacks the tumor necrosis and sub-nuclear vacuoles of the columnar variant. Consideration of metastatic colorectal carcinoma is another reasonable consideration, especially in FAP patients, but can usually be excluded by light microscopy alone (e.g. lack of cellular necrosis, admixture with other tumor growth patterns). If in doubt, the diagnosis of the cribriform variant of PTC can be confirmed immunohistochemically using thyroglobulin and/or TTF-1.

Early indications suggest that the behavior of the cribriform variant is similar to conventional PTC. As emphasized above, the main importance in recognizing this unusual variant is to alert the pathologist and clinician to the possibility of an unrecognized FAP, and to avoid confusion with some other more aggressive tumor type.