Answer: Papillary carcinoma, cribriform-morullar variant

Histology: On cut section, the tumor was unifocal, measured 3 cm, and was sharply demarcated. Histologically, the tumor exhibits a mixed pattern of growth with solid areas, focal cribriform areas (follicular epithelial cells forming anastomosing bars and arches in the absence of an intervening fibrovascular stroma), and whorls of slightly spindled cells. The cells lining the follicles have tall cytoplasm and elongated nuclei with crowding and stratification. Mitotic figures and necrosis are not identified. An immunohistochemical stain for beta-catenin is strongly positive in both the cytoplasm and the nuclei of the tumor cells.

Discussion: The cribriform-morullar 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, this variant of PTC will occur due to a sporadic mutation of the APC gene and will be unassociated with the FAP syndrome. In any event, the diagnosis of cribriform-morullar variant of PTC should prompt further investigation by a gastroenterologist for 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 morullar 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. cribriform and morullar 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-morullar variant of PTC can be confirmed immunohistochemically using TTF-1 (they are sometimes thyroglobulin negative).

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.