Cribriform-morular variant of papillary thyroid carcinoma: molecular characterization of a case with neuroendocrine differentiation and aggressive behavior.

We describe an especially aggressive case of cribriform-morular variant (C-MV) of papillary thyroid carcinoma (PTC) in a 42-year-old man with familial adenomatous polyposis who died with lung and brain metastases 17 months after thyroidectomy. The angioinvasive neoplasm combined a mixture of trabecular, solid, cribriform, and follicular patterns of growth with CD10+ morules. Follicles were devoid of colloid, and the nuclear features typical of PTC were present in some areas and missing in others. Tumor cells were positive for thyroid transcription factor-1 and, in 40% of the tumoral mass, also were positive for chromogranin and synaptophysin and were negative for thyroglobulin and calcitonin. Strong nuclear staining for beta-catenin was found in all tumor cells, as was positivity for p53 and cyclin D1. In addition to the germline heterozygous APC Ex 2-3 duplication mutation, a somatic homozygous silent p. Thr1493Thr gene variant was found in the neoplastic cells along with RET/PTC rearrangement. This tumor represents the first case of C-MV of PTC showing neuroendocrine differentiation.