Unusual thyroid tumors: a review of pathologic and molecular diagnosis

The most common thyroid neoplasms are either follicular derived (papillary, follicular and Hürthle cell lesions) or C-cell derived (medullary carcinoma). The diagnosis of these tumors can usually be made at the histologic level, with immunohistochemical stains necessary in some circumstances. Specific molecular mutations have been described that can be diagnostically useful or explain, in part, their pathogenesis, including the well-known Ret/PTC and PPARgamma-PAX8 translocations, point mutations in the Ret, Ras and BRAF genes, and loss of heterozygosity of multiple different tumor suppressor genes. Some unusual tumors of the thyroid gland are more difficult to diagnose. In examining these lesions, the pathologist may use the hematoxylin and eosin-stained morphology, coupled with an analysis of the immunohistochemical staining profiles and possibly analysis of the underlying molecular mutational patterns. These less common thyroid tumors include tall cell and cribriform-morular variants of papillary carcinoma, hyalinizing trabecular tumor, mucoepidermoid and sclerosing mucoepidermoid carcinoma with eosinophilia, poorly differentiated (insular) carcinoma, and undifferentiated (anaplastic) carcinoma. The diagnostic features of these rare tumors, including the histology, immunohistochemical expression profiles and the known molecular mutational profiles of each, are reviewed.