Anaplastic thyroid carcinoma: Immunocytochemical study of 32 cases

To study the histogenesis of and determine the most useful markers for diagnosing anaplastic thyroid carcinoma (ATC), 32 cases, including 2 with numerous osteoclast-like cells, were stained with a battery of antibodies to epithelial (keratin, epithelial membrane antigen [EMA], carcinoembryonic antigen [CEA]), mesenchymal (vimentin, desmin, muscle-specific actin [MSA], Factor VIII-related antigen [FVIII:RAg]), endocrine (thyroglobulin, calcitonin, chromogranin [Cg]), lymphocytic (leukocyte common antigen [LCA]), histiocytic (alpha-1-antitrypsin [α1AT], alpha-1-antichymotrypsin [α1AChy], KP1), melanocytic (HMB-45), and Schwann cell (S-100 protein) markers. Five tumors were associated with papillary carcinoma. In one of these cases, a morphologic continuum between the well-differentiated carcinoma and the ATC was visualized by their positive immunostaining for both vimentin and keratin, thus supporting the hypothesis that the latter tumor originated from the former. Twenty-five (78.1%) tumors expressed keratin, 10 (31.3%) reacted for EMA, and 3 (9.4%) expressed CEA, confirming the epithelial nature of this neoplasm. Reactivity for thyroglobulin was seen in a small number of cells in five (15.6%) ATCs. Because all of the cases that expressed keratin also stained positively for EMA, CEA, or thyroglobulin, it is believed that keratin is the most useful epithelial marker for diagnosis of ATC. A lack of reactivity for calcitonin and Cg indicates that these tumors are not derived from C cells, as has been proposed by some authors. Reactivity for KP1 (CD68), a monoclonal antibody that reacts with a macrophage-associated antigen, occurred in the osteoclast-like cells but not in the anaplastic tumor cells. This finding, together with negative keratin staining of the osteoclast-like cells, indicates that these cells are not epithelial in nature and therefore should be considered reactive rather than neoplastic. Thirty tumors (93.8%) expressed vimentin, 15 (46.9%) marked for α1AChy, 11 (34.4%) exhibited α1AT, and 11 (34.4%) expressed S-100 protein. Because all of these markers can be seen in a wide variety of tumors of different histogeneses, they have no value in the diagnosis of ATC. Although immunostaining for FVIII:RAg, desmin, and MSA was negative in all of these tumors, these markers can help to differentiate between ATCs and some soft tissue sarcomas with which they can be confused.