Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma.

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1. Reverse transcriptase polymerase chain reaction using specific primers for RET/PTC1 and RET/PTC3 fusion genes identified a RET/PTC3 gene rearrangement in the rhabdoid tumor. Despite radiotherapy, the neoplasm rapidly progressed, with massive local and mediastinal metastasis leading to death 5 months after presentation. The hypothesis that rhabdoid tumor is a variant of anaplastic thyroid carcinoma is supported by the identification of a RET/PTC gene rearrangement, a feature of carcinomas of follicular cell derivation.

Aneuploidy in oncocytic lesions of the thyroid gland: diffuse accumulation of mitochondria within the cell is associated with trisomy 7 and progressive numerical chromosomal alterations.

Oncocytic cells are characterized by a greatly increased number of mitochondria that distend the cell cytoplasm and result in a distinctive granular appearance of the cell on conventional histology sections. Oncocytes are frequently found in metabolically active human tissues including the thyroid gland, and, as a general rule, when their proportion in a thyroid tumor is greater than 75% the tumor is referred to as oncocytic (Hürthle cell) adenoma or carcinoma. Such tumors represent a subset of thyroid lesions, and recently, both interphase fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) studies reported that they may show aneuploidy, with widespread numerical chromosomal alterations. In contrast, very few cases have been studied by conventional cytogenetic analysis. Whether the cells with chromosomal changes are the same as those with mitochondrial accumulation or whether lesions only partially composed of oncocytic cells also have cytogenetic alterations is unclear. To investigate the relationship between acquisition of the oncocytic phenotype and numerical chromosomal changes, we analyzed a random selection of thyroid lesions with (18 cases) and without (11 cases) morphological evidence of oncocytic differentiation. Lesions with oncocytes included hyperplastic nodules, adenomas, Hürthle cell tumors, and papillary carcinomas with lymphocytic stroma (Whartin-like tumors of the thyroid). Karyotypic changes were analyzed by cytogenetic analysis, FISH, or CGH, and the results were compared with in situ analysis of mitochondrial accumulation by immunofluorescence. A striking correlation between the presence of oncocytes and the presence of aneuploid katyotypes was seen in the oncocytic follicular thyroid nodules, but not in the oncocytic papillary tumors. Structural chromosome changes or normal karyotypes were observed in the lesions lacking oncocytic features. Extending the FICTION technique to the evaluation of a cytoplasmic antigen (mitochondrial membrane antigen), we pursued the simultaneous visualization of both mitochondrial increase and numerical chromosomal alterations, and showed that oncocytes of follicular lesions are prone to become aneuploid. Our data support the contention that follicular tumors composed of oncocytes should be regarded as a distinct subset.