THE ASSOCIATION OF WELL-DIFFERENTIATED THYROID-CARCINOMA WITH INSULAROR ANAPLASTIC THYROID-CARCINOMA - EVIDENCE FOR DEDIFFERENTIATION IN TUMOR PROGRESSION

The sequence of tumorigenesis in the thyroid is unclear. It has been p roposed that anaplastic carcinomas of the thyroid develop by dediffere ntiation in pre-existing differentiated carcinomas. We reviewed all an aplastic and insular (poorly differentiated) thyroid carcinomas in a c onsultation practice of thyroid pathology that included more than 400 thyroid cancers. Sixteen tumors (4%) were classified as anaplastic or insular (poorly differentiated) thyroid carcinomas. We examined these cases to determine whether these carcinomas were associated with well- differentiated neoplasms of follicular cell derivation. Ten patients w ere women and 6 were men, and ages ranged from 29 to 85 years; 10 pati ents with anaplastic carcinomas and 2 with insular carcinomas were 56 years or older, whereas 3 of the 6 patients with insular carcinomas we re 31 years or younger. Four tumors were composed exclusively of anapl astic carcinoma; all were represented only by incisional biopsies. One insular carcinoma infiltrated and destroyed all underlying thyroid ti ssue. In the remaining total, subtotal, or hemithyroidectomy specimens , areas of well-differentiated papillary or follicular carcinoma were found. Some differentiated papillary lesions had a wide spectrum of mo rphologies. including Hurthle cell, tall cell, and columnar cell featu res. In the literature, simultaneous or previous occurrence of well-di fferentiated thyroid carcinomas with anaplastic carcinomas is extremel y variable, ranging from 7-89% of cases. In experimental animals, seri al transplantation of differentiated thyroid tumors has been shown to lead to anaplastic transformation. Our findings suggest that the major ity of anaplastic thyroid carcinomas in humans arise from well-differe ntiated tumors. However, only a very small number of differentiated ca rcinomas progress to anaplastic lesions, the factors underlying this p henomenon remain to be identified.