INSULAR CARCINOMA - A DISTINCT DE-NOVO ENTITY AMONG FOLLICULAR CARCINOMAS OF THE THYROID-GLAND

We reclassified 720 nonmedullary invasive thyroid carcinomas diagnosed and treated between 1975 and 1993. Twenty-seven cases met the criteri a of insular carcinoma and 29 cases those of widely invasive follicula r carcinoma. Comparison of these histotypes with respect to pathologic stage and overall, relative, and visceral metastasis-free survival sh owed a significant association between histotype and pT and pN categor ies. In particular, pT4 (p < 0.001) and pN1 (p < 0.001) categories wer e more frequent in the insular carcinoma histotype. By contrast, no si gnificant differences in overall, relative, or visceral metastasis-fre e survival were observed between insular carcinoma and widely invasive follicular carcinoma. Molecular analysis by polymerase chain reaction -single-strand conformation poly morphism demonstrated RAS gene family point mutations in five of eight cases analyzed in each of the two hi stotypes, with a high proportion of CAA-->AAA transversion at codon 61 of the N-RAS gene in insular carcinoma. These findings suggest that i nsular carcinoma represents a de novo entity distinct from widely inva sive follicular carcinoma, that widely invasive follicular carcinoma h as biologic characteristics more consistent with poorly differentiated than well-differentiated carcinomas, and that both insular carcinoma and widely invasive follicular carcinoma share similar molecular alter ations.