Molecular and Histopathological Features of Multifocal Papillary Thyroid Carcinomas
M Bansal, G Mantha, YE Nikiforov. University of Pittsburgh, Pittsburgh, PA
Background: Papillary thyroid carcinoma (PTC) frequently presents as a multifocal tumor. The multifocality may be due to either intraglandular tumor spread or synchronous independent primary tumors (SIPT). It is not known if SIPT develop through genetically similar or different mutations and have particular histopathological characteristics.
Design: Sixty cases of PTC containing 2-4 discrete foci were analyzed. All tumor foci were tested for BRAF, NRAS, HRAS, KRAS and RET/PTC mutations. The following histopathological features were also analyzed: tumor location, histological variant, architectural and cytological features, encapsulation, and microscopic peritumoral dissemination (MPD) which was defined as the presence of small tumor foci in the stroma or in lymphatic channels surrounding the primary tumor.
Results: The molecular analysis of 60 cases revealed 4 different patterns of mutation occurrence: (i) 18 cases (30 %) with two foci containing different mutations; (ii) 19 cases (32%) with one tumor containing a mutation and another with no mutations; (iii) 15 cases (25%) with tumors containing the same mutation; and (iv) 8 (13%) with all tumors having no mutations. The 18 cases with two different mutations represent a group of tumors which are unequivocally SIPT. In this group, the most common combination of mutations was BRAF and RAS (56%), followed by different types of RAS (33%) (i.e. NRAS and HRAS or two NRAS mutations with different nucleotide change), and the least common combination was BRAF and RET/PTC (11%). Of these cases, 14 (78%) had tumors located in different lobes, 2 (11%) in different poles of the same lobe, and 2 (11%) had tumors separated by a distance of 0.6 cm. Eleven (61%) of these cases had tumors of different histological variant, and 4 of the remaining 7 cases had tumors of the same variant but displaying significantly different architectural/cytological features. Among the 18 tumor pairs, 61% were encapsulated and only 8% showed MPD.
Conclusions: Multiple discrete foci of PTC frequently represent SIPT tumors which develop via distinct molecular alterations. Most common combination of mutations was BRAF and RAS, followed by different types of RAS mutations. SIPT typically occur in different lobes, although they can be located as close as 0.6 cm from each other. Histopathologically, these tumors typically demonstrate distinct histological variants/microscopic features, are encapsulated, and do not show MPD.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 38, Tuesday Afternoon