BRAFV600E Mutation in Papillary Thyroid Carcinomas (PTC) Associated with Hashimoto Thyroiditis (HASHI): A Clinicopathological Correlation
Sudhir Perincheri, Matthew Horne, Renu K Virk, Pei Hui, Manju L Prasad. Yale University, New Haven, CT
Background: The pathogenesis of PTC arising in HASHI is not well understood. HASHI has been suggested to be a premalignant counterpart of PTC. It has also been proposed that the intense lymphocytic response in HASHI may have a mitigating role in cancer progression. BRAFV600E mutation has emerged as a frequent genetic abnormality in PTC (upto 70% in our institution) and has been shown to be associated with aggressive pathologic features. We explore the incidence of BRAFV600E mutation in PTC associated with HASHI and correlate the findings with clinical and pathological features.
Design: 45 PTCs arising in the background of HASHI diagnosed between August 2011 and July 2012 that were analyzed for BRAFV600E mutation were correlated with their clinicopathological features. HASHI was diagnosed based on morphological criteria that included moderate to severe chronic lymphocytic thyroiditis with germinal center formation, and follicular destruction with Hurthle cell metaplasia. BRAFV600E mutation was detected by single strand conformational polymorphism.
Results: Patients included 40 women and 5 men aged 18 to 85 years (median 42). Tumor size varied from 0.4 cm to 5 cm (median 1.1 cm). The histologic subtypes included 29 classic variants (63%), 11 follicular variants (24%), the rest included subcapsular sclerosing type and tall cell variants of PTC. Lymph nodes were examined in 42 patients (central neck dissections with additional lateral neck dissection in 5 patients). 19 of 42 cases (45%) showed metastatic disease, 14(33%) had pN1a stage disease and 5(12%) had pN1b stage disease. 6 tumors(13%) had extrathyroidal extension. BRAFV600E mutation was identified in 21 tumors (47%). Table 1 summarizes the clinocopathological characteristic of PTCs arising in HASHI. Median age and tumor size were significantly lower in the BRAFV600E mutation positive group (p<0.05).
|Clinicopathological features||BRAFV600E Positive (n=21; 47%)||BRAFV600E Negative (n=24; 53%)|
|Median age (range)||37 (18-59)||44 (21-85)|
|Median size (range)||0.8 (0.5-3.2)||1.7 (0.4-5)|
|Lymph nodes metastasis|