A combined molecular-pathologic score improves risk stratification of thyroid papillary microcarcinoma

BACKGROUND: Thyroid papillary microcarcinoma (TPMC) is an incidentally discovered papillary carcinoma that measures =1.0 cm in size. Most TPMCs are indolent, whereas some behave aggressively. The objective of the study was to evaluate whether the combination of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation and specific histopathologic features allows risk stratification of TPMC. METHODS: A group aggressive TPMCs was selected based on the presence of lymph node metastasis or tumor recurrence. Another group of nonaggressive tumors included TPMCs matched with the first group for age, sex, and tumor size, but with no extrathyroid spread. A molecular analysis was performed, and histologic slides were scored for multiple histopathologic criteria. A separate validation cohort of 40 TPMCs was evaluated. RESULTS: BRAF mutations were detected in 77% of aggressive TPMCs and in 32% of nonaggressive tumors (P.001). Several histopathologic features differed significantly between the groups. By using multivariate regression analysis, a molecular-pathologic (MP) score was developed that included BRAF status and 3 histopathologic features: superficial tumor location, intraglandular tumor spread/ multifocality, and tumor fibrosis. By adding the histologic criteria to BRAF status, sensitivity was increased from 77% to 96%, and specificity was increased from 68% to 80%. In the independent validation cohort, the MP score stratified tumors into lowrisk, moderate-risk, and high-risk groups with the probability of lymph node metastases or tumor recurrence in 0%, 20%, and 60% of patients, respectively. CONCLUSIONS: BRAF status together with several histopathologic features allowed clinical risk stratification of TPMCs. The combined MP risk stratification model was a better predictor of extrathyroid tumor spread than either mutation or histopathologic findings alone. Cancer 2012; 118: 2069-77. VC 2011 American Cancer Society.