A Combined Molecular-Pathological Score To Predict Aggressiveness of Thyroid Papillary Microcarcinoma
LA Niemeier, HA Kuffner, S Carty, AF Stewart, YE Nikiforov. UPMC, Pittsburgh, PA
Background: Papillary thyroid microcarcinoma (TPM) is an incidentally discovered papillary carcinoma of the thyroid that is less than 1.0 cm in greatest dimension. Most of these tumors are indolent and are cured by lobectomy, although some of them are aggressive and result in local and distant metastases and may lead to patient death. Currently, there is no standardized clinical management for patients with these lesions. The aim of our study was to evaluate the utility of a combination of molecular and histological criteria to differentiate those TPM that behave more aggressively and need more expensive treatment.
Design: TPM cases were selected from the University of Pittsburgh Thyroid Cancer Database from 1991-2004. Two groups were selected. The aggressive tumor group (AG) consisted of microcarcinomas with lymph node metastasis, distant metastasis, or tumor recurrence after surgery (n=29). The non-aggressive tumor group (NAG) was selected from tumors with no such complications that were matched for tumor size, patient gender, and length of follow-up (n=30). Histologic slides were reviewed and scored for multiple microscopic criteria and molecular analysis for BRAF and RAS mutations was performed using DNA isolated from tumor sections after microdissection.
Results: BRAF mutations were detected in 20/26 (77%) of AG tumors and in 8/25 (32%) of NAG (p<0.002). In addition, the following histological features were found with statistically significant difference between the two groups: extrathyroidal extension, superficial tumor location (less than 1.0 mm from thyroid capsule), infiltrative border, tall cell variant, intrathyroidal tumor spread, tumor encapsulation, and significant tumor fibrosis. Based on these findings, a molecular-pathological sore (MPS) was developed with 2 points given for a BRAF mutation and 1 point for presence of each of the following five features: extrathyroidal extension, superficial location, intrathyroidal spread, tumor fibrosis, and tall cell variant. Based on this, tumors with an MPS of 0-2 were all NAG, whereas an MPS of 3 correlated with the 75% of AG tumors and an MPS of 4 or more with 83% of AG tumors.
Conclusions: We developed a diagnostically simple and practical scoring system based on the combination of one molecular and 5 histopathologic parameters that can reliably separate TPM into high-risk (score 3 and higher) and low-risk (score 0-2) groups.
Monday, March 22, 2010 8:15 AM
Platform Session: Section H 1, Monday Morning