Papillary Thyroid Microcarcinoma: Clinicopathological Correlation with BRAF V600E Mutation
Renu K Virk, Alexander Finkelstein, Avinash Prasad, Pei Hui, Tobias Carling, Sanziana A Roman, Julie A Sosa, Robert Udelsman, Manju Prasad. Yale School of Medicine, New Haven, CT; New York University, New York, NY; Hartford Hospital, Hartford, CT
Background: Papillary thyroid microcarcinoma (PTMC: papillary carcinoma ≤1cm) are increasingly being detected due to the frequent use of ultrasonography. Their biology and management remains controversial despite the excellent prognosis. In recent years BRAF V600E mutation has emerged as a marker of aggressive behavior in papillary thyroid carcinoma (PTC) but its significance in PTMC is not clear.
Design: Clinical and histopathological features were reviewed in 90 PTMCs. The latter included histologic variant, tumor interface with non-neoplastic thyroid, nuclear features of PTC (well-developed or subtle), presence of cystic change, tall or polygonal eosinophilic (plump pink) cells, extrathyroidal extension (ETE), tumor-associated fibrosis/sclerosis/desmoplasia, stromal calcification, psammoma bodies and osteoclast-like multinucleated giant cells. These features were correlated with BRAF V600E mutational analysis performed in all cases by single strand confirmation polymorphism.
Results: Table 1 summarizes significant clinicopathological differences in BRAF V600E mutation positive and negative PTMCs.
|Clinicopathologic features (n=90)||BRAF V600E mutation positive (n=66;73%)||BRAF V600E mutation negative (n=24; 27%)||p value|
|Subcapsular sclerosing variant (n=30; 33%)||26 (87%)||4 (13%)||0.04|
|Follicular variant (n=10; 11%)||3 (30%)||7 (70%)||0.003|
|Lymph node positive (n=20/65; 31%)||19 (95%)||1 (5%)||0.01|
|Extrathyroidal extension (n=3; 3.4%)||3 (100%)||0|
|Infiltrative interface with adjacent thyroid (n=72; 78%)||60 (83%)||12 (17%)||0.0001|
|Stromal fibrosis/desmoplasia/Sclerosis (n=79; 86%)||63 (79%)||16 (21%)||0.0009|
|Classic well-developed nuclear features of PTC (n=73; 80%)||59 (81%)||14 (19%)||0.001|
|Multinucleated Giant cells (n=29; 31%)||26 (90%)||3 (10%)||0.02|