Papillary Thyroid Microcarcinoma: Clinico-pathological Correlation with BRAF V600E Mutation
Renu K Virk, MD1, Alexander Finkelstein, MD3, Joanna Gibson, MD1, Avinash Prasad, MD4, Pei Hui, MD1, Constantine G Theoharis, MD1, Tobias Carling, MD, PhD2, Sanziana A Roman, MD2, Julie A Sosa, MD2, Robert Udelsman, MD2 and Manju L Prasad1
Departments of 1Pathology and 2Surgery, Yale School of Medicine, New Haven, CT, Department of 3Pathology, New York University, New York, NY, and the Department of 4Neurology, Hartford Hospital, Hartford, CT, USA
ABSTRACT
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 129 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 conformational polymorphism.
Results:
Table† summarizes significant clinico-pathological differences in BRAF V600E mutation positive and negative PTMCs. No significant difference was found between the two groups of PTMCs in age, sex, tumor size, multifocality, psammoma bodies, stromal calcification, multinucleated giant cells and polygonal eosinophilic tumor cells.
Conclusion:
BRAF V600E mutation was significantly associated with the subcapsular sclerosing variant of PTMC but not with the follicular variant, and with lymph node metastasis. Histological features characteristic of BRAF V600E mutation positive tumors included infiltrative interface with non-neoplastic thyroid, stromal fibrosis / sclerosis / desmoplasia and well-developed characteristic nuclear features of PTC.
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