Papillary Thyroid Carcinoma with Prominent Hobnail Features: A New Aggressive Variant of Moderately Differentiated Papillary Carcinoma – A Clinicopathological, Immunohistochemical and Molecular Study of 8 Cases
S Asioli, LA Erickson, TJ Sebo, J Zhang, L Jin, GB Thompson, RV Lloyd. Mayo Clinic, Rochester, MN; Turin University, Italy
Background: Papillary thyroid carcinomas (PTC) are the most common thyroid tumors and usually have a good prognosis. Recurrence, metastases and cancer death may occur in a few patients and are usually associated with more aggressive variants of PTC and with the presence of BRAF mutation. We present the clinicopathological, immunohistochemical and molecular features of a novel rare aggressive variant of PTC showing prominent hobnail features.
Design: We reviewed 2,534 primary PTC from patients who underwent primary surgical treatment between 1955-2004, at one institution in the USA. Six cases were identified according to following criteria: 1) non-solid type of PTC; 2) ≤ 10% of the tumor showed tall/columnar or diffuse sclerosing features; 3) loss of polarity/cohesiveness with hobnail features in ≥ 30% of the tumor cells; 4) available clinical data and follow-up. Two additional cases were included from the consultation files of the authors. We assessed epithelial membrane antigen, TTF1, thyroglobulin, HBME1, E-cadherin, β-catenin, cytokeratin 7, cytokeratin 19, p53, Ki67/MIB1 expression in all 8 cases by immunohistochemistry. Tumor samples were also analyzed for BRAF mutation using PCR amplification and DNA sequencing.
Results: The patients included 6 women and 2 men with a mean age of 57.6 years. Patients presented with a neck mass and cervical lymphadenopathy. Tumor size ranged from 1.0 to 4.0 cm. The tumors were usually multifocal with variably-sized complex papillary structures lined by cells with increased nuclear cytoplasmatic ratios and apically placed nuclei that produced a surface bulge leading to hobnail appearance. Thyroglobulin, TTF1, HBME1 and p53 were diffusely positive in all cases, and there was membrane staining for β-catenin and E-cadherin. The proliferative index with Ki67/MIB1 showed a mean of 10%. BRAF mutation was found in 4/7 (57.1%) cases. The average follow-up time was 77 months. Four patients died of disease after a mean of 42 months. Two patients are alive with disease after 4 and 87 months, respectively. Two patients are alive without disease after 120 and 236 months.
Conclusions: PTC with a prominent hobnail pattern is a moderately differentiated PTC variant with aggressive clinical behavior and significant mortality.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 45, Tuesday Afternoon