Clinico-Pathological and Molecular Characteristics of Tall Cell Variant of Papillary Thyroid Microcarcinoma
Jane Bernstein, Renu Virk, William H Westra, Giovanni Tallini, Pei Hui, Robert Udelsman, Clarence T Sasaki, Sanziana Roman, Julie A Sosa, Manju L Prasad. Yale School of Medicine, New Haven, CT; Johns Hopkins School of Medicine, Baltimore, MD; Bologna University School of Medicine, Bologna, Italy
Background: Papillary thyroid microcarcinomas (PTMC) are papillary thyroid carcinomas (PTC) measuring ≤1 cm. Their prognosis is excellent. However, a subset of them behave aggressively with recurrence, metastasis and cancer-specific mortality of up to 2%. The tall cell variant of PTC is a particularly aggressive tumor that generally presents in advanced stage and is associated with higher disease-related mortality. Recognizing this variant in PTMC may help select aggressive microcarcinomas for a more intensive therapy.
Design: Clinico-pathological features of 12 tall cell variant (TCV) PTMC in 10 patients were reviewed. DNA was extracted from tumor tissue and BRAF V600E mutational analysis was performed by single stranded conformational polymorphism electrophoresis.
Results: The patients included 8 women and 2 men aged 34 to 66 years (mean 52.8 years). All patients underwent total thyroidectomy. Nine of ten thyroids (90%) contained multifocal PTMC. In 2 thyroids both tumors were TCV while in the remaining 7 thyroids the additional PTMCs were classic types. Nine TCV were located within the left lobes and three in the right lobes. The tumors varied from 3 mm to 10 mm in size (mean 6.5 mm). The tumor cells had moderate to abundant eosinophilic cytoplasm and the majority of them were at least twice as tall as wide. The nuclear features were those of classic PTC and intranuclear inclusions were frequent. All tumors were associated with fibrosis and a minimal lymphocytic response (100%). All but one of the tumors exhibited an infiltrative interface with the non-neoplastic thyroid (92%). None of the tumors were cystic or exhibited psammoma bodies. Three tumors exhibited extrathyroidal extension (pT3) and three showed lymphovascular invasion (25%). Lymph nodes were dissected in seven patients, and showed metastases (43%) to level VI nodes in one (pN1a) and lateral cervical lymph nodes in 2 patients (pN1b). Nine of eleven tumors had BRAF V600E mutations (82%). Two TCV with wild-type BRAF arose within the same thyroid, both were subcapsular and one showed extrathyroidal extension and lymphovascular invasion.
Conclusions: The tall cell variant of papillary microcarcinoma is frequently associated with multifocality, extrathyroidal extension, advanced nodal stage at presentation and BRAF V600E mutation. Recognition of TCV among the papillary microcarcinomas may help select patients for more aggressive treatment.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 30, Tuesday Afternoon