Distinctive Hobnail Variant of Papillary Thyroid Carcinoma: A Case Series From a Tertiary Referral Center

Introduction: The hobnail variant of papillary thyroid carcinoma (HVPTC) is a rare and aggressive subtype, comprising 1-2% of all PTC cases. It is characterized by poor prognosis, frequent BRAF and p53 mutations, and a high recurrence rate. Given the limited data on HVPTC, especially in the Indian population, this case series aims to provide valuable insights into its clinical behavior, mutational profile, and treatment outcomes. Materials and Methods: A retrospective analysis was conducted from January 2021 to December 2023. Histological reports were reviewed for cases with ≥5% hobnail features, and molecular testing was performed for BRAF and p53 mutations. Patient demographics, tumor characteristics, and follow-up data were collected. Follow-up included clinical exams, thyroid function tests, thyroglobulin, anti-thyroglobulin antibody levels, and imaging when necessary. Results: Among 600 PTC cases, 4 were identified as HVPTC (0.67% incidence). The median follow-up was 40 months. Mean tumor size of 3.3 cm. BRAF and p53 positivity were found in 75%. Lymphovascular invasion (LVI) was present in 50% of patients. Recurrence occurred in two patients, both with LVI, despite receiving radioactive iodine and radiotherapy. The largest tumor (6 cm) did not show lymph node metastasis, while smaller tumors (2.2 cm, 2.3 cm) were metastatic. Neither BRAF nor p53 positivity correlated with thyroglobulin levels. Conclusion: HVPTC exhibits aggressive behavior, particularly in cases with LVI. While BRAF and p53 mutations are common and cause aggressiveness. Risk stratification, early, aggressive management and molecular characterization are essential to improve treatment and outcomes.