Recurrent primary hyperparathyroidism with ipsilateral multifocal papillary thyroid carcinoma of classical, warthin-like, and follicular variants harboring distinct BRAF and NRAS mutations: a rare case report

BACKGROUND: The coexistence of primary hyperparathyroidism (PHPT) and papillary thyroid carcinoma (PTC) occurs in 2-5% of surgical series. Recurrent PHPT following parathyroidectomy presents additional clinical challenges. While synchronous PHPT and PTC have been documented, the simultaneous occurrence of multifocal PTC exhibiting three distinct histological variants with different oncogenic driver mutations, accompanied by ipsilateral parathyroid pathology, appears not to have been previously reported in the available literature. CASE PRESENTATION: A 48-year-old Saudi female with hypothyroidism underwent left inferior parathyroidectomy and left hemithyroidectomy for biochemically confirmed PHPT. Initial histopathology revealed Hashimoto's thyroiditis and parathyroid follicular cell lesion. Six months postoperatively, she developed biochemical recurrence (serum calcium 2.77 mmol/L; PTH 21 pg/mL). Subsequent neck ultrasound demonstrated a suspicious right thyroid nodule (TIRADS 5), confirmed as Bethesda category V on fine-needle aspiration cytology. Completion right thyroidectomy with right inferior parathyroidectomy revealed multifocal PTC comprising classical variant foci, a 1.2 cm Warthin-like variant harboring BRAF V600E mutation, and a 0.2 cm follicular variant with NRAS G13R mutation. Concurrent right inferior parathyroid adenoma/hyperplasia was identified. Molecular testing (Idylla Biocartis platform) confirmed distinct mutational profiles, establishing independent clonal origins. CONCLUSION: To our knowledge, after review of the available literature, this appears to be the first reported case of recurrent PHPT with synchronous ipsilateral parathyroid adenoma/hyperplasia and multifocal PTC comprising three histological variants with distinct molecular alterations. This unique presentation underscores the necessity for comprehensive thyroid evaluation in PHPT patients, the utility of molecular profiling in establishing tumor clonality, and the importance of individualized surgical planning in complex endocrine neoplasia.