Treating microsatellite unstable metastatic parathyroid carcinoma with anti-PD1 therapy

Parathyroid carcinoma (PC) is a rare endocrine malignancy that often clinically mimics primary hyperparathyroidism (PHPT) caused by parathyroid adenoma or hyperplasia. Complete resection of malignancy is the only curative treatment, and to date, there is no effective systemic therapy for advanced disease. A 60-year-old woman was referred for evaluation of hypercalcemia. Laboratory studies were consistent with PHPT. She underwent right superior parathyroidectomy, and pathology revealed PC with lymphovascular invasion. Postoperatively, calcium and parathyroid hormone levels normalized but recurred 6 months later. Imaging identified metastatic PC. Somatic genetic testing revealed a MutS homolog 2 (MSH2) splice-site mutation, indicating microsatellite instability. The patient started pembrolizumab immunotherapy, resulting in normalization of laboratory values and partial regression of metastases. This case highlights the diagnostic challenges of PC and underscores the potential role of immunotherapy in selected patients, particularly those with microsatellite instability, given the absence of established systemic treatment options.