SAT-818 - Non-Functioning Parathyroid Carcinoma with Rapid Metastases

Introduction
Parathyroid carcinoma is a rare and aggressive endocrine tumor and uncommon cause of primary hyperparathyroidism. Non-functional parathyroid carcinoma (NFPC), with normal parathyroid hormone (PTH) and calcium levels, is extremely rare and represents a diagnostic challenge, with only about 50 cases reported worldwide. NFPC often presents as a thyroid nodule and is diagnosed post-operatively after surgical resection and histopathological examination. Because of this, there is limited data regarding its clinical behavior and optimal treatment strategies.

Case Presentation
The patient is a 41-year-old woman who presented with a tender right neck mass with no compressive symptoms, identified as 4.3 cm right inferior TR3 thyroid nodule. Two fine-needle aspirations (FNA) resulted in non-diagnostic and atypia of undetermined significance with benign Afirma results. Due to the persistent neck mass, she underwent total thyroidectomy. Final pathology revealed 3.5 cm poorly differentiated parathyroid carcinoma with extrathyroidal extension into strap and skeletal muscle and lymphatic invasion. Immunohistochemistry staining was positive for PTH, chromogranin, synaptophysin, and GATA3, and negative for thyroid markers, with an elevated Ki-67 proliferation index of 60%. NFPC was diagnosed in the setting of normal serum calcium and PTH.

She underwent another neck dissection followed by adjuvant radiation therapy after the post-op PET scan showed activity within the right thyroid bed extending through the isthmus just to the left of midline and thymic remnant. Molecular profiling showed low tumor mutational burden, microsatellite stability, high PD-L1 expression (~60%), alterations in MEN1, PTEN, CDKN2A/B, and TERT, without CDC73 mutation. Germline testing was negative. Given aggressive behavior and high PD-L 1 expression, immunotherapy with pembrolizumab was initiated. Despite aggressive multimodal therapies, the disease progressed with the development of bilateral lung, bone, liver, mediastinal, and pelvic metastases within 6 months after initial surgery. The patient is currently treated with platinum-based chemotherapy and stereotactic body radiation therapy to lungs.

Discussion
This case features that NFPC is a biologically distinct and extremely aggressive entity. It should be considered in patients with atypical neck masses, even with normal calcium and PTH levels. FNA cytology and benign molecular thyroid classifiers can lead to diagnostic delays. The aggressive biological behavior of NFPC, along with limited effective systemic therapeutic options and the lack of biochemical markers for surveillance, necessitates a multidisciplinary approach to treatment and long-term monitoring. This case highlights the need for improved preoperative diagnostic methods, standardized surveillance protocols, and development of targeted therapies for NFPC.

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