Malignant transformation of parathyromatosis to parathyroid carcinoma with invasive growth and distant metastasis.

: Parathyroid carcinoma (PC) is a rare endocrine malignancy. It accounts for about 1% of all primary hyperparathyroidism (PHPT) cases and 0.005% of all malignancies. PC presents with severe hypercalcemia, often refractory to standard medical treatment, which is crucial for improving patient outcomes. Differentiating PC from atypical parathyroid adenomas and parathyromatosis can be challenging. PC is diagnosed by angio-invasion, lymphatic and perineural invasion, and local malignant invasion with regional and distant metastasis. CD31 positivity on immunohistochemistry, indicating tumor cells within blood vessels in the pseudocapsule (vascular invasion), and a Ki-67% proliferative index of 8% confirm the diagnosis. We describe a 67-year-old man who presented with neck swelling, abdominal pain, and weight loss. Five years prior, he underwent a left inferior parathyroidectomy for a mass, which histological examination identified as clear cell parathyroid adenoma. Three years post-parathyroidectomy, he developed recurrent left-sided neck swelling. Magnetic resonance imaging revealed a lesion with mediastinal extension but no lymph node metastasis. During surgery, the lesion was adherent to the common carotid artery, and histopathological examination confirmed parathyromatosis. Recently, he presented again with new-onset neck swelling, abdominal pain, and weight loss. Biochemical investigations confirmed primary hyperparathyroidism. Invasive growth into surrounding tissues, blood vessels, and nerves, along with lymph node involvement and lung metastasis, with histopathology showing CD31 positivity and a Ki-67% proliferative index of 8%, confirmed the diagnosis of PC. As the tumor was inoperable, hypercalcemia was managed with cinacalcet, resulting in a decline in serum calcium levels. Parathyroid carcinoma is one of the rarest malignancies.Parathyromatosis is parathyroid tissue displaced in the neck and mediastinum due to prior surgery or aberrant embryonic development.The diagnosis of parathyroid carcinoma on histopathology is based on:Local invasion into adjacent structures, such as adipose tissues/skeletal muscle bundles.Loco-regional invasion-lymphatic (D240 IHC+), angio-invasion (CD31 IHC+), and perineural invasion.Nuclear pleomorphism, hyperchromatic nuclei, and increased mitosis (high Ki-67 proliferative index of >5%).Regional and distant metastasis in the lungs and other organs.Management of severe hypercalcemia is crucial for improving patient outcomes.