Medullary thyroid carcinoma: a 25-year perspective.

This article summarizes the major clinical, pathological, and molecular features of medullary thyroid carcinoma (MTC), based on a review of the most significant advances in our understanding of this tumor type over the last 25 years. MTC is a neuroendocrine carcinoma that shows evidence of C-cell differentiation. The tumor has a distinctive morphologic appearance, including the presence of amyloid deposits. Immunostaining for calcitonin, carcinoembryonic antigen, calcitonin gene-related peptide, and thyroid transcription factor 1 is helpful in differential diagnosis. Identification of RET mutations in familial and sporadic MTC has brought important changes in early diagnosis and treatment. Surgery remains the cornerstone of effective therapy. Understanding the molecular basis of MTC will allow identification of novel approaches for individualized treatment.

Life-threatening hypercalcemia from a hepatocellular carcinoma secreting intact parathyroid hormone: localization by sestamibi single-photon emission computed tomographic imaging.

OBJECTIVE: To describe a patient with severe hypercalcemia and elevated intact parathyroid hormone (iPTH) levels associated with a hepatocellular carcinoma. METHODS: We present a case report, detailing the laboratory, surgical, and sestamibi scanning findings. Moreover, the literature relating to paraneoplastic ectopic production of iPTH is reviewed. RESULTS: A 72-year-old man had the following laboratory results at the time of initial assessment: serum calcium of 14.5 mg/dL, ionized calcium of 6.8 mg/dL, serum iPTH of 92 pg/mL, and a PTH-related peptide of <0.7 pg/mL. Findings on preoperative sestamibi scanning were suggestive of a parathyroid adenoma, with additional uptake in the dome of the liver. He was diagnosed as having primary hyperparathyroidism, and a neck exploration was undertaken. The right superior, right inferior, and left superior parathyroid glands were mildly enlarged and were excised. The left inferior parathyroid gland could not be identified, despite an extensive neck exploration. Bilateral internal jugular vein sampling demonstrated elevated iPTH levels, an indication of a systemic origin of the hormone. Postoperatively, a repeated sestamibi scan confirmed hyperactivity in the liver, and a subsequent computed tomographic scan revealed masses in segments IV, VII, and VIII of the liver in conjunction with portal vein involvement. Tissue biopsy confirmed the presence of hepatocellular carcinoma, and the fluid obtained with the biopsy specimen was strongly positive for iPTH. The patient was treated with transarterial chemoembolization but subsequently died. CONCLUSION: This case demonstrates the rare occurrence of hepatocellular carcinoma producing iPTH as the cause of life-threatening hypercalcemia. Sestamibi scans were accurate in detecting focal hyperactivity that correlated with the malignant involvement.