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Clinicopathological correlates of hyperparathyroidism
  1. Kai Duan1,2,
  2. Karen Gomez Hernandez3,4,
  3. Ozgur Mete1,2,3
  1. 1Department of Pathology, University Health Network, Toronto, Ontario, Canada
  2. 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
  3. 3Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  4. 4Department of Medicine, University Health Network, Toronto, Ontario, Canada
  1. Correspondence to Dr Ozgur Mete, Department of Laboratory Medicine and Pathobiology, University of Toronto; Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, University Health Network; Department of Pathology, Toronto, ON M5G 2C4 Canada; ozgur.mete2{at}uhn.ca

Abstract

Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

  • PARATHYROID
  • GENETICS
  • ENDOCRINE PATHOLOGY

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