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2015, Volume 31, Supplement
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DOI: 10.5146/tjpath.2015.01316 |
Parathyroid Carcinoma: Diagnosis and Clinical Implications |
Kai Duan1,2, Özgür Mete1,2,3 |
1Department of Pathology, University Health Network, Toronto, Ontario, Canada 2Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada 3Endocrine Oncology Site Group, Princess Margaret Cancer Centre, Toronto, Ontario, Canada |
Keywords: Parathyroid neoplasms, Hyperparathyroidism, Atypical adenoma, HRPT2 protein, Parafibromin protein |
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Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone
(PTH)-mediated hypercalcemia. Concerning clinical features for parathyroid cancer include severe hypercalcemia (albumin-corrected calcium
>3 mmol/L), a palpable neck mass (>3 cm), 3rd/2nd generation PTH assay ratio (>1), and intraoperative suspicion of local invasion or regional
metastasis. A definite diagnosis of malignancy is rendered when a parathyroid tumor presents one of the following clinicopathological features:
(1) vascular invasion, (2) perineural invasion, (3) gross invasion into adjacent anatomical structures, and/or (4) metastasis. In difficult cases,
the use of ancillary biomarkers is critical to establish an accurate diagnosis. Recent advances in molecular pathology have uncovered the
important role of CDC73/HRPT2, a tumor suppressor gene deregulated in parathyroid carcinomas. Loss of nuclear and/or nucleolar expression
of parafibromin (the gene product of CDC73/HRPT2) is now regarded as a diagnostic, prognostic and predictive biomarker for parathyroid
carcinoma. Furthermore, over 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline CDC73/HRPT2 mutations. As
a result, many centers have integrated the use of ancillary biomarkers, notably parafibromin staining, in their routine practise. Radical surgery
with en bloc resection has emerged as a primary treatment modality in parathyroid cancer, achieving cure in some patients. However, in those
with inoperable disease, there remains a dire need for new therapies, as current treatments are largely ineffective. This review provides an update
on the current knowledge of parathyroid carcinoma and highlights its exciting changes in endocrine practice. |
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