Parathyroid carcinoma: diagnosis and clinical implications

Abstract

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.

Sychronous parathyroid carcinoma and multifocial papillary thyroid carcinoma: a case report

“…In most cases, presence of calcium level higher than 14 mg/dL, presence of PTH at least 3 times higher than the upper limit of normal, presence of a palpable mass in the neck, neck pain, hoarseness, visualization of invasion to surrounding tissues, presence of severe level of bone or renal involvement, or presence of family history are risk factors that inform the clinician regarding the likelihood of PC. [1,13] Detection of locally invasive and/or regional metastasis intraoperatively by the surgeon is also an important risk factor for PC. [13] Surgery was planned in our case with idea of parathyroid adenoma biochemically and hormonally prior to surgery.…”

“…[1,13] Detection of locally invasive and/or regional metastasis intraoperatively by the surgeon is also an important risk factor for PC. [13] Surgery was planned in our case with idea of parathyroid adenoma biochemically and hormonally prior to surgery. Invasion of the common carotid artery and the surrounding tissues was detected intraoperatively, and the surgery was completed with en bloc resection and ipsilateral hemithyroidectomy, considering it PC.…”

Atypical parathyroid adenoma with clinically aggressive course of hyperparathyroidism: clinical case report

“…Опухоли ОЩЖ, в которых отсут-ствуют достоверные признаки инвазивного роста, но есть морфологические изменения, подозрительные в отношении злокачествен-ности, могут быть классифицированы как атипичные аденомы ОЩЖ. К таким настора-живающим критериям относятся: некрозы, широкие фиброзные тяжи, количество мито-зов, сращение с соседними структурами (но не пенетрация в них), наличие опухо-левых комплексов в окружающей аденому капсуле (но без ее полного прорастания), солидный или трабекулярный тип строения, ядерная атипия, четкие ядрышки [14,15].…”

The relation of parafibromin expression with clinicopathological factors in invasive breast carcinomas

“…Inactivity (germ-line mutations / somatic mutations) of the HRPT2 tumor suppressor gene is associated with the Hereditary Hyperparathyroidism-jaw syndrome (HHJTS) and sporadic parathyroid carcinoma. While the expression decreases and disappears in parathyroid carcinomas, the expression in sporadic parathyroid adenoma and hyperplasia is high (6)(7)(8)(9). Due to the fact that it is a tumor suppressor gene, it could be predicted that the malignancy potential and aggressiveness increases as the parafibromin expression decreases.…”