Approach to the Patient With Parathyroid Carcinoma

Abstract

Parathyroid carcinoma (PC) is usually associated with severe symptomatic primary hyperparathyroidism (PHPT) and accounts for less than 1% of all cases of PHPT and approximately 0.005% of all cancers. PC most commonly occurs as a sporadic disease and somatic CDC73 mutations can be detected in up to 80% of cases. Approximately 30% of patients harbor a germline mutation of the CDC73 gene. Preoperative diagnosis of PC is difficult because no disease-specific markers are available, and PC should be suspected in patients with severe hypercalcemia and end-organ complications. The diagnosis is based on the evidence of invasive tumor growth at histology and/or metastases. En bloc resection of the tumor, together with the ipsilateral thyroid lobe and adjacent structures should be performed by an experienced surgeon when PC is suspected. This surgical approach reduces the risk of recurrence and metastasis and offers the highest chance of cure. Nonetheless PC has a recurrence rate of 40-60% and, if feasible, multiple surgical procedures should be performed. When surgery is no longer an option, medical treatment is aimed to reduce hypercalcemia and target organ complications. Targeted agents have been effectively used in a few cases. We describe herein a patient with severe PHPT due to PC and provide a systematic diagnostic and treatment approach. A thorough review of the medical history, a typical clinical and biochemical phenotype and, in some cases, the revision of the histological examination provide the clues for the diagnosis of PC.

Insights into Hyperparathyroidism–Jaw Tumour Syndrome: From Endocrine Acumen to the Spectrum of CDC73 Gene and Parafibromin-Deficient Tumours

“…The sample-focused analysis included 17 studies from retrospective cohorts to case series of at least four patients per paper according to our methods of research, aiming to describe the clinical presentation, particularly, PHP and non-parathyroid tumours, genetic configuration, and the outcome in HJT amid CDC73 spectrum [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46]. In accordance with prior data [16], most patients that were confirmed with the syndrome were usually young with mean age at the onset of disease between 20.8 and 39.5 years, while the largest study found that 71% of patients had the diagnosis before the age of 30 [31]. The early age at presentation strongly indicated a familial form of PHP [49].…”

“…The most common manifestation of HJT is PHP; in the majority this is a single-gland disease of the adenoma type (despite being a genetic form of PHP). However, parathyroid carcinoma has been described as well, and although it is a rare disease in the general population [16], it occurs at much higher rates in patients with HJT than non-HJT individuals [17,18]. While no multidisciplinary guideline specifically addresses the issue of HJT, the current recommendations for HJT-related PHP include an early parathyroidectomy due to the elevated risk of a parathyroid carcinoma under these specific circumstances [19,20].…”

Turning Points in Cross-Disciplinary Perspective of Primary Hyperparathyroidism and Pancreas Involvements: Hypercalcemia-Induced Pancreatitis, MEN1 Gene-Related Tumors, and Insulin Resistance

“…As a general note, the rate of gestational hyperparathyroidism in this study was double when compared to most studies on the general population [31,43,44] (Table 2). An extremely high calcium concentration causing acute pancreatitis may be induced by a parathyroid carcinoma, a dramatic orphan endocrine malignancy [45,46]. In 2021, a novel adult case was reported showing a misdiagnosis of pancreatic malignancy due to distant metastases from a parathyroid carcinoma complicated with acute pancreatitis.…”

“…An extremely high calcium concentration causing acute pancreatitis may be induced by a parathyroid carcinoma, a dramatic orphan endocrine malignancy [ 45 , 46 ]. In 2021, a novel adult case was reported showing a misdiagnosis of pancreatic malignancy due to distant metastases from a parathyroid carcinoma complicated with acute pancreatitis.…”