Diagnosis and management of parathyroid carcinoma: a state-of-the-art review

Abstract

Parathyroid carcinoma is one of the least common endocrine malignancies, and accounts for approximately 1% of all patients with primary hyperparathyroidism. A systematic review of peer-reviewed literature published between January 2000 and March 2022 via Medline, Embase, Cochrane Central Register of Controlled Trials, EudraCT, ClinicalTrials.gov, CINAHL and SCOPUS was conducted. Manuscripts were eligible if they included data on adult non-pregnant populations with parathyroid carcinoma. No restrictions regarding interventions, comparators or duration of follow-up were imposed. Single case reports, reviews or meta-analyses were excluded. Outcomes of interest were molecular pathogenesis, clinical presentation, differential diagnosis, treatment, follow-up and overall survival. Study quality was evaluated using the Newcastle-Ottawa Scale for observational studies. Seventy-five studies were included from 17 countries, reporting on more than 3000 patients with parathyroid carcinoma. CDC73 mutation has been recognised as playing a pivotal role in molecular pathogenesis. Parathyroid carcinoma typically presents with markedly increased calcium and parathyroid hormone levels. The most frequently described symptoms were bone and muscle pain or weakness. En bloc resection remains the gold standard for the surgical approach. The five-year overall survival ranged from 60% to 93%, with resistant hypercalcaemia a significant cause of mortality. Emerging evidence indicating that targeted therapy, based on molecular biomarkers, presents a novel treatment option. The rarity of PC and need for personalised treatment warrants multidisciplinary management in a ‘centre of excellence’ with a track record in PC management.

Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report

“…PTH, neuroendocrine tumor markers SYN, and CgA are helpful in the diagnosis of PC; when the Ki-67 index is greater than 5%, it is alert to consider the possibility of malignancy. 3 In this case, the tumor tissue was heavily fibroussegregated and the tumor cells were heterogeneous with obvious Radical resection of the tumor lesions at the first surgery is the only chance to cure PC potentially. 3 Up to now, there is no evidence to show survival benefits from chemotherapy, radiotherapy and immunotherapy in the treatment of PC.…”

“…7 Mutations of the cell division cycle 73 (CDC73) gene has been reported as the most common tumor suppressor gene associated with PC and the absence of parafibromin caused by mutations of CDC73 makes parathyroid tissue more susceptible to carcinogenesis. 3,6 In addition, studies have also suggested that repeated mutations of the Prune Homolog 2 with BCH Domain (PRUNE2) gene and AarF Domain-Containing Kinase 1 (ADCK1) gene, genetic amplification of Cyclin D1 gene, and abnormal activation of PI3K/AKT/mTOR signaling pathway are related to the occurrence of PC. 6,8 In this case, there were not any abnormalities found in the above common genes' detection, and the specific etiology of this patient still needs to further study.…”

“…1,8,9 In the presented case, the patient had severe osteoporosis with multiple pathological fractures as the main symptom, accompanied by generalized bone also leads to decreased muscle strength, especially the proximal parts of the limbs; and some patients present muscle pain and muscle atrophy. 3,10 In addition, PTH also regulates the metabolism of fat and muscle tissues.…”

“…3 Up to now, there is no evidence to show survival benefits from chemotherapy, radiotherapy and immunotherapy in the treatment of PC. 3,13 Most PC patients will significantly improve their life quality after operation with bone pain, muscle weakness, fatigue and other symptoms being relieved, and recover from severe osteoporosis effectively. HBS is a rare postoperative complication in some patients with PHPT, and the mechanism is the action of osteoclasts after radical resection of PC.…”

“…2 Whole radical excision of the tumor lesion at the first surgery is the key point to cure PC. 3 Hungry bone syndrome (HBS), a serious complication after parathyroid surgery, characterized by severe hypocalcemia following parathyroidectomy due to rapid drop of PTH after a previous long-term elevated concentration and associated bone remineralization, usually accompanied by hypophosphatemia and hypomagnesemia. 4,5 So far, few cases of PC with muscle atrophy as the main symptom have been reported.…”