Treatment and outcome of metastatic parathyroid carcinoma: A systematic review and pooled analysis of published cases

Abstract

BackgroundParathyroid carcinoma (PC) is an extremely rare malignant tumor with an incidence of about 6 new cases per 10 million inhabitants per year. While several papers have been published on treatments and outcomes of PC patients with loco-regional disease, little is known about the prognosis, treatment strategies, and prognostic factors of patients with distant metastasis.Materials and methodsWe performed a systematic review and a pooled analysis of histopathologically confirmed PC cases published in literature using the following keywords: “metastasis–metastatic–secondary nodes” AND “parathyroid carcinoma”. Original case reports and case series reporting metastatic parathyroid carcinoma were included. Data from 58 articles were extracted in a piloted form by five reviewers on a shared database.ResultsSeventy-nine patients with metastatic PC were identified between 1898 and 2018. Ten (13%) patients had synchronous metastases, while metachronous metastases occurred in 43 (54%) patients. The remaining 26 patients developed metastatic disease concomitantly to local recurrence. Primary hyperparathyroidism guided the diagnosis of metastatic recurrence in 58 (73%) patients. Surgery was the main primary approach adopted, as it was performed in 43 (54%) patients. Twenty (25%) patients underwent systemic antineoplastic therapy, consisting of chemotherapy, immunotherapy, tyrosine kinase inhibitors, and hexestrol therapy. Bone resorption inhibitors had a limited efficacy in the long-term control of hypercalcemia. After a median follow-up of 37.5 months, 43 (55%) patients died, 22 (51%) due to the consequences of uncontrolled PHPT. The median overall survival was 36 months (range: 1–252). Surgery was associated with a better OS (HR 0.48, 95% CI 0.26–0.88), whereas bone metastases represented a negative prognostic factor (HR 2.7, 95% CI 1.4–5.2).ConclusionMetastatic PC has a relatively poor prognosis. The main goals of treatment are to counteract tumor growth and control hypercalcemia. Surgery of metastases is the best approach to achieve rapid control of PHPT and longer survival. Target therapies and immunotherapy deserve to be extensively tested in metastatic PC and strategies to better control hypercalcemia should be implemented.

Diagnostic dilemma in a rare case of nonfunctional parathyroid carcinoma at a referral facility in Northern Tanzania

“…Sporadic PTC has been associated with radiation exposure 7 and, less frequently, secondary and tertiary HPT brought on by chronic renal failure. There has also been evidence linking PTC, whether synchronous or metachronous, to a history of PT gland hyperplasia, PA, or thyroid malignancy with concurrent parathyroid adenoma 4,8 . The parafibromin gene (CDC73/HRPT2) inactivating somatic mutations are the most frequent genetic abnormalities linked to PTC; other abnormalities include altered expression of the p53 and retinoblastoma proteins, as well as oncosuppressor genes on chromosome 13 5 .…”

“…While benign parathyroid diseases are four times predominant in the female population, PTC occurs equally in both sexes where the age of diagnosis is a decade earlier in the mid-40s compared to mid-50s in the benign variant. [1][2][3][4] Etiology of PTC remains unclear, and there is no proof that it develops from parathyroid lesions that had already been present. 5 Instead, the recently discovered aberrant microRNA expression profile and methylation signature in PTCs show that benign lesions and cancers of the parathyroid gland are two different things.…”

“…Patients that present with hyperparathyroidism have high chances of having disease clinically detected early due to signs and symptoms of profound hypercalcemia. These include but not limited to kidney stones, nausea, abdominal pain, musculoskeletal aches, confusion, generalized body malaise, pancreatitis, headaches, osteoporosis, and depression 2–4 …”

“…These include but not limited to kidney stones, nausea, abdominal pain, musculoskeletal aches, confusion, generalized body malaise, pancreatitis, headaches, osteoporosis, and depression. [2][3][4] Patients with PTC who show normal or slight elevated serum levels of calcium and PTH are diagnosed as nonfunctioning PTC. The nonfunctional PTC is even rarer.…”

An updated mini-review on parathyroid cancer

“…Adjuvant therapies, including radiation therapy and chemotherapy, have shown limited efficacy in improving outcomes. Targeted therapies, such as tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors, are currently being investigated in clinical trials (17,18).…”