Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are ...currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.
Parathyroid cancer: An update Rodrigo, Juan P.; Hernandez-Prera, Juan C.; Randolph, Gregory W. ...
Cancer treatment reviews,
06/2020, Volume:
86
Journal Article
Peer reviewed
Open access
•Parathyroid cancer comprises 0.5–5% of patients with primary hyperparathyroidism.•15–70% of sporadic parathyroid carcinomas carry a somatic mutation of the CDC73 gene.•Complete surgical resection is ...the only known curative treatment.•Recurrence is frequent (20–50%) but long-term survival is favorable due to its slow-growing nature.
Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5–5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic, although it may also occur as a feature of various genetic syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT) and multiple endocrine neoplasia (MEN) types 1 and 2A. Although PC is characterized by high levels of serum ionized calcium (Ca) and parathyroid hormone (PTH), the challenge to the clinician is to distinguish PC from the far more common entities of parathyroid adenoma (PA) or hyperplasia, as there are no specific clinical, biochemical, or radiological characteristic of PC. Complete surgical resection is the only known curative treatment for PC with the surgical approach during initial surgery strongly influencing the outcome. In order to avoid local recurrence, the lesion must be removed en-bloc with clear margins. PC has high recurrence rates of up to 50% but with favorable long-term survival rates (10-year overall survival of 60–70%) due to its slow-growing nature. Most patients die not from tumor burden directly but from uncontrolled severe hypercalcemia. In this article we have updated the information on PC by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period.
Parathyroid carcinoma Salcuni, Antonio Stefano; Cetani, Filomena; Guarnieri, Vito ...
Best Practice & Research Clinical Endocrinology & Metabolism,
December 2018, 2018-Dec-01, 2018-12-00, 20181201, Volume:
32, Issue:
6
Journal Article
Peer reviewed
Parathyroid carcinoma (PC) is a rare disease with an indolent behavior due to the low malignant potential. The etiology is unknown. Somatic mutations of CDC73 gene, the same gene involved in the ...hyperparathyroidism-jaw tumor syndrome, can be identified in up to 70% of patients with PC and in one-third of cases the mutations are germline. Therefore, in patients who carry germline CDC73 gene mutations, its finding permits to identify the carriers among relatives and sometimes to early detect a parathyroid lesion in such subjects. The diagnosis of PC is commonly made after surgery, however there are some clinical/biochemical features that should raise the suspicion of PC, namely markedly elevated serum calcium and PTH levels, a large parathyroid lesion with suspected ultrasonographic features of malignancy, the damages of kidney and bones. The best chance of cure is the complete surgical resection with the en-bloc excision at the first operation, however several recurrences are often observed during the follow-up. Since PC is an indolent tumor with long-lasting survival and the death is due to complications of untreatable hypercalcemia, multiple surgical interventions with debulking of tumoral tissues along with medical treatment for reducing hypercalcemia are often needed. Patients with PC should be followed up along their lifetime.
Parathyroid carcinoma (PTC) is an uncommon endocrine neoplasm. There are well-established criteria for its diagnosis, but diligent practical application of these criteria can be challenging for even ...the most discerning pathologist. We report a case of PTC demonstrating classical lymphovascular invasion, and review how pathologists can confidently and effectively diagnose PTC utilising the correct morphological histopathological features, supported by a panel of immunohistochemical stains and ancillary molecular testing.
Atypical parathyroid adenomas represent a group of intermediate form of parathyroid neoplasms of uncertain malignant potential which show some atypical histological features that represent a ...challenge for the differential diagnosis with parathyroid carcinomas. They may occur as sporadic or as a part of hereditary syndromes. The molecular signature of these neoplasms is still unknown and the germline CDC73 mutations appears to be the most common anomaly in this setting suggesting that these cases might represent variants of the hyperparathyroidism-jaw tumor syndrome. The identification of markers predicting the outcome is of great importance to guide an adequate postoperative monitoring and, the same time, relieve of the anxiety of relatively strict monitoring patients not at risk. This review will summarize the current knowledge of the clinical, biochemical, molecular and histological profile of atypical parathyroid adenomas.
The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the
gene: it has been suggested that early onset of the disease and high Ca
levels may predict the presence of a
mutation. ...We searched for large deletions at the
locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a
gene mutation, clinical/histological diagnosis, age at onset, Ca
, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a
gene mutation. A novel genomic deletion of the first 10 exons of the
gene was found in a 3-generation HPT-JT family, confirmed by SNP array analysis. A classification tree built on the published data, showed the highest probability of having a
mutation in subjects with age at the onset < 41.5 years (44/47 subjects, 93.6%, had the mutation). Whereas the lowest probability was found in subjects with age at the onset ≥ 41.5 years and Ca
levels <13.96 mg/dL (7/20 subjects, 35.0%, had the mutation, odds ratio = 27.1,
< 0.001). We report a novel large genomic CDC73 gene deletion identified in an Italian HPT-JT family. Age at onset < 41.5 ys and Ca
> 13.96 mg/dL are predictive for the presence of a CDC73 genetic lesion.
Approach to the Patient With Parathyroid Carcinoma Cetani, Filomena; Pardi, Elena; Torregrossa, Liborio ...
The journal of clinical endocrinology and metabolism,
2023-Dec-21, Volume:
109, Issue:
1
Journal Article
Peer reviewed
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% to 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.
The gene CDC73 (previously known as HRPT2) encodes the protein parafibromin. Biallelic mutation of CDC73 is strongly associated with malignancy in parathyroid tumors. Heterozygous germline mutations ...cause hyperparathyroidism jaw tumor syndrome,which is associated with a high life-time risk of parathyroid carcinoma. Therefore loss of parafibromin expression by immunohistochemistry may triage genetic testing for hyperparathyroidism jaw tumor syndrome and be associated with malignant behavior in atypical parathyroid tumors. We share our experience that parafibromin-negative parathyroid tumors show distinctive morphology. We searched our institutional database for parathyroid tumors demonstrating complete loss of nuclear expression of parafibromin with internal positive controls. Forty-three parafibromin-negative tumors from 40 (5.1%) of 789 patients undergoing immunohistochemistry were identified. Thirty-three (77%) were external consultation cases; the estimated incidence in unselected tumors was 0.19%. Sixteen (37.2%) fulfilled World Health Organization 2017 criteria for parathyroid carcinoma and 63% had serum calcium greater than 3mmol/L. One of 27 (3.7%) noninvasive but parafibromin-negative tumors subsequently metastasized. Parafibromin-negative patients were younger (mean, 36 vs. 63 y; P<0.001) and had larger tumors (mean, 3.04 vs. 0.62 g; P<0.001). Not all patients had full testing, but 26 patients had pathogenic CDC73 mutation/deletions confirmed in tumor (n=23) and/or germline (n=16). Parafibromin-negative tumors demonstrated distinctive morphology including extensive sheet-like rather than acinar growth, eosinophilic cytoplasm, nuclear enlargement with distinctive coarse chromatin, perinuclear cytoplasmic clearing, a prominent arborizing vasculature, and, frequently, a thick capsule. Microcystic change was found in 21 (48.8%). In conclusion, there are previously unrecognized morphologic clues to parafibromin loss/CDC73 mutation in parathyroid tumors which, given the association with malignancy and syndromic disease, are important to recognize.
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