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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant transformation of parathyroid tumours is rare. Nevertheless, this small subset of malignant tumours often creates diagnostic and therapeutic problems. In this work, the morphological characteristics of 26 primary parathyroid carcinomas and seven metastases have been studied. Furthermore, immunohistochemical expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1), and Ki-67 were determined for parathyroid carcinomas and compared with adenomas and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31% of carcinomas demonstrated down-regulation of CASR. A significant correlation was found between CASR expression and the Ki-67 proliferation index. Chromosome 1q and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%) carcinomas, in contrast to the low percentage of LOH reported in both regions in adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation of the CASR protein is seen in a proportion of parathyroid carcinomas with a high proliferation index.
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PMID:Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinoma. 1469 25

Parathyroid carcinoma is a rare tumor that is responsible for <1% of cases of hyperparathyroidism in most parts of the world. An increased incidence of this tumor has been reported in patients with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, but the etiology of most other cases is unknown. Parathyroid carcinomas tend to occur a decade earlier than adenomas, and the sex ratio approaches unity in contrast to the female preponderance of adenomas. Most patients with carcinomas present with marked hypercalcemia and are more likely to have associated bone and renal disease than those with adenomas. Although fibrosis and mitotic activity are common in carcinomas, these features are not specific for malignancy. The diagnosis of carcinoma should be restricted to those tumors that show invasion of blood vessels, perineural spaces, soft tissues, thyroid gland, or other adjacent structures or to tumors with documented metastases. Mutations of the HRPT2 gene (1q21-q32), which are responsible for the HPT-JT syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. A subset of patients with mutation-positive carcinomas have germline mutations of the HRPT2 gene. This finding suggests that some patients with apparent sporadic parathyroid carcinomas may have the HPT-JT syndrome or a variant of this syndrome. Because of the high frequency of local recurrence following incomplete excision, an en bloc resection is the preferred surgical approach for treatment of parathyroid carcinomas.
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PMID:Parathyroid carcinoma: an overview. 1573 73

Parathyroid neoplasms encompass a spectrum of proliferative lesions that include adenomas, atypical adenomas, and carcinomas. While the diagnosis of adenomas is usually straightforward, parathyroid carcinomas (PTCAs) often present considerable diagnostic challenges. Fibrosis and mitotic activity are common in PTCAs, but these features are not specific for malignancy. An unequivocal diagnosis of PTCA should be restricted to those tumors that invade adjacent soft tissues, thyroid gland, blood vessels, or perineural spaces or to those cases with documented metastases. Atypical adenomas include those tumors that share some of the features of PTCA but lack evidence of invasive growth. A variety of genetic abnormalities, including HRPT2 mutations, occur in PTCAs. Mutations of the HRPT2 gene, which encodes parafibromin, are responsible for the development of the hyperparathyroidism-jaw tumor syndrome and have also been implicated in the development of a high proportion of sporadic PTCAs. Correlative immunohistochemical studies have revealed nuclear parafibromin immunoreactivity in adenomas but absence or partial loss of staining in PTCAs. While parafibromin immunohistochemistry represents an important step in the ability to diagnose PTCA, additional studies will be required to test the validity of this approach and to determine the roles of other genes in the development of these tumors.
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PMID:Challenging lesions in the differential diagnosis of endocrine tumors: parathyroid carcinoma. 1905 32

Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually resulting from intractable hypercalcemia. Inactivation of the HRPT2/CDC73 gene, encoding the putative tumor-suppressor protein parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, is a common, somatic event in most parathyroid cancers. Approximately 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation. Germline DNA analysis for HRPT2/CDC73 mutation is recommended in all patients with parathyroid cancer because of the potential benefit for first-degree relatives, who should nevertheless undergo serum calcium screening. The histopathologic diagnosis of parathyroid cancer is nonspecific unless vascular, lymphatic, capsular, or soft tissue invasion is seen, or metastases are clinically evident. Immunohistochemical analysis of parathyroid tumors for loss of parafibromin expression offers promise as a diagnostic tool. En bloc tumor resection offers the highest chance of cure in patients with suspected parathyroid carcinoma. No adjuvant chemotherapy regimen has yet proven effective, and the role of local adjuvant radiotherapy is being evaluated. Metastatic disease can be palliated with surgical debulking. Medical therapy with the calcimimetic cinacalcet and bisphosphonates can ameliorate hypercalcemia in patients with inoperable disease.
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PMID:Parathyroid cancer. 2116 77

The diagnosis of parathyroid carcinoma requires an invasive growth pattern or metastases detected at histopathological examination; unfortunately, not all carcinomas exhibit visible malignant properties at the initial assessment. Therefore, immunohistochemical markers have been sought for the recognition of parathyroid malignancy. In 2003, the Hyperparathyroidism 2 (HRPT2) gene was found mutated in the majority of sporadic parathyroid carcinomas investigated, and studies regarding the protein product parafibromin proposed loss of nuclear parafibromin as a highly sensitive marker for the detection of parathyroid carcinoma. Recent studies have not fully reproduced these findings, as subsets of carcinomas display positive parafibromin immunoreactivity, and fractions of adenomas demonstrate absent expression. Overall, parafibromin is a marker of value to the endocrine pathologist, but it cannot be recommended as a sole indicator of parathyroid carcinoma. Additional markers such as protein gene product 9.5 (PGP9.5) and adenomatous polyposis coli (APC) could complement parafibromin when assessing malignant potential of parathyroid tumours.
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PMID:Parafibromin as a diagnostic instrument for parathyroid carcinoma-lone ranger or part of the posse? 2119 63

Parathyroid cancer is a rare, clinically aggressive cause of primary hyperparathyroidism, and whether these malignancies generally evolve from pre-existing benign adenomas or arise de novo is unclear. Furthermore, while inactivation of the CDC73 (HRPT2) tumor suppressor gene, encoding parafibromin, is a major contributor, other genes essential to parathyroid carcinogenesis remain unknown. We sought to identify genomic regions potentially harboring such oncogenes or tumor suppressor genes, and to gain insight into the origins and molecular relationship of malignant versus benign parathyroid tumors. We performed genome-wide copy-number and loss of heterozygosity analysis using Affymetrix 50K SNP mapping arrays and/or comparative genomic hybridization on 16 primary parathyroid carcinomas, local recurrences or distant metastases, and matched normal controls, from 10 individuals. Recurrent regions of allelic loss were observed on chromosomes 1p, 3, and 13q suggesting that key parathyroid tumor suppressor genes are located in these chromosomal locations. Recurrent allelic gains were seen on chromosomes 1q and 16, suggesting the presence of parathyroid oncogenes on these chromosomes. Importantly, the most common alteration in benign parathyroid adenomas, loss of 11q, was not found as a recurrent change in the malignant parathyroid tissues. Molecular allelotyping using highly polymorphic microsatellite markers provided further confirmation that the prevalence of 11q loss is markedly and significantly lower in carcinomas as compared with adenomas. Our observations provide molecular support for the concept that sporadic parathyroid cancer usually arises de novo, rather than evolving from a pre-existing typical benign adenoma. Furthermore, these results help direct future investigation to ultimately determine which of the candidate genes in these chromosomal locations make significant contributions to the molecular pathogenesis of parathyroid cancer.
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PMID:Allelic imbalance in sporadic parathyroid carcinoma and evidence for its de novo origins. 2343 13

Parathyroid carcinoma has always been difficult to diagnose pathologically. In fact, most parathyroid tumors which are classified as carcinoma do not recur after excision, and most parathyroid tumors which actually metastasize or recur repeatedly in the neck are not recognized as malignant at first presentation. In 2002, germline HRPT2 (also known as CDC73) mutation was reported as the cause of hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant hereditary tumor syndrome associated with a lifetime risk of parathyroid carcinoma approaching 15 %. Subsequently, bi-allelic inactivation or mutation of HRPT2 has been reported in the majority of parathyroid carcinomas that actually behave in a malignant manner but very rarely in sporadic benign parathyroid disease. Furthermore, germline testing for HRPT2 mutation in patients presenting with parathyroid carcinoma often identifies occult HPT-JT syndrome even in the absence of a family history or other syndromic manifestations. HRPT2 mutation testing is not readily available, and loss of expression of parafibromin (the protein encoded by HRPT2) as determined by immunohistochemistry has been used as a surrogate marker of HRPT2 mutation. Immunohistochemistry for parafibromin can be technically difficult and has been deployed by different investigators with variable enthusiasm and success. However, proponents have found immunohistochemistry for parafibromin useful to definitively confirm a pathological diagnosis of parathyroid carcinoma, predict a worse outcome in definite parathyroid carcinomas, triage formal genetic testing for HPT-JT syndrome, and predict the outcome of histologically atypical parathyroid adenomas.
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PMID:Understanding the genetic basis of parathyroid carcinoma. 2440 36

Parathyroid carcinoma is a rare endocrine malignancy that is typically difficult to diagnose at presentation. Here, we report a 63 year-old man who had symptomatic hypercalcemia. Investigations revealed a thyroid nodule and a lateral neck mass that was biopsied and diagnosed as "suspicious for a neuroendocrine neoplasm." He underwent total thyroidectomy with central and left neck node dissection. Histology and immunohistochemistry revealed an intrathyroidal angioinvasive parathyroid carcinoma with lymph node metastases. The tumor showed loss of parafibromin expression; germline testing revealed no pathogenic germline variants of CDC73, suggesting either a cryptic germline variant or a sporadic malignancy. Multiple pulmonary nodules consistent with metastatic disease explained persistent hypercalcemia and the patient was treated with denosumab as well as Sorafenib resulting in early regression of the lung nodules. This case illustrates an unusual parathyroid carcinoma with respect to anatomic presentation and the importance of complete pathological workup in securing the diagnosis. The management of these rare malignancies is discussed.
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PMID:Intrathyroidal Parathyroid Carcinoma: An Atypical Thyroid Lesion. 3045 68

Background: Parathyroid carcinoma is rare, representing <1% of primary hyperparathyroidism cases. Methods: Retrospective data of patients referred for evaluation of parathyroid disease between 2001 and 2018 were reviewed. The goal was to describe the clinical presentation, histopathologic characteristics, and treatment outcomes of parathyroid carcinoma. Results: We identified 8 cases of parathyroid carcinoma from the outpatient practice of a quaternary care Endocrine Oncology practice in Toronto, Canada. The clinical presentation was as follows: 5/8 cases (62.5%) of symptomatic hypercalcemia and 3/8 cases (37.5%) of a suspicious thyroid nodule. Hypercalcemia was evident in all 7 cases with pre-operative calcium measurements. Histopathologic features included: vascular invasion in 7/8 cases (87.5%) and immunohistochemical loss of either parafibromin, retinoblastoma, or p27 in all 8 cases. Additional treatment included: external beam radiotherapy in 5/8 cases (62.5%), chemotherapy for 2/8 patients (25%), and additional surgery for 3/8 patients (37.5%). Only 2 patients (25%) had long-term remission following surgical treatment, and the others had either persistent (3 patients) or recurrent disease (3 patients). Five patients developed metastatic disease, all involving lung. In one of two patients treated with Sorafenib there was evidence of regression of lung metastases. One patient died of disease progression. Conclusion: In this series of patients with parathyroid carcinoma largely presenting with symptomatic hypercalcemia and angioinvasive disease, only a minority achieved a durable remission. Lung was the most common site of distant metastasis. Surgery led to remission in two cases, but none of the six patients with persistent or recurrent disease ultimately achieved disease remission.
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PMID:The Clinicopathological Spectrum of Parathyroid Carcinoma. 3170 75