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Endocrine Pathology Mar 2021The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually... (Review)
Review
The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate endpoint for any molecular marker discovered through laboratory investigations is to be introduced in clinical routine practice and guide the surgical pathologist in terms of diagnostics and prognostication. For parathyroid tumors, the two main diagnostic challenges include the distinction between parathyroid adenoma and parathyroid carcinoma, as well as the pinpointing of hereditable disease for familial screening purposes. While numerous markers on genetic, epigenetic, and protein levels have been proposed as discriminative in these aspects, this review aims to condense the scientific coverage of these enigmatic topics and to propose a focused surgical pathology approach to the subject.
Topics: Animals; Epigenesis, Genetic; Epigenomics; Genomics; Humans; Parathyroid Neoplasms; Pathology, Surgical
PubMed: 33269427
DOI: 10.1007/s12022-020-09656-9 -
The Journal of Clinical Endocrinology... Sep 2023Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and...
CONTEXT
Parathyroid cancer (PC) is a rare endocrine neoplasm with high mortality. While surgery is the treatment for patients with the disease, recurrence rates are high, and patients usually succumb to severe hypercalcemia. There is no effective systemic therapy for the disease.
OBJECTIVE
To investigate for novel genes causing parathyroid cancer.
METHODS
We analyzed the germline DNA of 17 patients with "sporadic" PC and 3 with atypical parathyroid tumors (APTs) who did not have germline CDC73 or MEN1 pathogenic variants. Sequencing of available tumor tissue from 14 patients with PC and 2 with APT was also performed (including 2 patients with no available germline DNA). In addition, sporadic parathyroid adenomas from 74 patients were analyzed for FLCN variants.
RESULTS
We identified germline FLCN variants in 3 unrelated patients with PC. The 2 frameshift variants have been described in patients with Birt-Hogg-Dubé (BHD) syndrome, while the pathogenicity of the missense variant c.124G > C (p.G42R) has not been definitively established. Functional analysis of the missense variant showed a potential effect on posttranslational modification. All 3 patients with germline FLCN variants were noted to have renal cysts and 2 had lung cysts, features associated with BHD syndrome. Somatic FLCN variants were identified in tumors from 2 (1 APT) of 16 patients with PC/APT and in none of the 74 sporadic parathyroid adenomas. No second hits in FLCN were noted on sequencing; however, loss of heterozygosity at the locus was demonstrated in 2 of 3 patients with the identified germline FLCN variant.
CONCLUSION
The finding of FLCN variants associated with PC may provide the foundation for the development of therapy for this malignancy.
Topics: Humans; Parathyroid Neoplasms; Birt-Hogg-Dube Syndrome; Kidney Neoplasms; Germ-Line Mutation; DNA; Cysts; Proto-Oncogene Proteins; Tumor Suppressor Proteins
PubMed: 36935552
DOI: 10.1210/clinem/dgad136 -
The Oncologist 2010Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of... (Review)
Review
Parathyroid carcinoma is an indolent but ultimately life-threatening malignancy. Due to the lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism (PHPT), this disease is often misdiagnosed as parathyroid adenoma. Therefore, a high index of suspicion preoperatively and early intraoperative recognition with en bloc surgical resection are crucial for favorable outcome. Owing to the rarity of the disease, little is known about the molecular pathogenesis of parathyroid carcinoma. Here, we review the literature to present current understanding of the disease and provide new information on gene expression and use of intraoperative parathyroid hormone (PTH) monitoring in the surgical management of this rare malignancy. Specifically, using microarray transcriptome analysis of an unequivocal case of parathyroid carcinoma and a biopsy from the same patient's normal parathyroid gland, we identify APP, CDH1, KCNJ16, and UCHL1 as differentially expressed genes in parathyroid carcinoma. Further, using case records from four cases of unequivocal parathyroid carcinoma, we compared intraoperative PTH kinetics of these patients to 475 patients with benign PHPT, and show that intraoperative PTH monitoring is accurate in predicting postoperative normocalcemia in initial en bloc operations for parathyroid carcinoma.
Topics: Biopsy; Cinacalcet; Diagnostic Imaging; Gene Expression; Humans; Hypercalcemia; Hyperparathyroidism; Immunohistochemistry; Intraoperative Care; Monitoring, Physiologic; Mutation; Naphthalenes; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Risk Factors; Tumor Suppressor Proteins
PubMed: 20051478
DOI: 10.1634/theoncologist.2009-0185 -
Frontiers in Endocrinology 2022Parathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most... (Review)
Review
INTRODUCTION
Parathyroid carcinoma (PC) is a very rare endocrine malignancy occurring in less than 1% of all cases of primary hyperparathyroidism (pHPT). The liver is the second most common target organ for distant metastases of PC, but no guidelines are available for the diagnosis and treatment of liver metastases. In this study, we attempted to summarize the characteristics of the diagnosis and treatment of liver metastases based on our patients and other cases reported in the literature.
MATERIALS AND METHODS
The files of all patients diagnosed with PC with liver metastases summarized at our center between 2000 and 2022 were reviewed, and three datasets from Medline, Web of Science, and Embase were systematically searched to identify relevant articles.
RESULTS
Three patients with liver metastases from our center and 11 patients from the literature were included in the study. All patients had pHPT with borderline remission of hypercalcemia after each operation. A total of 71.4% of the patients' liver lesions were found by abdominal CT scans, while 35.7% were found by MRI, PET-CT, and fine-needle aspiration biopsy (FNAB), which were also helpful for diagnosis. Eight of nine patients (88.9%) who underwent surgery, radiofrequency ablation (RFA), or transcatheter arterial embolization (TAE) were alive, and only one postoperative patient died after a follow-up of 60 months.
CONCLUSIONS
PC is a rare malignant tumor prone to recurrence and metastasis, and postoperative reviews should be carried out routinely. Abnormally elevated parathyroid hormone (PTH) and serum calcium can indicate recurrence or metastasis. Enhanced CT and MRI can provide valuable support for the diagnosis of liver metastases, but whether [18F]FDG-PET-CT, [18F]FCH-PET-CT, or [11C]choline-PET-CT can be used as a diagnostic basis requires further study. Resection of liver metastases, segmental hepatectomy, or RFA can significantly improve patients' symptoms.
Topics: Humans; Liver Neoplasms; Parathyroid Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 36303876
DOI: 10.3389/fendo.2022.982972 -
International Journal of Surgery... 2011Parathyroid carcinoma is a malignant neoplasm affecting 05-2 per cent of all patients with primary hyperparathyroidism that was first described by de Quevain in 1904. To... (Review)
Review
Parathyroid carcinoma is a malignant neoplasm affecting 05-2 per cent of all patients with primary hyperparathyroidism that was first described by de Quevain in 1904. To day it continues to defy diagnosis and treatment. It is difficult to diagnose in part because of its rarity, lack of definitive diagnostic markers and overlapping clinical features of benign primary hyperparathyroidism. As a result initial surgical treatment is inadequate essentially leading to disease recurrence where complete cure is unlikely. En bloc surgical resection remains the only curative treatment, and high priorities are improving diagnostic methods, and clinical staging for resection once the disease is suspected. Margin status at resection is related to prognosis. Thus, a trend towards aggressive surgical management has improved outcomes. The recurrence rate of parathyroid carcinoma is as high as 80% with survival rates <50% at 10 years. Results of chemotherapy are disappointing. However, recent trials using radiation therapy are promising, but require further study.
Topics: Carcinoma; Humans; Parathyroid Neoplasms
PubMed: 20887820
DOI: 10.1016/j.ijsu.2010.09.003 -
Revista Medica de Chile Mar 2021Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic...
Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.
Topics: Female; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Neoplasm Recurrence, Local; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy
PubMed: 34479319
DOI: 10.4067/s0034-98872021000300399 -
BMJ Case Reports Mar 2015Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical...
Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels.
Topics: Adenoma; Adult; Female; Humans; Hyperparathyroidism; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Parathyroidectomy; Treatment Outcome
PubMed: 25737222
DOI: 10.1136/bcr-2014-208277 -
Endokrynologia Polska 2022Parathyroid carcinoma is a rare condition and accounts for < 1% of cases of sporadic primary hyperparathyroidism. It accounts for 0.005% of all cancers. Often the...
INTRODUCTION
Parathyroid carcinoma is a rare condition and accounts for < 1% of cases of sporadic primary hyperparathyroidism. It accounts for 0.005% of all cancers. Often the differentiation between adenoma and carcinoma is challenging and requires multidisciplinary cooperation. Complete surgical resection is the treatment of choice. We present a retrospective analysis of 29 patients who were surgically treated for parathyroid cancer.
MATERIAL AND METHODS
Between the years 1983 and 2018, 71 (7.0%) patients were treated for suspicion of parathyroid cancer among a group of 1019 operated for primary hyperparathyroidism.
RESULTS
We confirmed the diagnosis of parathyroid cancer in 29 (2.8%) patients, 12 men and 17 women, aged 27 to 77 years, mean 55.1 years. That constituted 43.9% of the 71 patients with initial suspicion of cancer diagnosis. All operated patients were under long-term observation.
CONCLUSIONS
A diagnosis of parathyroid carcinoma should always be considered during surgery in patients diagnosed with primary hyperparathyroidism, especially in patients with severe hypercalcaemia, significantly enlarged neck circumference, and concomitant diseases of the renal and skeletal system. Parathyroid carcinoma is rarely definitively diagnosed preoperatively or even intraoperatively, and the final diagnosis can be made exclusively after operation. The optimal treatment is a complete surgical resection at a reference centre - specialized in parathyroid surgery - to improve outcomes and provide the best chance of recovery.
Topics: Adenoma; Adult; Aged; Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Neoplasms; Parathyroidectomy; Retrospective Studies
PubMed: 35156702
DOI: 10.5603/EP.a2022.0003 -
Head and Neck Pathology Dec 2018Metastases to the head and neck organs are uncommon, potentially representing the initial presentation of an occult malignancy. Single case reports and small series... (Review)
Review
Metastases to the head and neck organs are uncommon, potentially representing the initial presentation of an occult malignancy. Single case reports and small series report metastases to the parathyroid gland, but there is no large review of the literature on secondary tumors involving the parathyroid glands. A review of the English literature between 1950 and 2017 was performed of all metastases or secondary involvement of the parathyroid glands. One hundred and twenty-seven cases of metastatic tumors were reported, although potentially significantly unrepresented in autopsy series (parathyroid glands are not routinely examined) and due to reporting bias. Women were affected more commonly than men (5.8:1; 99 vs. 17, respectively), with a mean age at presentation of 58.5 years, when reported. The most common primary sites of malignancies that metastasized to the parathyroid glands were breast carcinomas (66.9%, n = 85), melanoma (11.8%, n = 15), and lung carcinoma (5.5%, n = 7), with carcinomas representing 86.6% of metastases. Metastases were nearly always identified as part of widely metastatic disease, with only five (3.2%) cases reported as isolated metastases. Tumor-to-tumor metastases comprised 5.5% of all metastases to the parathyroid glands (metastases to parathyroid adenoma). A significant clinical finding of metastases to the parathyroid glands was the development of deranged calcium homeostasis, well beyond the 9 (7.2%) cases with primary parathyroid gland disease present. Although concurrent conditions (renal disease; bone metastases) may partially affect calcium metabolism, the onset of calcium derangement seemed to coincide with parathyroid gland metastases and not systemic disease. In summary, metastases to the parathyroid glands are uncommon, potentially under-recognized in patients who have otherwise widely metastatic tumors. Women are affected more often than men, with breast carcinomas (66.9%) and melanoma (11.8%) the most common primary tumors. Calcium homeostasis is affected, probably as a result of parathyroid gland parenchymal destruction.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Parathyroid Neoplasms
PubMed: 28875280
DOI: 10.1007/s12105-017-0850-x -
Head & Neck Mar 2023Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively,... (Review)
Review
Intrathyroidal parathyroid adenomas (IPAs) are a rare cause of primary hyperparathyroidism. They are often difficult to localize preoperatively and intraoperatively, making diagnosis and treatment challenging. Current data on IPAs are sparse and fragmented in the literature. This makes it difficult to compare the effectiveness of different imaging and surgical techniques. To address this issue, this scoping review maps the literature on IPAs, focusing on four domains: clinical presentation, current localization methods, different surgical techniques, and histopathological features. A search of MEDLINE, Embase, and the Cochrane Library was conducted, with 19 studies meeting the inclusion criteria. The characteristics of IPAs on ultrasound, fine-needle aspiration, CT, MRI, sestamibi-based techniques, and selective venous sampling are summarized. Emerging imaging modalities, including autofluorescence, are introduced. Surgical methods and intraoperative factors that correlate with high success rates for removal are highlighted. This review also identifies gaps in knowledge to guide further research into this area.
Topics: Humans; Parathyroid Neoplasms; Parathyroid Glands; Diagnostic Imaging; Radiopharmaceuticals; Ultrasonography; Adenoma; Technetium Tc 99m Sestamibi
PubMed: 36563301
DOI: 10.1002/hed.27287