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Frontiers in Endocrinology 2023The malignant potential and molecular signature of atypical parathyroid adenoma (APA) remain elusive. Data from Asia are still lacking.
CONTEXT
The malignant potential and molecular signature of atypical parathyroid adenoma (APA) remain elusive. Data from Asia are still lacking.
DESIGN AND SETTING
This was a retrospective study on a large APA cohort in a single center from mainland China.
METHODS
A total of 320 patients with primary hyperparathyroidism (PHPT), containing 79 APA, 79 Parathyroid cancer (PC) and 162 benign lesions cases, were enrolled after surgery for collection of clinical data and genetic analysis.
RESULTS
APA patients showed earlier mean onset age than benign group (46.9 ± 17.1 vs. 52.0 ± 14.3 yrs). Less bone involvement and gastrointestinal symptoms were presented in APA compared to PC (35.4% vs. 62.0%, and 17.7% vs. 41.8%), while more urolithiasis was seen in APA than in benign lesions (57.0% vs. 29.6%). The APA group had moderate hypercalcemia (mean 3.02 ± 0.44mmol/L) with elevated serum PTH (median 593.0pg/ml) and proportion of hypercalcemic crisis as 22.8%, all higher than those of benign lesions but lower than those of PC group. The recurrence/no remission rate of the APA group was significantly lower than that of the PC and similar to the benign group (5.1% vs. 31.6% vs. 3.1%). Germline CDC73 mutation was the most common molecular abnormality in both PC and APA subjects. APA patients with nonsynonymous germline variants showed earlier onset age (28.5 ± 16.9 vs. 48.1 ± 17.7 yrs) and more cases developing no remission/recurrence (25.0% vs. 0.0%).
CONCLUSIONS
Patients with APA presented clinical and biochemical characteristics much less severe than PC and resembling the benign neoplasms, with a relatively good prognosis. Germline gene variations were associated with earlier onset and probably more recurrence of PHPT in APA.
Topics: Humans; Parathyroid Neoplasms; Retrospective Studies; East Asian People; Germ-Line Mutation; Adenoma; Precancerous Conditions; Hypercalcemia
PubMed: 36777354
DOI: 10.3389/fendo.2023.1027598 -
Indian Journal of Cancer 2004Parathyroid carcinoma constitutes less than 1% of primary hyperparathyroidism. The exact etiology is not known. Prior radiation to neck, chronic renal failure and... (Review)
Review
Parathyroid carcinoma constitutes less than 1% of primary hyperparathyroidism. The exact etiology is not known. Prior radiation to neck, chronic renal failure and genetic factors are thought to play a role. The male to female ratio is one. Parathyroid carcinomas are slow growing, have a tendency to recur locally and metastasize late. 95% of parathyroid carcinomas are functioning. The major distinguishing features of malignant hyperparathyroidism are presence of a palpable mass in the neck and features of severe hypercalcemia. By far the most important test to diagnose primary hyperparathyroidism is serum level of Immunoreactive PTH. The diagnosis of primary hyperparathyroidism is essentially clinical and biochemical. Biopsy is not necessary before definitive surgery. CT scan appears to be the best investigation for detecting the primary tumor, its local extent and metastases. Most of the symptoms are attributable to hypercalcemia, which needs to be treated aggressively. Early surgery with 'en bloc' resection of the tumor is the only potentially curative treatment. Parathyroid carcinoma is traditionally said to be resistant to radiotherapy. Various chemotherapeutic agents have been used with partial anecdotal responses. The 5-year survival is about 50% and 10-year survival varies from 13-49%.
Topics: Carcinoma; Humans; Neoplasm Staging; Parathyroid Neoplasms
PubMed: 15318009
DOI: No ID Found -
European Journal of Endocrinology Sep 2019PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary... (Review)
Review
PARAT, a new European Society of Endocrinology program, aims to identify unmet scientific and educational needs of parathyroid disorders, such as primary hyperparathyroidism (PHPT), including parathyroid cancer (PC), and hypoparathyroidism (HypoPT). The discussions and consensus statements from the first PARAT workshop (September 2018) are reviewed. PHPT has a high prevalence in Western communities, PHPT has a high prevalence in Western communities, yet evidence is sparse concerning the natural history and whether morbidity and long-term outcomes are related to hypercalcemia or plasma PTH concentrations, or both. Cardiovascular mortality and prevalence of low energy fractures are increased, whereas Quality of Life is decreased, although their reversibility by treatment of PHPT has not been convincingly demonstrated. PC is a rare cause of PHPT, with an increasing incidence, and international collaborative studies are required to advance knowledge of the genetic mechanisms, biomarkers for disease activity, and optimal treatments. For example, ~20% of PCs demonstrate high mutational burden, and identifying targetable DNA variations, gene amplifications and gene fusions may facilitate personalized care, such as different forms of immunotherapy or targeted therapy. HypoPT, a designated orphan disease, is associated with a high risk of symptoms and complications. Most cases are secondary to neck surgery. However, there is a need to better understand the relation between disease biomarkers and intellectual function, and to establish the role of PTH in target tissues, as these may facilitate the appropriate use of PTH substitution therapy. Management of parathyroid disorders is challenging, and PARAT has highlighted the need for international transdisciplinary scientific and educational studies in advancing in this field.
Topics: Education; Endocrinology; Europe; Humans; Hyperparathyroidism, Primary; Parathyroid Diseases; Parathyroid Hormone; Parathyroid Neoplasms; Societies, Medical
PubMed: 31176307
DOI: 10.1530/EJE-19-0316 -
Journal of Surgical Oncology Mar 2005Parathyroid carcinoma is an uncommon malignancy. It accounts for less than 1% of cases of primary hyperparathyroidism (HPT). It is manifested by severe hypercalcemia and... (Review)
Review
Parathyroid carcinoma is an uncommon malignancy. It accounts for less than 1% of cases of primary hyperparathyroidism (HPT). It is manifested by severe hypercalcemia and up to 50% of patients will have concomitant kidney or bone disease. The etiology of parathyroid carcinoma is unknown, however, the recently discovered HRPT2 gene, a tumor suppressor gene encoding for the protein parafibromin, has been implicated in the pathogenesis. Identification of inactivating germ-line mutations in HRPT2 has significant implications for diagnosis and management. This article summarizes the genetic aspects of parathyroid carcinoma, reviews its clinical manifestations, and outlines the principles of surgical therapy, the indications for adjuvant therapy, and the use of bisphosphonate and calcimimetic agents for management of hypercalcemia.
Topics: Carcinoma; Cyclin D1; Genes, Retinoblastoma; Genes, Tumor Suppressor; Germ-Line Mutation; Humans; Hypercalcemia; Hyperparathyroidism; Parathyroid Hormone; Parathyroid Neoplasms; Proteins; Proto-Oncogene Proteins; Tumor Suppressor Proteins
PubMed: 15719375
DOI: 10.1002/jso.20182 -
The Journal of International Medical... Jun 2022An uncommon cause of primary hyperparathyroidism is a cystic parathyroid adenoma. This paper describes two patients with hypercalcemia and right knee disease. Their... (Review)
Review
An uncommon cause of primary hyperparathyroidism is a cystic parathyroid adenoma. This paper describes two patients with hypercalcemia and right knee disease. Their serum calcium concentration was high, phosphorus concentration was low, and parathyroid hormone (PTH) concentration was high. Ultrasound and computed tomography scans of the neck indicated a cystic mass near the thyroid. Parathyroid scintigraphy showed no focal uptake in one patient and low tracer concentration in the cystic mass in the other patient. Following resection of the cystic masses, both were pathologically confirmed to be a cystic parathyroid adenoma with predominantly cystic degeneration. The calcium and PTH concentrations gradually decreased to the reference range. Both patients were stable at their last follow-up. The diagnosis of a functional cystic parathyroid adenoma is highly challenging because of the different clinical manifestations and negative result on parathyroid tracer scintigraphy. For patients with high serum calcium and PTH concentrations and a cystic mass in the neck, resection of the mass and subsequent postoperative pathological diagnosis is necessary even if the clinical diagnosis of a parathyroid adenoma cannot be confirmed preoperatively. Decreases in the PTH and serum calcium concentrations indicate successful resection of a functional parathyroid adenoma.
Topics: Calcium; Humans; Hypercalcemia; Neck; Parathyroid Hormone; Parathyroid Neoplasms
PubMed: 35734999
DOI: 10.1177/03000605221106419 -
Bioscience Reports Apr 2019The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We... (Meta-Analysis)
Meta-Analysis
The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We performed a meta-analysis to examine the rate of loss of parafibromin expression from 18 eligible studies. In addition, a diagnostic test accuracy review was conducted to investigate the diagnostic role of parafibromin in PC. The rates of loss of parafibromin expression were 0.522 (95% CI: 0.444-0.599), 0.291 (95% CI: 0.207-0.391), 0.027 (95% CI: 0.011-0.064), and 0.032 (95% CI: 0.008-0.119) in PC, atypical parathyroid adenoma (APA), parathyroid adenoma (PA), and parathyroid hyperplasia, respectively. In the diagnostic test accuracy review for diagnosis of PC, the pooled sensitivity and specificity of parafibromin IHC was 0.53 (95% CI: 0.46-0.59) and 0.96 (95% CI: 0.95-0.97), respectively. The diagnostic odds ratio and the area under curve on summary receiver operating characteristic curve was 25.31 (95% CI: 8.91-71.87) and 0.7954, respectively. In addition, the meta-analysis demonstrated that loss of parafibromin expression was significantly correlated with worse disease-free survival (hazard ratio: 2.832; 95% CI: 1.081-7.421). Loss of parafibromin IHC expression was significantly higher in PC than in APA, PA, and parathyroid hyperplasia. Parafibromin IHC could be useful for diagnosis and prediction of prognosis of PC in daily practice.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Hyperplasia; Immunohistochemistry; Parathyroid Glands; Parathyroid Neoplasms; Prognosis; ROC Curve; Tumor Suppressor Proteins
PubMed: 30926677
DOI: 10.1042/BSR20181778 -
Endocrine Journal Aug 2003The incidence of parathyroid carcinoma is rare. We recently encountered a case of double carcinoma, located in the right and left upper parathyroid glands. A 67-year old...
The incidence of parathyroid carcinoma is rare. We recently encountered a case of double carcinoma, located in the right and left upper parathyroid glands. A 67-year old man came to the Teikyo University Hospital because of his bilateral parathyroid masses with hypercalcemia and high parathyroid hormone (PTH). Preoperative diagnoses were parathyroid adenoma in the left lobe and papillary thyroid carcinoma or parathyroid carcinoma in the right lobe. First, the left tumor was removed; however, iPTH was still high. The right mass was then resected and iPTH fell to normal range. Histological examination revealed both tumors were parathyroid carcinoma. To the best of our knowledge, this is the first report of double parathyroid carcinoma confirmed histologically.
Topics: Aged; Carcinoma; Humans; Hypercalcemia; Male; Parathyroid Hormone; Parathyroid Neoplasms
PubMed: 14599124
DOI: 10.1507/endocrj.50.477 -
Journal of Bone and Mineral Research :... Jan 2019We review advancing and overlapping stages for our understanding of the expressions of six hyperparathyroid (HPT) syndromes: multiple endocrine neoplasia type 1 (MEN1)... (Review)
Review
We review advancing and overlapping stages for our understanding of the expressions of six hyperparathyroid (HPT) syndromes: multiple endocrine neoplasia type 1 (MEN1) or type 4, multiple endocrine neoplasia type 2A (MEN2A), hyperparathyroidism-jaw tumor syndrome, familial hypocalciuric hypercalcemia, neonatal severe primary hyperparathyroidism, and familial isolated hyperparathyroidism. During stage 1 (1903 to 1967), the introduction of robust measurement of serum calcium was a milestone that uncovered hypercalcemia as the first sign of dysfunction in many HPT subjects, and inheritability was reported in each syndrome. The earliest reports of HPT syndromes were biased toward severe or striking manifestations. During stage 2 (1959 to 1985), the early formulations of a syndrome were improved. Radioimmunoassays (parathyroid hormone [PTH], gastrin, insulin, prolactin, calcitonin) were breakthroughs. They could identify a syndrome carrier, indicate an emerging tumor, characterize a tumor, or monitor a tumor. During stage 3 (1981 to 2006), the assembly of many cases enabled recognition of further details. For example, hormone non-secreting skin lesions were discovered in MEN1 and MEN2A. During stage 4 (1985 to the present), new genomic tools were a revolution for gene identification. Four principal genes ("principal" implies mutated or deleted in 50% or more probands for its syndrome) (MEN1, RET, CASR, CDC73) were identified for five syndromes. During stage 5 (1993 to the present), seven syndromal genes other than a principal gene were identified (CDKN1B, CDKN2B, CDKN2C, CDKN1A, GNA11, AP2S1, GCM2). Identification of AP2S1 and GCM2 became possible because of whole-exome sequencing. During stages 4 and 5, the newly identified genes enabled many studies, including robust assignment of the carriers and non-carriers of a mutation. Furthermore, molecular pathways of RET and the calcium-sensing receptor were elaborated, thereby facilitating developments in pharmacotherapy. Current findings hold the promise that more genes for HPT syndromes will be identified and studied in the near future. © 2018 American Society for Bone and Mineral Research.
Topics: History, 20th Century; History, 21st Century; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Neoplasm Proteins; Parathyroid Neoplasms; Syndrome
PubMed: 30536424
DOI: 10.1002/jbmr.3650 -
The Israel Medical Association Journal... Jun 2003
Topics: Adenoma; Gamma Rays; Humans; Minimally Invasive Surgical Procedures; Monitoring, Intraoperative; Parathyroid Neoplasms; Parathyroidectomy; Radiography, Interventional; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Treatment Outcome
PubMed: 12841019
DOI: No ID Found -
European Journal of Radiology Sep 2016This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive...
OBJECTIVES
This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method.
METHODS
This prospective study examined 57 consecutive patients with biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma identified by ultrasound and confirmed by at least one of the following: surgical resection, positive Technetium-99m Sestamibi Scintigraphy (MIBI) scan, or fine needle aspiration biopsy with positive PTH washout (performed only in MIBI negative patients). Vascularity and shear wave elastography were performed for all patients. Parathyroid adenoma stiffness was measured as shear wave velocity in meters per second.
RESULTS
The median (range) pre-surgical value for PTH and calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37 patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy, and an adenoma was confirmed in all. The median (range) shear wave velocity for all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70). The shear wave velocity of the adenomas was independent of adenoma size, serum parathyroid hormone concentration, or plasma parathyroid hormone concentration.
CONCLUSIONS
Tissue elasticity of parathyroid adenoma is significantly lower than thyroid tissue. B-mode features and distinct vascularity pattern are helpful tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography may provide valuable information in diagnosing parathyroid adenoma.
Topics: Adult; Aged; Aged, 80 and over; Elasticity Imaging Techniques; Female; Humans; Male; Middle Aged; Parathyroid Glands; Parathyroid Neoplasms; Prospective Studies; Reproducibility of Results; Young Adult
PubMed: 27501893
DOI: 10.1016/j.ejrad.2016.06.009