Parathyroid Pathology: Hyperparathyroidism and Parathyroid Tumors

2010 ◽  
Vol 134 (11) ◽  
pp. 1639-1644 ◽  
Author(s):  
Diane Carlson
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Carcinoma ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Outpatient Setting ◽  
Cancer Center ◽  
Parathyroid Tumors ◽  
Parathyroid Adenomas ◽  
Parathyroid Lesions ◽  
Hrpt2 Gene

Abstract Context.—Primary hyperparathyroidism is the most common cause of hypercalcemia in the outpatient setting. Parathyroid adenomas are common, unlike other parathyroid tumors. This review presents a brief summary of current updates in parathyroid pathology. Objective.—To review parathyroid development and discuss issues in hyperparathyroidism and diagnosis of parathyroid lesions, including the application of immunohistochemistry and molecular biology. Data Sources.—Current texts, PubMed (National Library of Medicine) articles, and Memorial Sloan-Kettering Cancer Center archives. Conclusions.—Primary hyperparathyroidism is most commonly seen with sporadic adenomas, followed by hyperplasia, multiple adenomas, and carcinoma. Autosomal dominant familial hyperparathyroidism syndromes should be considered in the evaluation of patients with parathyroid lesions, particularly in association with parathyroid carcinoma. While the incidence of parathyroid carcinoma is quite low, it is seen with a greater frequency in those patients with hyperparathyroidism-jaw tumor syndrome. Inactivation of the tumor suppressor gene HRPT2 can be identified in a large number of parathyroid carcinomas. Hence, germline HRPT2 gene mutations may reflect unrecognized syndromic patients.

Detection of parathyroid adenomas with 4DCT: Towards a true four-dimensional technique

2021 ◽  
Author(s):  
Steven Raeymaeckers ◽  
Yannick De Brucker ◽  
Tim Vanderhasselt ◽  
Nico Buls ◽  
Johan De Mey
Keyword(s):  
Primary Hyperparathyroidism ◽  
Thyroid Tissue ◽  
Motion Artifacts ◽  
P Value ◽  
Normal Thyroid Tissue ◽  
Dose Length Product ◽  
Normal Thyroid ◽  
Parathyroid Adenomas ◽  
Parathyroid Lesions ◽  
Over Time

Abstract Background. 4DCT is a commonly performed examination in the management of primary hyperparathyroidism, combining three-dimensional imaging with enhancement over time as the fourth dimension. We propose a novel technique consisting of 16 different contrast phases, instead of three or four different phases. The main aim of this study was to see if this protocol allows for the detection of parathyroid adenomas within dose limits. Our secondary aim was examining the enhancement of parathyroid lesions over time.Methods. For this prospective study, we included 15 patients with primary hyperparathyroidism prior to surgery. We obtain a 4DCT with 16 different phases: an unenhanced phase followed by 11 consecutive arterial phases and 4 venous phases. Centered on the thyroid, continuous axial scanning is performed over a fixed 8cm or 16cm coverage volume after start of contrast administration.Results. In all patients an enlarged parathyroid can be demonstrated, mean lesion size is 13.6mm. Mean peak arterial peak enhancement for parathyroid lesions is 384 HU compared to 333 HU for the normal thyroid. No statistical difference could be found. Time to peak (TTP) is significantly earlier for parathyroid adenomas compared to normal thyroid tissue: 30.8s versus 32.3s (p value 0.008). Mean Slope of Increase (MSI) of the enhancement curve is significantly steeper compared to normal thyroid tissue: 29.8% versus 22.2% (p value 0.012). Mean dose length product was 890.7 mGy.cm with a calculated effective dose of 6.7 mSv.Conclusion. We propose a feasible 4DCT scanning-protocol for the detection of parathyroid adenomas. We manage to obtain a multitude of phases, allowing for a dynamic evaluation within an acceptable exposure range when compared to classic helical 4DCT. Our 4DCT protocol may allow for a better visualization of the pattern of enhancement of parathyroid lesions, as enhancement over time curves can be drawn. This way wash-in and wash-out of contrast in suspected lesions can be readily demonstrated. Motion artifacts are less problematic as multiple phases are available.

scholarly journals Parathyroid Imaging by 18F-Fluorocholine PET/CT in Patients With Primary Hyperparathyroidism and Inconclusive Conventional Methods: Clinico-Pathological Correlations

2018 ◽  
pp. S551-S557 ◽  
Author(s):  
K. ZAJÍČKOVÁ ◽  
D. ZOGALA ◽  
J. KUBINYI
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Glands ◽  
Emission Tomography ◽  
Positron Emission ◽  
Pet Ct ◽  
Parathyroid Adenomas ◽  
Parathyroid Lesions ◽  
Mean Size ◽  
Parathyroid Imaging ◽  
Mibi Scintigraphy

18F-fluorocholine positron emission tomography/computed tomography (FCH) was performed after inconclusive neck ultrasound and 99Tc-sestaMIBI SPECT (MIBI) scintigraphy in patients with primary hyperparathyroidism (PHPT) to localize abnormal parathyroid glands before surgery. The results were retrospectively evaluated and compared to postoperative histopathological findings. 13 patients with PHPT were enrolled (mean age 64.3 years, preoperative calcium 2.74 mmol/l and parathyroid hormone 114.6 ng/l). FCH localized hyperfunctioning parathyroid glands in 12 patients of 13 (per patient sensitivity 92 % and positive predictive value (PPV) 100 %). Fourteen parathyroid lesions (11 adenomas, 3 hyperplastic glands) were resected with a mean size of 11.9 mm (per lesion sensitivity 93 % and PPV 81 %). Four adenomas and one hyperplastic gland were composed of only chief cells, whereas five lesions contained both chief and oxyphil cells. In three patients an exclusively oxyphil adenoma was found, surprisingly with negative MIBI scintigraphy in spite of a high mitochondria content in the oxyphil parathyroid cells. 12 of 13 patients had thyroid disease. In our limited study sample, FCH correctly identified parathyroid adenomas and/or hyperplastic glands in 92 % of patients with previously inconclusive conventional imaging. Unlike MIBI, FCH successfully localized small, hyperplastic and multiple hyperfunctioning parathyroid glands, irrespective of their histopathological composition.

scholarly journals Somatostatin receptor expression in parathyroid neoplasms

2019 ◽  
Vol 8 (8) ◽  
pp. 1213-1223 ◽  
Author(s):  
Sara Storvall ◽  
Helena Leijon ◽  
Eeva Ryhänen ◽  
Johanna Louhimo ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Carcinoma ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Expression ◽  
Benign Tumors ◽  
Receptor Subtypes ◽  
Receptor Imaging ◽  
Somatostatin Receptor Subtypes ◽  
Parathyroid Adenomas

Introduction Parathyroid carcinoma represents a rare cause of primary hyperparathyroidism. Distinguishing carcinoma from the benign tumors underlying primary hyperparathyroidism remains challenging. The diagnostic criteria for parathyroid carcinoma are local and/or metastatic spreading. Atypical parathyroid adenomas share other histological features with carcinomas but lack invasive growth. Somatostatin receptors are commonly expressed in different neuroendocrine tumors, but whether this also holds for parathyroid tumors remains unknown. Aim Our aim is to examine the immunohistochemical expression of somatostatin receptor 1–5 in parathyroid typical adenomas, atypical adenomas and carcinomas. Methods We used a tissue microarray construct from a nationwide cohort of parathyroid carcinomas (n = 32), age- and gender-matched typical parathyroid adenomas (n = 72) and atypical parathyroid adenomas (n = 27) for immunohistochemistry of somatostatin receptor subtypes 1–5. We separately assessed cytoplasmic, membrane and nuclear expression and also investigated the associations with histological, biochemical and clinical characteristics. Results All parathyroid tumor subgroups expressed somatostatin receptors, although membrane expression appeared negligible. Except for somatostatin receptor 1, expression patterns differed between the three tumor types. Adenomas exhibited the weakest and carcinomas the strongest expression of somatostatin receptor 2, 3, 4 and 5. We observed the largest difference for cytoplasmic somatostatin receptor 5 expression. Conclusions Parathyroid adenomas, atypical adenomas and carcinomas all express somatostatin receptor subtypes 1–5. Somatostatin receptor 5 may serve as a potential tumor marker for malignancy. Studies exploring the role of somatostatin receptor imaging and receptor-specific therapies in patients with parathyroid carcinomas are needed.

scholarly journals A Case of Primary Hyperparathyroidism due to Intrathyroidal Parathyroid Cyst

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Yavuz Yalcin ◽  
Turkan Mete ◽  
Recep Aktimur ◽  
Gultekin Ozan Kucuk ◽  
Gulhan Duman ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Cystic Degeneration ◽  
Ipth Level ◽  
Parathyroid Cyst ◽  
Parathyroid Adenomas ◽  
Parathyroid Lesions ◽  
Cyst Aspiration ◽  
Left Lobectomy ◽  
Parathyroid Cysts ◽  
Left Thyroid Lobe

Parathyroid cysts constitute 0.08–3.41% of all parathyroid masses. Intrathyroidal parathyroid cysts, however, are rare conditions with only a few cases being reported. Most of the parathyroid cysts are found to be nonfunctional and functional cysts are generally thought to be due to cystic degeneration of parathyroid adenomas. A cystic, smooth contoured lesion of 24 × 19 × 16 mm was observed in left thyroid lobe of a 76-year-old woman during ultrasonography which was performed as routine workup for primary hyperparathyroidism. It was defined as a cystic thyroid nodule at first. Tc99msestamibi scintigraphy was performed to see any parathyroid lesions, but no radioactive uptake was observed. Intact parathormone (iPTH) level was found to be >600 pg/mL in cyst aspiration fluid. Left lobectomy was performed, with a diagnosis of primary hyperparathyroidism due to functional parathyroid cyst. Serum iPTH level was decreased >50% postoperatively and histopathological evaluation was consistent with an encapsulated parathyroid adenoma with a cystic center. Parathyroid cysts are among rare causes of primary hyperparathyroidism. Diagnosis is made by markedly increased iPTH level in cyst fluid and observation of parathyroid epithelium lining the cyst wall.

scholarly journals Primary Hyperparathyroidism Focused on Molecular Pathogenesis

2014 ◽  
Vol 10 (2) ◽  
pp. 153
Author(s):  
José Manuel Gómez Sáez ◽  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Multiple Endocrine Neoplasia ◽  
Medullary Thyroid Cancer ◽  
Susceptibility Gene ◽  
Gene Mutations ◽  
Chromosome 1 ◽  
Endocrine Neoplasia ◽  
Parathyroid Adenomas ◽  
Multiple Endocrine Neoplasia 2A ◽  
Parathyroid Disease

Primary hyperparathyroidism (PHPT) is a common cause of hypercalcaemia. The most common lesion found in patients is the solitary benign parathyroid adenoma. Multiple parathyroid adenomas have also been reported. Parathyroid carcinomas are an uncommon cause of PHPT. In 15% of patients, all four parathyroid glands are involved and it may be associated with a familial hereditary syndrome, such as multiple endocrine neoplasia, types 1, 2A and 4. PHPT jaw tumour syndrome is associated with fibromas in the mandible and tumours can also be present in the kidneys and the uterus. No predisposing germline DNA variants in parathyroid adenomas have been demonstrated and only a few clonally altered genes that drive parathyroid tumorigenesis have been identified. Frequently parathyroid adenomas haveHRPT2gene mutations that are likely to be of pathogenetic importance. Mutations in theMEN1gene (localised to 11q13) are responsible for multiple endocrine neoplasia 1. Multiple endocrine neoplasia 2A, which can be associated with medullary thyroid cancer, is due to a germline mutation of theRETproto-oncogene located on chromosome 10. In MEN1-like negative patients some of the germline mutations in this new susceptibility gene were due to gene CDKN1B (12p13). This new syndrome was classified as multiple endocrine neoplasia 4. In PHPT jaw tumour syndrome,HRPT2, the gene on the long arm of chromosome 1, is responsible for the syndrome. It is suggested to perform genetic testing in patients with PHPT below the age of 30 years, but at any age in patients presenting with multigland parathyroid disease.

Expression and somatic mutations of SDHAF2 (SDH5), a novel endocrine tumor suppressor gene in parathyroid tumors of primary hyperparathyroidism

Endocrine ◽  
2010 ◽  
Vol 38 (3) ◽  
pp. 397-401 ◽  
Author(s):  
Lee F. Starker ◽  
Alberto Delgado-Verdugo ◽  
Robert Udelsman ◽  
Peyman Björklund ◽  
Tobias Carling
Keyword(s):  
Tumor Suppressor ◽  
Primary Hyperparathyroidism ◽  
Tumor Suppressor Gene ◽  
Somatic Mutations ◽  
Endocrine Tumor ◽  
Suppressor Gene ◽  
Parathyroid Tumors

scholarly journals A retrospective review of the role of B-mode and color Doppler ultrasonography in the investigation of primary hyperparathyroidism: Features that differentiate benign from malignant lesions

Ultrasound ◽  
2018 ◽  
Vol 26 (2) ◽  
pp. 110-117 ◽  
Author(s):  
Cheng Fang ◽  
Eleni Konstantatou ◽  
Nicola J Mulholland ◽  
Serena Baroncini ◽  
Mohammad A Husainy ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Carcinoma ◽  
Color Doppler ◽  
Lesion Size ◽  
Irregular Shape ◽  
Cystic Change ◽  
Parathyroid Lesions ◽  
Cystic Changes ◽  
Malignant Lesions ◽  
N 93

Purpose To identify the variant features encountered in parathyroid abnormalities and document those suggesting malignant change. Materials and methods Data were collected from a cohort of patients who underwent investigation for primary hyperparathyroidism over a 10-year period. Ultrasonographic features: shape, presence of calcification, cystic changes, heterogeneous echogenicity, vascularity, capsular thickening, local invasion, and vascularity were reviewed retrospectively and were used to correlate with final histological findings. Results One hundred forty-seven patients with histology and concurrent ultrasonographic scans were reviewed, and divided into benign parathyroid lesions (nodular hyperplasia ( n = 44), adenoma ( n = 93)) and parathyroid carcinoma ( n = 10). Parathyroid carcinomas were significantly larger than benign parathyroid lesions ( P = 0.030). Benign parathyroid lesions showed variant sonographic features: irregular shape (16.8%), heterogenous echogenicity (24.1%), calcification (1.5%), capsular thickening (1.5%), and cystic change (19.7%). A significantly higher proportion of parathyroid carcinomas demonstrated heterogenous echogenicity ( P = 0.022), capsular thickening ( P = 0.023), and infiltrative margin ( P < 0.0001) than benign parathyroid lesions. Of the 137 benign parathyroid lesions, 38 (27.7%), 76 (55.5%), 23 (16.8%) were avascular, vascular, and hypervascular, respectively. Of the 10 parathyroid carcinomas, 4 (40%), 3 (30%), and 3 (30%) of lesions were avascular, vascular, and hypervascular, respectively. The vascularity of the lesions did not differ significantly between the parathyroid carcinoma and benign parathyroid lesions ( P = 0.281). Conclusion Ultrasonographic features such as irregular shape, heterogeneous echogenicity, cystic change, and vascularity are nondiscriminatory features between benign or malignant lesions. Large lesion size together with the presence of calcification, capsular thickening, or infiltrative margin strongly raises the suspicion of a malignant parathyroid lesion, and management should be altered.

scholarly journals Benign, Malignant or Something in Between: A Rapidly Developing Atypical Parathyroid Adenoma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A183-A184
Author(s):  
Albana Sykja ◽  
Ye Lynn Ko ◽  
Rajeev Raghavan ◽  
Harit Buch
Keyword(s):  
Primary Hyperparathyroidism ◽  
Parathyroid Adenoma ◽  
Parathyroid Carcinoma ◽  
Malignant Potential ◽  
Thyroid Lobe ◽  
Uncertain Malignant Potential ◽  
Parathyroid Adenomas ◽  
Atypical Parathyroid Adenoma ◽  
Left Thyroid Lobe

Abstract Introduction: Although Primary Hyperparathyroidism (PHPT) is the third most common endocrine disorder, parathyroid carcinoma and atypical parathyroid adenoma are the rarest of endocrine tumours. The true incidence of atypical parathyroid adenomas has been elusive to endocrinologists since it is not possible to differentiate clinically between parathyroid carcinoma and atypical parathyroid adenomas before histological analysis. Atypical parathyroid adenoma represents a group of an intermediate form of parathyroid neoplasms with uncertain malignant potential. The majority of patients present with hypercalcaemia, however the development of atypical adenoma in patients with known PHPT is extremely rare. Clinical Case: A 78-year-old gentleman presented at the emergency department with lethargy and slurred speech which had started 1 week ago. Blood tests revealed severe hypercalcaemia. (Ca 4.98 mmol/L, PTH 114.2 pmol/L). The patient had a background of primary hyperparathyroidism which was diagnosed due to incidental mild hypercalcaemia (Ca 2.71 mmol/L, PTH 17.57 pmol/L, 25OH-vitamin D3 55 nmol/L). 2 weeks prior to presentation to the Emergency Department calcium and PTH levels were stable. On clinical examination, he was found mildly confused with no other clinical findings. No precipitating factors were identified. Hydration with IV crystalloids commenced and bisphosphonate IV was given. In view of PHPT Cinacalcet was added to treatment (30 mg BD). While the calcium levels seemed to improve initially, (lowest level achieved Ca 3.05 mmol/L) a week later they started to rise gradually. Hypercalcaemia proved refractory to medical treatment despite concomitant use of aggressive hydration, increased cinacalcet dose, second intravenous bisphosphonate, and intravenous calcitonin. Neck U/S revealed a probable parathyroid adenoma measuring 2cm axially at the inferior pole of the left thyroid lobe. In view of the severity and refractory nature of hypercalcaemia, a PET CT was requested which identified an 18 mm soft tissue mass in the left lower neck posterior to the left thyroid lobe with moderate to intense FDG uptake. There was no evidence of increased uptake elsewhere. The patient required 2 sessions of haemodialysis to maintain calcium levels around 3.5 preoperatively. He underwent parathyroidectomy with histological findings in keeping with atypical parathyroid adenoma. Gradual reduction of calcium levels was noted post-operatively with the lowest on day 10 (1.99) when he was started on oral calcium supplementation. The patient remains under follow-up with normal calcium levels 6 months postoperatively while remains on calcium and vitamin D3 supplements. Conclusion: To our knowledge, this is the only case of a patient with known primary hyperparathyroidism and mild hypercalcaemia, to develop severe parathyroid crisis with refractory to medical management hypercalcaemia within 2 weeks. Prompt surgical intervention remains of paramount importance in the management of these patients. They should have lifelong follow up in the view of uncertain malignant potential of the atypical parathyroid adenoma.

scholarly journals Parathyroid Tumors: Molecular Signatures

2021 ◽  
Vol 22 (20) ◽  
pp. 11206
Author(s):  
Francesca Marini ◽  
Francesca Giusti ◽  
Teresa Iantomasi ◽  
Maria Luisa Brandi
Keyword(s):  
Current Knowledge ◽  
Gene Mutations ◽  
Molecular Heterogeneity ◽  
Molecular Signatures ◽  
Epigenetic Changes ◽  
Parathyroid Tumor ◽  
Diagnostic Biomarkers ◽  
Tumor Subtypes ◽  
Parathyroid Tumors ◽  
Parathyroid Adenomas

Parathyroid tumors are rare endocrine neoplasms affecting 0.1–0.3% of the general population, including benign parathyroid adenomas (PAs; about 98% of cases), intermediate atypical parathyroid adenomas (aPAs; 1.2–1.3% of cases) and malignant metastatic parathyroid carcinomas (PCs; less than 1% of cases). These tumors are characterized by a variable spectrum of clinical phenotypes and an elevated cellular, histological and molecular heterogeneity that make it difficult to pre-operatively distinguish PAs, aPAs and PCs. Thorough knowledge of genetic, epigenetic, and molecular signatures, which characterize different parathyroid tumor subtypes and drive different tumorigeneses, is a key step to identify potential diagnostic biomarkers able to distinguish among different parathyroid neoplastic types, as well as provide novel therapeutic targets and strategies for these rare neoplasms, which are still a clinical and therapeutic challenge. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of different clinical types of parathyroid tumors, both in familial and sporadic forms of these endocrine neoplasms.

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