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Surgical Pathology Clinics Dec 2019Proliferative pathologic lesions of parathyroid glands encompass a spectrum of entities ranging from benign hyperplastic processes to malignant neoplasia. This review... (Review)
Review
Proliferative pathologic lesions of parathyroid glands encompass a spectrum of entities ranging from benign hyperplastic processes to malignant neoplasia. This review article outlines the pathophysiologic classification of parathyroid disorders and describes histologic, immunohistochemical, and molecular features that can be assessed to render accurate diagnoses.
Topics: Adenoma; Humans; Hyperparathyroidism; Immunohistochemistry; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 31672291
DOI: 10.1016/j.path.2019.08.006 -
Frontiers in Endocrinology 2021The goal of parathyroid imaging is to identify all sources of excess parathyroid hormone secretion pre-operatively. A variety of imaging approaches have been evaluated... (Review)
Review
The goal of parathyroid imaging is to identify all sources of excess parathyroid hormone secretion pre-operatively. A variety of imaging approaches have been evaluated and utilized over the years for this purpose. Ultrasound relies solely on structural features and is without radiation, however is limited to superficial evaluation. 4DCT and 4DMRI provide enhancement characteristics in addition to structural features and dynamic enhancement has been investigated as a way to better distinguish parathyroid from adjacent structures. It is important to recognize that 4DCT provides valuable information however results in much higher radiation dose to the thyroid gland than the other available examinations, and therefore the optimal number of phases is an area of controversy. Single-photon scintigraphy with 99mTc-Sestamibi, or dual tracer 99mTc-pertechnetate and 99mTc-sestamibi with or without SPECT or SPECT/CT is part of the standard of care in many centers with availability and expertise in nuclear medicine. This molecular imaging approach detects cellular physiology such as mitochondria content found in parathyroid adenomas. Combining structural imaging such as CT or MRI with molecular imaging in a hybrid approach allows the ability to obtain robust structural and functional information in one examination. Hybrid PET/CT is widely available and provides improved imaging and quantification over SPECT or SPECT/CT. Emerging PET imaging techniques, such as 18F-Fluorocholine, have the exciting potential to reinvent parathyroid imaging. PET/MRI may be particularly well suited to parathyroid imaging, where available, because of the ability to perform dynamic contrast-enhanced imaging and co-registered 18F-Fluorocholine PET imaging simultaneously with low radiation dose to the thyroid. A targeted agent specific for a parathyroid tissue biomarker remains to be identified.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Neoplasms; Positron Emission Tomography Computed Tomography; Technetium Tc 99m Sestamibi
PubMed: 35283807
DOI: 10.3389/fendo.2021.760419 -
The Quarterly Journal of Nuclear... Jun 2022Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical...
Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.
Topics: Humans; Nuclear Medicine; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Technetium Tc 99m Sestamibi
PubMed: 35166093
DOI: 10.23736/S1824-4785.22.03427-6 -
Cancer Apr 2018Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further...
BACKGROUND
Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test.
METHODS
ThyroSeq v3 is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions. It was validated in 238 tissue samples and 175 FNA samples with known surgical follow-up. Analytical performance studies were conducted.
RESULTS
In the training tissue set of samples, ThyroSeq GC detected more than 100 genetic alterations, including BRAF, RAS, TERT, and DICER1 mutations, NTRK1/3, BRAF, and RET fusions, 22q loss, and gene expression alterations. GC cutoffs were established to distinguish cancer from benign nodules with 93.9% sensitivity, 89.4% specificity, and 92.1% accuracy. This correctly classified most papillary, follicular, and Hurthle cell lesions, medullary thyroid carcinomas, and parathyroid lesions. In the FNA validation set, the GC sensitivity was 98.0%, the specificity was 81.8%, and the accuracy was 90.9%. Analytical accuracy studies demonstrated a minimal required nucleic acid input of 2.5 ng, a 12% minimal acceptable tumor content, and reproducible test results under variable stress conditions.
CONCLUSIONS
The ThyroSeq v3 GC analyzes 5 different classes of molecular alterations and provides high accuracy for detecting all common types of thyroid cancer and parathyroid lesions. The analytical sensitivity, specificity, and robustness of the test have been successfully validated and indicate its suitability for clinical use. Cancer 2018;124:1682-90. © 2018 American Cancer Society.
Topics: Biomarkers, Tumor; Biopsy, Fine-Needle; DNA Mutational Analysis; Diagnosis, Differential; Follow-Up Studies; High-Throughput Nucleotide Sequencing; Humans; Parathyroid Glands; Parathyroid Neoplasms; Reproducibility of Results; Sensitivity and Specificity; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 29345728
DOI: 10.1002/cncr.31245 -
The Journal of International Medical... Jan 2020
Topics: Calcium; Delayed Diagnosis; Humans; Hyperparathyroidism; Hypocalcemia; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Renal Insufficiency, Chronic; Ultrasonography; Vitamin D Deficiency
PubMed: 31997682
DOI: 10.1177/0300060519827415 -
Archives of Endocrinology and Metabolism Nov 2022Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is... (Review)
Review
Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is typically treated with surgery, and it remains the only definitive therapy, whose techniques have evolved over previous decades. Advances in preoperative localization exams and the intraoperative PTH monitoring have become the cornerstones of recent parathyroidectomy techniques, as minimally invasive techniques are appropriate for most patients. Nevertheless, these techniques, are not suitable for PHPT patients who are at risk for multiglandular disease, especially in those who present with familial forms of PHPT that require bilateral neck exploration. This manuscript also explores other conditions that warrant special consideration during surgical treatment for PHPT: normocalcemic primary hyperparathyroidism, pregnancy, reoperation for persistent or recurrent PHPT, parathyroid carcinoma, and familial and genetic forms of hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Parathyroid Neoplasms; Parathyroid Hormone; Parathyroid Glands
PubMed: 36382757
DOI: 10.20945/2359-3997000000557 -
Frontiers in Endocrinology 2022Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism... (Review)
Review
Parathyroid carcinoma (PC) is an extremely rare malignancy, accounting less than 1% of all parathyroid neoplasms, and an uncommon cause of primary hyperparathyroidism (PHPT), characterized by an excessive secretion of parathyroid hormone (PTH) and severe hypercalcemia. As opposed to parathyroid hyperplasia and adenomas, PC is associated with a poor prognosis, due to a commonly unmanageable hypercalcemia, which accounts for death in the majority of cases, and an overall survival rate of 78-85% and 49-70% at 5 and 10 years after diagnosis, respectively. No definitively effective therapies for PC are currently available. The mainly employed treatment for PC is the surgical removal of tumoral gland(s). Post-surgical persistent or recurrent disease manifest in about 50% of patients. The comprehension of genetic and epigenetic bases and molecular pathways that characterize parathyroid carcinogenesis is important to distinguish malignant PCs from benign adenomas, and to identify specific targets for novel therapies. Germline heterozygote inactivating mutations of the tumor suppressor gene, with somatic loss of heterozygosity at 1q31.2 locus, account for about 50-75% of familial cases; over 75% of sporadic PCs harbor biallelic somatic inactivation/loss of . Recurrent mutations of the gene, a recurrent mutation in the gene, genetic amplification of the gene, alterations of the PI3K/AKT/mTOR signaling pathway, and modifications of microRNA expression profile and gene promoter methylation pattern have all been detected in PC. Here, we review the current knowledge on gene mutations and epigenetic changes that have been associated with the development of PC, in both familial and sporadic forms of this malignancy.
Topics: Adenoma; Epigenesis, Genetic; Humans; Hypercalcemia; Parathyroid Neoplasms; Phosphatidylinositol 3-Kinases
PubMed: 35282432
DOI: 10.3389/fendo.2022.834362 -
Cancer Dec 2014In the Western world, primary hyperparathyroidism is now a relatively common disorder that is diagnosed in 0.7% of the general population and in 2% of postmenopausal... (Review)
Review
In the Western world, primary hyperparathyroidism is now a relatively common disorder that is diagnosed in 0.7% of the general population and in 2% of postmenopausal women. Although patients today typically present with less severe manifestations of disease, the evaluation and management of patients with parathyroid disease remains challenging. Primary hyperparathyroidism is a complex disease process that requires careful diagnosis and thoughtful medical and surgical management. The surgical management of patients with persistent or recurrent disease, inherited primary hyperparathyroidism syndromes, and parathyroid carcinoma is particularly challenging. High-quality imaging and reliable intraoperative adjuncts are critical to success.
Topics: Adenoma; Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Radiopharmaceuticals; Technetium Tc 99m Sestamibi; Tomography, Emission-Computed, Single-Photon; Ultrasonography
PubMed: 25042934
DOI: 10.1002/cncr.28891 -
Journal of Bone and Mineral Research :... Jul 2023Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the...
Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Parathyroid Neoplasms; Transcriptome; Endothelial Cells; Adenoma; Carcinogenesis; Tumor Microenvironment
PubMed: 37191193
DOI: 10.1002/jbmr.4824 -
Journal of Bone and Mineral Research :... Nov 2022
Topics: Humans; Parathyroid Diseases; Parathyroid Neoplasms
PubMed: 36223904
DOI: 10.1002/jbmr.4718