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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 -
Radiologic Clinics of North America Nov 2020Primary hyperparathyroidism (PHPT) is a common endocrine abnormality, caused in most cases by a single parathyroid adenoma. Surgery remains the first-line curative... (Review)
Review
Primary hyperparathyroidism (PHPT) is a common endocrine abnormality, caused in most cases by a single parathyroid adenoma. Surgery remains the first-line curative therapy in PHPT. Imaging plays a vital role in presurgical localization of parathyroid adenomas. Ultrasound provides a safe and quick imaging modality free of ionizing radiation, but is operator dependent. Sestamibi scan offers comparable sensitivity to ultrasound, improved with concurrent tomographic imaging. 4DCT remains a problem-solving technique in challenging cases and after failed neck exploration. We present an overview of various parathyroid imaging modalities, including protocols and findings, in addition to relevant pearls and pitfalls.
Topics: Diagnostic Imaging; Female; Humans; Hyperparathyroidism, Primary; Imaging, Three-Dimensional; Male; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Radiographic Image Enhancement; Radiopharmaceuticals; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler
PubMed: 33040849
DOI: 10.1016/j.rcl.2020.07.006 -
Seminars in Nuclear Medicine Jul 2023Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid... (Review)
Review
Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid adenomas. 1° HPT causing hypercalcemia, kidney stones and/or osteoporosis should be treated whenever possible by parathyroidectomy. Accurate preoperative location of parathyroid adenomas is crucial for surgery planning, mostly when performing minimally invasive surgery. Cervical ultrasonography (US) is usually performed to localize parathyroid adenomas as a first intention, followed by Tc- sestamibi scintigraphy with SPECT/CT whenever possible. 4D-CT is a possible alternative to Tc- sestamibi scintigraphy. Recently, F-fluorocholine positron emission tomography/computed tomography (F-FCH PET/CT) has made its way in the clinics as it is the most sensitive method for parathyroid adenoma detection. It can eventually be combined to 4D-CT to increase its diagnostic performance, although this results in higher dose exposure to the patient. Other forms of hyperparathyroidism consist in secondary (2° HPT) and tertiary hyperparathyroidism (3° HPT). As parathyroidectomy is not usually part of the management of patients with 2° HPT, parathyroid imaging is not routinely performed in these patients. In patients with 3° HPT, total or subtotal parathyroidectomy is often performed. Localization of hyperfunctional glands is an important aid to surgery planning. As F-FCH PET/CT is the most sensitive modality in multigland disease, it is the preferred imaging technic in 3° HPT patients, although its cost and availability may limit its widespread use in this setting.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Parathyroid Glands; Hyperparathyroidism; Technetium Tc 99m Sestamibi; Radiopharmaceuticals
PubMed: 36922339
DOI: 10.1053/j.semnuclmed.2023.02.004 -
Mayo Clinic Proceedings Nov 2022
Topics: Humans; Parathyroid Neoplasms; Adenoma, Oxyphilic; Adenoma
PubMed: 36333022
DOI: 10.1016/j.mayocp.2022.09.015 -
Academic Radiology May 2023
Topics: Humans; Parathyroid Neoplasms; Tomography, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Mass Screening; Technetium Tc 99m Sestamibi
PubMed: 36941157
DOI: 10.1016/j.acra.2023.02.021 -
Advances in Anatomic Pathology Jan 2023Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary,... (Review)
Review
Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.
Topics: Humans; Hyperparathyroidism, Primary; Hyperplasia; Parathyroid Glands; Parathyroid Neoplasms; Adenoma
PubMed: 36315270
DOI: 10.1097/PAP.0000000000000379 -
Cancer Treatment Reviews Jun 2020Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5-5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic,... (Review)
Review
Parathyroid cancer (PC) is a rare malignant tumor which comprises 0.5-5% of patients with primary hyperparathyroidism (PHPT). Most of these cancers are sporadic, although it may also occur as a feature of various genetic syndromes including hyperparathyroidism-jaw tumor syndrome (HPT-JT) and multiple endocrine neoplasia (MEN) types 1 and 2A. Although PC is characterized by high levels of serum ionized calcium (Ca) and parathyroid hormone (PTH), the challenge to the clinician is to distinguish PC from the far more common entities of parathyroid adenoma (PA) or hyperplasia, as there are no specific clinical, biochemical, or radiological characteristic of PC. Complete surgical resection is the only known curative treatment for PC with the surgical approach during initial surgery strongly influencing the outcome. In order to avoid local recurrence, the lesion must be removed en-bloc with clear margins. PC has high recurrence rates of up to 50% but with favorable long-term survival rates (10-year overall survival of 60-70%) due to its slow-growing nature. Most patients die not from tumor burden directly but from uncontrolled severe hypercalcemia. In this article we have updated the information on PC by reviewing the literature over the past 10 years and summarizing the findings of the largest series published in this period.
Topics: Humans; Hyperparathyroidism; Neoplasm Recurrence, Local; Parathyroid Neoplasms
PubMed: 32247225
DOI: 10.1016/j.ctrv.2020.102012 -
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 -
Endocrine Sep 2023Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly... (Review)
Review
Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly characterized by severe and unmanageable hypercalcemia, aggressive behavior, high metastatic potential, and poor prognosis. PC manifests prevalently as a sporadic tumor and only occasionally it is part of congenital syndromic and non-syndromic endocrine diseases. Molecular pathogenesis of this form of parathyroid tumor is not fully elucidated and it appears to be caused by multiple genetic and epigenetic drivers, differing among affected patients and not yet clearly stated in distinguishing PC from the benign parathyroid adenoma (PA). Congenital forms of PC have been prevalently associated with germline heterozygous loss-of-function mutations of the CDC73 tumor suppressor gene, both in the context of the hyperparathyroidism jaw-tumor syndrome (HPT-JT) and of the isolated familial hyperparathyroidism (FIPH). Currently, surgical en bloc resection of affected gland(s) and other involved structures is the elective therapy for both primary and recurrent PC. However, it usually results ineffective for advance and metastatic disease, and a high percentage of post-operative recurrence is reported. Targeted medical therapies for surgically untreatable PC, based on the molecular profile of PC samples, are, therefore, needed. The characterization of genetic and epigenetic alterations and deregulated pathways in PC samples will be of fundamental importance to tailor treatment for each patient. Here, we reviewed main findings on molecular pathogenetic aspects of PC, and the current state of the art of therapies.
Topics: Humans; Parathyroid Neoplasms; Tumor Suppressor Proteins; Neoplasm Recurrence, Local; Jaw Neoplasms; Hyperparathyroidism, Primary
PubMed: 37160841
DOI: 10.1007/s12020-023-03376-w