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Endocrine Pathology Mar 2022This review summarizes the classification of tumors of the adrenal medulla and extra-adrenal paraganglia as outlined in the 5th series of the WHO Classification of... (Review)
Review
This review summarizes the classification of tumors of the adrenal medulla and extra-adrenal paraganglia as outlined in the 5th series of the WHO Classification of Endocrine and Neuroendocrine Tumors. The non-epithelial neuroendocrine neoplasms (NENs) known as paragangliomas produce predominantly catecholamines and secrete them into the bloodstream like hormones, and they represent a group of NENs that have exceptionally high genetic predisposition. This classification discusses the embryologic derivation of the cells that give rise to these lesions and the historical evolution of the terminology used to classify their tumors; paragangliomas can be sympathetic or parasympathetic and the term pheochromocytoma is used specifically for intra-adrenal paragangliomas that represent the classical sympathetic form. In addition to the general neuroendocrine cell biomarkers INSM1, synaptophysin, and chromogranins, these tumors are typically negative for keratins and instead have highly specific biomarkers, including the GATA3 transcription factor and enzymes involved in catecholamine biosynthesis: tyrosine hydroxylase that converts L-tyrosine to L-DOPA as the rate-limiting step in catecholamine biosynthesis, dopamine beta-hydroxylase that is present in cells expressing norepinephrine, and phenylethanolamine N-methyltransferase, which converts norepinephrine to epinephrine and therefore can be used to distinguish tumors that make epinephrine. In addition to these important tools that can be used to confirm the diagnosis of a paraganglioma, new tools are recommended to determine genetic predisposition syndromes; in addition to the identification of precursor lesions, molecular immunohistochemistry can serve to identify associations with SDHx, VHL, FH, MAX, and MEN1 mutations, as well as pseudohypoxia-related pathogenesis. Paragangliomas have a well-formed network of sustentacular cells that express SOX10 and S100, but this is not a distinctive feature, as other epithelial NENs also have sustentacular cells. Indeed, it is the presence of such cells and the association with ganglion cells that led to a misinterpretation of several unusual lesions as paragangliomas; in the 2022 WHO classification, the tumor formerly known as cauda equina paraganglioma is now classified as cauda equina neuroendocrine tumor and the lesion known as gangliocytic paraganglioma has been renamed composite gangliocytoma/neuroma and neuroendocrine tumor (CoGNET). Since the 4th edition of the WHO, paragangliomas have no longer been classified as benign and malignant, as any lesion can have metastatic potential and there are no clear-cut features that can predict metastatic behavior. Moreover, some tumors are lethal without metastatic spread, by nature of local invasion involving critical structures. Nevertheless, there are features that can be used to identify more aggressive lesions; the WHO does not endorse the various scoring systems that are reviewed but also does not discourage their use. The identification of metastases is also complex, particularly in patients with germline predisposition syndromes, since multiple lesions may represent multifocal primary tumors rather than metastatic spread; the identification of paragangliomas in unusual locations such as lung or liver is not diagnostic of metastasis, since these may be primary sites. The value of sustentacular cells and Ki67 labeling as prognostic features is also discussed in this new classification. A staging system for pheochromocytoma and extra-adrenal sympathetic PGLs, introduced in the 8th Edition AJCC Cancer Staging Manual, is now included. This paper also provides a summary of the criteria for the diagnosis of a composite paragangliomas and summarizes the classification of neuroblastic tumors. This review adopts a practical question-answer framework to provide members of the multidisciplinary endocrine oncology team with a most up-to-date approach to tumors of the adrenal medulla and extra-adrenal paraganglia.
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Paraganglioma, Extra-Adrenal; Pheochromocytoma; Repressor Proteins; World Health Organization
PubMed: 35285002
DOI: 10.1007/s12022-022-09704-6 -
Journal of Radiology Case Reports Aug 2019The carotid body is the largest collection of paraganglia in the head and neck and is found on the medial aspect of the carotid bifurcation bilaterally. Carotid body... (Review)
Review
The carotid body is the largest collection of paraganglia in the head and neck and is found on the medial aspect of the carotid bifurcation bilaterally. Carotid body tumors are rare neoplasms arising from the chemoreceptor cells of the carotid bulb. We report a case of carotid body tumor in a 42-year-old female, who presented with painless, pulsatile, gradually progressive lateral neck swelling. The diagnosis is suspected on the basis of history, clinical and radiological examination findings and a successful surgical excision of the tumor is performed. Histopathological examination confirms the diagnosis of carotid body tumor. We also present brief literature about carotid body tumors in terms of its clinical and imaging presentation, evaluation, and management.
Topics: Adult; Carotid Body Tumor; Computed Tomography Angiography; Contrast Media; Female; Humans; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color
PubMed: 31558967
DOI: 10.3941/jrcr.v13i8.3681 -
Frontiers in Endocrinology 2023Pheochromocytomas and Paragangliomas (Pheo/PGL) are rare catecholamine-producing tumours derived from adrenal medulla or from the extra-adrenal paraganglia respectively.... (Review)
Review
Pheochromocytomas and Paragangliomas (Pheo/PGL) are rare catecholamine-producing tumours derived from adrenal medulla or from the extra-adrenal paraganglia respectively. Around 10-15% of Pheo/PGL develop metastatic forms and have a poor prognosis with a 37% of mortality rate at 5 years. These tumours have a strong genetic determinism, and the presence of succinate dehydrogenase B (SDHB) mutations are highly associated with metastatic forms. To date, no effective treatment is present for metastatic forms. In addition to cancer cells, the tumour microenvironment (TME) is also composed of non-neoplastic cells and non-cellular components, which are essential for tumour initiation and progression in multiple cancers, including Pheo/PGL. This review, for the first time, provides an overview of the roles of TME cells such as cancer-associated fibroblasts (CAFs) and tumour-associated macrophages (TAMs) on Pheo/PGL growth and progression. Moreover, the functions of the non-cellular components of the TME, among which the most representatives are growth factors, extracellular vesicles and extracellular matrix (ECM) are explored. The importance of succinate as an oncometabolite is emerging and since Pheo/PGL SDH mutated accumulate high levels of succinate, the role of succinate and of its receptor (SUCNR1) in the modulation of the carcinogenesis process is also analysed. Further understanding of the mechanism behind the complicated effects of TME on Pheo/PGL growth and spread could suggest novel therapeutic targets for further clinical treatments.
Topics: Humans; Pheochromocytoma; Tumor Microenvironment; Paraganglioma; Adrenal Gland Neoplasms; Succinates
PubMed: 37033265
DOI: 10.3389/fendo.2023.1137456 -
Abdominal Radiology (New York) Apr 2022Bladder paragangliomas (bPGL) are rare neuroendocrine tumors arising from the sympathetic paraganglia present in the bladder wall. Bladder PGLs are typically submucosal... (Review)
Review
Bladder paragangliomas (bPGL) are rare neuroendocrine tumors arising from the sympathetic paraganglia present in the bladder wall. Bladder PGLs are typically submucosal or intramural but when subserosal may not be readily visible at cystoscopy. The average size at presentation is 3.9 cm (range 1.0-9.1 cm). When small, bPGL are usually spherical, well-marginated and homogeneous. Larger bPGL are typically more complex with peri- and intra-tumoral neovascularity and central necrosis. On ultrasound, increased color Doppler signal is typical. The increased soft tissue resolution of MRI enables localization of bPGL within the bladder wall more accurately than CT. Restricted diffusion and avid contrast enhancement help differentiate small bPGLs from leiomyomas, which have similar appearances on ultrasound and CT. Nuclear medicine techniques identify bPGLs and their metastases with high specificity, Ga-DOTATATE PET/CT having largely replaced I-mIBG SPECT/CT as the first line functional investigation. Imaging is essential to aid surgical planning, as endoscopic resection is often not possible or incomplete due to tumor location. For patients with advanced disease, Ga-DOTATATE PET/CT and I-mIBG SPECT/CT assess suitability for peptide receptor radionuclide therapy. Up to 63% of bPGL patients have a germline mutation, most commonly in the SDHB subunit gene, increasing their risk of developing pheochromocytomas and further paragangliomas; lifelong annual biochemical and periodic imaging screening from skull base to pelvis is therefore recommended.
Topics: Adrenal Gland Neoplasms; Humans; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radionuclide Imaging; Urinary Bladder
PubMed: 35157102
DOI: 10.1007/s00261-022-03443-2 -
Journal of the Endocrine Society Feb 2022Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia,... (Review)
Review
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the highest degree of heritability among endocrine tumors. Currently, ~40% of individuals with PPGLs have a genetic germline and there are at least 12 different genetic syndromes related to these tumors. Metastatic PPGLs are defined by the presence of distant metastases at sites where chromaffin cells are physiologically absent. Approximately 10% of pheochromocytomas and ~40% of sympathetic paragangliomas are linked to metastases, explaining why complete surgical resection is the first-choice treatment for all PPGL patients. The surgical approach is a high-risk procedure requiring perioperative management by a specialized multidisciplinary team in centers with broad expertise. In this review, we summarize and discuss the most relevant aspects of perioperative management in patients with pheochromocytomas and sympathetic paragangliomas.
PubMed: 35128297
DOI: 10.1210/jendso/bvac004 -
Radiology. Cardiothoracic Imaging Aug 2023Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1%...
Paragangliomas are rare neuroendocrine tumors of extra-adrenal autonomic paraganglia origin. Paragangliomas rarely involve the heart, and they account for less than 1% of primary cardiac tumors. Most cardiac paragangliomas are incidentally detected at echocardiography or CT or during the workup of symptomatic patients with high catecholamine levels. Paragangliomas are typically located around the great vessels, coronary arteries (atrioventricular groove), or the atria, which can be explained by the tumor origin from the paraganglia and the distribution of the cardiac plexus. At MRI, cardiac paragangliomas typically have low to intermediate signal on T1-weighted images and high signal on T2-weighted images. The tumors are strongly vascularized, with high uptake on first-pass perfusion images and a heterogeneous pattern on late gadolinium enhancement images. Functional imaging is indicated for diagnostic confirmation and to screen for additional tumor locations or metastatic disease. Surgical excision is the only curative treatment. Cardiac CT angiography or invasive angiography should be performed preoperatively to precisely delineate tumor vascularization. In particular, its relation with the coronary arteries should be determined, as paragangliomas can be perfused by the coronary arteries, posing additional surgical challenges and the need for coronary revascularization. This imaging essay reviews the characteristics of paragangliomas and the use of multimodality imaging for diagnosis and treatment. CT Angiography, Molecular Imaging, MR Imaging, PET/CT, Cardiac, Heart, Neoplasms-Primary © RSNA, 2023.
PubMed: 37693206
DOI: 10.1148/ryct.230049