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Trends in Cancer Jan 2018Recent comprehensive molecular analysis allowed the identification of unique molecular signatures in pheochromocytomas (PHEOs) and paragangliomas (PGLs). Here we... (Review)
Review
Recent comprehensive molecular analysis allowed the identification of unique molecular signatures in pheochromocytomas (PHEOs) and paragangliomas (PGLs). Here we summarize the main pathway clusters activated by PHEO- and PGL-susceptibility genes: pseudohypoxic, kinase, and Wnt signaling. Molecular characterization and clustering of PHEOs and PGLs may help in the application of principles of personalized medicine and in decision making for targeted therapy of these tumors.
Topics: Adrenal Gland Neoplasms; Genomics; Humans; Molecular Targeted Therapy; Mutation; Paraganglioma; Pheochromocytoma; Precision Medicine; Signal Transduction; Wnt Proteins
PubMed: 29413423
DOI: 10.1016/j.trecan.2017.11.001 -
Hormones (Athens, Greece) Jun 2021Pheochromocytoma/paraganglioma (PPGL)-induced catecholamine crisis is a rare endocrine emergency leading to life-threatening hemodynamic instability causing end-organ... (Review)
Review
Pheochromocytoma/paraganglioma (PPGL)-induced catecholamine crisis is a rare endocrine emergency leading to life-threatening hemodynamic instability causing end-organ damage or dysfunction. As it is associated with a significant mortality rate of approximately 15%, recognizing the signs and symptoms and making the appropriate diagnosis are critical. For this purpose, we report the clinical course of the crisis in four out of a total of six patients with a PPGL crisis from a cohort of 199 PPGL patients of a single tertiary referral center for PPGL patients in the Netherlands diagnosed between 2002 and 2020. Successful treatment of a PPGL crisis demands prompt diagnosis, vigorous pharmacological therapy, and emergency tumor removal if the patient continues to deteriorate.
Topics: Adrenal Gland Neoplasms; Catecholamines; Humans; Paraganglioma; Pheochromocytoma; Tertiary Care Centers
PubMed: 33575936
DOI: 10.1007/s42000-021-00274-6 -
Acta Biochimica Polonica Sep 2023Pheochromocytoma (PPC) and paraganglioma (PGL) are the tumors that rarely occur in the pediatric population (PPGL). Both originate from chromaffin cells,...
Pheochromocytoma (PPC) and paraganglioma (PGL) are the tumors that rarely occur in the pediatric population (PPGL). Both originate from chromaffin cells, pheochromocytoma is localized in the adrenal gland, whereas paragangliomas are regarded as the tumors present in other localizations, from head to the pelvis. The clinical image is characterized by the presence of the sustained hypertension, headaches, sweating, palpitations. The symptoms are caused by the catecholamine secretion or are related to tumor mass pressure on different organs. The catecholamines and their metabolites levels in urine collection or plasma are necessary for further evaluation of the diagnosis. In pediatric population the tumors occur in multiple familial syndromes such as Multiple Endocrine type 2, Neurofibromatosis type 1, Von Hippel-Lindau syndrome, Familial Paraganglioma syndrome are related to specific mutations (SDHx, RET, VHL, NF1) leading to the characteristic phenotype. The radiological and nuclear imaging are an important part of the examination. Although CT and MR are reported to have overall good sensitivity for the tumor detection, further analysis with nuclear imaging is recommended for the specified diagnosis. Right now 68GA-DOTATATE is regarded as the tracer of choice, leading to the complex evaluation of patients with different mutations and metastatic disease. The treatment of choice is the tumor excision. Also, lately new therapeutic approaches including genetically targeted therapies are under investigation for more complex treatment of tumors with underlying genetic cause or metastatic disease. Long term follow-up after treatment to avoid recurrence or to detect it in early stadium must be performed.
Topics: Child; Humans; Adolescent; Pheochromocytoma; Paraganglioma; Biological Transport; Catecholamines; Adrenal Gland Neoplasms
PubMed: 37717273
DOI: 10.18388/abp.2020_6955 -
Clinical Radiology Mar 2019Paragangliomas are rare vascular tumours of the autonomic nervous system. They can be classified as sympathetic or parasympathetic. Sympathetic paragangliomas, which... (Review)
Review
Paragangliomas are rare vascular tumours of the autonomic nervous system. They can be classified as sympathetic or parasympathetic. Sympathetic paragangliomas, which include phaeochromocytomas, tend to be functional and symptomatic. Parasympathetic paragangliomas are usually non-functional and may present with mass effect. Forty percent of paragangliomas are linked to genetic syndromes, most commonly due to mutations of the succinate dehydrogenase (SDH) enzyme complex and are collectively known as paraganglioma syndromes, of which five are described. Genetic testing is recommended for all patients, and their first-degree relatives, diagnosed with paragangliomas. When SDH mutations are discovered, biochemical screening and imaging surveillance is indicated. There is currently no consensus on imaging surveillance protocols. Most advocate full-body imaging, but the choice of technique and frequency varies. If paragangliomas are demonstrated, functional imaging to look for synchronous tumours or metastases is indicated. 2-[F]-fluoro-2-deoxy-d-glucose (F-FDG) positron-emission tomography (PET)-computed tomography (CT) is the technique of choice for metastatic evaluation, but [I]-metaiodobenzylguanidine or [In]-DTPA-octreotide scintigraphy are also utilised. Current research into emerging positron-emitting radiolabelled somatostatin analogues have yielded promising results, which is likely to be reflected in future guidelines. As genetic testing becomes increasingly prevalent, the need to answer the remaining questions regarding surveillance imaging is paramount.
Topics: Humans; Mutation; Paraganglioma; Succinate Dehydrogenase; Syndrome; Whole Body Imaging
PubMed: 30551795
DOI: 10.1016/j.crad.2018.11.004 -
Archivos Espanoles de Urologia May 2021Description of two incidental cases of bladder paraganglioma in women and review of the published literature. (Review)
Review
OBJECTIVE
Description of two incidental cases of bladder paraganglioma in women and review of the published literature.
METHODS
A bibliographic search was carried out in Medline over the last 10 years according to the terms "urinary bladder" and "paraganglioma".
RESULTS
Bladder paraganglioma (BP) accounts for less than 0.06% of bladder tumors and 10% of all paragangliomas. It may be sporadic or associated with hereditary predisposition syndromes such as Hereditary Paraganglioma- Pheochromocytoma Syndrome. Due to its rarity, there are no recommendations for treatment and monitoring but, their risk of malignancy forces a long-term follow up. The study of germinal mutations through massive sequencing ruled out the association with a hereditary syndrome. Initial management included early reassessment by cystoscopy, transurethral bladder resection (TURB) and imaging.
CONCLUSIONS
Bladder paragangliomas are rare tumors that can be associated to hereditary syndromes. Its treatment and follow - up must be based on a multidisciplinary approach.
Topics: Adrenal Gland Neoplasms; Female; Humans; Paraganglioma; Pheochromocytoma; Urinary Bladder Neoplasms
PubMed: 33942738
DOI: No ID Found -
Clinics and Research in Hepatology and... Apr 2022Paragangliomas are extra-adrenal pheochromocytomas that arise from chromaffin cells in the sympathetic or parasympathetic neural paraganglia. Surgery remains the only...
Paragangliomas are extra-adrenal pheochromocytomas that arise from chromaffin cells in the sympathetic or parasympathetic neural paraganglia. Surgery remains the only curative treatment, although prominent vascularity can make excision difficult. We have recently encountered a patient with a retropancreatic celio-mesenteric paraganglioma unusually located between celiac trunk (CT) and superior mesenteric artery.
Topics: Adrenal Gland Neoplasms; Humans; Mesentery; Paraganglioma; Pheochromocytoma
PubMed: 35038577
DOI: 10.1016/j.clinre.2022.101866 -
Current Opinion in Otolaryngology &... Apr 2023This review summarizes practical recommendations for screening, work-up, and management of hereditary head and neck paragangliomas based on the growing molecular and... (Review)
Review
PURPOSE OF REVIEW
This review summarizes practical recommendations for screening, work-up, and management of hereditary head and neck paragangliomas based on the growing molecular and empirical understanding of this disease.
RECENT FINDINGS
The proportion of hereditary cases among head and neck paragangliomas is significant (∼33 to 50%), and specific genetic alterations may increase the risk of malignancy. Genotyping should be performed for each case, and patients carrying a pathological mutation should be regularly screened for new tumors. Computed tomography (CT), magnetic resonance imaging (MRI), digital subtraction angiography (DSA), and functional positron emission tomography (PET) can provide a reliable preoperative diagnosis in the absence of histology. Comparative data on therapeutic outcome and morbidity now render radiation, stereotactic radiosurgery, and active surveillance preferable over surgery in highly advanced cases of jugulotympanic and vagal paragangliomas, whereas surgery remains the first choice for most carotid body paragangliomas.
SUMMARY
Complete paraganglioma removal continues to be the primary therapeutic goal; however, this is sometimes impossible to accomplish with acceptable morbidity. In these cases, therapy selection should focus on preserving cranial nerve function and minimizing both tumor-associated and therapy-associated complications, particularly in genetically predisposed patients. An interdisciplinary approach to the management of hereditary head and neck paragangliomas is strongly recommended.
Topics: Humans; Head and Neck Neoplasms; Paraganglioma, Extra-Adrenal; Paraganglioma; Magnetic Resonance Imaging; Tomography, X-Ray Computed
PubMed: 36912223
DOI: 10.1097/MOO.0000000000000867 -
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 -
Current Opinion in Endocrinology,... Jun 2017Pheochromocytomas and paragangliomas (PPGs) are rare neuroendocrine tumors. Over the last 15 years, substantial progress has been made toward understanding the clinical... (Review)
Review
PURPOSE OF REVIEW
Pheochromocytomas and paragangliomas (PPGs) are rare neuroendocrine tumors. Over the last 15 years, substantial progress has been made toward understanding the clinical aspects and molecular origins of this disease. Nevertheless, predicting and managing malignancy remains the biggest challenge in clinical practice. The natural history of patients with malignant PPGs has not yet been described, and their prognosis varies. Currently, the diagnosis of malignant PPGs relies on the presence of metastases, by which time the disease is usually advanced. Better understanding of the clinical and molecular characteristics of patients with malignant PPGs has spurred several prospective clinical trials.
RECENT FINDINGS
Several molecular targeted therapies, a novel radiopharmaceutical medication that targets the catecholamine transporter, and immunotherapy are under evaluation for the treatment of patients with malignant PPGs. Furthermore, the identification of clinical predictors of malignancy and survival has led to the first TNM staging classification for PPGs.
SUMMARY
Prospective clinical trials are providing patients with therapeutic options beyond systemic chemotherapy. The knowledge derived from these trials and from the evaluation of the TNM staging in clinical practice will help to clarify how to most effectively treat malignant PPGs.
Topics: Adrenal Gland Neoplasms; Humans; Molecular Targeted Therapy; Neoplasm Staging; Paraganglioma; Pheochromocytoma; Prognosis; Radiopharmaceuticals
PubMed: 28234804
DOI: 10.1097/MED.0000000000000330 -
Hematology/oncology Clinics of North... Feb 2016Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare but unique neuroendocrine tumors. The hypersecretion of catecholamines from the tumors can be associated with... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare but unique neuroendocrine tumors. The hypersecretion of catecholamines from the tumors can be associated with high morbidity and mortality, even when tumors are benign. Up to 40% of PCCs/PGLs are associated with germline mutations in susceptibility genes. About one-quarter are malignant, defined by the presence of distant metastases. Treatment options for unresectable metastatic disease, including chemotherapy, (131)I-MIBG, and radiation, can offer limited tumor and hormone control, although none are curative. This article reviews the inherited genetics, diagnosis, and treatment of PCCs and PGLs.
Topics: Catecholamines; Drug Therapy; Genetic Predisposition to Disease; Humans; Molecular Targeted Therapy; Mutation; Paraganglioma; Pheochromocytoma; Radiotherapy; Tumor Burden
PubMed: 26614373
DOI: 10.1016/j.hoc.2015.09.006