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International Braz J Urol : Official... 2023Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other... (Review)
Review
Pheochromocytomas/paragangliomas (PPGL) are rare, metastatic, and potentially fatal neuroendocrine tumors, often neglected because they present symptoms similar to other prevailing clinical conditions such panic syndrome, thyrotoxicosis, anxiety, hypoglycemia, etc., delaying diagnosis and treatment. The rate of diagnosis of PPGL has been increasing with the improvement in the measurement of catecholamine metabolites and the expanding availability of imaging procedures. Its essential genetic nature has been extensively investigated, comprising more than 20 genes currently related to PPGL and more new genes will probably be revealed. This overview will shed some light on the clinical, laboratory, topographical, genetic diagnosis, and management of PPGL.
Topics: Humans; Pheochromocytoma; Paraganglioma; Adrenal Gland Neoplasms
PubMed: 37115176
DOI: 10.1590/S1677-5538.IBJU.2023.0038 -
Frontiers in Endocrinology 2023Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several... (Review)
Review
Pheochromocytoma/paraganglioma (PPGL) are neuroendocrine tumors that frequently produce and release catecholamines. Catecholamine excess can manifest in several cardiovascular syndromes, including cardiomyopathy. PPGL-induced cardiomyopathies occur in up to 11% of cases and are most often associated with an adrenal pheochromocytoma (90%) and rarely with a paraganglioma derived from the sympathetic ganglia (10%). PPGL-associated cardiomyopathies can be chronic or acute, with takotsubo cardiomyopathy being the most often reported. These two types of PPGL-induced cardiomyopathy seem to have different pathophysiological backgrounds. Acute catecholaminergic stress inundates myocardial β-adrenoceptors and leads to left ventricle stunning and slight histological apoptosis. In chronic cardiomyopathy, prolonged catecholamine exposure leads to extended myocardial fibrosis, inflammation, and necrosis, and ultimately it causes dilated cardiomyopathy with a low ejection fraction. Sometimes, especially in cases associated with hypertension, hypertrophic cardiomyopathy can develop. The prognosis appears to be worse in chronic cases with a higher hospital mortality rate, higher cardiogenic shock rate at initial presentation, and lower left ventricular recovery rate after surgery. Therefore, establishing the correct diagnosis at an early stage of a PPGL is essential. This mini-review summarizes current data on pathophysiological pathways of cardiac damage caused by catecholamines, the clinical presentation of PPGL-induced cardiomyopathies, and discusses treatment options.
Topics: Humans; Pheochromocytoma; Paraganglioma; Cardiomyopathies; Adrenal Gland Neoplasms; Catecholamines
PubMed: 37522121
DOI: 10.3389/fendo.2023.1204851 -
The Journal of Clinical Endocrinology... Dec 2020The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict...
PURPOSE
The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) are scoring systems to predict metastatic potential in pheochromocytomas (PCC) and paragangliomas (PGLs). The goal of this study is to assess PASS and GAPP as metastatic predictors and to correlate with survival outcomes.
METHODS
The cohort included PCC/PGL with ≥5 years of follow-up or known metastases. Surgical pathology slides were rereviewed. PASS and GAPP scores were assigned. Univariable and multivariable logistic regression, Kaplan-Meier survival analysis, and Cox proportional hazards were performed to assess recurrence-free survival (RFS) and disease-specific survival (DSS).
RESULTS
From 143 subjects, 106 tumors were PCC and 37 were PGL. Metastases developed in 24%. The median PASS score was 6.5 (interquartile range [IQR]: 4.0-8.0) and median GAPP score was 3.0 (IQR: 2.0-4.0). Interrater reliability was low-moderate for PASS (intraclass correlation coefficient [ICC]: 0.6082) and good for GAPP (ICC 0.7921). Older age (OR: 0.969, P = .0170) was associated with longer RFS. SDHB germline pathogenic variant (OR: 8.205, P = .0049), extra-adrenal tumor (OR: 6.357, P < .0001), Ki-67 index 1% to 3% (OR: 4.810, P = .0477), and higher GAPP score (OR: 1.537, P = .0047) were associated with shorter RFS. PASS score was not associated with RFS (P = .1779). On Cox regression, a GAPP score in the moderately differentiated range was significantly associated with disease recurrence (HR: 3.367, P = .0184) compared with well-differentiated score.
CONCLUSION
Higher GAPP scores were associated with aggressive PCC/PGL. PASS score was not associated with metastases and demonstrated significant interobserver variability. Scoring systems for predicting metastatic PCC/PGL may be improved by incorporation of histopathology, clinical data, and germline and somatic tumor markers.
Topics: Adrenal Gland Neoplasms; Adult; Biomarkers, Tumor; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Paraganglioma; Pennsylvania; Pheochromocytoma; Prognosis; Research Design; Retrospective Studies; Survival Analysis
PubMed: 32877928
DOI: 10.1210/clinem/dgaa608 -
Clinical Cancer Research : An Official... Jun 2021Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic... (Review)
Review
Targeted radionuclide therapies (TRT) using I-metaiodobenzylguanidine (I-MIBG) and peptide receptor radionuclide therapy (Lu or Y) represent several of the therapeutic options in the management of metastatic/inoperable pheochromocytoma/paraganglioma. Recently, high-specific-activity-I-MIBG therapy was approved by the FDA and both Lu-DOTATATE and I-MIBG therapy were recommended by the National Comprehensive Cancer Network guidelines for the treatment of metastatic pheochromocytoma/paraganglioma. However, a clinical dilemma often arises in the selection of TRT, especially when a patient can be treated with either type of therapy based on eligibility by MIBG and somatostatin receptor imaging. To address this problem, we assembled a group of international experts, including oncologists, endocrinologists, and nuclear medicine physicians, with substantial experience in treating neuroendocrine tumors with TRTs to develop consensus and provide expert recommendations and perspectives on how to select between these two therapeutic options for metastatic/inoperable pheochromocytoma/paraganglioma. This article aims to summarize the survival outcomes of the available TRTs; discuss personalized treatment strategies based on functional imaging scans; address practical issues, including regulatory approvals; and compare toxicities and risk factors across treatments. Furthermore, it discusses the emerging TRTs.
Topics: 3-Iodobenzylguanidine; Adrenal Gland Neoplasms; Humans; Iodine Radioisotopes; Lutetium; Octreotide; Organometallic Compounds; Paraganglioma; Pheochromocytoma; Positron Emission Tomography Computed Tomography; Radioisotopes; Radiopharmaceuticals; Radiotherapy
PubMed: 33685867
DOI: 10.1158/1078-0432.CCR-20-3703 -
Clinical & Translational Oncology :... Oct 2021Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic...
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic/parasympathetic neural ganglia, respectively. The heterogeneity in its etiology makes PPGL diagnosis and treatment very complex. The aim of this article was to provide practical clinical guidelines for the diagnosis and treatment of PPGLs from a multidisciplinary perspective, with the involvement of the Spanish Societies of Endocrinology and Nutrition (SEEN), Medical Oncology (SEOM), Medical Radiology (SERAM), Nuclear Medicine and Molecular Imaging (SEMNIM), Otorhinolaryngology (SEORL), Pathology (SEAP), Radiation Oncology (SEOR), Surgery (AEC) and the Spanish National Cancer Research Center (CNIO). We will review the following topics: epidemiology; anatomy, pathology and molecular pathways; clinical presentation; hereditary predisposition syndromes and genetic counseling and testing; diagnostic procedures, including biochemical testing and imaging studies; treatment including catecholamine blockade, surgery, radiotherapy and radiometabolic therapy, systemic therapy, local ablative therapy and supportive care. Finally, we will provide follow-up recommendations.
Topics: Adrenal Gland Neoplasms; Aftercare; Algorithms; Biomarkers, Tumor; Catecholamines; Diagnostic Imaging; Genetic Counseling; Genetic Predisposition to Disease; Genetic Testing; Humans; Neoplasm Staging; Paraganglioma; Pheochromocytoma; Societies, Medical; Spain; Symptom Assessment
PubMed: 33959901
DOI: 10.1007/s12094-021-02622-9 -
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 -
Journal of Medical Genetics Feb 2023pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal...
pathogenic germline variants (PGVs) are identified in up to 10% of patients with paraganglioma and phaeochromocytoma and up to 30% with wild-type gastrointestinal stromal tumours. Most PGV carriers present with an apparently sporadic tumour, but often the pathogenic variant has been inherited from parent who has the variant, but has not developed any clinical features. Studies of PGV carriers suggest that lifetime penetrance for SDHA-associated tumours is low, particularly when identified outside the context of a family history. Current recommended surveillance for PGV carriers follows an intensive protocol. With increasing implementation of tumour and germline large panel and whole-genome sequencing, it is likely more PGV carriers will be identified in patients with tumours not strongly associated with or outside the context of a strong family history. This creates a complex situation about what to recommend in clinical practice considering low penetrance for tumour development, surveillance burden and patient anxiety. An expert working group was formed to discuss and consider this situation. This paper outlines the recommendations from this working group for testing and management of PGV carriers in clinical practice.
Topics: Humans; Genetic Testing; Paraganglioma; Pheochromocytoma; Germ-Line Mutation; Adrenal Gland Neoplasms; United Kingdom; Genetic Predisposition to Disease; Electron Transport Complex II
PubMed: 35260474
DOI: 10.1136/jmedgenet-2021-108355 -
Endocrine-related Cancer Apr 2023Paragangliomas (PGL) of the adrenal (also known as pheochromocytomas) or extra-adrenal neural crest-derived cells are highly heritable tumors, usually driven by single... (Review)
Review
Paragangliomas (PGL) of the adrenal (also known as pheochromocytomas) or extra-adrenal neural crest-derived cells are highly heritable tumors, usually driven by single pathogenic variants that occur mutually exclusively in genes involved in multiple cellular processes, including the response to hypoxia, MAPK/ERK signaling, and WNT signaling. The discovery of driver mutations has led to active clinical surveillance with outcome implications in familial PGL. The spectrum of mutations continues to grow and reveal unique mechanisms of tumorigenesis that inform tumor biology and provide the rationale for targeted therapy. Here we review recent progress in the genetics and molecular pathogenesis of PGLs and discuss new prospects for advancing research with new disease models and ongoing clinical trials presented at the recent International Symposium of Pheochromocytomas and Paragangliomas (ISP2022) held in October 2022 in Prague.
Topics: Humans; Pheochromocytoma; Paraganglioma; Mutation; Adrenal Gland Neoplasms
PubMed: 36748842
DOI: 10.1530/ERC-22-0373 -
Current Opinion in Pediatrics Aug 2021Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in... (Review)
Review
PURPOSE OF REVIEW
Great progress has been made in understanding the genetic and molecular basis of pheochromocytoma and paragangliomas (PPGLs). This review highlights the new standards in the diagnosis and management of pediatric PPGLs.
RECENT FINDINGS
The vast majority of pediatric PPGLs have an associated germline mutation, making genetic studies imperative in the work up of these tumors. Somatostatin receptor-based imaging modalities such as 68Ga-DOTATATE and 64Cu-DOTATATE are shown to have the greatest sensitivity in pediatric PPGLs. Peptide receptor radionuclide therapies (PRRTs) such as 177Lu-DOTATATE are shown to have efficacy for treating PPGLs.
SUMMARY
Genetics play an important role in pediatric PPGLs. Advances in somatostatin receptor-based technology have led to use of 68Ga-DOTATATE and 64Cu-DOTATATE as preferred imaging modalities. While surgery remains the mainstay for management of PPGLs, PRRT is emerging as a treatment option for PPGLs.
Topics: Adrenal Gland Neoplasms; Child; Copper Radioisotopes; Humans; Paraganglioma; Pheochromocytoma
PubMed: 34039901
DOI: 10.1097/MOP.0000000000001029 -
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