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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 -
Endocrine Sep 2019Takotsubo syndrome (TS), also known as neurogenic stunned myocardium or broken heart syndrome, is a recognized acute cardiac syndrome. In about 70% of cases, the... (Review)
Review
Takotsubo syndrome (TS), also known as neurogenic stunned myocardium or broken heart syndrome, is a recognized acute cardiac syndrome. In about 70% of cases, the syndrome is preceded by an emotional or a physical stressor. Among the innumerable physical trigger factors that may induce TS are pheochromocytomas and paragangliomas (PPGLs). PPGL-associated cardiovascular complications as "myocarditis", "myocardial infarction", "reversible cardiomyopathies", and "transient repolarization electrocardiographic changes" have been described since more than 70 years. During the last two decades, dozens of cases of PPGL-induced TS have been reported. PPGLs display increased catecholamine levels, sometimes massively elevated, which may trigger TS, most likely through hyperactivation of sympathetic nervous system including the cardiac sympathetic nerve terminal disruption with norepinephrine seethe and spillover. PPGL-induced TS is characterized by a dramatic clinical presentation with hemodynamic compromise and high complication rates. The prevalence of global and apical sparing pattern of TS in PPGL-induced TS is significantly higher than in other TS populations. In this report, the associations of PPGL-induced cardiovascular complications are analyzed, and clinical features, complications, outcome and treatment of PPGL-induced TS are reviewed.
Topics: Adrenal Gland Neoplasms; Humans; Paraganglioma; Pheochromocytoma; Takotsubo Cardiomyopathy
PubMed: 31399912
DOI: 10.1007/s12020-019-02035-3 -
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 -
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 -
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 -
Surgical Pathology Clinics Dec 2019Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine neoplasms with characteristic histologic and immunohistochemical features. These tumors can... (Review)
Review
Pheochromocytomas and extra-adrenal paragangliomas are rare neuroendocrine neoplasms with characteristic histologic and immunohistochemical features. These tumors can arise in several anatomic locations, necessitating that their diagnostic recognition extends beyond the realm of endocrine disorders. A practical and reproducible risk stratification system for these tumors is still in development. In this rapidly evolving era of molecular medicine, it is essential for pathologists to equip themselves with a framework for understanding the classification of paragangliomas and pheochromocytomas and be informed of how they might advise their colleagues with regard to prognostication and appropriate follow-up.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Mutation; Neoplasm Grading; Paraganglioma; Pheochromocytoma; Succinate Dehydrogenase
PubMed: 31672301
DOI: 10.1016/j.path.2019.08.009 -
Archives of Pathology & Laboratory... Aug 2015Thyroid paragangliomas are rare tumors that arise from the inferior laryngeal paraganglia. Most patients are female and present with an asymptomatic thyroid nodule.... (Review)
Review
Thyroid paragangliomas are rare tumors that arise from the inferior laryngeal paraganglia. Most patients are female and present with an asymptomatic thyroid nodule. Histologically, the tumor is composed of cells arranged in a well-defined nest (zellballen) pattern surrounded by a thin fibrovascular stroma. It is a diagnostic pitfall and is occasionally misdiagnosed as follicular neoplasm, medullary thyroid carcinoma, intrathyroid parathyroid proliferation, and especially secondary neuroendocrine tumors. Immunohistochemical stains (cytokeratin, parathyroid hormone, thyroid transcription factor 1, tyrosine hydroxylase, chromogranin A, synaptophysin, S100, calcitonin, carcinoembryonic antigen) are essential in establishing the diagnosis. Loss of succinate dehydrogenase complex, subunit B (SDHB), immunoexpression can be used to triage genetic testing because some mutations are associated with a higher risk for developing metastasis. Total thyroidectomy or lobectomy for solitary lesion is the preferred treatment. Elective lymph node dissection is usually not indicated. Postoperatively, patients should receive hormonal evaluation for functional disease and imaging for evaluation of multifocal or metastatic disease.
Topics: Adult; Female; Humans; Male; Middle Aged; Paraganglioma; Thyroid Neoplasms
PubMed: 26230601
DOI: 10.5858/arpa.2013-0703-RS -
Frontiers in Endocrinology 2022Although pediatric pheochromocytomas and paragangliomas (PPGLs) are rare, they have important differences compared to those in adults. Unfortunately, without timely... (Review)
Review
Although pediatric pheochromocytomas and paragangliomas (PPGLs) are rare, they have important differences compared to those in adults. Unfortunately, without timely diagnosis and management, these tumors have a potentially devastating impact on pediatric patients. Pediatric PPGLs are more often extra-adrenal, multifocal/metastatic, and recurrent, likely due to these tumors being more commonly due to a genetic predisposition than in adults. This genetic risk results in disease manifestations at an earlier age giving these tumors time to advance before detection. In spite of these problematic features, advances in the molecular and biochemical characterization of PPGLs have heralded an age of increasingly personalized medicine. An understanding of the genetic basis for an individual patient's tumor provides insight into its natural history and can guide clinicians in management of this challenging disease. In pediatric PPGLs, mutations in genes related to pseudohypoxia are most commonly seen, including the von Hippel-Lindau gene () and succinate dehydrogenase subunit () genes, with the highest risk for metastatic disease associated with variants in and . Such pathogenic variants are associated with a noradrenergic biochemical phenotype with resultant sustained catecholamine release and therefore persistent symptoms. This is in contrast to paroxysmal symptoms (e.g., episodic hypertension, palpitations, and diaphoresis/flushing) as seen in the adrenergic, or epinephrine-predominant, biochemical phenotype (due to episodic catecholamine release) that is commonly observed in adults. Additionally, PPGLs in children more often present with signs and symptoms of catecholamine excess. Therefore, children, adolescents, and young adults present differently from older adults (e.g., the prototypical presentation of palpitations, perspiration, and pounding headaches in the setting of an isolated adrenal mass). These presentations are a direct result of genetic determinants and highlight the need for pediatricians to recognize these differences in order to expedite appropriate evaluations, including genetic testing. Identification and familiarity with causative genes inform surveillance and treatment strategies to improve outcomes in pediatric patients with PPGL.
Topics: Adrenal Gland Neoplasms; Catecholamines; Genetic Testing; Humans; Paraganglioma; Pheochromocytoma
PubMed: 35903274
DOI: 10.3389/fendo.2022.936178 -
International Journal of Molecular... Oct 2020Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which... (Review)
Review
Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors. Head and neck paragangliomas (HNPGL) can be categorized into carotid body tumors, which are the most common, as well as jugular, tympanic, and vagal paraganglioma. A review of the current literature was conducted to consolidate knowledge concerning PGL mutations, familial occurrence, and the practical application of this information. Available scientific databases were searched using the keywords head and neck paraganglioma and genetics, and 274 articles in PubMed and 1183 in ScienceDirect were found. From these articles, those concerning genetic changes in HNPGLs were selected. The aim of this review is to describe the known genetic changes and their practical applications. We found that the etiology of the tumors in question is based on genetic changes in the form of either germinal or somatic mutations. 40% of PCC and PGL have a predisposing germline mutation (including and ). Approximately 25-30% of cases are due to somatic mutations, such as , and . The tumors were divided into three main clusters by the Cancer Genome Atlas (TCGA); namely, the pseudohypoxia group, the Wnt signaling group, and the kinase signaling group. The review also discusses genetic syndromes, epigenetic changes, and new testing technologies such as next-generation sequencing (NGS).
Topics: Genetic Predisposition to Disease; Head and Neck Neoplasms; Humans; Mutation; Paraganglioma
PubMed: 33081307
DOI: 10.3390/ijms21207669 -
Cancer Imaging : the Official... May 2012The accurate diagnosis of adult pheochromocytoma and paraganglioma necessitates a multidisciplinary approach that includes clinical history, biochemical testing, and... (Review)
Review
The accurate diagnosis of adult pheochromocytoma and paraganglioma necessitates a multidisciplinary approach that includes clinical history, biochemical testing, and multimodality imaging such as computed tomography, magnetic resonance imaging, and nuclear medicine studies. This review illustrates the different imaging characteristics of primary adult pheochromocytomas as well as both sympathetic and parasympathetic paragangliomas. The review also describes known genetic associations and shows common metastatic patterns. Knowledge of the diverse appearance of pheochromocytomas and paragangliomas can result in early initial diagnosis or detection of disease recurrence thereby affecting patient management and prognosis.
Topics: Adrenal Gland Neoplasms; Biomarkers, Tumor; Contrast Media; Humans; Magnetic Resonance Imaging; Neoplasm Metastasis; Neoplastic Syndromes, Hereditary; Paraganglioma; Pheochromocytoma; Positron-Emission Tomography; Radiopharmaceuticals; Soft Tissue Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed
PubMed: 22571874
DOI: 10.1102/1470-7330.2012.0016