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Cureus May 2020Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare tumors originated in cells derived from the neural crest. The first ones are located in the adrenal medulla,... (Review)
Review
Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare tumors originated in cells derived from the neural crest. The first ones are located in the adrenal medulla, and the second ones in the sympathetic and parasympathetic nervous system. These kind of tumors may secrete excess catecholamines, including epinephrine, norepinephrine, dopamine and/or their metabolite metanephrine, normetanephrine and 3-methoxytyramine, respectively. Its clinical manifestations depend on the location, the secretory profile and the malignant potential of the tumor. These tumors are frequently benign in their presentation. Some arise in the context of familiar syndromes, accounting for up to one-third of the total of diagnosis. The metastatic form is the most common presentation of the tumors with familiar origin and due to their rarity, their diagnosis and management is often difficult. Over the years, our knowledge and perception of PHEO and PGL has greatly expanded and changed. This review article aims to focus on the genetic, clinical, diagnostic, therapeutic and prognostic approaches, to give the clinician knowledge of the most recent updates regarding these themes.
PubMed: 32523826
DOI: 10.7759/cureus.7969 -
Frontiers in Endocrinology 2015Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they... (Review)
Review
Pheochromocytomas (PCCs) and paragangliomas (PGLs) are neuroendocrine tumors derived from the chromaffin tissue. Diagnosis of these tumors is extremely important as they are linked to the hypertension syndrome with great cardiovascular morbidity and mortality. A great majority of PCCs and PGLs are sporadic and benign tumors; however, the classic idea of 10% exception of these features is changing. The description of new genes linked to familial forms of PCC/PGLs, such as succinate dehydrogenase (SDH) complex subunits, KIF1Bβ, EGLN1, TMEM127, and MAX, added to the well-known PCC familial syndrome (MEN2, VHL, and neurofibromatosis type 1) presents new challenges for diagnosis. In this review, we discuss the diversity of clinical and genetic approaches to this syndrome as well the diverse criteria that should guide genetic investigation.
PubMed: 26347711
DOI: 10.3389/fendo.2015.00126 -
Cancer Genetics 2012Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors... (Review)
Review
Pheochromocytomas and paragangliomas (PCC/PGL) are tumors derived from the adrenal medulla or extra-adrenal ganglia, respectively. They are rare and often benign tumors that are associated with high morbidity and mortality due to mass effect and high circulating catecholamines. Although most PCCs and PGLs are thought to be sporadic, over one third are associated with 10 known susceptibility genes. Mutations in three genes causing well characterized tumor syndromes are associated with an increased risk of developing PCCs and PGLs, including VHL (von Hippel-Lindau disease), NF1 (Neurofibromatosis Type 1), and RET (Multiple Endocrine Neoplasia Type 2). Mutations in any of the succinate dehydrogenase (SDH) complex subunit genes (SDHA, SDHB, SDHC, SDHD) can lead to PCCs and PGLs with variable penetrance, as can mutations in the subunit cofactor, SDHAF2. Recently, two additional genes have been identified, TMEM127 and MAX. Although these tumors are rare in the general population, occurring in two to eight per million people, they are more commonly associated with an inherited mutation than any other cancer type. This review summarizes the known germline and somatic mutations leading to the development of PCC and PGL, as well as biochemical profiling for PCCs/PGLs and screening of mutation carriers.
Topics: Adrenal Gland Neoplasms; Animals; Comprehension; Genetic Heterogeneity; Genetic Predisposition to Disease; Humans; Multiple Endocrine Neoplasia; Paraganglioma; Pheochromocytoma; Syndrome; von Hippel-Lindau Disease
PubMed: 22429592
DOI: 10.1016/j.cancergen.2012.01.009 -
American Journal of Cancer Research 2020Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL... (Review)
Review
Pheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors that arising from the adrenal medulla or extra-adrenal autonomic ganglia. Traditionally, PPGL was classified as benign or malignant based on the presence of distant metastasis at the time of initial surgery. However, according to WHO 2017 Classification of Tumors of Endocrine Organs, all PPGL has metastatic potential. The term "metastatic" is used, replacing "malignant" in this group of tumors. The prediction of PPGL's metastatic potential is a clinical concern, although many relevant indicators such as genetics, histology, pathology and molecular biology markers have been proved to be related to the metastasis of PPGL, but none of them is 100% predictive; various types of prediction systems had been created, but previous studies had demonstrated that they still need to be validated in multicenter studies. There is no unified clinical standard to differentiate metastatic from non-metastatic and a highly effective prediction system is of urgent need. In this review, we summarized all reported prediction systems, including the PASS system, the GAPP system, the COPPs system and the ASES system. Additional potential indicators that related to metastatic PPGL were also introduced.
PubMed: 32266090
DOI: No ID Found -
Head and Neck Pathology Jun 2016Paragangliomas are rare, typically benign neuroendocrine tumors that represent a small portion of head and neck tumors. A small percentage of these are known to have...
Paragangliomas are rare, typically benign neuroendocrine tumors that represent a small portion of head and neck tumors. A small percentage of these are known to have malignant potential. They arise from the carotid body, jugular bulb or vagus nerves. There is limited literature discussing the management of malignant vagal paragangliomas. We present a case of a 25 year old female with a left malignant vagal paraganglioma. The following case presentation will describe the presentation, classic radiologic findings, and management of a malignant vagal paraganglioma along with a review of the literature.
Topics: Adult; Female; Humans; Lymphatic Metastasis; Paraganglioma, Extra-Adrenal; Vagus Nerve Diseases
PubMed: 25712400
DOI: 10.1007/s12105-015-0621-5 -
GMS Current Topics in... 2011Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation.In the head and neck...
Paragangliomas are rare tumors of neural crest origin. They are benign in the majority of cases and are characterized by a strong vascularisation.In the head and neck region they most commonly occur as carotid body tumors. Jugulotympanic and especially vagal paragangliomas are seen less frequently. Complete surgical resection represents the only curative treatment option even though resection of locally advanced tumors regularly results in lesions of the lower cranial nerves and major vessels. Appoximately 30% of all head and neck paragangliomas (HNPs) are hereditary and associated with different tumor syndromes. The paraganglioma syndromes 1, 3 and 4 (PGL 1, 3 and 4) make up the majority of those familial cases. PGL 1 is associated with mutations of the succinate dehydrogenase subunit D (SDHD) gene, PGL 3 is caused by SDHC and PGL 4 by SDHB gene mutations. Multiple HNPs and the occurance of HNPs together with pheochromocytomas are seen in SDHD as well as SDHB mutation carriers. In patients with SDHB mutations the risk for the development of malignant paraganglial tumors is significantly higher compared to SDHC and SDHD patients as well as patients with sporadic tumors. SDHC mutation carriers almost exclusively present with benign HNP that are unifocal in the majority of cases. The role of transmission is autosomal dominant for all three symptoms. Interestingly, there is a "parent-of-origin-dependent-inheritance" in subjects with SDHD gene mutations. This means that the disease phenotype may only become present if the mutation is inherited through the paternal line. We recommend screening for mutations of the genes SDHB, SDHC and SDHD in patients with HNPs. Certain clinical parameters can help to set up the order in which the three genes should be tested.
PubMed: 22558053
DOI: 10.3205/cto000076 -
Langenbeck's Archives of Surgery Feb 2012Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from... (Comparative Study)
Comparative Study Review
INTRODUCTION
Malignant pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare disorders arising from the adrenal gland, from the glomera along parasympathetic nerves or from paraganglia along the sympathetic trunk. According to the WHO classification, malignancy of PCCs and PGLs is defined by the presence of metastases at non-chromaffin sites distant from that of the primary tumor and not by local invasion. The overall prognosis of metastasized PCCs/PGLs is poor. Surgery offers currently the only change of cure. Preferably, the discrimination between malignant and benign PCCs/PGLs should be made preoperatively.
METHODS
This review summarizes our current knowledge on how benign and malignant tumors can be distinguished.
CONCLUSION
Due to the rarity of malignant PCCs/PGLs and the obvious difficulties in distinguishing benign and malignant PCCs/PGLs, any patient with a PCC/PGL should be treated in a specialized center where a multidisciplinary setting with specialized teams consisting of radiologists, endocrinologist, oncologists, pathologists and surgeons is available. This would also facilitate future studies to address the existing diagnostic and/or therapeutic obstacles.
Topics: Adrenal Gland Neoplasms; Adrenalectomy; Animals; Biopsy, Needle; Chemotherapy, Adjuvant; Diagnosis, Differential; Diagnostic Imaging; Female; Humans; Immunohistochemistry; Male; Neoplasm Staging; Paraganglioma; Pheochromocytoma; Prognosis; Radiotherapy, Adjuvant; Survival Analysis
PubMed: 22124609
DOI: 10.1007/s00423-011-0880-x -
Autopsy & Case Reports 2021Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas...
Paragangliomas are rare, encapsulated, benign neuroendocrine tumors that can arise from the adrenal medulla or extra-adrenal paraganglia. Extra-adrenal paragangliomas may develop a gangliocytic component with ganglion cells (Gangliocytic paragangliomas). Nearly 25%of cauda equina paragangliomas are gangliocytic paragangliomas. Here, we describe the case of a 35-year-old male who presented with weakness of both lower limbs over the last two months. Radiological findings were suggestive of myxopapillary ependymoma. However, the histopathological examination revealed a tumor with cells arranged in sheets, papillae, lobules, and around vessels forming pseudo rosettes. Ganglion cells were seen in small groups and, also singly. Tumor cells were immunopositive for chromogranin, synaptophysin, and S-100. Ganglion cells were immunopositive for synaptophysin, NSE, and NFP. A final histological diagnosis of Gangliocytic paraganglioma (WHO grade I) was made. To date, only nine gangliocytic paraganglioma cases have been previously reported, and to the best of our knowledge, this is the largest gangliocytic paraganglioma.
PubMed: 34307231
DOI: 10.4322/acr.2021.277 -
Hormones (Athens, Greece) 2009The widespread application of abdominal imaging procedures has resulted in an increased frequency of clinically silent adrenal masses. Adrenal incidentaloma (AI) is a... (Review)
Review
The widespread application of abdominal imaging procedures has resulted in an increased frequency of clinically silent adrenal masses. Adrenal incidentaloma (AI) is a term applied to an accidentally discovered adrenal mass on imaging performed for the investigation of an unrelated complaint. Adrenal incidentalomas (AIs) are a cluster of different pathologies, the majority of which are benign and non-functioning adrenal adenomas. However, mild hormonal alterations as well as metabolic abnormalities may be present in patients with AIs. Thus, a multidisciplinary approach with biochemical and radiologic evaluation is needed to characterize these lesions and identify patients who are at high risk for hormonal or malignant evolution. Significant new information has helped resolve controversies regarding the most reliable approach to this clinical problem. The present review considers the prevalence, pathology and natural history of AIs. We also discuss the reliability of available screening methods and localization techniques and consider optimal management and follow-up strategies.
Topics: Adrenal Gland Neoplasms; Adrenocortical Adenoma; Algorithms; Biopsy, Fine-Needle; Cushing Syndrome; Humans; Incidental Findings; Magnetic Resonance Imaging; Pheochromocytoma; Tomography, X-Ray Computed
PubMed: 19671516
DOI: 10.14310/horm.2002.1233 -
Indian Journal of Endocrinology and... 2015Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL...
BACKGROUND
Pheochromocytomas (PHEO) and paragangliomas (PGL) are derived from paraganglia of the sympathetic and parasympathetic nervous system. Most of the sympathetic PHEO/PGL secrete either catecholamine or their metabolites, metanephrines, whereas parasympathetic PHEO/PGL are nonsecretory. We assessed the utility of plasma free 3-methoxytyramine (3MT), normetanephrine (NM), and metanephrine (MN) for the diagnosis of PHEO/PGL.
MATERIALS AND METHODS
Sixty-five patients referred to endocrine/ENT clinics were enrolled. Twelve patients with von Hippel-Lindau (VHL), neurofibromatosis type 1 (NF1) and multiple endocrine neoplasia type 2 (MEN2) syndromes were excluded. Remaining 53 patients (39 patients with adrenal, abdominal, cervical and thoracic PHEO/PGL and 14 patients with head and neck PGL (HNPGL) were taken for this study. Sixty-five age- and sex-matched subjects were taken as controls. Plasma levels 3MT, NM, and MN were measured using high-performance liquid chromatography. Receivers operating characteristics was plotted and cut-off levels were established.
RESULTS
When compared with controls, there was a 36-, 8.7- and 9.5-fold increase in levels of NM, 3MT and MN in the patients with PHEO/PGL and 7.2- and 2.7-fold increase in 3MT and NM, in the patients with HNPGL, respectively. In malignant PHEO/PGL, there was a 99-, 16- and 20-fold increase and in benign PHEO/PGL, there was 19-, 6.8- and 6.4-fold increase in levels of NM, 3MT, and MN, respectively. NM in combination with MN was high in 97% of the patients with PHEO/PGL. All three metabolites in combination were high in 83% of patients with HNPGL. In malignant PHEO/PGL, 50% subjects had increased levels of both NM and 3MT.
CONCLUSIONS
Measurement of plasma-free NM along with 3MT and MN provides a better tool for the diagnosis of PHEO/PGL as well as HNPGL. Further, NM in combination with 3MT can be used for the diagnosis of malignant PHEO/PGL.
PubMed: 26425473
DOI: 10.4103/2230-8210.163183