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Endocrine Practice : Official Journal... Feb 2023To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas. (Review)
Review
OBJECTIVE
To review the epidemiology, presentation, diagnosis, and management of head and neck paragangliomas.
METHODS
A literature review of english language papers with focus on most current literature.
RESULTS
Paragangliomas (PGLs) are a group of neuroendocrine tumors that arise in the parasympathetic or sympathetic ganglia. Head and neck PGLs (HNPGLs) comprise 65% to 70% of all PGLs and account for 0.6% of all head and neck cancers. The majority of HNPGLs are benign, and 6% to 19% of all HNPGLs develop metastasis outside the tumor site and significantly compromise survival. PGLs can have a familial etiology with germline sequence variations in different susceptibility genes, with the gene encoding succinate dehydrogenase being the most common sequence variation, or they can arise from somatic sequence variations or fusion genes. Workup includes biochemical testing to rule out secretory components, although it is rare in HNPGLs. In addition, imaging modalities, such as computed tomography and magnetic resonance imaging, help in monitoring in surgical planning. Functional imaging with DOTATATE-positron emission tomography, 18F-fluorodeoxyglucose, or 18F-fluorohydroxyphenylalanine may be necessary to rule out sites of metastases. The management of HNPGLs is complex depending on pathology, location, and aggressiveness of the tumor. Treatment ranges from observation to resection to systemic treatment. Similarly, the prognosis ranges from a normal life expectancy to a 5-year survival of 11.8% in patients with distant metastasis.
CONCLUSION
Our review is a comprehensive summary of the incidence, mortality, pathogenesis, presentation, workup and management of HNPGLs.
Topics: Humans; Fluorodeoxyglucose F18; Head and Neck Neoplasms; Paraganglioma; Paraganglioma, Extra-Adrenal; Succinate Dehydrogenase; Tomography, X-Ray Computed
PubMed: 36252779
DOI: 10.1016/j.eprac.2022.10.002 -
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 -
Endocrine-related Cancer Jun 2014Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to... (Comparative Study)
Comparative Study
Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0-2 points), moderately differentiated (MD, 3-6 points) and poorly differentiated (PD, 7-10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08±0.17 and 5.33±0.43 (mean±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=-0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5±2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.
Topics: Adrenal Gland Neoplasms; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Case-Control Studies; Catecholamines; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Prognosis; Succinate Dehydrogenase; Survival Rate; Young Adult
PubMed: 24521857
DOI: 10.1530/ERC-13-0494 -
The Journal of Craniofacial Surgery Sep 2019Paragangliomas are groups of neuroendocrine neoplasms originating from neural crest cells throughout the body, but are rarely observed within the orbit.
BACKGROUND
Paragangliomas are groups of neuroendocrine neoplasms originating from neural crest cells throughout the body, but are rarely observed within the orbit.
CASE REPORT
Two patients, a 4-year-old male and 27-year-old female, presented with a slow-growing proptosis. Well-defined masses were located in the superomedial (male) and temporal (female) portion of the right orbit and involved the entire bodies of either the superior (male) or lateral (female) rectus muscles. B-mode ultrasound scan revealed a homogeneous, well-defined, hypoechoic mass, with rich blood flow signals inside the mass on CDI. CT scans indicated a well-defined, homogeneous mass with moderate enhancement, while MRI showed a well-defined mass with a salt and pepper appearance due to the prominence of blood vessels in the form of flow-void areas. Anterior orbitotomy and total tumor excision were performed on both patients. Subsequent histological and immunohistochemistry assays confirmed the diagnosis of orbital paraganglioma. The male patient is currently at 14 years of follow-up without recurrence or metastasis. The female patient developed recurrence at 3 months post-surgery. After a second surgery and local radiotherapy, there were no signs of the recurrence as assessed at 13 years of follow-up in this female patient.
CONCLUSION
Orbital paraganglioma is an extremely rare benign tumor. The salt-and-pepper appearance as observed with MRI scan represents a relatively salient characteristic of this condition. Total excision of the lesion by orbitotomy is the treatment of choice and the possibility of tumor recurrence warrants diligent consideration. Radiotherapy is useful in patients with tumor recurrence or subtotal surgical excision.
Topics: Adult; Exophthalmos; Female; Humans; Immunohistochemistry; Magnetic Resonance Imaging; Oculomotor Muscles; Orbital Neoplasms; Paraganglioma; Paraganglioma, Extra-Adrenal; Tomography, X-Ray Computed
PubMed: 30896513
DOI: 10.1097/SCS.0000000000005408 -
Current Opinion in Oncology Jan 2020Although the majority of pheochromocytoma and paraganglioma are benign, 15-17% develop metastatic disease, being present at the initial diagnosis in about 11-31% of... (Review)
Review
PURPOSE OF REVIEW
Although the majority of pheochromocytoma and paraganglioma are benign, 15-17% develop metastatic disease, being present at the initial diagnosis in about 11-31% of cases. The natural course of metastasized disease is highly heterogeneous, with an overall 5-year survival rate varying between 40% and 85%. For individual patients, overall survival, progression-free survival, and clinical outcome are difficult to predict. Management of metastasized pheochromocytoma and paraganglioma is challenging. Currently available therapeutic options are surgical debulking, treatment with radiopharmaceuticals (I-MIBG, Y and Lu-DOTATATE), chemotherapy and targeted therapy.
RECENT FINDINGS
The pathogenesis of pheochromocytoma and paraganglioma (PPGL) is largely driven by genomic alterations in PPGL susceptibility genes related to three different clusters: altered pseudo-hypoxic signaling (cluster-1), altered MAP-kinase signaling (cluster-2) and altered Wnt signaling (cluster-3). Novel targeted therapies (tyrosine kinase inhibitors) and potential future therapeutic options, guided by improved knowledge about the oncogenic cluster 1-3 signaling pathways, will be discussed.
SUMMARY
Treatment of metastasized pheochromocytoma and paraganglioma remains challenging. Profiling of gene expression and methylation can serve as a powerful tool for characterizing disease clusters and for guiding targeted therapy to improve selectivity and efficacy. Current knowledge of signatures involved in molecular signaling, metabolism, and resistance mechanisms of PPGLs suggests that therapeutic regimens can be optimized to each molecular subtype.
Topics: Adrenal Gland Neoplasms; Humans; Molecular Targeted Therapy; Neoplasm Metastasis; Paraganglioma; Pheochromocytoma; Radiopharmaceuticals; Randomized Controlled Trials as Topic
PubMed: 31599769
DOI: 10.1097/CCO.0000000000000589 -
Hormone and Metabolic Research =... May 2012Patients with pheochromocytoma or paraganglioma are at risk of developing tumor recurrences or new tumors after successful resection of the primary tumor. This review... (Review)
Review
Patients with pheochromocytoma or paraganglioma are at risk of developing tumor recurrences or new tumors after successful resection of the primary tumor. This review summarizes current knowledge concerning the incidence and risk factors for such events. The overall incidence exceeds 15%. Patients with inherited tumors have a higher probability of recurrence or new tumors. Most recurrences are metastatic, particularly in patients with SDHB mutations or nonhereditary tumors. We recommend the determination of plasma or urinary metanephrines (normetanephrine and metanephrine) 1 month after surgery. In patients with sporadic, single tumors ≤5 cm in diameter, clinical and biochemical follow-up should be performed every 2 years. However, this follow-up period can be reduced to yearly, if it is more simple and more convenient for patients and physicians. Patients with larger or multiple but apparently benign tumors and/or inherited disease should be tested 6 months after surgery and then every year for the rest of their lives. Imaging follow-up is also required in patients with inherited or malignant tumors.
Topics: Adrenal Gland Neoplasms; Follow-Up Studies; Humans; Metanephrine; Paraganglioma; Pheochromocytoma; Postoperative Care; Postoperative Complications
PubMed: 22351478
DOI: 10.1055/s-0031-1301339 -
Journal of Clinical Neuroscience :... Aug 2016Spinal paragangliomas (SP) are benign and overall rare extra-adrenal neuroendocrine tumors often diagnosed during workup for lower back pain. Complete surgical resection...
Spinal paragangliomas (SP) are benign and overall rare extra-adrenal neuroendocrine tumors often diagnosed during workup for lower back pain. Complete surgical resection achieves both symptomatic relief and cure. We present a 32-year-old man with a longstanding history of lumbago and bilateral lower extremity pain found to have a lumbar paraganglioma at the level of the L3 vertebrae. The clinical, histopathological, and radiological characteristics are described, including the rare finding of superficial siderosis on MRI of the brain. A laminectomy with microscopic dissection of the intradural mass achieved complete debulking without evidence of residual tumor. Excellent prognosis can be achieved with complete surgical resection of SP without the need for adjuvant therapy. Therefore, care should be taken to distinguish these spinal tumors from those that appear similar but are more aggressive. As such, the radiological finding of superficial siderosis should raise the suspicion for SP when a vascular intradural extramedullary spinal tumor is observed.
Topics: Adult; Humans; Laminectomy; Lumbar Vertebrae; Magnetic Resonance Imaging; Male; Paraganglioma; Spinal Cord Neoplasms
PubMed: 27032749
DOI: 10.1016/j.jocn.2016.01.019 -
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 -
The Journal of the Louisiana State... 2012Paragangliomas are tumors of the sympathetic and parasympathetic paraganglia. While most paraganglioma are of parasympathetic origin and present as benign palpable... (Review)
Review
Paragangliomas are tumors of the sympathetic and parasympathetic paraganglia. While most paraganglioma are of parasympathetic origin and present as benign palpable masses of the neck, sympathetic paraganglioma are often secretory, presenting with symptoms related to excess catecholamines. Such symptoms include hypertension, headache, palpitations, and diaphoresis. Most sympathetic paraganglioma form within the adrenal medulla, the largest sympathetic paraganglia, and are commonly known as pheochromocytomas. However, sympathetic paragangliomas may present extra-adrenally, carrying a significantly higher risk of malignancy. In this manuscript, we examine a case of a young man with an extra-adrenal sympathetic paraganglioma of the Organ of Zuckerkandl. Furthermore, we discuss appropriate diagnostic workup and treatment of pheochromocytomas and sympathetic paragangliomas.
Topics: Aorta, Abdominal; Catecholamines; Dissection; Humans; Male; Monitoring, Physiologic; Para-Aortic Bodies; Paraganglioma; Preoperative Care; Prognosis; Radiography; Treatment Outcome; Young Adult
PubMed: 22533110
DOI: No ID Found -
Archives of Pathology & Laboratory... Jan 2016Gangliocytic paraganglioma is a rare tumor that occurs most commonly in the second portion of the duodenum. It is characterized by its triphasic cellular... (Review)
Review
Gangliocytic paraganglioma is a rare tumor that occurs most commonly in the second portion of the duodenum. It is characterized by its triphasic cellular differentiation: epithelioid neuroendocrine cells, spindle cells with Schwann cell differentiation, and ganglion cells. Most gangliocytic paragangliomas are considered benign and are amenable to local excision. However, to our knowledge, 23 cases with lymph node metastasis have been reported, 1 case of bone metastasis, and 2 cases of liver metastases. Predictive factors that have been suggested for lymph node metastasis include size (larger than 2 cm), young age, and tumors exceeding the submucosal layer. Our objective was to review the clinical features, the histopathologic characteristics, and the differential diagnosis of gangliocytic paraganglioma and to discuss the value of the predictive factors for lymph node metastasis.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Duodenal Neoplasms; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Paraganglioma; Young Adult
PubMed: 26717062
DOI: 10.5858/arpa.2014-0456-RS