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Cancers Feb 2019Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia,... (Review)
Review
The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas-A Meta-Analysis and Systematic Review of the Literature.
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia, respectively. These tumors exhibit malignant potential but seldom display evidence of metastatic spread, the latter being the only widely accepted evidence of malignancy. To counter this, pre-defined histological algorithms have been suggested to stratify the risk of malignancy: Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP). The PASS algorithm was originally intended for PCCs whereas the GAPP model is proposed for stratification of both PCCs and PGLs. In parallel, advances in terms of coupling overtly malignant PPGLs to the underlying molecular genetics have been made, but there is yet no combined risk stratification model based on histology and the overall mutational profile of the tumor. In this review, we systematically meta-analyzed previously reported cohorts using the PASS and GAPP algorithms and acknowledge a "rule-out" way of approaching these stratification models rather than a classical "rule-in" strategy. Moreover, the current genetic panorama regarding possible molecular adjunct markers for PPGL malignancy is reviewed. A combined histological and genetic approach will be needed to fully elucidate the malignant potential of these tumors.
PubMed: 30769931
DOI: 10.3390/cancers11020225 -
Frontiers in Endocrinology 2022Pheochromocytomas and paragangliomas (PGLs) are rare non-epithelial neuroendocrine neoplasms of the adrenal medulla and extra-adrenal paraganglia respectively. Duodenal... (Review)
Review
Pheochromocytomas and paragangliomas (PGLs) are rare non-epithelial neuroendocrine neoplasms of the adrenal medulla and extra-adrenal paraganglia respectively. Duodenal PGL is quite rare and there are only two previous reports. Herein, we report a case of multiple catecholamines (CAs)-producing PGLs in the middle ear, retroperitoneum, and duodenum, and review the literature of duodenal PGLs. A 40-year-old man complained right-ear hearing loss, and an intracranial tumor was suspected. Magnetic resonance imaging of the head revealed a 3-cm mass at the right transvenous foramen, which was surgically resected following preoperative embolization. The pathological diagnosis was a sympathetic PGL of the right middle ear. Six years later, family history of PGL with germline mutation of succinate dehydrogenase complex iron sulfur subunit B, SDHB: c.268C>T (p.Arg90Ter) was clarified. The patient had elevated levels of plasma and urine CAs again. Abdominal computed tomography scanning revealed two retroperitoneal tumors measuring 30-mm at the anterior left renal vein and 13-mm at near the ligament of Treitz. The larger tumor was laparoscopically resected, but the smaller tumor was not identified by laparoscopy. After the operation, the patient remained hypertensive, and additional imaging tests suggested a tumor localized in the duodenum. The surgically resected tumor was confirmed to be a duodenal PGL. After that, the patient remained hypertension free, and urinary levels of noradrenaline and normetanephrine decreased to normal values. No recurrence or metastasis has been found at 1 year after the second operation. CAs secretion from PGLs in unexpected location, like the duodenum of our patient, may be overlooked and leads to a hypertensive crisis. In such cases, comprehensive evaluation including genetic testing, fluorodeoxyglucose-positron emission tomography scanning, and measurement of CAs will be useful for detecting PGLs. Most previous reports on duodenal PGL were gangliocytic PGL which has been renamed composite gangliocytoma/neuroma and neuroendocrine tumor, and defined the different tumor from duodenal PGL. We reviewed and discussed duodenal PGLs in addition to multiple PGLs associated with SDHB mutation.
Topics: Male; Humans; Adult; Succinate Dehydrogenase; Paraganglioma; Pheochromocytoma; Genetic Testing; Catecholamines; Adrenal Gland Neoplasms
PubMed: 36704041
DOI: 10.3389/fendo.2022.1054468 -
Case Reports in Otolaryngology 2024The carotid body paraganglioma is a rare benign neoplasm arising from the chemoreceptor cells of the carotid bulb. The carotid body has the largest collection of...
The carotid body paraganglioma is a rare benign neoplasm arising from the chemoreceptor cells of the carotid bulb. The carotid body has the largest collection of paraganglia in the head and neck with 60-70% of head and neck paraganglioma. Paraganglia are clusters of cells originating from the neural crest with histological and cytochemical characteristics of neuroendocrine cells. It is mostly asymptomatic in early presentation but become symptomatic and difficult to manage when the tumor is large. We present a case of a 26-year-old male who presented with a painless, pulsatile, progressively increasing left lateral neck swelling of 5 years duration with Shamblin IIIa. The diagnosis of the tumor was confirmed based on clinical features, histology, and radiological findings. We had difficult surgical dissection of the tumor with neurovascular damage.
PubMed: 38715736
DOI: 10.1155/2024/9963521 -
Journal of Clinical Medicine Dec 2022Paragangliomas are highly vascularised and often heritable tumors derived from the paraganglia. They are typically discovered in the retroperitoneal space as well as the...
Paragangliomas are highly vascularised and often heritable tumors derived from the paraganglia. They are typically discovered in the retroperitoneal space as well as the head and neck region but are rarely encountered in the liver parenchyma. We report a case of a primary functioning hepatic paraganglioma and provide an up-to-date literature review of patients with such tumors. We present a case of functioning paraganglioma in a 34-year-old female patient who suffered a solitary lesion in her left lateral lobe with symptoms of hypertension since pregnancy. She did not have any family history and her pre-pregnancy examination was negative. An abdominal CT imaging revealed a 6.5 × 5.7 cm liver lesion in segments II and III. Laboratory investigations identified elevation in plasma-free catecholamines. With sufficient preoperative preparation, the patient underwent laparoscopic left hemihepatectomy. Immunohistochemical staining revealed Syn (+) tumor cell nests surrounded by S-100 sustentacular cells (+), providing a definitive diagnosis of paraganglioma. The patient recovered uneventfully without signs of recurrence during a 1-year follow-up period. Our case demonstrates that primary refractory hypertension in pregnancy should be screened for paraganglioma through abdominal ultrasound and plasma free catecholamines. On the other hand, laparoscopic surgery is technically safe and feasible for the treatment of patients with hepatic paragangliomas in favorable locations.
PubMed: 36555899
DOI: 10.3390/jcm11247282 -
Endocrinology and Metabolism Clinics of... Jun 2011Pheochromocytoma is a tumor of the chromaffin cells in the adrenal medulla and sympathetic paraganglia, which synthesizes and secretes catecholamines. Norepinephrine,...
Pheochromocytoma is a tumor of the chromaffin cells in the adrenal medulla and sympathetic paraganglia, which synthesizes and secretes catecholamines. Norepinephrine, epinephrine, and dopamine all act on their target receptors, which causes a physiologic change in the body. High circulating levels of catecholamines can lead to severe hypertension and can have devastating effects on multiple body systems (eg, cardiovascular, cerebrovascular), and can lead to death if untreated. Although surgical treatment represents the only modality of ultimate cure, pharmacologic preoperative treatment remains the mainstay of successful outcome.
Topics: Adrenal Gland Neoplasms; Adult; Child; Dopamine; Epinephrine; Humans; Hypertension; Norepinephrine; Paraganglioma, Extra-Adrenal; Pheochromocytoma
PubMed: 21565668
DOI: 10.1016/j.ecl.2011.02.002 -
World Journal of Clinical Cases Sep 2022Kidney transplantation is associated with an increased risk of tumors in the urinary bladder. Among all the pathological types of tumors in the bladder, paraganglioma,...
BACKGROUND
Kidney transplantation is associated with an increased risk of tumors in the urinary bladder. Among all the pathological types of tumors in the bladder, paraganglioma, which arises from extra-adrenal paraganglia and consists of chromaffin cells, is rare. Paragangliomas might cause severe clinical symptoms due to catecholamine hypersecretion or mass compression. Bladder paragangliomas are rare, especially those appearing after kidney transplantation. Here, we report a case of bladder paraganglioma developing after kidney transplantation.
CASE SUMMARY
A 63-year-old woman received a kidney transplant 12 years ago and took oral immunosuppressants (cyclosporine, mizoribine, and methylprednisolone) for regular post-transplant treatment. The patient felt no discomfort and she came to the hospital for a routine checkup. A mass located in the bladder was incidentally discovered by computed tomography, and she underwent surgical treatment. A 2 cm × 2 cm invasive mass was found in the trigone of the bladder and the mass was removed. The diagnosis of paraganglioma was confirmed by morphology and immunophenotyping. The patient had a good prognosis and is still alive.
CONCLUSION
Paraganglioma can grow in the bladder, which might cause no clinical symptoms. The diagnosis mainly depends on morphology and immunophenotyping. Surgical resection is an important treatment option for such patients.
PubMed: 36157666
DOI: 10.12998/wjcc.v10.i25.9044 -
The Permanente Journal 2015Neuroendocrine tumors are either epithelial or neural in origin. Neuroendocrine tumors of the retroperitoneum are mostly metastatic. Primary epithelial neuroendocrine... (Review)
Review
Neuroendocrine tumors are either epithelial or neural in origin. Neuroendocrine tumors of the retroperitoneum are mostly metastatic. Primary epithelial neuroendocrine tumors of the retroperitoneum are exceedingly rare. We describe a case of a retroperitoneal tumor that was discovered incidentally during exploratory laparotomy for small-bowel obstruction. Histopathologic and immunochemical analyses of the biopsied mass were consistent with an epithelial neuroendocrine tumor. The tumor was subsequently removed and final analyses confirmed the initial diagnosis. No evidence of lymph nodes or paraganglia were found within the tumor on histologic examination. Extensive evaluation did not reveal any other primary or metastatic lesions. Therefore, the diagnosis of primary epithelial neuroendocrine tumor of the retroperitoneum was made. The literature is reviewed and discussed. To date, this is only the fifth reported case of primary epithelial retroperitoneal neuroendocrine tumor. Although extremely rare, the possibility of such diagnosis should be included in the differential diagnosis of a retroperitoneal tumor.
Topics: Aged; Female; Humans; Intestinal Diseases; Necrosis; Neuroendocrine Tumors; Retroperitoneal Neoplasms
PubMed: 26517438
DOI: 10.7812/TPP/15-058 -
Annals of Oncology : Official Journal... 2001Somatostatin and other neuropeptides are expressed in tumors originating from neuronal precursors and paraganglia, namely medulloblastoma, central Primitive...
Somatostatin and other neuropeptides are expressed in tumors originating from neuronal precursors and paraganglia, namely medulloblastoma, central Primitive Neuro-Ectodermal Tumors (cPNETs), neurocytoma, gangliocytoma. olfactory neuroblastoma, paraganglioma. In medulloblastoma, the most common malignant tumor in childhood, there is an extensive expression of somatostatin in addition to somatostatin receptors (SSTR) type 2. Although density of SSTR-2 and intensity of expression of somatostatin genes have no prognostic significance in medulloblastoma. their presence may bring along important information on oncogenesis and relate medulloblastoma to cPNETs. Radio-labeled octreotide scintigraphy may be useful in the follow-up of these patients. allowing differentiation between scar and tumoral tissue. Moreover, on the basis of octreotide-induced inhibition of cell proliferation in medulloblastoma, a trial with octreotide in patients with recurrent or high-risk tumor is warranted. Meningiomas and low-grade astrocytic gliomas, even if not displaying a clear neuroendocrine phenotype, have high levels of SSTR-2. In meningiomas, SSTRs-scintigraphy is not part of the routine pre-operative assessment; moreover, a therapeutic trial with somatostatin-analogues in patients with recurrent or inoperable meningiomas should be carried-out with great caution, because somatostatin and octreotide slightly increase cell proliferation in cultured meningiomatous cells. Low-grade gliomas (WHO grade 2), and a smaller fraction of anaplastic astrocytomas, express SSTR-2, while glioblastomas usually do not. Unfortunately, radiolabeled-octreotide scintigraphy is not useful in the differential diagnosis of gliomas, because the results are altered by the disruption of the blood brain barrier (BBB); in addition, radionuclide-labeled somatostatin analogues are not useful in the therapy of low-grade gliomas, because the intact BBB prevents them from reaching the target SSTR-2. Recently, a pilot study in gliomas, has proposed the use of a radio-labeled somatostostatin analogue with a loco-regional approach in order to overcome the intact BBB.
Topics: Antineoplastic Agents; Brain Neoplasms; Cell Differentiation; Cell Division; Gene Expression Regulation, Neoplastic; Glioma; Humans; Medulloblastoma; Meningeal Neoplasms; Meningioma; Neuroectodermal Tumors, Primitive; Neuroendocrine Tumors; Octreotide; Phenotype; Radionuclide Imaging; Radiopharmaceuticals; Receptors, Somatostatin
PubMed: 11762340
DOI: 10.1093/annonc/12.suppl_2.s131 -
Ear, Nose, & Throat Journal Sep 2023Paragangliomas are rare, slow-growing, hypervascular, catecholamine-secreting neuroendocrine tumors arising from the paraganglia. Paragangliomas are rarely found in the...
Paragangliomas are rare, slow-growing, hypervascular, catecholamine-secreting neuroendocrine tumors arising from the paraganglia. Paragangliomas are rarely found in the head and neck and are typically benign, presenting as a painless, slow-growing mass. Surgical extirpation in combination with long-term surveillance has been long regarded as the standard of care; however, the advances in imaging, radiation therapy, and embolization techniques have improved diagnostic and therapeutic modalities. We present a case of an 87-year-old female who had previously undergone resection of a paraganglioma in 1998, with no evidence of disease in 2002. Eighteen years later, the patient presented to the clinic with otogenic complaints. Imaging showed an expansive mass from the jugular foramen with bone destruction and opacification within the ear canal. The patient opted for observation. The patient eventually presented to the emergency room with neurologic manifestations. Imaging showed a cerebellar abscess prompting emergency drainage. Intraoperative cultures grew and , and the patient was started on 6 weeks of IV antibiotic therapy. Debulking of the paraganglioma was performed followed several months by mastoid and ear canal obliteration; however, the patient experienced complications, including dehiscence of the external auditory canal and infection. The patient was eventually treated successfully, marked by a reduction in complaints, a return to baseline activities, and imaging showing no increase in tumor size.
Topics: Female; Humans; Aged, 80 and over; Paraganglioma; Diagnostic Imaging; Head and Neck Neoplasms; Neck; Mastoid
PubMed: 37551648
DOI: 10.1177/01455613231187762 -
Cancers Jun 2022Hypoxia-inducible factors (HIF) 2α and 1α are the major oxygen-sensing molecules in eukaryotic cells. HIF2α has been pathogenically linked to paraganglioma and...
Hypoxia-inducible factors (HIF) 2α and 1α are the major oxygen-sensing molecules in eukaryotic cells. HIF2α has been pathogenically linked to paraganglioma and pheochromocytoma (PPGL) arising in sympathetic paraganglia or the adrenal medulla (AM), respectively. However, its involvement in the pathogenesis of paraganglioma arising in the carotid body (CB) or other parasympathetic ganglia in the head and neck (HNPGL) remains to be defined. Here, we retrospectively analyzed HIF2α by immunohistochemistry in 62 PPGL/HNPGL and human CB and AM, and comprehensively evaluated the HIF-related transcriptome of 202 published PPGL/HNPGL. We report that HIF2α is barely detected in the AM, but accumulates at high levels in PPGL, mostly (but not exclusively) in those with loss-of-function mutations in and genes encoding components of the succinate dehydrogenase (SDH) complex. This is associated with upregulation of and the HIF2α-regulated genes and . In contrast, HIF2α and HIF2α-regulated genes are highly expressed in CB and HNPGL, irrespective of VHL and SDH dysfunctions. We also found that HIF2α and HIF1α protein expressions are not correlated in PPGL nor HNPGL. In addition, HIF1α-target genes are almost exclusively overexpressed in -mutated HNPGL/PPGL. Collectively, the data suggest that involvement of HIF2α in the physiology and tumor pathology of human paraganglia is organ-of-origin-dependent and HIF1α-independent.
PubMed: 35740651
DOI: 10.3390/cancers14122986