Presentation and management of pheochromocytomas and paragangliomas: about 40 cases

Background Pheochromocytoma and paraganglioma are rare neuroendocrine tumors of the chromaffin tissue, which may produce catecholamines. The aim of our study was to analyze the clinical and para-clinical aspects as well as the therapeutic and evolutionary aspects of pheocromocytomas and paragangliomas based on a series of 40 cases. Methods Our retrospective population-based research study includes 40 patients. Then, a statistical analysis was carried out using the SPSS software (version21). Results Our study involves 40 patients, including 23 women (57, 5%) and 17 men (42,5%). The mean age at the time of the diagnosis was 43.8 ± 16.8 years. The circumstances of the discovery were mainly characterized by adrenal incidentaloma and hypertension. The biological diagnosis was based on the dosage of urinary metanephrines and plasma-free metanephrines in, respectively, 61.5% and 18% of cases. A computerized tomography scan and/or a magnetic resonance imaging scan could help to locate the tumor in 100% of cases. Our series includes 3 cases of bilateral pheochromocytoma, 3 cases of paragangliomas and 1 case of malignant pheochromocytoma, while a hereditary form was retained in 3 patients. In fact, thirty-two patients were operated; cure was clinically labeled in 100% and biologically in 87.5% of patients. Conclusions The main points for improvement that our study has revealed are; a patient follow-up after surgery, which was not always regular, and an insufficient screening for genetic diseases associated with pheochromocytomas and paragangliomas.

Deep Membrane Proteome Profiling Reveals Overexpression of Prostate-Specific Membrane Antigen (PSMA) in High-Risk Human Paraganglioma and Pheochromocytoma, Suggesting New Theranostic Opportunity

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal medulla or sympathetic or parasympathetic paraganglia, respectively. To identify new therapeutic targets, we performed a detailed membrane-focused proteomic analysis of five human paraganglioma (PGL) samples. Using the Pitchfork strategy, which combines specific enrichments of glycopeptides, hydrophobic transmembrane segments, and non-glycosylated extra-membrane peptides, we identified over 1800 integral membrane proteins (IMPs). We found 45 “tumor enriched” proteins, i.e., proteins identified in all five PGLs but not found in control chromaffin tissue. Among them, 18 IMPs were predicted to be localized on the cell surface, a preferred drug targeting site, including prostate-specific membrane antigen (PSMA), a well-established target for nuclear imaging and therapy of advanced prostate cancer. Using specific antibodies, we verified PSMA expression in 22 well-characterized human PPGL samples. Compared to control chromaffin tissue, PSMA was markedly overexpressed in high-risk PPGLs belonging to the established Cluster 1, which is characterized by worse clinical outcomes, pseudohypoxia, multiplicity, recurrence, and metastasis, specifically including SDHB, VHL, and EPAS1 mutations. Using immunohistochemistry, we localized PSMA expression to tumor vasculature. Our study provides the first direct evidence of PSMA overexpression in PPGLs which could translate to therapeutic and diagnostic applications of anti-PSMA radio-conjugates in high-risk PPGLs.

Intraoperative Anesthetic Management in an Asymptomatic and Biochemically Silent Pheochromocytoma

Pheochromocytomas are tumors that originate from the chromaffin tissue of the adrenal medulla and commonly produce catecholamines. The diagnosis is typically established by the measurement of catecholamines or their metabolites in urine or plasma and tumors are localized with the use of radiographic and scintigraphic studies. Pheochromocytomas can occur in asymptomatic patients and the preferred treatment is surgical removal of the tumor. These chromaffin tissue tumors are not uncommon in anesthetic practice and have varied manifestations. The perioperative management of these tumors has improved remarkably over the yearsin conjunction with the evolution of surgical techniques (laparotomy to laparoscopic techniques and now to robotic approaches.). Majority of the patients present with normal clinical and biochemical parameters in the preoperative period, the incidence of hypertension being only 50 %. Even though patients may be clinically asymptomatic, surveillance and proper preoperative evaluation is important, as surgery for associated tumors may precipitate a hypertensive crisis and result in severe complications. We report an intraoperative anesthetic management of 32-year-old female with a left adrenal mass (pheochromocytoma) and left ovarian cyst. Throughout her entire course of treatment she was asymptomatic with normal blood pressure readings. Her biochemical screening was unremarkable. She underwent open surgical resection of the adrenal mass with confirmation of pheochromocytoma on histology. Pheochromocytoma represents very significant challenges to the anesthesiologist’s especially when undiagnosed. This case illustrates how paucity of literature on perioperative preparation of clinically and biochemically silent Pheochromocytomas led to serious intraoperative complications even in an asymptomatic, biochemically negative patient.

Laparoscopic removal of a large pheochromocytoma-paraganglioma of the Zuckerkandl organ

Paragangliomas represent 15 to 20% of all chromaffin tissue tumors. Most often, paragangliomas are located in the abdominal cavity along the large vessels — in the para-aortic region from the diaphragm to the aortic bifurcation. One of the most common extra-adrenal pheochromocytomas is the Zuckerkandl tumor, originating from the para-aortic accumulation of sympathetic tissue located in the area of the inferior mesenteric artery’s origine or in the zone of the aortic bifurcation itself. Due to the technical difficulty in performing laparoscopic removal of paragangliomas, conversion to laparotomy is frequent and reaches 80%. The article describes a clinical case of a patient suffering from this type of neoplasm, with diagnosis details and treatment by a successful radical laparoscopic intervention with a large chromaffinnoma located in a difficult anatomical zone removal.

Pheochromocytoma: a retrospective study from a single center

Objectives. Pheochromocytoma (PCC) is a neuroendocrine tumor derived from chromaffin tissue more frequently found in the adrenal medulla. Many discoveries over the last decade have significantly improved our understanding of PCC. Methods. We retrospectively reviewed all patients with a histological diagnosis of PCC at the Centro Hospitalar Universitario de Sao Joao, a tertiary and university hospital in Oporto, Portugal, between January 2009 and December 2017. Results. The study group included 33 patients. In most cases the diagnosis was suspected with more than half of patients presenting with hypertension and the third diagnosed during the work-up of an adrenal incidentaloma. About half of the patients was referred for genetic testing and 6 patients had a positive inherited susceptibility genetic pathogenic variant associated with classic cancer predisposition syndromes and also associated with newly described genes. In the incidentaloma group, genetic testing was performed in 3 (9%) patients with only 1 positive result. In the suspected group, 15 (45%) genetic tests were performed. Conclusions. In contrast to other studies, where only a minority of patients with PCC were referred for genetic counselling, in our study 54% of patients was referred for genetic testing. This study suggests that clinicians were correctly recognizing the need to refer young patients and patients with positive family history. However, opportunities for genetic testing are frequently missed due to low referral rates in patients with apparently sporadic PCC, particularly older than 30 years old. It is imperative that all the providers involved in the multidisciplinary care of patients with pheochromocytomas are aware of the genetic disorders associated with these unique tumors.

Asymptomatic and Biochemically Silent Pheochromocytoma with Characteristic Findings on Imaging

Pheochromocytomas are tumors that originate from the chromaffin tissue of the adrenal medulla and commonly produce catecholamines. The diagnosis is typically established by the measurement of catecholamines or their metabolites in urine or plasma, and tumors are localized with the use of radiographic and scintigraphic studies. Pheochromocytomas can occur in asymptomatic patients, and the preferred treatment is surgical removal of the tumor. We report a 48-year-old male with a left adrenal incidentaloma, which progressively increased in size from 1.1 cm to 2.6 cm over a 4-year period, as measured by an adrenal computed tomography (CT) scan. Throughout his entire course of treatment, he was asymptomatic with normal blood pressure readings. His biochemical screening was unremarkable for the first three years of tumor surveillance. Follow-up imaging, including CT and MRI, showed findings suspicious for pheochromocytoma, and the diagnosis was ultimately made with the combination of imaging and laboratory studies. He underwent laparoscopic resection of the adrenal mass with confirmation of pheochromocytoma on histology. This case illustrates how CT and MRI findings can alert providers to the presence of a pheochromocytoma, even in an asymptomatic, biochemically negative patient.

Pelvic and Bladder Catecholamine-Producing Tumors A Review of the Literature

Purpose. Starting from the description of two interesting cases, we wondered to review the literature on pelvic and bladder paragangliomas (PGLs) in order to illustrate clinical characteristics and current management, lightening the needed of a prompt diagnosis to avoid the onset of several complications. Although PGLs may arise at any site where physiologically chromaffin tissue exists, pelvic origins are not frequent (less than 2%), and the most common localization is the retroperitoneal space, whereas bladder PGLs account for less than 0.06% of all bladder neoplasms and less than 1% of all PGLs. Methods . We herein performed a brief review of the literature about pelvic PGLs in the PubMed library, conducted according to the PRISMA statement, including studies published from 1954 to 2019. We also discuss clinical presentation, morphologic appearance, and management of two cases of pelvic PGL, both of them characterized by an history of paroxysmal high blood pressure episodes uncontrolled by antihypertensive therapy associated with disabling symptoms, not clearly understood for many years. Results . Overall, we evaluated 108 case reports. The majority were females, presenting typical signs and symptoms, such as arterial hypertension (54.2%), hematuria (35.1%), and headache (33.6%). After treatment, the clinical and biochemical remission was evident in only 55% of analyzed cases. Conclusions . For their singular localization, pelvic and bladder PGLs often might be misdiagnosed. The significant delay in the proper treatment could be responsible for the relative low percentage of complete clinical and biochemical remission.

Pelvic and Bladder Catecholamine-Producing Tumors A Review of the Literature

Purpose . Starting from the description of two interesting cases, we wondered to review the literature on pelvic and bladder paragangliomas (PGLs) in order to illustrate clinical characteristics and current management, lightening the needed of a prompt diagnosis to avoid the onset of several complications. Although PGLs may arise at any site where physiologically chromaffin tissue exists, pelvic origins are not frequent (less than 2%), and the most common localization is the retroperitoneal space, whereas bladder PGLs account for less than 0.06% of all bladder neoplasms and less than 1% of all PGLs. Methods . We herein performed a brief review of the literature about pelvic PGLs in the PubMed library, conducted according to the PRISMA statement, including studies published from 1954 to 2019. We also discuss clinical presentation, morphologic appearance, and management of two cases of pelvic PGL, both of them characterized by an history of paroxysmal high blood pressure episodes uncontrolled by antihypertensive therapy associated with disabling symptoms, not clearly understood for many years. Results . Overall, we evaluated 108 case reports. The majority were females, presenting typical signs and symptoms, such as arterial hypertension (54.2%), hematuria (35.1%), and headache (33.6%). After treatment, the clinical and biochemical remission was evident in only 55% of analyzed cases. Conclusions . For their singular localization, pelvic and bladder PGLs often might be misdiagnosed. The significant delay in the proper treatment could be responsible for the relative low percentage of complete clinical and biochemical remission.

Pheochromocytomas and Paragangliomas: From Genetic Diversity to Targeted Therapies

Pheochromocytoma and paraganglioma (PCPGs) are rare neuroendocrine tumors that arise from the chromaffin tissue of adrenal medulla and sympathetic ganglia. Although metastatic PCPGs account for only 10% of clinical cases, morbidity and mortality are high because of the uncontrollable mass effect and catecholamine level generated by these tumors. Despite our expanding knowledge of PCPG genetics, the clinical options to effectively suppress PCPG progression remain limited. Several recent translational studies revealed that PCPGs with different molecular subtypes exhibit distinctive oncogenic pathways and spectrum of therapy resistance. This suggests that therapeutics can be adjusted based on the signature molecular and metabolic pathways of PCPGs. In this review, we summarized the latest findings on PCPG genetics, novel therapeutic targets, and perspectives for future personalized medicine.

Mesenteric paraganglioma a rare mesenteric tumor

Paragangliomas arise from chromaffin tissue, most commonly found in the Zuckerkandl body, the sympathetic plexus of the urinary bladder, the kidneys, the heart or in the sympathetic ganglia of the head or neck. Some paragangliomas have been described in the Gastrointestinal System, the majority of which were associated with the duodenum. Only a very select few were described to arise from the mesentery.