Anesthesia Management in Hereditary Pheochromocytoma and Paraganglioma:Updated Insights into Clinical Features and Perioperative Care

Approximately 40% of pheochromocytoma and paraganglioma(PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau(VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2(MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1(NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team(MDT) approach is often invaluable in perioperative management.

Subclinical paraganglioma of the retroperitoneum:A case report

BACKGROUND Paraganglioma(PGL)located in the retroperitoneum presents challenges in diagnosis and treatment due to its hidden location,lack of specific symptoms in the early stages,and absence of distinctive manifestations on imaging.CASE SUMMARY A 56-year-old woman presented with a left upper abdominal mass discovered 1 wk ago during a physical examination.She did not have a history of smoking,alcohol consumption,or other harmful habits,no surgical procedures or infectious diseases,and had a 4-year history of hypertension.Upon admission,she did not exhibit fever,vomiting,or abdominal distension.Physical examination indicated mild percussion pain in the left upper abdomen,with no palpable enlargement of the liver or spleen.Laboratory tests and tumor markers showed no significant abnormalities.Enhanced computed tomography and magnetic resonance imaging of the upper abdomen revealed a cystic solid mass in the left epigastrium measuring approximately 6.5 cm×4.5 cm,with inhomogeneous enhancement in the arterial phase,closely associated with the lesser curvature of the stomach and the pancreas.The patient underwent laparoscopic resection of the retroperitoneal mass,which was successfully removed without tumor rupture.A 12-month postoperative follow-up period showed good recovery.CONCLUSION This case report details the successful laparoscopic resection of a retroperitoneal subclinical PGL,resulting in a good recovery observed at the 12-month follow-up.Interestingly,the patient also experienced unexpected cure of hypertensive disease.

Treatment for paraganglioma with stereotactic radiotherapy

BACKGROUND Paragangliomas(PG)are rare neoplasms of neuroendocrine origin that tend to be highly vascularized,slow-growing,and usually sporadic.To date,common treatment options are surgical resection(SR),with or without radiation therapy(RT),and a watch-and-wait approach.AIM To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT(FSRT)treatment in unresectable PG(uPG).METHODS We retrospectively evaluated patients with uPG(medically inoperable or refused SR)treated with FSRT with a Cyberknife System(Accuray Incorporated,Sunnyvale,California).Toxicity and initial efficacy were evaluated.RESULTS From May 2009 to January 2023,6 patients with a median age of 68(range 20-84)were treated with FSRT.The median delivered dose was 21 Gy(range 20-30 Gy)at a median isodose line of 75.5%(range 70%-76%)in 4 fractions(range 3-5 fractions).The median volume was 13.6 mL(range 12.4-65.24 mL).The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively.Site of origin involved were the timpa-nojugular glomus(4/6),temporal bone,and cervical spine.In 1 of the 6 patients,the follow-up was insufficient;5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%.We observed negligible toxicities during and after RT.The majority of patients showed stable symptoms during follow-up.Only 1 patient developed spine metastases.CONCLUSION Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.

Utilizing bioinformatics for integrated analysis of multiple genes in the diagnosis and pathogenesis of metastatic pheochromocytoma and paraganglioma

Objective:The aim of the study was to investigate effective diagnostic molecular markers and the specific mechanisms of metastatic pheochromocytomas and paragangliomas(PPGLs).Methods:Data were collected from GEO datasets GSE67066 and GSE60458.The R software and various packages were utilized for the analysis of differentially expressed genes,Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,receiver operating characteristic curve assessment,logistic model construction,and correlation analysis.The NetworkAnalyst tool was used to analyze gene-miRNA interactions and signaling networks.In addition,the TIMER database was used to estimate the immune scores.Results:A total of 203 and 499 differentially expressed genes were identified in GSE67066 and GSE60458,respectively.These genes are implicated in cytokine and cytokine receptor interactions,extracellular matrix–receptor interactions,and platelet activation signaling pathways.Notably,MAMLD1,UST,MATN2,LPL,TWIST1,SFRP4,FRMD6,RBM24,PRIMA1,LYPD1,KCND2,CAMK2N1,SPOCK3,and ALPK3 were identified as the key genes.Among them,MATN2 and TWIST1 were found to be coexpressed with epithelial-mesenchymal transition–linked markers,whereas KCND2 and LPL exhibited associations with immune checkpoint expression and immune cell infiltration.Eight miRNAs were identified as potential regulators of key gene expression,and it was noted that TWIST1 might be regulated by SUZ12.Notably,the area under the curve of the 4-gene model for distinguishing between malignant and benign groups was calculated to be 0.918.Conclusions:The combined gene and mRNA expression model enhances the diagnostic accuracy of assessing PPGL metastatic potential.These findings suggest that multiple genes may play a role in the metastasis of PPGLs through the epithelial-mesenchymal transition and may influence the immune microenvironment.

Primary intra-abdominal paraganglioma:A case report

BACKGROUND Paragangliomas are rare neuroendocrine tumors.We hereby report a case of a localized paraganglioma found in the abdominal cavity,and review the relevant literature to improve the understanding of this disease.CASE SUMMARY A 29-year-old Chinese female patient was referred to our hospital due to an abdominal mass found on physical examination.Imaging revealed a mass in the left upper abdomen,suggestive of either a benign stromal tumor or an ectopic accessory spleen.Laparoscopic radical resection was subsequently performed,and histopathological analysis confirmed the diagnosis of a paraganglioma.The patient was followed up 3 months post-operation,and reported good recovery with no metastasis.CONCLUSION Radical resection can effectively treat intra-abdominal paragangliomas,with few side effects and low recurrence risk.In addition,early and accurate diagnosis and timely intervention are essential for the prognosis of this disease.

Intrapericardial Paraganglioma, an Exceedingly Rare Finding: A Case Report

Paragangliomas are rare tumors that arise from the sympathetic or the parasympathetic ganglia. Parasympathetic paragangliomas are usually nonfunctional. They are often found in the pre aortic and paravertebral sympathetic plexus or at the base of the skull. 80% of these are Glomus jugulare and carotid body paragangliomas. Intrapericardial paragangliomas are exceedingly rare. Less than 2% of paragangliomas are found in the chest and most of them are situated in the posterior mediastinum. As such, there are no clear guidelines on how to treat intrapericardial paragangliomas. We present here the case of a patient with an intrapericardial paraganglioma who was evaluated by cardiology, cardiac surgery, and endocrinology. In this case cardiac surgery opted for a conservative approach and did not offer surgery to the patient. There is some literature supporting a surgical approach but no specific guidelines about this have been written. The patient is currently being monitored since she did not have metastatic disease and her paraganglioma was nonfunctioning. With this case we want to add to the body of evidence that this type of cases does not need an urgent surgical approach.

Per-Operative Discovery of Tympanic Paraganglioma: A Case Report

Background: Tympanic paragangliomas are common middle ear benign neoplasias that develop from endocrines cells situated along the great blood vessels of the head and neck, as well as those of the thoracic and lumbar spine. Primary symptoms of tympanic locations include hearing loss and pulsatile tinnitus. Otoscopy often shows a retrotympanic reddish mass, causing tympanic bulging. Computerized tomography scan findings include a tissue density regular mass located at the promontory and limited within the middle ear cavity. Surgical management comprises tumour excision with control of bleeding, with or without prior embolization. Aim: The aim of this presentation is to report an unusual case of tympanic paraganglioma. Case Presentation: We report the case of a 56-year-old patient whose clinical and paraclinical presentations were consistent with cholesteatoma, though a tympanic paraganglioma was discovered per-operatively. Conclusion: In some rare cases, tympanic paraganglioma can be present like a cholesteatoma.

Combined thoracoscopic and laparoscopic approach to remove a large retroperitoneal compound paraganglioma:A case report

BACKGROUND Paragangliomas(PGLs)are rare catecholamine-secreting neuroendocrine tumors,which often present with secondary hypertension.The most common location is the retroperitoneal space.For the first time,we report a rare case of large retroperitoneal compound PGL,and we have innovatively applied a new surgical plan to completely remove the tumor.CASE SUMMARY A 55-year-old middle-aged man was admitted to the hospital for fluctuating blood pressure for more than 1 year with intermittent headache.He suffered dozens of attacks every day.Blood and urine catecholamines were elevated,somatostatin receptor imaging was positive,and the diagnosis of PGL was clear.The imaging examination revealed a large tumor on the right front of the mediastinal spine at the level of T10-L1(the posterior space of the right phrenic foot).For the first time in our department,a combined thoracoscopic and laparoscopic operation was used to detect and remove large tumors.CONCLUSION This is the first reported case of using a thoracoscopic and laparoscopic approach simultaneously to remove a large retroperitoneal compound PGL,which may provide a new surgical approach for similar cases.

Cardiac Paraganglioma—A Rare Subset of a Rare Tumor

Background: Cardiac paraganglioma is a rare entity of an uncommon neuroendocrine tumor. Clinically, non-secreting tumors are often diagnosed because of their growth effects, secreting tumors present symptoms related to catecholamine. Correct diagnosis of a paraganglioma can be reached by biochemical investigations and imaging. Surgical resection is the treatment of choice and has to be planned carefully and interdisciplinarily. Aim: On the basis of a patient with a vague clinical presentation and an unclear situation after primary investigations, we highlight the diagnostic challenge of this rare subset of paragangliomas. Case presentation: We present the case of a 42-year-old woman whose unspecific symptoms and further investigations revealed a paracardiac mass with unknown local behavior and dignity. Surgical resection and histopathological examination led to the diagnosis of a cardiac paraganglioma. Conclusion: Cardiac paragangliomas are extremely rare, but may be treated curatively by resection after careful preoperative investigation and interdisciplinary planning.

Duodenal gangliocytic paraganglioma with lymph node metastases: a case report and comparative review of 31 cases

Gangliocytic paraganglioma(GP) is a rare tumor of uncertain origin most often located in the second portion of the duodenum. It is composed of three cellular components: Epithelioid endocrine cells, spindlelike/sustentacular cells, and ganglion-like cells. While this tumor most often behaves in a benign manner, cases with metastasis are reported. We describe the case of a 62-year-old male with a periampullary GP with metastases to two regional lymph nodes who was successfully treated with pancreaticoduodenectomy. Using Pub Med, EMBASE, EBSCOhost MEDLINE and CINAHL, and Google Scholar, we searched the literature for cases of GP with regional lymph node metastasis and evaluated the varying presentations, diagnostic workup, and disease management of identified cases. Thirty-one cases of GP with metastasis were compiled(30 with at least lymph node metastases and one with only distant metastasis to bone), with age at diagnosis ranging from 16 to 74 years. Ratio of males to females was 19:12. The most common presenting symptoms were abdominal pain(55%) and gastrointestinal bleeding or sequelae(42%). Twenty-five patients underwent pancreaticoduodenectomy. Five patients were treated with local resection alone. One patient died secondary to metastatic disease, and one died secondary to perioperative decompensation. The remainder did well, with no evidence of disease at follow-up from the most recent procedure(except two in which residual disease was deliberately left behind). Of the 26 cases with sufficient histological description, 16 described a primary tumor that infiltrated deep to the submucosa, and 3 described lymphovascular invasion. Of the specific immunohistochemistry staining patterns studied, synaptophysin(SYN) stained all epithelioid endocrine cells(18/18). Neuron specific enolase(NSE) and SYN stained most ganglion-like cells(7/8 and 13/18 respectively), and S-100 stained all spindle-like/sustentacular cells(21/21). Our literature review of published cases of GP with lymph node metastasis underscores the excellent prognosis of GP regardless of specific treatment modality. We question the necessity of aggressive surgical intervention in select patients, and argue that local resection of the mass and metastasis may be adequate. We also emphasize the importance of pre-surgical assessment with imaging studies, as well as post-surgical follow-up surveillance for disease recurrence.

Primary pancreatic paraganglioma:A report of two cases and literature review

Paraganglioma is a rare tumor of paraganglia,derived from neural crest cells in sympathetic or parasympathetic ganglions.Primary paraganglioma originating from the pancreas is rare.We report two patients with paraganglioma in the head of the pancreas,in whom computed tomography showed a sharply marginated,hypervascular tumor with cystic areas.Significant intratumoral vessels and early contrast filling of the draining veins from the mass were not found.Although the pancreatic paraganglioma was located at the pancreatic head,the bile ducts often revealed no dilation,and sometimes the main pancreatic duct was mildly dilated.These findings are helpful in differentiating pancreatic paraganglioma from other pancreatic neoplasms.It is often difficult to distinguish between nonfunctional pancreatic paragangliomas and pancreatic endocrine tumors.In many reports,pancreatic paragangliomas show the retroperitoneal extension of a paraganglioma into the pancreas rather than a true pancreatic neoplasm.In surgical treatment,we could select simple excision of the tumor rather than radical surgery.

Malignant gangliocytic paraganglioma of the duodenum with distant metastases and a lethal course

Gangliocytic paraganglioma (GP) is rare and has been regarded as benign in general with a good prognosis. We present a patient with duodenal GP showing a malignant and lethal clinical course. A 47-year-old male patient was found to have a duodenal tumor and enlarged regional lymph nodes. The patient initially underwent a pancreaticoduodenectomy to resect the tumor and involved lymph nodes completely. Histological and immunohistochemical analyses showed findings typical of GP. However, the distant metastatic lesions in the liver and pelvic cavity were rapidly observed after surgery. The patient underwent chemotherapy and radiotherapy, as well as a second surgery to partly remove the metastatic mass in the pelvic cavity. The histological examination revealed no significant difference in histological features between the primary duodenal tumor and the metastatic pelvic mass. However, the patient finally died of the tumor due to the recurrence of the residual pelvic lesion and increased liver mass. To our knowledge, this is the first report of lethal GP with multifocal metastases. Our case confirms that GP should be regarded as a malignant potential tumor with behavior code of “1”, rather than a benign tumor of “0”.

Clinicopathological analysis of paraganglioma with literature review

AIM： To investigate the 152 cases of paragangliomas resected over the past 32 years in West China Hospital dinicopathologically.METHODS： All cases of paragangliomas diagnosed at the Department of Gastrointestinal Surgery and Department of Pathology, West China Hospital, China were reviewed. The pathological documents were supplied by the Department of Pathology, West China Hospital, and other necessary data were extracted from the hospital records. The statistical analyses were performed by survival analysis （Kaplan-Meier method）, descriptive statistical analyses and Х^2 analysis.RESULTS： The neuroendocrine marker vimentin was found to be selectively expressed in the benign tumors, and there were significant differences in the expression of those markers in both benign and malignant tumors. The survival analysis revealed that survival correlated significantly with the malignancy, metastasis and nodal status.CONCLUSION： Vimentin may be useful in the differential diagnosis between malignant and benign tumors. The difference in the expression of this marker in the tumors could be a clue to the future clinical diagnosis. The malignancy, metastasis and the nodal status may predict the prognosis of this disease.

Retroperitoneal paragangliomas:Report of 4 cases

We reviewed the data of all patients managed for retroperitoneal paragangliomas(PGLs)between June 2010and June 2011 to present our experience concerning this uncommon entity to highlight diagnostic and therapeutic challenges of retroperitoneal PGLs.All patients were admitted to the department of general and hepatobiliary surgery in the regional hospital of Jendouba,Tunisia.The size of the tumor was taken at its largest dimension,as determined in a computed tomography(CT)scan and pathological reports.There were 4 patients(all women)with a median age of 48 years(range46-56 years).Abdominal pain was the commonest presentation.CT showed and localized the tumors which were all retroperitoneal.All patients had successfu surgical resection of the tumors under invasive arterial blood pressure monitoring.One patient underwent surgery for a presumed tumor of the pancreatic head.The fresh-mount microscopic study of the peroperative biopsy yielded inflammatory tissue without malignancy and no resection was performed.Final histologica examination of the biopsy concluded PGL.A secondlaparotomy was performed and the tumor was entirely resected.The diagnosis was made after surgery by histology in all patients.The control of the blood pressure was improved after surgery in 3 patients.Paragangliomas are rare tumors.The retroperitoneal localization is uncommon.Complete surgical resection remains the only curative treatment but it is often challenging as these tumors are located near multiple vital blood vessels.

Concomitant paraganglioma and thyroid carcinoma:A case report

BACKGROUND Paraganglioma/pheochromocytoma and medullary thyroid carcinoma can coexist and are often found in multiple endocrine neoplasia(MEN). However,very few cases highlight papillary thyroid carcinoma. We present herein a rare case of head and neck paraganglioma associated with papillary thyroid carcinoma.CASE SUMMARY A 51-year-old man presented to our department with right-sided neck swelling and hypertension. Physical examination showed neck masses with obvious pulsation. Concentrations of serum calcium, phosphorus, parathormone, thyroid stimulating hormone, free thyroxine, and calcitonin were within normal limits.Enhanced computed tomography revealed an irregular solid nodule, located in the carotid artery bifurcation. A low-density nodule of the thyroid isthmus with a spot-like dense shadow was also detected. The diagnosis of carotid body tumor was raised and an ultrasound-guided fine needle aspiration biopsy of the thyroid nodule revealed papillary thyroid carcinoma. The patient underwent surgery for lesion excision, total thyroidectomy, and neck dissection, and the pathology was reported as paraganglioma and papillary carcinoma. Genetic studies showed negative results for germline mutation of succinate dehydrogenase subunit D on 11q23. He was treated with ^(131)I after surgery and remained disease-free so far.CONCLUSION The presence of concomitant paraganglioma and thyroid papillary carcinoma could be either coincidental or a result of an unknown mutation.

Bladder paraganglioma: A report of case series and critical review of current literature

Extra-adrenal chromaffin cell-related tumours or paragangliomas are rare, especially in the bladder. In this article, we reported three different clinical cases of bladder paraganglioma, followed by a review of current literature on the pathophysiology and management of bladder paraganglioma. Case 1 involved a 23 years old female patient who complained of a 10-year history of micturition-related headaches, palpitations and diaphoresis; while in case 2, a 58 years old female patient presented with history of painless haematuria and an incidentally diagnosis of a functioning paraganglioma during endoscopic transurethral resection of bladder tumour; and lastly in case 3, a 54 years old male renal transplant recipient was referred to the urology outpatient with a suspicious bladder mass found incidentally on routine transplant workshop.

Pancreatic paraganglioma diagnosed by endoscopic ultrasoundguided fine needle aspiration: A case report and review of literature

BACKGROUND Pancreatic paragangliomas(PPGL)are rare benign neuroendocrine neoplasms but malignancy can occur.PPGL are often misdiagnosed as pancreatic neuroendocrine tumor or pancreatic adenocarcinoma.CASE SUMMARY We reviewed 47 case reports of PPGL published in PubMed to date.Fifteen patients(15/47)with PPGL underwent endoscopic ultrasound-guided fine needle aspiration(EUS-FNA).Only six(6/15)were correctly diagnosed as PPGL.All patients with PPGL underwent surgical resection except three(one patient surgery was aborted because of hypertensive crisis,two patients had metastasis or involvement of major vessels).Our patient remained on close surveillance as she was asymptomatic.CONCLUSION Accurate preoperative diagnosis of PPGL can be safely achieved by EUS-FNA with immunohistochemistry.Multidisciplinary team approach should be considered to bring the optimal results in the management of PPGL.

Large gangliocytic paraganglioma of the duodenum:A rare entity

Gangliocytic paragangliomas are rare tumors that almost exclusively occur within the second portion of the duodenum. Although these tumors generally have a benign clinical course, they have the potential to recur or metastasize to regional lymph nodes. The case report presented here describes a 57-year-old female patient with melena, progressive asthenia, anemia, and a mass in the second-third portion of the duodenum that was treated by local excision. The patient was diagnosed with a friable bleeding tumor. The histologic analysis showed that the tumor was a 4 cm gangliocytic paraganglioma without a malignant cell pattern. In the absence of local invasion or distant metastasis, endoscopic resection represents a feasible, curative therapy. Although endoscopic polypectomy is currently considered the treatment of choice, it is not recommended if the size of the tumor is > 3 cm and/or there is active or recent bleeding. Patients diagnosed with a gangliocytic paraganglioma should be closely followed-up for possible local recurrence.

Vertigo as the sole complaint of tympanomastoid paraganglioma

Background: Tympanomastoid paragangliomas are usually benign, slowly growing, painless tumors. The common presenting symptoms of this tumor are pulsatile tinnitus and conductive hearing loss. Vertigo as the cardinal or initial symptom is extremely rare, especially in the early stages of the disease.Case presentation: A 53-year-old female patient presented only with intermittent recurrent vertigo and was later found to have a tympanomastoid paraganglioma. Her symptoms disappeared completely after resection of the tumor. This is the first report in literature of a case of tympanomastoid paraganglioma with vertigo as the single symptom.Conclusion: The tympanomastoid paraganglioma is rare and its clinical symptoms are nonspecific, so it is easy to be misdiagnosed or missed. It is worth noting that although clinically uncommon, vertigo can also be the first or sole symptom of tympanomastoid paraganglioma. Detailed physical examination and imaging examination of the ear are necessary and should be carried out meticulously.

Pancreatic paraganglioma with draining vessels

A pancreatic paraganglioma is a rare neoplasm that is difficult to distinguish from a pancreatic neuroendocrine tumour. Here we present a case of pancreatic paraganglioma that was surgically resected following preoperative diagnosis of a pancreatic neuroendocrine tumour. Careful evaluation of the endoscopic ultrasonography findings revealed abundant draining ves-sels,which could have led to a correct preoperative diagnosis of pancreatic paraganglioma.