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.

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.

CLINICAL DIAGNOSIS AND TREATMENT OF NONFUNCTIONING PHEOCHROMOCYTOMAS IN 14 PATIENTS

Objective To analyze the clinical characteristics of nonfunctioning pheochromocytoma, and to evaluate the efficacy of 131I-metaiodobenzylguanidine (MIBG) scan in the diagnosis and perioperative treatment of nonfunctioning pheochromocy- toma. Methods The clinical data of 14 patients with nonfunctioning pheochromocytoma were analyzed retrospectively. Plasma free corticoid, renin, aldosterone, and urine catecholamines levels were estimated. B-mode ultrasonography, computed tomo- graphy scan, thoracic X-ray and 131I-MIBG were used. Results All patients with nonfunctioning pheochromocytoma had no hypertension and the tumors were found inciden- tally. The 24 hours urine catecholamines levels in 80% (8/10) patients were normal. The positive rate of 131I-MIBG was 80% (8/10) and the specificity was 100%. All patients underwent surgical operation of tumor resection. No preoperative volume expansion was given to all patients. All tumors were resected completely, and no death accident happened. There was no recurrence and metastasis after operation by long-term follow-up. Conclusion 131I-MIBG scan is the first choice technique for the diagnosis of nonfunctioning pheochromocytoma. Blood volume expansion is unnecessary before resection of pheochromocytoma.no recurrence and metastasis})

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.

EXPRESSION OF CYCLOOXYGENASE-2 IN MALIGNANT PHEOCHROMOCYTOMAS AND ITS RELATIONSHIP WITH MICROVESSEL DENSITY

Objective To investigate the expression of cyclooxygenase-2 （ Cox-2 ） and microvessel density （MVD） in benign and malignant pheochromocytomas, and the relationship between Cox-2 and MVD. Methods Specimens and clinical data from 38 patients （ 21 benign and 17 malignant pheochromocytomas ） were studied. Slides of normal adrenal glands in nephrectomy specimens from another 20 patients with benign renal tumors were used as control. Irnmunohistochemical technology was performed to detect the Cox-2 and MVD in all specimens. Results Expression of Cox-2 was observed in 5 of the 21 benign pheochromocytomas （23. 8% ） , and in 14 of the 17 malignant （82.4%）. No expression of Cox-2 was observed in control slides. There were significant differences of Cox-2 expression between benign and malignant pheochromocytomas, as well as between malignant pheochromocytomas and control （ P 〈0. 05）. Expressions of MVD were 36. 41 ±13. 00, 21.43 ±8. 05, and 13. 36 ±4.34 in malignant, benign pheochromocytomas, and in control, respectively. Conclusion Cox-2 may contribute to the invasive characteristics of malignant pheochromocytomas and be used as a marker to distinguish malignant from benign pheochromocytomas. Expression of MVD in malignant pheochromocytomas was directly correlated with Cox-2.

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.

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.

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.

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.

Mesenteric paraganglioma: Report of a case

We report a rare case of paraganglioma that developed in the mesentery of terminal ileum. A 78-year-old woman complained of right-sided abdominal pain. Abdominal computed tomography revealed a solid heterogeneously enhanced mass in the right lower abdomen. The tumor was laparoscopically excised. The mesenteric tumor was well circumscribed, ovoid, and encapsulated and measured 3 cm × 1.5 cm × 1.5 cm. Histological examination showed a cellular neoplasm comprised of nests and groups of tumor cells separated by fibrovascular connective tissue, giving a characteristic nested Zellballen pattern. Immunohistochemically, the tumor cells were positive for chromogranin, synaptophysin, CD56, and vimentin and negative for cytokeratins, SMA, CD34, CD117/c-kit and S100. On the basis of histologic and immunohistochemical features, a diagnosis of mesenteric paraganglioma was made. The operative and postoperative courses were unremarkable, and the patient was discharged on postoperative day 7. She was doing well 1 year after the surgery with no signs of recurrence. Extra-adrenal paragangliomas most commonly develop adjacent to the aorta, particularly the area corresponding to the organ of Zuckerkandl. Mesenteric paraganglioma, as in our case, is extremely rare; only 11 cases have been reported in the literature. We herein discuss the clinical findings of these cases.

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.

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.

Case Report:Diagnosis and treatment of pheochromocytoma in urinary bladder

Objective： To study the diagnosis and treatment ofpheochromocytoma in urinary bladder. Methods： Six cases of bladder pheochromocytoma were studied. Four cases showed hypertension, 3 of which were paroxysmal hypertension during urination. Catecholamine （CA） was increased in a case, and vanillymandelic acid （VMA） was increased in 2 cases. Bladder submucosal mass was detected by B-ultrasound in 5 cases （5/5）, computerized tomography （CT） in 3 cases （3/3）, cystoscopy in 5 cases （5/6）. Four cases took a-receptor blocker for 2 weeks, 1 case took β-receptor blocker to decrease heart rate. All patients were treated with surgical operation including 4 partial cystectomies, 2 excavations. Results： Three cases had manifestations including headache, excessive perspiration and hypertension during cystoscopy. Four cases were confirmed before operation. Two cases showed hypertension during operation. All patients were pathologically diagnosed as pheochromocytoma post- operatively. In five cases followed up, blood pressure returned to normal. No patient had relapse and malignancy. Conclusions： Typical hypertension during urination comprised the main symptoms. We should highly suspect bladder pheochromocytoma if a submucosal mass was discovered with B-ultrasound, CT, ^131I-M1BG （methyliodobenzylguanidine） and cystoscopy. The determination of CA in urine is valuable for qualitative diagnosis. The preoperative management of controlling blood pressure and expansion of the blood volume are very important. Surgical operation is a good method for effective treatment. Postoperative long-time followed up is necessary.

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.

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.

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”.

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.

Functional paragangliomas of the urinary bladder:a report of 9 cases

Background and Objective: Functional paraganglioma of the urinary bladder (FPUB) is a rare tumor. Misdiagnosis of FPUB before operation can lead to serious intraoperative consequences. In this article, we reported our experience in preoperative diagnosis and surgical treatment of FPUB. Methods: Clinical data of nine patients with FPUB treated between June 1985 and January 2009 at Peking Union Medical College Hospital were analyzed. Results: All patients underwent urinary catecholamine (CA) detection, B-ultrasound, CT and/or MRI scan; 5 underwent nailfola microcirculation inspection; 4 underwent 131I-metaiodobenzyl guanidine (MIBG) detection; and 6 underwent 111In-DTPA-Octreotide (OCT) scintiscan. According to the UICC bladder tumor classification, 5 patients had T2, 3 had T3, and 1 had T4 disease. All patients underwent surgical treatment, and 1 received 131I-MIBG therapy. All patients had paroxysmal hypertension and palpitation and six had cold sweat, headache, and dizziness after emphatic urination. The definitive diagnosis was made by histopathologic examination of the removed tumors and was confirmed in 7 cases by the immunohistochemical staining of chromogranin A, Ki-67 and S100 protein. The tumor consisted of discrete aggregates of zellballen cells separated by a network of vascular channels. One patient had metastases in the pelvic lymph nodes, liver and colon. Follow-up ranged from 7 to 289 months (mean, 127.2 ± 34.2). Six of the nine cases reported here were found in the usual locations. One patient had multiple tumors. The catecholamine level was elevated under basal conditions in 8 patients and during endoscopic resection of the tumor in 1 patient; it returned to normal after surgery in 8 patients. Three patients had recurrence and 1 had metastasis following surgery. Conclusions: Early preoperative diagnosis of FPUB is difficult, but it should be suspected in patients with typical tetrad symptoms: headache and micturition syncope, sweating, palpitation and hematuria. In those patients with unresectable multiple tumors, medicine and 131I-MIBG therapy may be helpful for controlling hypertension and delaying disease progression. Advanced classification (≥T3), multifocal tumors and CgA expression are risk factors of recurrence and metastasis.

Management of bladder pheochromocytoma by transurethral resection

Bladder pheochromocytoma is the most common extra-adrenal genitourinary tumor.Endoscopic management is feared due to the risk of intra-operative hypertensive crisis.We described a case of successful endoscopic management of a bladder pheochromocytoma and discussed its technical aspects.

Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis

The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively. After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors. Discussion includes review of the literature.