Paraganglioma Research Articles

Glomus jugulare tumors treatment by gamma knife radiosurgery: A single center study.

Glomus jugulare tumor are benign vascular tumors and surgical resection is almost impossible. We have treated these tumors by Gamma knife radiosurgery and share our experience. This study was conducted at the Neurospinal and Cancer Care Institute, Karachi from January 2010 to May 2020. Thirty-four patients with glomus jugulare tumors treated with gamma knife radiosurgery were included in the study. The comprehensive clinical and demographic characteristics of all patients were collected through a manually designed questionnaire. Computed tomography, digital subtraction angiography and magnetic resonance imaging were used to make the diagnosis. Data was incorporated and analyzed by SPSS version 26. A total of 34 patients were included in the study of which 16(47%) were males and 18(53%) were females with first follow up after 6-month up to two year clinical and radiological follow-up. The mean age of the patients was 42.5±13.5 with a minimum age of 20 years and maximum age of 65 years. The KPS scale was 2.09±0.45 and the volume of the tumor was 33.8±22.5 cm3. The improvement was shown in 27 patients of which 14 were males and 13 were females showing insignificance post radiation change. Of all 34 patients, the outcome was recorded as 3(9%) for excellent, 22(64%) for good, 6(17%) for fair and 3(9%) were poor results. Gamma Knife radiosurgery is a safe and effective primary therapy and salvage therapy for residual and recurrent cases of glomus jugulare and tympanicum tumors.

Risk Factors for Stroke After Carotid Paraganglioma Surgery

The Carotid Paraganglioma Cooperative International Registry (CAPACITY) is an international registry composed of 1,432 patients with carotid body tumors (CBT) from 11 centers from 4 countries. The aim of this study was to identify risk factors for patients who presented stroke after carotid paraganglioma resection. Clinical characteristics and demographics of patients who presented transoperatively and postoperatively stroke from the CAPACITY database were retrospectively gathered. Regression analysis was performed using single logistic regression with Omnibus' test for possible factors that might contribute to present stroke. Out of 1,432 patients, 8 (0.5%) female patients presented stroke. Median age was 53years (range: 41-70years). Six strokes occurred transoperatively, diagnosed clinically in the immediate postoperative period. Of them, none of the patients received any further treatment. Three of them died on postoperative day 2, 3, and 4. Two patients developed stroke during the first 24 postoperative hours, patients showed dysarthria, and aphasia. One of them was reintervened with thrombectomy due to thrombosis of the common carotid artery the other patient was treated conservatively. Median follow-up was 16months (range: 2-72months). Single logistic regression analysis revealed a history of diabetes mellitus (odds ratio (OR) 7.62), carotid artery disease (OR 17.51), and vascular lesion (OR 2.37) to have significantly increased odds of stroke during CBT surgery. In the present study history of diabetes mellitus, carotid artery disease, and vascular lesion had increased odds of stroke during CBT surgery. Findings are limited by low event rate and even larger cohorts are needed to fully define preventive preoperative strategies for preventing stroke.

Pictorial Essay of Cervical Duplex Ultrasonography.

Objectives: Cervical duplex ultrasonography (CDU) is a simple, non-invasive, portable technique, that provides valuable high-quality visual information about the integrity of the carotid and vertebral vessels, plaque morphology and flow hemodynamics. CDU is useful in the assessment and follow up of patients with cerebrovascular disease as well as other conditions like inflammatory vasculitis, carotid artery dissection and carotid body tumours. CDU is inexpensive and invaluable in smaller centres. Methods: CDU was performed in all patients in both longitudinal and transverse planes in the out-patient clinic. Brightness mode (B-mode) and Doppler waveforms were obtained. Relevant findings were presented. Results: CDU provides real time visualisation of plaque characteristics and follow up, hemodynamic characteristics in Takayasu arteritis, visualisation of dissection. Conclusion: With availability of MR/CT angiography, CDU can be an adjuvant in follow up, triage and early bed-side diagnosis of the vascular diseases. We present our experience with CDU in the out-patient clinics in this pictorial essay.

Physiological and clinical impact in the carotid baroreceptor function following the surgical management of bilateral carotid body tumors.

The bilateral presentation of Carotid Body Tumors (CBT) is rare; the surgical resection of these masses remains the mainstay management due to the malignant potential. We aim to describe, classify, and quantify baroreceptor failure (BRF) after the surgical management of patients with bilateral CBT to better understand the clinical consequences. Retrospective review of patients that underwent bilateral CBT resection to assess the changes in baroreceptor function. We describe the clinical events associated to BRF after surgery, baseline patient's demographics, characteristics, comorbidities. Additionally, clinical and a quantitative evaluation of baroreceptor sensitivity were conducted using the Composite Autonomic Severity Score (CASS). From 1986 to 2020, a total 146 CBT resections were performed in 132 patients in our institution. Tumors were removed bilaterally in staged procedures in seven patients with a mean age of 61years (Standard Deviation 11), six (85%) were females, and there was no family history of paragangliomas. The clinical presentation were palpable masses in 5 (71%), and odynophagia in 2 (29%) cases; malignant histopathology following surgery was found in one case. BRF occurred in one patient after unilateral CBT resection, consisting of bradycardia and a 40s asystole that was not previously associated to BR sensitivity. Three (43%) patients presented BRF in the immediate postoperative period of the contralateral CBT excision, consisting of volatile hypertensive crisis in two cases, and supraventricular tachycardia in one. All the patients developed (100%) chronic baroreceptor sensitivity symptoms consisting in syncope, vertigo and fatigue in 4 (57%), tachycardia in 2 (28%), and orthostatic headache in one (14%). Autonomic testing showed mixed sympathetic and parasympathetic failure in five (71%), severe sympathetic failure in 1 (14%), and parasympathetic dysfunction in one patient (14%). Postoperative autonomic assessment confirmed BRF in all studied patients that underwent staged bilateral CBT resection with mixed, sympathetic, and parasympathetic dysfunction. Further studies are necessary to evaluate the incidence and physiological mechanisms of these sequelae to anticipate possible complications and offer the appropriate perioperative management.

Somatic IDH1 Hotspot Variants in Chinese Patients With Pheochromocytomas and Paragangliomas.

IDH1 is a pheochromocytoma/paraganglioma (PPGL) susceptibility gene; however, its role, especially in the Chinese population, has not been characterized. To determine the prevalence of somatic IDH1 hotspot variants in a large cohort of Chinese patients with PPGLs and to summarize associated phenotypes. This retrospective cross-sectional study was based on a main cohort of 1141 patients with PPGLs from 2 tertiary-care centers in China. We included 50 cases with urinary bladder paragangliomas (UBPGLs), of whom 29 were part of the main cohort and 21 were from other centers. Two additional cases with IDH1 hotspot variants not part of the main cohort were also included for summarizing IDH1-associated phenotypes. Next-generation sequencing of tumor DNA was used to analyze a customized panel of genes. The overall prevalence of IDH1 hotspot variants in the main cohort was 0.5% (6/1141). Among those PPGLs without mutations in 15 common driver genes, the prevalence of IDH1 variants was 0.9% (4/455). When restricted to paraganglioma (PGL) without mutations, the prevalence reached 4.7% (4/86). Among UBPGLs, IDH1 hotspot variants accounted for 8% (4/50). Together, all 10 patients (9 PGLs and 1 pheochromocytoma) with IDH1 hotspot variants, including 3 females with concurrent EPAS1 hotspot variants, had apparently sporadic tumors, without metastasis or recurrence. There were 3 patients with biochemical data, all showing a non-adrenergic phenotype. The somatic IDH1 hotspot variants cause PPGL development in some Chinese patients, especially among those apparently sporadic PGLs with a non-adrenergic phenotype and without mutations in major PPGL driver genes.

Cauda equina neuroendocrine tumors show biological features distinct from other paragangliomas and visceral neuroendocrine tumors.

Cauda equina neuroendocrine tumors (CENETs) are neoplasms of uncertain histogenesis with overlapping features between those of paragangliomas (PGs) and visceral neuroendocrine tumors (NETs). We have explored their biological relationship to both subsets of neuroendocrine neoplasms. The clinical and radiological features of a cohort of 23 CENETs were analyzed. A total of 21 cases were included in tissue microarrays, along with a control group of 38 PGs and 83 NETs. An extensive panel of antibodies was used to assess epithelial phenotype (cytokeratins, E-cadherin, EpCAM, Claudin-4, EMA, CD138), neuronal and neuroendocrine features (synaptophysin, chromogranin A, INSM1, neurofilaments, NeuN, internexin-α, calretinin), chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase), and possible histogenesis (Sox2, T-brachyury, Oct3/4, Sox10). The cohort included 5 women (22%) and 18 men (78%). The average age at the time of surgery was 48.3 years (range from 21 to 80 years). The average diameter of the tumors was 39.27 mm, and invasion of surrounding structures was observed in 6/21 (29%) tumors. Follow-up was available in 16 patients (median 46.5 months). One tumor recurred after 19 months. No metastatic behavior and no endocrine activity were observed. Compared to control groups, CENETs lacked expression of epithelial adhesion molecules (EpCAM, CD138, E-cadherin, Claudin-4), and at the same time, they lacked features of chromaffin differentiation (GATA3, Phox2b, tyrosine hydroxylase). We observed no loss of SDHB. Cytokeratin expression was present in all CENETs. All the CENETs showed variable cytoplasmic expression of T-brachyury and limited nuclear expression of Sox2. These findings support the unique nature of the neoplasm with respect to NETs and PGs.

Multifocal Paraganglioma Including the Cervical Sympathetic Chain.

Multifocal head and neck paragangliomas are exceptionally rare. We present a patient with 4 synchronous tumors including a sympathetic chain lesion. This is a case report and literature review conducted from September 2021 to the present. Our 69-year-old male patient presented to the clinic with multifocal paraganglioma involving the right carotid body, right cervical sympathetic trunk, right glomus jugulare, and left glomus tympanicum. After preoperative embolization, successful surgical resection was performed for the right sympathetic trunk and right carotid body tumor. Postoperatively, the patient had a right Horner's syndrome but a strong voice and intact recurrent laryngeal nerve function. He also had first-bite syndrome and right cranial nerve XII weakness which resolved. Of interest, patient also has a strong family history of paragangliomas: his sister has malignant paragangliomas with lymph node involvement and his mother and nephew have non-malignant paragangliomas. To our knowledge, multifocal tumors including synchronous carotid body, sympathetic chain, glomus jugulare, and glomus tympanicum lesions occurring in 1 person have not been reported until now. As a result of this study, there is new light shed on the treatment and evaluation of patients who present with multifocal paraganglioma involving the sympathetic chain.

SINGLE CENTRE EXPERIENCE WITH CAROTID BODY TUMOUR

Background: Carotid Body tumours (CBTs) are rare neuroendocrine tumours. Due to their proximity to vital structures including major vessels and cranial nerves, Surgical excision requires meticulous dissection and any injury to major vessels requires prompt repair. This study aimed to review our experience with the surgical management of Carotid Body Tumours. A Methods: retrospective study was performed on 20 patients who underwent excision of carotid body tumours at Vardhaman Mahavir Medical college and Safdarjung hospital, New Delhi between January 2003 to June 2022. Demographic data describing the presentation, preoperative and intraoperative details, and postoperative complications reported were tabulated and descriptive statistical analysis was done A total of 20 Results: patients were operated on. Complete resection was possible in all the patients. Vascular injury occurred in only 2 patients which were repaired promptly. Cranial nerve injury was reported in only 1 patient which resolved on follow-up. There was no incidence of stroke or recurrence. Conclusions: Periadventitial Excision is the treatment of choice for carotid body tumours and is a safe and effective procedure with minimal intraoperative and postoperative complications.

OR12-5 | LBSAT57 Long-term Follow-Up of Pheochromocytoma/Paraganglioma (PPGL) after first diagnosis: a retrospective single-center study of 173 patients

Abstract Background Pheochromocytoma (Pheo)/Paraganglioma (PGL), together PPGL, are rare but life-threatening tumors, with tumor relapse (TR) rates after initial surgery of 16.5%, and genetic mutations in about 30-40% of patients. Long-term follow-up (FU) and genetic testing in all patients are recommended. Questions remain, however, as to the most suitable duration of FU, the prognostic value of genetic diagnoses and of clinical, biochemical or radiological findings during FU, of the incidence of TR after recommended 10 years FU of low-risk sporadic Pheos, or of TR on morbidity and mortality. Objective, patients, and methods: We retrospectively determined the overall survival (OAS), progression-free survival (PFS) and tumor-recurrence (TR) in 173 patients with PPGL initially operated and followed-up at a single tertiary referral center from 1988 to 2020 by Kaplan-Meier Estimates, and assessed age, sex, hormonal activity, tumor size, and metastatic spread at first diagnosis, pathohistological PASS score, mutation-positive PPGLs (MP-PPGL), TR, and comorbidities (associated with increased cardiovascular risk) as to independent prognostic markers thereof by multivariate Cox-regression. Certificats of the Austrian death registry were also obtained. Results In 8 (5%) PPGLs there was no FU in the charts, but death certified occurring 65±28 (mean±SD, median 2.7) months after first diagnosis. Mean (±SD) age of the remaining 165 (43.9% female) patients (94.5 Pheos, 3.0% multiple PGLs, 2.5% head-and-neck PGLs) was 49(±16) years, mean (range) FU 90(3-537) months. 93 (54%) patients underwent genetic testing, 37 (40%, 21% of entire cohort) had MP-PPGL (mean±SD age 33.8±13.2 yrs, OAS 391 months). 5 of these 37 (13.5%), and 7 of 57 (12%) mutation-negative (MN-PPGL, mean±SD age 53.3±14.8 years, p<0.01 vs. MP-PPGL, OAS 190 months) died during FU (p=0.03). Male sex, higher age, presence of comorbidities, and primary metastatic disease were independent negative prognostic factors for OAS by univariate, but only age and metastatic disease remained significant by multivariate analysis. As to PFS, higher age and no hormonal activity were negatively associated by univariate, but not by multivariate analysis, as were all other tested parameters. Conclusions The cohort of our study is the third-largest original report on long-term FU and prognostic markers in PPGL. While others (Ayola-Ramirez et al, JECM 2011) in 371 patients found tumor size and sympathetic PGL independently associated with OAS, we did not. Patients may have harbored more aggressive tumors in that study, as higher primary metastatic spread (25% of Pheos, 60% of sympathetic PGL) was identified. We identified only age and metastatic disease as independent predictors of OAS, in line with data from Korea (Kim J H, et al., Endocrinol Metab. [Seoul]) in 1048 patients (9% with primary metastatis) and with a metaanalysis comprising 703 PPGLs (Crona J, Endocr Relat Cancer, 2019). Presentation: Sunday, June 12, 2022 12:00 p.m. - 12:15 p.m.

ODP549 From Positive to Negative, a Histidine to Aspartic Acid Change in SDHB is Breaking Bad in Cardiac Paraganglioma

Abstract Introduction Cardiac paraganglioma (PGL) are extremely rare tumors. They are derived from chromaffin cells of the neural crest. Up to 40% of PGL foster germline mutations, while some bear somatic mutations. Here, we describe a sympathetic paraganglioma presenting as a cardiac mass, found to have a novel mutation of SDHB. Clinical Case A 64-year-old man with uncontrolled type 2 diabetes mellitus presented with chest pain, progressive fatigue and unintentional weight loss. An echocardiogram demonstrated a right atrial mass. Cardiac magnetic resonance imaging showed a 6.9×5.8×4.9 cm mass in the lateral right atrial wall and right atrioventricular groove, encasing the right coronary artery. Surgical removal was attempted and aborted due to involvement of the tricuspid valve. Incisional biopsy was consistent with paraganglioma. Plasma free normetanephrine was elevated at 1.87 nmol/L (ULN 0.89 nmol/L) and plasma free metanephrine was normal at 0.14 nmol/L (ULN 0.49 nmol/L). Chromogranin A was elevated at 1,038 ng/mL (normal <93 ng/mL). Iodine-123 meta-iodobenzylguanidine scan demonstrated increased and persistent MIBG activity of the cardiac mass. Ga-68 DOTATATE PET/CT scan revealed DOTATATE avidity of the mass without evidence of distant metastatic disease. Next-generation sequencing of the specimen revealed a variant of unknown significance of SDHB H244D at a variant allele frequency of 62.2%. This missense mutation replaces the histidine to aspartic acid, resulting in changes in charge of the side chain from positive to negative. Systemic treatment with tyrosine kinase inhibitor (TKI) cabozantinib was initiated due to unresectable tumor. Three month surveillance with Ga-68 PET/CT DOTATATE scan revealed partial response to treatment. Chromogranin A and normetanephrine are trending down, suggesting biochemical response. Conclusion Cardiac PGL are rare and SDHB mutations are associated with worse prognosis. This is the first case of a missense mutation of SDHB at H244D, which may be clinically relevant in characterizing cardiac paraganglioma and potential response to TKI therapy. Presentation: No date and time listed

ODP051 Presymptomatic Genetic Screening Leading to the Diagnosis of Paraganglioma Associated with Duodenal and Pancreatic Neuroendocrine Tumours in a Carrier of a Pathogenic MAX Variant

Abstract Introduction MAXpathogenic variants have been found to predispose to pheochromocytomas and paragangliomas (PPGLs) and more recently to pituitary tumors 1. Clinical Case A 30 yo man presented to the emergency department for diplopia and high blood pressure (200/100mmHg). His workup showed elevated plasmatic normetanephrines (9. 01nmol/L; N <0.92) and a 3.7cm right adrenal mass with a density of 30HU. The patient underwent right laparoscopic adrenalectomy and the pathologist reported a 4.5cm pheochromocytoma with a PASS score of 4 and a Ki-67 of 2-4%. The patient was screened with a panel of 14 susceptibility genes for PPGLs (INVITAE, CA, USA) that revealed a pathogenic germline nonsense heterozygous MAX mutation (c.223C>Tp. Arg75*). This mutation was previously described in a family where four members suffered from bilateral PHEOs at a young age (28-35 yo) 2 . Following the identification of the pathogenic variant of MAX gene, the patient's father (61 yo) underwent genetic counselling and was found to carry the same germline mutation. His past medical history included long-standing hypertension with hypertensive cardiomyopathy and diabetes. His blood work showed a mildly elevated plasmatic normetanephrine (1.41nmol/L; N <1.2) with normal metanephrine. An abdominal CT-scan showed a 1.5cm precaval nodularity. On a complementary 18 F-FDG PET/CT, the precaval mass had a 3.5 SUVMax and a second mass was identified in the duodenum (D3) with an uptake of 4.9 SUVMax. The 68 GaDOTATE PET/CT confirmed the precaval (SUVMax36.3) and duodenal (SUVMax51.6) lesion and in addition, revealed a pancreatic mass (SUVMax9.3). The patient underwent a distal pancreatic, duodenal and precaval node resection. The pathology report showed a 1.7cm G1 pancreatic neuroendocrine tumor (NET) (Ki-67 <3%) and a 2.3cmG1 duodenal NET (Ki-67 <3%). The precaval node was a paraganglioma (PGL) with a preserved SDHB staining, negative cytokeratine 8/18 and a Ki-67 of 1.65%. The son had normal imaging of his pancreas. To our knowledge we report the second case of association of MAXmutation with gastrointestinal TNE. Conclusion This case presents the rare association of a familial MAX mutation presenting with a pheochromocytoma in the index case and a presymptomatic discovery of a PGL and multiple NETs in the father. This supports the hypothesis that MAXmutations might be associated with multiendocrinetumors 3.

ODP020 A Challenging Case of Poorly Differentiated Carcinoma with Neuroendocrine Differentiation and Adrenal Mass

Abstract Background Neuroendocrine tumors (NETs) account for about 0.5% of all newly diagnosed malignancies. The most frequent primary sites are the gastrointestinal tract or pancreatic (62%-67%) and the lung (22%-27%). All poorly differentiated NETs have a Ki-67 index of greater than 20% and WHO grade of 3. The determination of the site of origin can be challenging in widely metastatic poorly differentiated NETs. Clinical Case A 51-year man with a history of hypertension and type 2 diabetes mellitus presented with angioedema while on lisinopril for years. Apart from a month's history of bilateral flank pain, he denied diarrhea, flushing, stridor, or shortness of breath. CT abdomen showed an 8.2×8. 0×7.9 cm right adrenal mass with a few punctate calcifications, hepatomegaly with multiple liver metastases, multiple retroperitoneal, hepatoduodenal, retrocrural adenopathy, and T4 metastatic lesion. CT chest showed bulky mediastinal and supraclavicular lymph nodes with trachea narrowing. All those lesions were FDG avid on PET/CT scan. Core biopsy of right supraclavicular lymph node revealed a poorly differentiated carcinoma with neuroendocrine differentiation and high proliferative index (25-50%). On cell block, it was negative for (AE1/AE3 (-), CAM5.2 (-), CK7, CK20, vimentin, desmin, CEA, EMA, CD45, CD20, and TTF-1 but positive for CK903 (focal +), synaptophysin (+), chromogranin (+), calretinin (focally +), inhibin (focally +). Based on the immunohistochemical stain, it was concluded as a metastatic small cell carcinoma of unknown origin. He was treated with carboplatin, etoposide, and atezolizumab and received 5 cycles. Endocrine was consulted two months after his initial presentation. Urine normetanephrine was > 4-fold elevated. Blood pressure was controlled on Doxazosin at 4 mg bid. The 10 gene-panel for hereditary pheochromocytoma and Paraganglioma (PGL) was negative. There was a progression of mediastinal adenopathy while on treatment with narrowing of proximal intrathoracic trachea requiring elective tracheostomy. Based on imaging findings and elevated normetanephrine, we believe he has metastatic pheochromocytoma and PGL. His chemo regimen was switched to Cyclophosphamide, Vincristine, and Dacarbazine (CVD). He finished 8 cycles of CVD with an overall reduction in the size of lymph nodes (both above and below the diaphragm) and right adrenal mass. His plasma normetanephrine level was also significantly improved. Presentation: No date and time listed

PMON85 Co-occurrence of Carotid Body Tumor, Meningioma and Schwannoma in a Symptomatic Patient, Incidental Findings Vs Genetic Syndrome: A Case Report

Abstract Carotid body tumors, also known as chemodectomas/paraganglionomas; are rare neuroendocrine tumors that arise from parasympathetic ganglionic cells. They are usually benign with incidence of malignancy is <10%. In majority of cases, tumors are asymptomatic and found incidentally on clinical exam or radiological imagining. Their association with other non-neuroendocrine tumors as seen in present case; has not been well documented in literature. Case presentation 43 y/o female with PMH of GERD, obesity, asthma and anxiety disorder who came to endocrine clinic for left middle thyroid lobe nodule(0.9×0.6×0.6cm) evaluation; incidentally noted to have a multilobulated heterogeneous hypo echoic and iso-echoic mildly vascularized solid nodular mass (3.46×1.83×1.93 cm) in the left carotid bifurcation area; splaying the common and the internal carotid arteries on US. Review of systems was positive for left sided neck pain, intermittent palpitations, headaches, anxiety, and sleep disturbances. Clinical exam was remarkable for thyromegaly and a palpable non-tender 3cm left neck mass with no cervical lymphadenopathy. Initial labs were notable for mild elevation of chromogranin A (108.4 ng/ml) with normal levels of TSH, free T3, free T4, plasma metanephrines and 24-hour urinary metanephrines. Considering patient's persistent symptoms; plasma catecholamines levels were done and were negative. MRI soft tissue neck confirmed 2.8 cm lobular mass suggestive of paraganglioma. Metastatic work up was negative. Patient was referred for genetic testing considering young age and to rule out hereditary disorders. Interim, patient presented to the ED with complain of sudden onset lumbar backache without sphincteric involvement; neurological exam was unrevealing but on MRI lumbar spine found to have a 5.7×4.8×4cm lobulated well-circumscribed homogeneous soft tissue mass suggestive of schwannoma. Cervical and thoracic spine imaging was unremarkable. MRI brain showed a 1.1cm enhancing mass in right Meckel cave suggestive of meningioma. PET-DOTATATE scan was performed that revealed left neck mass as intensely avid, Right petrous apex mass as moderately avid and lumbar mass as not avid at all, consistent with the diagnosis of paraganglionoma, meningioma and schwannoma respectively. No evidence of DOTATATE avid nodal/ distant metastatic disease was found. Initially a hereditary etiology was suspected but genetic testing including (VHL, NF1/2, SDHD, SDHB) came back negative. Case was discussed with multidisciplinary teams; Neurosurgery service recommends conservative management of both meningioma and schwannoma at the moment considering benign course. Regarding paraganglioma, as tumor is non-secretory on repeated work up; sympathetic blockade is not warranted and patient is scheduled for pre-op embolization and surgical resection by Head and Neck surgery. Conclusion Paraganglionomas are generally benign non-secretory tumors that usually occur with other neuroendocrine tumors both as hereditary syndromes and sporadic cases. But their association with non-neuroendocrine tumors is mere incidental or has a genetic causation; is still unclear and warrants further research. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

PMON85 Co-occurrence of Carotid Body Tumor, Meningioma and Schwannoma in a Symptomatic Patient, Incidental Findings Vs Genetic Syndrome; a case report.

Abstract Carotid body tumors, also known as chemodectomas/paraganglionomas; are rare neuroendocrine tumors that arise from parasympathetic ganglionic cells. They are usually benign with incidence of malignancy is <10%. In majority of cases, tumors are asymptomatic and found incidentally on clinical exam or radiological imagining. Their association with other non-neuroendocrine tumors as seen in present case; has not been well documented in literature. Case presentation 43 y/o female with PMH of GERD, obesity, asthma and anxiety disorder who came to endocrine clinic for left middle thyroid lobe nodule(0.9×0.6×0.6cm) evaluation; incidentally noted to have a multilobulated heterogeneous hypo echoic and iso-echoic mildly vascularized solid nodular mass (3.46×1.83×1.93 cm) in the left carotid bifurcation area; splaying the common and the internal carotid arteries on US. Review of systems was positive for left sided neck pain, intermittent palpitations, headaches, anxiety, and sleep disturbances. Clinical exam was remarkable for thyromegaly and a palpable non-tender 3cm left neck mass with no cervical lymphadenopathy. Initial labs were notable for mild elevation of chromogranin A (108.4 ng/ml) with normal levels of TSH, free T3, free T4, plasma metanephrines and 24-hour urinary metanephrines. Considering patient's persistent symptoms; plasma catecholamines levels were done and were negative. MRI soft tissue neck confirmed 2.8 cm lobular mass suggestive of paraganglioma. Metastatic work up was negative. Patient was referred for genetic testing considering young age and to rule out hereditary disorders. Interim, patient presented to the ED with complain of sudden onset lumbar backache without sphincteric involvement; neurological exam was unrevealing but on MRI lumbar spine found to have a 5.7×4.8×4cm lobulated well-circumscribed homogeneous soft tissue mass suggestive of schwannoma. Cervical and thoracic spine imaging was unremarkable. MRI brain showed a 1.1cm enhancing mass in right Meckel cave suggestive of meningioma.PET-DOTATATE scan was performed that revealed left neck mass as intensely avid, Right petrous apex mass as moderately avid and lumbar mass as not avid at all, consistent with the diagnosis of paraganglionoma, meningioma and schwannoma respectively. No evidence of DOTATATE avid nodal/ distant metastatic disease was found. Initially a hereditary etiology was suspected but genetic testing including (VHL, NF1/2, SDHD, SDHB) came back negative. Case was discussed with multidisciplinary teams; Neurosurgery service recommends conservative management of both meningioma and schwannoma at the moment considering benign course. Regarding paraganglioma, as tumor is non-secretory on repeated work up; sympathetic blockade is not warranted and patient is scheduled for pre-op embolization and surgical resection by Head and Neck surgery. Conclusion Paraganglionomas are generally benign non-secretory tumors that usually occur with other neuroendocrine tumors both as hereditary syndromes and sporadic cases. But their association with non-neuroendocrine tumors is mere incidental or has a genetic causation; is still unclear and warrants further research. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Quantitative analysis of catecholamines and their metabolites in 491 patients with adrenal tumors: a retrospective single-center cohort study.

Adrenal tumors, including benign cortical adenoma (BCA) and pheochromocytoma (PCC) or paraganglioma (PGL), have been more frequently detected during imaging examinations in recent years. However, the associated clinical or laboratory characteristics, especially on the Chinese population, still need to be investigated. We conducted a retrospective analysis of 491 patients pathologically diagnosed with adrenal tumors, from Jan 19, 2018 to Dec 17, 2019, at a tertiary referral hospital in Wuhan of China. Our findings including 247 (50.3%) BCA cases, and 92 (18.7) PCC/PGL cases and other cases. Both the clinical and laboratory parameters were reviewed and analyzed. Compared with other adrenal tumors, PCC/PGL showed larger tumor diameters and more frequently located on the right side, and were with higher levels of urinary catecholoamines and plasma metanephrines, especially for the 24h urinary vanilmandelic acid (VMA) and plasma normetanephrine (NMN). The optimal diagnostic thresholds were 29.40 ug/24h for VMA (sensitivity, 85%; specificity, 91%) and 0.63nmol/L for NMN (sensitivity, 91%; specificity, 92%). The 24h urinary VMA and plasma NMN also shared abilities to differentiate between different tumor laterality and different tumor size in PCC/PGL cases. In addition, compared with the other benign tumors, BCA were smaller in diameters (20 vs 35mm, p < 0.001), and seemed to be lower in levels of plasma epinephrine, dopamine and serum ACTH. 24h Urinary catecholoamines and plasma metanephrines, especially for the 24h urinary VMA and plasma MNM, showed higher diagnostic efficacies for PCC/PGL, and were tightly associated with the tumor laterality and tumor size.

Microsurgical treatment of carotid body tumors using periadventitial dissection: Analysis of outcomes and prognostic factors in a neurological referral center.

Surgical resection for carotid body tumors (CBTs) is the gold standard of treatment and continues to be a challenging procedure, commonly associated with high vascular injury rates and neurological complications. It is a retrospective case series study between January 2002 and November 2020, with a mean follow-up of 29 months in a single nationwide referral center. Thirty-one patients diagnosed with a carotid body tumor and treated with microsurgical periadventitial resection were included in the study. Patients' demographics, comorbidities, clinical, radiological factors, and tumor grade, evaluated by the Shamblin scale, were obtained. Statistical analysis was performed on all collected data. In this study, we included 31 patients (32 tumors), 80% of the patients were female, and 20% were male, with a mean age of 53 years. One patient presented with bilateral lesions, while 17 tumors were located on the left side. The most frequent symptom was a painless, slow-growing neck mass in 74% of patients. Using the Shamblin classification, 13% of tumors were Grade I, 53% Grade II, and 34% Grade III. In the postoperative period, 3% of patients presented with permanent cranial nerve deficit, while none had vascular injuries or postoperative stroke. A tumor >5 cm increased the risk for nerve lesion by 11 times (OR 12.6, CI 95% 7.4-11.4, P < 0.001). Preoperative embolization followed by periadventitial resection by means of a microsurgical technique is a safe and effective approach to remove CBT, with 3% cranial nerve injury rate and no need for vascular sacrifice or reconstruction.

Bladder paraganglioma, gastrointestinal stromal tumor, and SDHB germline mutation in a patient with Carney-Stratakis syndrome: A case report and literature review.

Carney-Stratakis syndrome (CSS) is a rare dyad of paraganglioma (PGL)/pheochromocytoma (PHEO) and gastrointestinal stromal tumor (GIST). PGLs are neuroendocrine tumors of neural crest origin which are mostly found in the head, neck, and retroperitoneal space. GISTs are the most common mesenchymal tumors of the digestive tract, usually caused by KIT/PDGFRA mutations. Here, we reported a case of CSS with unusual bladder PGL and succinate dehydrogenase (SDH) deficient GIST due to a germline mutation in SDH-subunit B (SDHB) gene. A 39-year-old female patient initially diagnosed with gastric GIST and isolated pelvic metastasis was eventually found to be CSS with bladder PGL and SDH-deficient GIST after surgery. This patient underwent resection of gastric and bladder tumors, and postoperative pathology confirmed the diagnosis of CSS. According to the next-generation sequencing (NGS), the patient carried a germline mutation in the SDHB gene, which was the cause of the disorder. The patient had no tumor recurrence with regular follow-up in 10 months. CSS is an autosomal genetic disorder with no gender difference in incidence, and PGLs are more frequent than GISTs. SDH germline mutation is the molecular biological mechanism of CSS while the most common type is SDHB mutation. The unique mechanism of tumorigenesis including hypoxia and hypermethylation caused by SDH deficiency renders target therapy with tyrosine kinase inhibitors ineffective, therefore complete surgical resection is the optimal treatment in the absence of tumor metastases.

Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment

Pheochromocytomas (PC) and paragangliomas (PG) are rare neuroendocrine tumors associated with autonomic nerves. Here we use single-nuclei RNA-seq and bulk-tissue gene-expression data to characterize the cellular composition of PCPG and normal adrenal tissues, refine tumor gene-expression subtypes and make clinical and genotypic associations. We confirm seven PCPG gene-expression subtypes with significant genotype and clinical associations. Tumors with mutations in VHL, SDH-encoding genes (SDHx) or MAML3-fusions are characterized by hypoxia-inducible factor signaling and neoangiogenesis. PCPG have few infiltrating lymphocytes but abundant macrophages. While neoplastic cells transcriptionally resemble mature chromaffin cells, early chromaffin and neuroblast markers are also features of some PCPG subtypes. The gene-expression profile of metastatic SDHx-related PCPG indicates these tumors have elevated cellular proliferation and a lower number of non-neoplastic Schwann-cell-like cells, while GPR139 is a potential theranostic target. Our findings therefore clarify the diverse transcriptional programs and cellular composition of PCPG and identify biomarkers of potential clinical significance.

Carotid Body Tumors: Institutional Experience of 10 Cases and a Review of Literature.

Carotid body tumors are slow growing neck masses that arise from the neural crest cells at the carotid bifurcation. Majority are asymptomatic and are diagnosed incidentally. Surgical excision is accepted as the treatment of choice to reduce complications. In the present series, we report 10 cases of carotid body tumors and our institutional experience. All patients underwent radiological evaluation with an ultrasonography with Doppler, contrast enhanced computed tomography and MR angiography. 6 cases were operated by a transcervical excision. The tumor was excised in tototranscervically. One of the cases required saphenous vein graft intraoperatively due to vascular injury and also had postoperative vocal cord palsy. The rest had an uneventful recovery. Carotid body tumors although rare and seemingly indolent can cause substantial symptoms if left untreated. A prompt multi modality approach is needed for both diagnosis and treatment to avoid major complications.

Carotid body tumor encounters over a two-decade period in an academic hospital.

Carotid body tumors (CBTs) are rare and mostly benign. Research outcomes usually arise from single-center data. We conducted this study to present the characteristics and outcomes of patients who underwent surgical resection of CBT at our hospital over the past 20 years. In this retrospective review, the records of CBTs in our hospital were reviewed between 1998 and 2021. All patients who underwent CBT resection were included. The follow-up period was 12 months. A total of 44 CBTs were treated in our hospital. The male-to-female ratio was 1:2.4. Only 4.5% of patients had Shamblin I tumors. Patients with Shamblin II and III tumors were 56.8% and 38.6%, respectively. Duplex scan was used to diagnose CBT in all of the patients. The majority of our patients (97.7%) did not receive any preoperative embolization despite an average tumor size of 4.9 cm. Cranial nerve injuries were observed in 29.5% of cases. Meanwhile, stroke was reported in only two cases (4.5%). No deaths were encountered. Surgery is the definitive treatment for CBT. Size and local extension appear to be the main reasons for adverse events rather than surgical techniques. Our results are consistent with those of previously published studies. Good outcomes are expected in high-volume centers with appropriate preoperative imaging.