Paraganglioma Research Articles

SAT329 Case Series Of Patients With FGFR-1 Related Pheochromocytoma With A Focus On Biochemical And Imaging Signatures

Abstract Disclosure: S. Jhawar: None. J. Del Rivero: None. K. Pacak: None. Introduction: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal gland and neural crest, respectively. 40% of cases are associated with germline mutations and 30-40% somatic driver mutations. Here, we present two patients with PCC who were found to have somatic FGFR1 mutation. FGFR signaling is involved in regulation of tissue repair, angiogenesis, and inflammation. Patient 1: A 70-year-old female with a history of resistant hypertension, episodic palpitations and sweating presented with diffuse abdominal pain and chest tightness. She was noted to have a blood pressure of 220/160 mm Hg. CT scan showed a 4.2 x 3.9 cm left adrenal mass, suspicious for malignancy and a <1 cm retroperitoneal mass. Blood work revealed elevated plasma normetanephrine (NM) 3543 pg/mL (normal 0- 145) and metanephrine (MN) 871 pg/mL (normal 0-62). 18F-FDG PET/CT showed a left adrenal mass without abnormal FDG activity. 68Ga-DOTATATE PET/CT was compatible with left PCC (SUVmax 28). 18F-DOPA PET/CT showed left PCC and a small retroperitoneal PGL. Two weeks after initiating phenoxybenzamine, she underwent total left adrenalectomy. Pathology was consistent with PCC. Molecular testing revealed FGFR1 pathogenic somatic mutation (c.1638C>G p.Asn546Lys). Patient 2: A 73-year-old male with known left renal cell carcinoma presented to our institution for management of recurrent right PCC. He was found to have a 3.8 cm right adrenal incidentaloma eight years ago and elevated plasma NM 6.3 nmol/L (normal <0.9), MN 1.5 nmol/L (normal <0.5). He underwent total right adrenalectomy, and the diagnosis of PCC was confirmed on histopathology. Two years later, he developed a 5.1 x 4.7 cm nodular mass in the right adrenal fossa and a <1 cm liver lesion on CT scan. The adrenal lesion showed intense avidity on 68Ga-DOTATATE PET/CT and 18F-DOPA PET/CT and mild avidity on 18FDG-PET/CT. 18F-DOPA PET/CT also showed avidity towards the liver lesion. He was started on doxazosin and underwent laparoscopic right adrenalectomy. Pathology demonstrated PCC. Whole exome sequencing of the tumor showed pathogenic FGFR1 mutation (c.1638C>G, p.Asn546Lys). Discussion: Activating FGFR1 mutations are associated with sporadic PCC. The biochemical phenotype of our patients showed higher levels of NM than MN. The imaging profile revealed that 18F-DOPA PET/CT was more sensitive than 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT as it showed avidity towards other extra-adrenal lesions. Further studies in larger cohorts are needed to enhance understanding of pathogenesis, biochemical and imaging phenotype, which will help tailor the treatment and potential development of novel targeted therapies. Presentation: Saturday, June 17, 2023

SAT487 A Case of Mistaken Identity: A Rare Presentation of Ectopic Thyroid Tissue

Abstract Disclosure: N. Doshi: None. R. Azimzade: None. A. Rajpal: None. Background: Ectopic thyroid tissue (ETT) lateral to the midline is very rare, and its presence at the carotid bifurcation is exceedingly unique. Paraganglioma is the most common primary tumor at the carotid bifurcation, often called a carotid body tumor. We hereby present a case of lateral ETT with radiological features similar to paraganglioma. Case Description: A 72-year-old female with history of GERD was referred to us for evaluation of a well-circumscribed, slightly tender left neck mass. She has had the mass for approximately 15 years with previous evaluation with ultrasound in Yemen, where she was told to undergo surgery to remove it. She did not pursue surgery at that time. She moved to the U.S. one year ago and was re-evaluated for the neck mass. On examination, a firm mass was noted on the left side of the neck, followed by an ultrasound which demonstrated a 4.5 cm mass at the left carotid bifurcation and an enlarged right thyroid lobe of the same echogenicity with no tissue in the left thyroid bed. She had no clinical symptoms suggesting of hypo or hyperthyroidism. Laboratory examination showed suppressed TSH with elevated T3 suggesting thyrotoxicosis. CT neck was obtained for further characterization of the left neck mass which showed a hyper-enhancing, lobular soft tissue mass at the carotid bifurcation extending from the mandible to the level of the thyroid isthmus, concerning for carotid body paraganglioma or schwannoma. An I-123 scan demonstrated 24% (increased) uptake in the right thyroid lobe and minimal uptake in the carotid bifurcation tissue. The patient is currently being treated medically for thyrotoxicosis. Based on its ultrasonographic appearance, mild uptake on the I-123 scan, and no clinical suggestion of paraganglioma, the left neck mass is presumed to be ETT and no surgical intervention is being pursued. It is possible that the right lobe is thyrotoxic, suppressing iodine uptake in the ectopic tissue. Conclusion: This case demonstrates a unique presentation of ETT in the left carotid bifurcation with a thyrotoxic right lobe. It is difficult to distinguish the precise composition of neck masses at the carotid bifurcation, which has important implications for management. Often, an official diagnosis of thyroid tissue is made with histopathology only after the mass is surgically excised. Most ETT is benign in nature, and many times it is the only thyroid tissue available, thus surgery is not indicated. It is especially difficult to distinguish between ETT and paraganglioma on imaging itself. Somatostatin receptor scintigraphy, Ga-68/PET scanning, or iodine uptake scan can be useful to distinguish ETT from paraganglioma. Despite its rarity, lateral ETT must be included in the differential diagnosis of carotid body paraganglioma. Presentation Date: Saturday, June 17, 2023

THU523 A Rare Case Of Functional Cervical Paraganglioma: Case Report

Abstract Disclosure: V.D. Oliveira: None. G.C. Vaccarezza: None. A.E. Vieira: None. N.M. Scalissi: None. A.R. dos Santos: None. P.R. Lazarini: None. A.B. Suehara: None. C. Olivati: None. J.V. Lima: None. INTRODUCTION: Head and neck paragangliomas (HNPGL) are rare tumors arising from cells associated with parasympathetic ganglia. Catecholamine hypersecretion is founded in less than 5% of the patients. Evidence is growing that about 50% of the HNPGL are associated with hereditary syndromes. CASE REPORT: Male patient, 34 years old, previously healthy, presented with a 1-year history of jaw pain and hypoacusis, associated with progressive symptoms of dysphagia, facial paralysis, dysphonia and hoarseness. He also had a 2-month history of hypertension and palpitations. On physical examination, the patient had deficits in cranial nerves (CN) VII, VIII, IX, X, XI and XII and blood pressure of 150x90mmHg. Head and neck MRI showed an expansive lesion occupying the right jugular foramen extending above the cistern at the cerebellopontine angle and below the carotid space in the ipsilateral infratemporal fossa, reaching 50% of the internal carotid artery and extending into the right internal auditory canal, suggestive of glomus jugulare paraganglioma. Laboratory examination showed normetanephrines 9.1 mmol/L (VR < 0.9), confirming catecholamine-secreting paraganglioma. Next Generation Sequence (NGS) genetic testing evaluating 24 genes (ATM, DLST, EGLN1, EGLN2, FH, EPAS1 (HIF2A), HRAS, KIF1B , MAX, MDH2, MEN1 , MERTK , MET, NF1, RET, SLC25A11, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53 and VHL) was positive for the pathogenic variant c.166_170del:p.(Pro56Tyfs*5) of the SHDB gene. Patient with no family history of paraganglioma. Alpha-adrenergic blockade was started with doxazosin and, after two weeks, beta-adrenergic blockade with propranolol. After 3 months, he underwent preoperative embolization 48 hours before surgery with total tumor resection. Patient did not require antihypertensive drugs after surgery. CONCLUSIONS: We reported a case of a young patient diagnosed with catecholamine secreting HNPGL that carries pathogenic variant of SHDB. Presentation: Thursday, June 15, 2023

Proteomics analysis of carotid body tumor revealed potential mechanisms and molecular differences among Shamblin classifications.

Carotid body tumors (CBTs) are a rare type of paraganglioma, and surgical resection is the only effective treatment. Because of the proximity of CBTs to the carotid artery, jugular vein, and cranial nerve, surgery is extremely difficult, with high risks of hemorrhage and neurovascular injury. The Shamblin classification is used for CBT clinical evaluation; however, molecular mechanisms underlying classification differences remain unclear. This study aimed to investigate pathogenic mechanisms and molecular differences between CBT types. In Shamblin I, II, and III tumors, differentially expressed proteins (DEPs) were identified using direct data-independent acquisition (DIA). DEPs were validated using immunohistochemistry. Proteomics profiling of three Shamblin subtypes differed significantly. Bioinformatics analysis showed that adrenomedullin signaling, protein kinase A signaling, vascular endothelial growth factor (VEGF) signaling, ephrin receptor signaling, gap junction signaling, interleukin (IL)-1 signaling, actin cytoskeleton signaling, endothelin-1 signaling, angiopoietin signaling, peroxisome proliferator-activated receptor (PPAR) signaling, bone morphogenetic protein (BMP) signaling, hypoxia-inducible factor 1-alpha (HIF-1α) signaling, and IL-6 signaling pathways were significantly enriched. Furthermore, 60 DEPs changed significantly with tumor progression. Immunohistochemistry validated several important DEPs, including aldehyde oxidase 1 (AOX1), mediator complex subunit 22 (MED22), carnitine palmitoyltransferase 1A (CPT1A), and heat shock transcription factor 1 (HSF1). To our knowledge, this is the first application of proteomics quantification in CBT. Our results will deepen the understanding of CBT-related pathogenesis and aid in identifying therapeutic targets for CBT treatment.

Our Experience in Managing Carotid Body Tumors in Tertiary Care Center

Abstract Introduction: Carotid body tumors (CBTs), also known as paragangliomas or chemodectomas, are rare neuroendocrine neoplasms that arise near the carotid bifurcation within glomus cells derived from the embryonic neural crest. The reported incidence of CBTs is 1–2 cases per 1 lakh cases. Surgery is the mainstay of treatment. Objectives: The objective of this study was to report our experience and describe the presentation, surgical approach, postoperative complications, and outcomes of surgical treatment. Materials and Methods: It is a single-institution experience where a retrospective analysis of 6 cases with CBTs of patients who were candidates for surgery from June 2018 to June 2021 with a mean follow-up period of 24 months was done. Results: The mean age was 37 years, with a female predominance of 66%. The mean size of the tumor was 4.4 ± 1 cm. Four (66%) cases were presented with pain and pulsating neck swelling, and 2 (33%) cases were incidentally detected. All the cases were unilateral tumors. Neck ultrasound was done in all cases as a primary investigation. Magnetic resonance imaging was performed in 5 (87.5%) cases, which revealed tumors having near circumferentially encasing the internal carotid artery (ICA). No cases were malignant. All cases were surgically approached through transcervical vertical incision. Four cases (66%) and 2 (33%) cases were classified as Shamblin’s type II and III, respectively. Two (33%) cases needed special maneuvers such as division of the posterior belly of digastric and nasal intubation for the extra length of ICA. No major complications occurred. One patient (16.6%), as the tumor could not be dissected from the adventitia of ICA so, had to resect it, and primary end-to-end anastomosis was done. External carotid artery ligation was performed in 1 (16.6%) case. Minor postoperative complications such as hoarseness of voice occurred in 2 (33%) patients. No operative mortality occurred. Conclusion: We found a predominance of women and pain as the most common presenting complaint. Resection of CBTs by surgeons with experience in vascular reconstruction is recommended. Early surgical management is recommended to avoid neurological deficit or vascular reconstruction due to a Shamblin’s class III tumor. Preferred approach was caudo–cranial during dissection. Cranial nerve injury continues to be the most common complication.

Outcomes and Predictors of Morbidity after Carotid Body Tumor Resection

Carotid body tumors (CBTs) are uncommon neuroendocrine tumors at the carotid bifurcation treated with resection. The goal of this study was to examine patient outcomes after CBT resection and establish predictors of morbidity. Patients undergoing CBT resection were identified from the National Surgical Quality Improvement Program (NSQIP) database over 11years. Demographics, past medical history, preoperative labs, procedural details, morbidity and mortality were recorded. Multivariable logistic regression (MLR) analysis was performed to determine independent predictors of morbidity. From 2010 to 2020, 668 CBT resections were identified. The majority of patients were female (65%) and White (72%) with a mean age of 56 (standard deviation [SD]±16). Average body mass index (BMI) was 29.9 (SD±7.1). Arterial resection occurred in 81 patients (12%). 6% of patients experienced morbidity, most commonly re-operation (2.4%). Morbidity was more common in patients with higher BMI (33.1 vs. 29.7, P=0.005), chronic obstruction pulmonary disease (10% vs. 1.9%, P=0.012), higher American Society of Anesthesiologists (P=0.005), and lower albumin (3.7 vs. 4, P=0.016). Morbidity was not increased with arterial resection (P=1) or based on length of operation (P=0.169). Morbidity did not impact mortality (P=0.06) though led to longer length of stay [LOS] (8days vs. 2.4, P<0.001). On MLR, preoperative BMI was the only risk factor for morbidity (odds ratio 1.06, 95% confidence interval 1.02-1.1, P=0.005). CBT resection is very well tolerated with low stroke rates, morbidity, and mortality. Arterial resection leads to increased transfusion requirements and LOS but did not increase stroke rates, mortality, or overall morbidity. Within the NSQIP database, preoperative BMI was the only predictor of postoperative morbidity, which leads to significantly longer LOS.

Surgical outcomes of carotid body tumors removal and analysis of cardinal predictors associated with neurovascular and bleeding complications

Surgical outcomes of carotid body tumors removal and analysis of cardinal predictors associated with neurovascular and bleeding complications

Regulation of epinephrine biosynthesis in HRAS-mutant paragangliomas.

The biochemical phenotype of paragangliomas (PGLs) is highly dependent on the underlying genetic background and tumor location. PGLs at extra-adrenal locations usually do not express phenylethanolamine N-methyltransferase (PNMT), the enzyme required for epinephrine production, which was explained by the absence of glucocorticoids. PGLs with pathogenic variants (PVs) in Harvey rat sarcoma viral oncogene homolog (HRAS) can occur in or outside of the adrenal, but always synthesize epinephrine independently of the localization. Here, we characterize the signaling pathways through which PVs in HRAS influence PNMT expression. Catecholamines, cortisol, and transcriptional features of PGL tissues with known genetic background were analyzed. Genetically modified rat pheochromocytoma cells carrying PVs in Hras were generated and analyzed for regulation of Pnmt expression. Elevated epinephrine contents in PGLs with PVs in HRAS were accompanied by enrichment in mitogen-activated protein kinase (MAPK) signaling compared to PGLs with PVs in genes that activate hypoxia pathways. In vitro, Hras PVs increased Pnmt expression and epinephrine biosynthesis through increased phosphorylation of stimulatory protein 1 via MAPK signaling. Here, we provide a molecular mechanism that explains the PV-dependent epinephrine production of PGLs.

Predictors for postoperative cranial nerve complications in carotid body tumor resection: a retrospective cohort study.

Carotid body tumors (CBTs) are slow-growing benign tumors. Therefore, surgical resection is considered in case of tumor growth. The timing of surgery is of the utmost importance as the risk of iatrogenic surgical complications increases when resecting larger tumors, whereas on the other hand, resections for asymptomatic small CBT should be prevented. The primary aim of this study was to identify which tumor size or dimension is most accurate to predict nerve injury in patients undergoing resection of a CBT. This retrospective cohort study included patients who underwent surgical resection of CBT at the university hospital in South-Holland. Baseline patient characteristics and tumor measurements were retrieved from the medical records. The authors assessed how the different methods of measuring the size of the tumor were interrelated using Pearson correlation. Logistic regression was used to assess which variables were independently associated with nerve injury, including age at surgery, Shamblin classification, and those dimensions that captured different aspects of tumor size (rather than measuring the same as shown by high correlations) as possible independent variables. In 125 patients, 143 CBTs were resected whereof in 35 cases cranial nerve injury occurred, (transient in 16 cases and permanent in 19 cases). The risks for nerve injury increased with larger tumor size and the Shamblin classification. Logistic regression analysis showed that the anterior-posterior (AP) diameter significantly increased the odds of a nerve injury, a doubling for every 1cm increase in AP diameter [odds ratio (95% CI) 2.12 (1.29-3.48), P =0.003]. This study shows that measured tumor size in the AP plane is a strong predictor for postoperative nerve injury of a CBT resection. This predictor can be used in the daily clinic to give insight in operative risks. More research is needed in order to select the most appropriate time window for CBT resection.

Pheochromocytoma and paraganglioma in children and adolescents.

Pheochromocytoma (PPC) and paraganglioma (PGL) are the tumors that rarely occur in the pediatric population (PPGL). Both originate from chromaffin cells, pheochromocytoma is localized in the adrenal gland, whereas paragangliomas are regarded as the tumors present in other localizations, from head to the pelvis. The clinical image is characterized by the presence of the sustained hypertension, headaches, sweating, palpitations. The symptoms are caused by the catecholamine secretion or are related to tumor mass pressure on different organs. The catecholamines and their metabolites levels in urine collection or plasma are necessary for further evaluation of the diagnosis. In pediatric population the tumors occur in multiple familial syndromes such as Multiple Endocrine type 2, Neurofibromatosis type 1, Von Hippel-Lindau syndrome, Familial Paraganglioma syndrome are related to specific mutations (SDHx, RET, VHL, NF1) leading to the characteristic phenotype. The radiological and nuclear imaging are an important part of the examination. Although CT and MR are reported to have overall good sensitivity for the tumor detection, further analysis with nuclear imaging is recommended for the specified diagnosis. Right now 68GA-DOTATATE is regarded as the tracer of choice, leading to the complex evaluation of patients with different mutations and metastatic disease. The treatment of choice is the tumor excision. Also, lately new therapeutic approaches including genetically targeted therapies are under investigation for more complex treatment of tumors with underlying genetic cause or metastatic disease. Long term follow-up after treatment to avoid recurrence or to detect it in early stadium must be performed.

A Laboratory Medicine Perspective on the Investigation of Phaeochromocytoma and Paraganglioma.

Phaeochromocytomas (PC) and sympathetic paragangliomas (PGL) are potentially malignant tumours arising from the adrenal medulla (PC) or elsewhere in the sympathetic nervous system (PGL). These tumours usually secrete catecholamines and are associated with significant morbidity and mortality, so accurate and timely diagnosis is essential. The initial diagnosis of phaeochromocytoma/paraganglioma (PPGL) is often dependent on biochemical testing. There is a range of pre-analytical, analytical and post-analytical factors influencing the analytical and diagnostic performance of biochemical tests for PPGL. Pre-analytical factors include patient preparation, sample handling and choice of test. Analytical factors include choice of methodology and the potential for analytical interference from medications and other compounds. Important factors in the post-analytical phase include provision of appropriate reference ranges, an understanding of the potential effects of various medications on metanephrine concentrations in urine and plasma and a consideration of PPGL prevalence in the patient population being tested. This article reviews these pre-analytical, analytical and post-analytical factors that must be understood in order to provide effective laboratory services for biochemical testing in the diagnosis of PPGL.

1233 Role of Preoperative Embolization in the Surgical Management of Carotid Body Tumors: A Systematic Review and Meta-Analysis

Abstract Aim The role of preoperative embolization in the surgical management of carotid body tumors (CBT) remains a topic of debate. The aim of this study was to evaluate the effect of preoperative embolization on CBT resection. Method A systematic review and meta-analysis was conducted following the PRISMA protocol. Pubmed, Scopus and Web of Science were screened for studies published between 2010-2022. Primary outcomes investigated were intraoperative blood loss, operative time, length of hospital stay, and perioperative complications such as TIA/stroke, vascular injury and cranial nerve injury. Quality assessment of selected studies was performed using the Newcastle-Ottawa Scale (NOS). Publication bias was assessed using funnel plots and Egger’s regression test. Results Twenty-five studies were included in the systematic review, involving 1649 patients. Twenty-three studies were eligible for meta-analysis. The incidence of vascular injury necessitating intervention was significantly less in the preoperative embolization group (OR = 0.60; 95% CI: 0.42-0.84; P = .003). There was no statistically significant difference between the two groups with regards to intraoperative blood loss, operative time, length of hospital stay, incidence of TIA/stroke and cranial nerve injury. Subgroup analyses did not show significant difference between Shamblin I, II and III subgroups with regards to operative time. Conclusions This systematic review and meta-analysis found preoperative embolization to be significantly beneficial in reducing vascular injury. No statistically significant difference was found between the two groups regarding intraoperative blood loss, operative time, length of hospital stay and complications such as TIA/stroke and cranial nerve injury.

Multidisciplinary care improves outcomes for patients with carotid body paragangliomas-The UCLA experience.

To evaluate the effects and outcomes of multidisciplinary surgical approaches in the management of carotid body tumors (CBT). A single-center retrospective study at the University of California-Los Angeles Medical Center was conducted on patients who presented with CBTs and underwent surgical resections from 1998 to 2020. Statistical analysis was performed using IBM SPSS v27 and Excel. A total of 75 patients with 79 CBT resections were included. Operating surgical subspecialties included: 41.8% vascular surgery, 24.1% otolaryngology head and neck surgeons (OHNS), and 31.6% combined OHNS and vascular. 68.4% of tumors underwent preoperative embolization. EBL was directly correlated with tumor size. CBT size was similar for OHNS (30 mm) and vascular (31 mm) but was significantly larger for combined OHNS and vascular cases (38 mm). EBL was higher in combined cases (301 mL) compared to OHNS (124 mL) or vascular (203 mL) alone. Incidence of postoperative cranial nerve deficits was 7.8%, with combined OHNS and vascular cases having an incidence of 4.0% when compared to OHNS (5.3%) versus vascular surgery alone (12.1%). CBTs can be managed effectively by single surgical specialties with similar outcomes between vascular surgery and OHNS. In larger, higher grade tumors, however, a combined vascular and OHNS approach had lower incidence of postoperative cranial nerve injuries when compared to single specialty resections, despite a larger EBL. Thus, a multidisciplinary surgical approach suggests favorable outcomes with fewer incidence of cranial nerve deficits for larger, more complex CBT resections. 2b-Individual retrospective cohort study.

Metastatic Malignant Glomus Jugulare Tumor: A Rare Case Report with Clinical Manifestations and Treatment Approach.

BACKGROUND Paragangliomas are neuroendocrine neoplasms derived from paraganglia of the sympathetic and parasympathetic nervous systems. Parasympathetic ganglia-derived tumors, also called non-chromaffin, are located almost exclusively in the neck and skull base and are usually non-secretory and inactive. A case of malignant glomus jugulare with a metastatic cervical lymph node is described here. CASE REPORT A 24-year-old woman was referred to an otolaryngology clinic for concern of voice change for 1 month, which was associated with right progressive hearing loss, pulsating tinnitus, and right facial weakness. A clinical examination revealed a reddish mass in the right ear behind an intact tympanic membrane with right facial weakness of House-Brackmann grade VI. A bedside flexible nasopharyngoscopy revealed an immobile right vocal fold. A computed tomography scan of the brain revealed a destructive lesion within the right jugular foramen. The patient underwent embolization followed by glomus tumor resection via infra-temporal fossa with Fisch type A approach. Pathology revealed that the tumor was an infiltrative epithelioid tumor with a spindle and nesting pattern separated by fibrovascular stroma. The submitted lateral neck lymph node revealed a metastatic tumor. CONCLUSIONS Glomus jugulare tumors are uncommon paragangliomas, and malignant behavior with metastasis is extremely rare. Metastatic tumors are often associated with facial and vagal nerves palsy. There are no histological features that distinguish malignant glomus jugulare tumors. Malignant neoplasms are characterized by the presence of metastases. Tumors of the glomus jugulare that are malignant are treated with surgery, radiotherapy, or both. However, our search of the literature revealed no clear guidelines, given the scarcity of cases. Moreover, the presence of metastasis increases the risk of death.

Immunoreactivity of HOXB13 in Neuroendocrine Neoplasms Is a Sensitive and Specific Marker of Rectal Well-Differentiated Neuroendocrine Tumors.

HoxB13 is a transcription factor involved in defining of posterior endodermal derivatives, including prostate and rectum. While it is used as a marker of prostatic adenocarcinoma, it has not been studied systematically in neuroendocrine neoplasms. Thus, we performed HoxB13 immunohistochemistry in tissue microarrays and the whole sections of 232 neuroendocrine neoplasms. These included 34 paragangliomas (PGs), 20 cauda equina neuroendocrine tumors (CENETs), 123 well-differentiated neuroendocrine tumors (WDNETs), and 55 neuroendocrine carcinomas (NECs). WDNETs were additionally analyzed with SATB2, and colorectal WDNETs with CDX2 and serotonin immunohistochemistry. In total, HoxB13 immunoreactivity was observed in 95% (19/20) CENETs, 10.6% (13/123) WDNETs, and 12.9% (7/54) NECs. No PGs were positive. Large intestine WDNETs expressed HoxB13 in 68.4% (13/19); five negative tumors originated in cecum and one in rectum. In rectum, 92.9% (13/14) WDNETs expressed HoxB13. HoxB13 was 92.9% sensitive and 100% specific, showing 100% positive predictive value for the rectal origin of WDNET. In NECs, HoxB13 was positive in 15.4% (2/13) GIT tumors and 80% (4/5) prostatic NECs, but in none of urinary bladder NECs (0/8). SATB2 was positive in 17.1% (21/123) WDNETs, including 78.9% (15/19) of colorectal WDNETs, 71.4% (5/7) appendiceal WDNETs, and 2.9% (1/34) small intestine WDNETs. All 4 SATB2-negative large bowel tumors originated in the cecum. When both markers combined, HoxB13+/SATB2+ immunoprofile was seen exclusively in rectal WDNETs (positive predictive value 100%), while HoxB13-/SATB2+ immunoprofile was highly suggestive of the appendiceal origin (positive predictive value 71.4%). Therefore, HoxB13 can be useful as an immunohistochemical marker of rectal WDNETs and prostatic NECs.

Bilateral visual disturbances caused by a glomus vagale: illustrative case.

A glomus vagale tumor is an infrequent paraganglioma primarily characterized by auditory symptoms, cranial nerve involvement, or autonomic symptoms. However, visual involvement is not commonly observed, and to date, no cases have been reported in the literature. The case involves a 62-year-old female patient with a history of right carotid body tumor resection. She presented to the emergency department with a sudden decrease in visual acuity and bitemporal hemianopsia, accompanied by a left parietal headache. Initial brain magnetic resonance imaging (MRI) revealed a pituitary macroadenoma, which was completely resected. However, postoperatively, the patient developed left amaurosis. Subsequent brain MRI showed the presence of hemostatic material mixed with blood in the sellar region, causing displacement of the optic chiasm. A repeat intervention was performed, identifying bleeding from both cavernous sinuses. Head and neck angiography demonstrated a right glomus vagale tumor with abundant blood drainage into the right cavernous sinus. Embolization of the glomus vagale tumor was performed, resulting in no further bleeding and improvement of symptoms. The aim of this case report is to describe a rare occurrence of bilateral visual disturbances caused by bleeding in both cavernous sinuses due to venous hypertension caused by a right glomus vagale tumor.

Surgical Management of Carotid Body Tumors: A Triple Center Retrospective Study in Sana’a City, Yemen

Surgical Management of Carotid Body Tumors: A Triple Center Retrospective Study in Sana’a City, Yemen

A case of successfully resected Shamblin type III carotid body tumour without vascular reconstruction

Carotid body tumours (CBT) are rare vascular neoplasms arising from the bifurcation of the common carotid artery, and are benign tumors with low incidence, slow growth, and low rate for malignant transformation. A rare functional CBT may produce neuroendocrine secretions causing catecholamine-related symptoms, such as palpitations, headaches, hypertension, tachycardia, or flushing. These tumours have classic radiographic features. These lesions splay apart the internal (ICA) and external carotid arteries (ECA), and as it enlarges, it will encase, but not narrow the ICA and ECA-Lyre’s sign. If a diagnosis of CBT is suspected following a detailed physical examination, the diagnosis is almost always established by radiological imaging methods such as duplex ultrasonography, computed tomography (CT) angiography, magnetic resonance (MR) angiography, and digital subtraction angiography. These tumours were classified by Shamblin, according to the gross tumor vessel relationship and was based on the radiology, intraoperative findings and postoperative specimen examination. Group 1 tumors were minimally attached to the vessels and easily resectable. Group 2 tumors seemed to partially surround the vessel and were more adherent to vessel adventitia. These tumors were difficult to dissect but amenable to careful resection. Shamblin group 3 tumors had an intimate adherent relationship to the entire circumference of the carotid bifurcation and are usually inoperable. Surgical excision still remains the gold standard therapeutic modality for the treatment of CBTs. Radiotherapy is an alternative treatment modality which may decrease the tumor size or stop its growth. It is recommended for patients who cannot undergo surgery on account of extensive involvement, multiple tumors, and high operative and anesthetic risk.

Cytoplasmic HIF-2α as tissue biomarker to identify metastatic sympathetic paraganglioma

Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors. PGLs can further be divided into sympathetic (sPGLs) and head-and-neck (HN-PGLs). There are virtually no treatment options, and no cure, for metastatic PCCs and PGLs (PPGLs). Here, we composed a tissue microarray (TMA) consisting of 149 PPGLs, reflecting clinical features, presenting as a useful resource. Mutations in the pseudohypoxic marker HIF-2α correlate to an aggressive tumor phenotype. We show that HIF-2α localized to the cytoplasm in PPGLs. This subcompartmentalized protein expression differed between tumor subtypes, and strongly correlated to proliferation. Half of all sPGLs were metastatic at time of diagnosis. Cytoplasmic HIF-2α was strongly expressed in metastatic sPGLs and predicted poor outcome in this subgroup. We propose that higher cytoplasmic HIF-2α expression could serve as a useful clinical marker to differentiate paragangliomas from pheochromocytomas, and may help predict outcome in sPGL patients.

Transcanal Endoscopic Excision of Glomus Tympanicum in can tho Ent Hospital: Three Cases Report

Glomus tympanicum (GT) is a highly vascular, benign, and slow-growing tumor of the middle ear. It can be confused with other common ear diseases such as acute middle ear infection, otitis media with effusion, ear trauma… It is accurately diagnosed by history and endoscopy. CT scan showing: the presence of eroding jugular bulb is the most important thing to distinguish glomus tympanicum and glomus jugulare and assess the extension of the tumor to make good surgical planning. We present here the three cases in Can Tho ENT hospital: where total excisions were achieved trans-canal endoscopically without embolization. These procedures were safe, quick, and effective due to the better visualization of the surgical field with the endoscope.