Transjugular Approach for Recurrent Intracranial Glomus Vagale Tumors: An Ideal Approach to Preserve Hearing and Facial Nerve Function

Lateral skull base paragangliomas (glomus tumors) are rare skull base tumors arising from neuroendocrine cells. These benign tumors can be locally aggressive with potential for intracranial extension and significant morbidity as they compromise cranial nerve structures. Treatment is highly patient dependent. Herein, we present a case of recurrent glomus vagale paraganglioma requiring a multidisciplinary transjugular and transcervical approach for complete resection. A 64-year-old male was referred to the neurotology clinic in 2019 for a left skull base tumor causing progressive dysphonia and dysphagia. Exam revealed left true vocal fold weakness and no other abnormalities. Hearing was normal on the left. Magnetic resonance imaging (MRI) revealed a large hyperintense lesion of the left jugular foramen with intracranial cerebellopontine angle extension and normal flow through the sigmoid sinus and jugular vein. The patient elected for surgical removal and near-total resection was achieved via retrosigmoid craniotomy. A small portion was intentionally left in the jugular foramen to preserve the intact eleventh cranial nerve, internal jugular vein, and sigmoid sinus. Surgical pathology confirmed glomus paraganglioma. Postoperative radiation was strongly recommended, but the patient was lost to follow-up due to the COVID-19 pandemic. The patient re-presented in late 2021 with worsened dysphonia and dysphagia. Exam confirmed left true vocal fold immobility consistent with vagal nerve paralysis and a new finding of left tongue weakness consistent with hypoglossal nerve injury. MRI revealed recurrence of the lesion to dimensions larger than original presentation and complete occlusion of the sigmoid-jugular system. Hearing and facial nerve function remained fully intact, thus a transjugular approach with hearing preservation and complete surgical resection was utilized. After combined retrosigmoid and transcervical incision, the transjugular approach was utilized to resect the sigmoid sinus, the tumor of the jugular foramen, and the intracranial extension. The ear canal and facial nerve canal were preserved. The sigmoid sinus was ligated with surgical clips and the jugular vein was ligated with suture thread. Intracranially, the hypoglossal nerve was identified and preserved, and the vagus nerve was seen eroded by tumor. Pathology confirmed recurrent paraganglioma. Postoperatively, the patient recovered well but continues to endorse persistent dysphonia. His treatment plan includes radiation and thyroplasty. Multiple surgical approaches for the treatment of skull base paragangliomas have been reported including infratemporal types A to D, among others. This report identifies a rare case of recurrent paraganglioma which necessitated removal via transjugular approach. While uncommon in skull base surgery, this approach allowed identification and preservation of important neck and skull base structures (e.g., facial nerve, ear canal, spinal accessory nerve) while achieving complete gross resection. Radiation techniques have become popular alternatives for treatment of glomus tumors of the skull base due to high levels of surgery-related adverse events. Thus, skull base surgeons should be aware of the utility of the transjugular surgical technique for patients with intact hearing and facial nerve function who seek removal of intracranial jugular foramen tumors.

Comprehensive analysis of the novel omicron receptor AXL in cancers.

The SARS-CoV-2 is constantly mutating, and the new coronavirus such as Omicron has spread to many countries around the world. Anexelekto (AXL) is a transmembrane protein with biological functions such as promoting cell growth, migration, aggregation, metastasis and adhesion, and plays an important role in cancers and coronavirus disease 2019 (COVID-19). Unlike angiotensin-converting enzyme 2 (ACE2), AXL was highly expressed in respiratory system cells. In this study, we verified the AXL expression in cancer and normal tissues and found AXL expression was strongly correlated with cancer prognosis, tumor mutation burden (TMB), the microsatellite instability (MSI) in most tumor types. Immune infiltration analysis also demonstrated that there was an inextricable link between AXL expression and immune scores in cancer patients, especially in BLCA, BRCA and CESC. The NK-cells, plasmacytoid dendritic cells, myeloid dendritic cells, as one of the important components of the tumor microenvironment, were highly expressed AXL. In addition, AXL-related tumor neoantigens were identified and might provide the novel potential targets for tumor vaccines or SARS-Cov-2 vaccines research in cancer patients.

Successful diagnosis and treatment of pheochromocytoma during severe coronavirus disease 2019 (COVID-19): a case report.

Pheochromocytoma is a rare but life-threatening condition due to catecholamine release induced by drug treatments such as ß-blockers or glucocorticoids. We present a case of hypertensive crisis due to pheochromocytoma, induced after the initiation of dexamethasone and landiolol during intensive care for severe coronavirus disease 2019 (COVID-19). Based on a detailed medical history review, the patient was previously diagnosed with primary aldosteronism by confirmatory tests, moreover, an abdominal computed tomography scan identified an adrenal tumor 2 years before current admission. We tentatively diagnosed the patient with pheochromocytoma and initiated α-blockers without conducting a catecholamine report, leading to stable hemodynamics. We present a successfully managed case of pheochromocytoma concomitant with COVID-19, which has become a global crisis.

High Altitude Carotid Body Tumors Growth During active Surveillance.

BACKGROUND: The gold standard for patients with carotid body tumors (CBT) is surgical resection; nevertheless, some patients are unfit for surgery or, for other reasons, could not be operated on. Active surveillance has been known to be a reasonable strategy for these cases. This study aimed to evaluate tumor growth in unoperated patients with CBTs. METHODS: A retrospective review of all unoperated patients with CBT from a single academic hospital diagnosed between 2014 and 2021 was performed. Results of nonparametric testing were presented using the median and ranges for Mann-Whitney-U or Kruskal-Wallis. Significance was defined as a 2-tailed P < .05. RESULTS: The cohort included a total of 31 patients, with a median age of 60 years (range: 37-80 years), of which 27 (87.1%) were females. The patients live at a median altitude of 2800 meters (range: 2756-2980 meters) above sea level. Twenty (64.5%) patients had Shamblin I tumors, eight (25.8%) patients had Shamblin II tumors, and three (9.7%) patients had Shamblin III tumors. Median CBT volume at diagnosis was 14.1 cm3 (range: .9 - 213.3 cm3). Median volume at diagnosis of symptomatic tumors was substantially larger than asymptomatic tumors, 49.2 cm3 vs 7.9 cm3, respectively (P = .03). Median growth of the tumors during a median 15-month follow-up (range: 3-43 months) was 3.3 cm3 (range: 0-199.9 cm3). Overall, 77% (n = 24) of the CBTs grew at least 1 cm3. CONCLUSION: Most patients in the present study had tumor growth by at least 1 cm3, with a median tumor growth of 3.3 cm.3 In the present study tumor growth was shown to be greater than other low altitude CBT active surveillance studies; therefore, surgical resection should be recommended in patients with CBT living at high altitudes.

Jugular Paraganglioma Presenting with a Tumor Thrombus Extending from Posterior Fossa to Right Atrium and Multiple Skeletal Metastases.

INTRODUCTION: Paragangliomas are tumors of neuroendocrine origin, may appear in different localizations, and are related to the autonomic nervous system. Paragangliomas are generally asymptomatic and may rarely appear with adrenergic symptoms, and clinical findings depend on the catecholamines they secrete. Extra-adrenal paragangliomas are mostly benign, like all paragangliomas. Malignancy criteria consist of local recurrence, metastasis after total resection, and presence of distant metastasis during primary diagnosis. CASE PRESENTATION: This report presents the case of a 31-year-old man with jugular paraganglioma, multiple skeletal metastases, and a long-segment tumor thrombus. Imaging procedures showed a continuous tumor thrombus extending from the posterior fossa to the right atrium and metastases in C2, T1, T6, T8, L5, and right humerus. Histopathological assessment of the metastasis in C2 identified malignant paraganglioma. Curative surgery was not an option for this patient, hence combined chemotherapy was given. CONCLUSION: In cases of malignant paraganglioma with multiple distant metastases, chemotherapy and radiotherapy are feasible treatment methods.

Impact of COVID-19 on individuals with paraganglioma/pheochromocytoma history and/or hereditary risk

Background: Patients with paraganglioma/pheochromocytoma (PPGL) or hereditary predisposition to PPGL often need screening with biochemical labs, imaging and physical exam. Given the rarity of PPGL and hereditary PPGL, care is often provided through specialty centers. Subsequently, patients may have experienced restrictions on travel and delayed scheduling of non-elective procedures due to COVID-19. This study aimed to analyze the impact of COVID-19 on seeking PPGL management. Methods: Patients with a personal history of PPGL or hereditary PPGL risk from the University of Michigan, Brigham Women's Hospital, and Huntsman Cancer Institute were sent a survey in 2021. The survey included questions regarding tumor history (Y/N), gene status, demographics, and experience with COVID. The survey assessed whether they missed any exams related to PPGL diagnosis or screening. Comparative analyses utilized regression and chi-square tests. Patient factors measured in analyses evaluated COVID surveillance (labs, imaging, doctor visit) as the primary outcome and age, institution, gene status, sex, and PPGL history as predicting variables. Results: In total, 241 respondents across three institutions completed the survey. The cohort was primarily female (n = 158, 65.6%). A majority of the cohort identified as White (n = 222, 92%) and non-Hispanic (n = 226, 93.8%). PPGL history was reported in 158 patients (65.6%), 43 of which were pheochromocytoma and 113 were paraganglioma, primarily in the head and neck (n = 78). At time of survey completion, 209 (87%) respondents answered COVID-related questions. Thirty-nine respondents (19.2%) reported missing doctor visits, while 31 (15.3%) report missing HPPGL imaging and 33 (16.3%) report missing lab tests. There were no differences by institution (p > 0.05) on patient reported missed visits. Logistic regression analysis showed no difference in missing visits based on having a hereditary PPGL predisposition gene or sex of respondent (all p-values > 0.05). There was no difference based on PPGL history, though it is unknown if patients missed PGL follow-up or screening. Individuals who missed imaging (Y/N) were more likely to report missing their lab tests (OR = 1.8, p < 0.01) and doctor visit (OR = 1.25, p < 0.01). Age was a significant predictor for missing doctor visits (p = 0.02) with an odds ratio of 1.002 per 1 year increase in age. Conclusions: Though institutions had different COVID-19 restrictions and guidelines by state, there was no difference on missing surveillance or screening. Over 15% of respondents reported missing at least one aspect of PPGL care, indicating a need to re-engage those with PPGL and hereditary PPGL to return to typical screening and surveillance. Patients who miss one aspect of surveillance are likely to have missed other aspects of surveillance and will require evaluation of all aspects of screening to return up to date on needed visits and procedures.

METASTATIC BLADDER PARAGANGLIOMA WITH UNDERLYING SHDB MUTATION

Introduction Phaeochromocytoma and paraganglioma (PPGL) are rare tumors with up to 40% associated with inherited germline mutations. SHDB mutation is associated with an increased risk of metastasis. Case A 36-year-old male presented with hypertensive emergency. He was diagnosed to have a bladder paraganglioma at age 32 when he presented with hypertensive crisis. Ga-68 DOTANOC PET/CT scan then showed a localized 4.7 x 5.3 cm bladder paraganglioma and he underwent complete surgical resection with resolution of his symptoms. Genetic testing done showed SHDB, deletion (exon 1), heterogenous pathogenic variant. He remained asymptomatic and was lost to follow-up due to COVID-19 until his recent admission. During this admission, he had labile blood pressure with symptoms of palpitations and lethargy. He was found to have a 4.3x elevated urine normetanephrine (1639 ug/day, N<374.7). Metanephrine and 3-methoxytyramine levels were normal. His blood pressure was controlled with phenoxybenzamine 20 mg TDS (1 mg/kg), telmisartan 40 mg OM and carvedilol 25 mg BD with improvement in his symptoms. Subsequent anatomical imaging with CT and functional imaging with Ga-68 DOTATATE showed a small recurrence at the bladder wall with metastatic lesions at the left sacral ala measuring 4.5 x 5.1 cm, and multiple lytic lesions over the spine, ribs and also the left acetabulum with the highest uptake of Ga-68 DOTATATE at the C2 vertebra (SUV max 93). He is now planned for peptide receptor radionuclide therapy (PRRT). SHDB mutation is associated with a higher risk of metastatic disease which has remained unexplained. Treatment for metastatic disease include surgical resection where possible, targeted therapy such as PRRT, meta-iodobenzylguanidine (MIBG) therapy, radiotherapy and also systemic therapy such as chemotherapy and tyrosine kinase inhibitors. Conclusion Patients with PPGL, especially those with SHDB mutation, require monitoring at regular intervals to screen and detect metastasis to reduce mortality and morbidity.

An incidental finding of retroperitoneal paraganglioma during the coronavirus disease 2019 pandemic: a case report.

BACKGROUND: Extra-adrenal paraganglioma of the retroperitoneum is a very rare neoplasm arising from cells of the primitive neural crest. Although paragangliomas are considered benign and are often found incidentally, they have the potential to metastasize. CASE PRESENTATION: We report the case of a 68-year-old Caucasian woman with an incidental diagnosis of retroperitoneal paraganglioma that was discovered on chest computed tomography performed for high suspicion of coronavirus disease 2019 pneumonia. The patient showed no metastasis and was successfully treated by complete surgical removal of the tumor. CONCLUSION: As the diagnosis of paragangliomas is often delayed because of absent clinical symptoms, they represent a significant diagnostic challenge. Although surgery may exacerbate coronavirus disease 2019 infection, surgical resection of this tumor is prioritized, given its malignancy potential, and it must be performed as soon as no infection is detected.

Management of Pheochromocytomas and Paragangliomas: A Case-Based Review of Clinical Aspects and Perspectives.

Paraganglioma and pheochromocytoma are rare medical conditions. Thus, there are still a small number of studies, clinical trials, and evidence-based data in this field. This makes clinical decisions more difficult. In this study, we present a case report enriched with a short review of available essential clinical data, indicating the need for constant metoxycatecholamine level observation and a proper diagnostic imaging approach, especially in terms of ongoing pandemics. Our research also provides a summary of the molecular background of these diseases, indicating their future role in clinical management. We analyzed the ClinicalTrials.gov dataset in order to show future perspectives. In this paper, the use of the PET-CT before MRI or CT is proposed in specific cases during diagnosis processes contrary to the guidelines. PET-CT may be as effective as standard procedures and may provide a faster diagnosis, which is important in periods with more difficult access to health care, such as during the COVID-19 pandemic.

Paraganglioma: An Unexpected Diagnosis in a Patient With Cerebral Venous Sinus Thrombosis and SARS-CoV-2 Infection.

Cerebral venous sinus thrombosis (CVST) is the complete or partial occlusion of the main venous sinuses or cortical veins. The most known risk factors are oral contraceptives, pregnancy, thrombophilias, malignancy and infections. The SARS-CoV-2 infection has been associated with a hypercoagulable state and there are some reported cases of CVST in SARS-CoV-2 patients. Although infection is one of the possible causes of CVST, it is important to rule out malignancy. We report a case of a 27-year-old male, with a recent SARS-CoV-2 infection, who went to the emergency department for a severe left occipital headache and was diagnosis with CVST. An etiological study revealed a retroperitoneal mass, compatible with a paraganglioma.