Efficacy and Safety of Preoperative Embolization in Glomus Jugulare Tumors: A Systematic Review and Meta-analysis of Clinical Outcomes and Complications.

PURPOSE: This study aims to provide a comprehensive review of the clinical benefits, complications, and safety profile associated with preoperative embolization in Glomus jugulare tumors (GJTs). MATERIALS AND METHODS: A comprehensive search in PubMed, Embase, and Web of Science was conducted for English articles published up to March 2023, focusing on GJTs and preoperative embolization. Included studies involved patients over 18 with GJTs. We excluded studies that explored embolization methods other than the standard endovascular approach, as well as studies involving paragangliomas that did not provide specific data related to GJTs. Key variables such as hemorrhage volume and surgical time, as well as clinical outcomes, were analyzed. Data were analyzed using a random-effects model meta-analysis, assessing heterogeneity with the I2 statistic. RESULTS: This review encompasses 19 studies with a total of 328 patients. The studies incorporated into our meta-analysis display considerable differences and inconsistencies in their data. The findings of the meta-analysis show a mean hemorrhage volume of 636 ml (95% confidence interval (CI) 473-799) following preoperative embolization, and a mean surgical duration of 487 min (95% CI 350-624). The study also notes potential complications: facial nerve deficits occurred in 20% of cases (95% CI 11-32%), and vagal nerve deficits in 22% (95% CI 13-31%). CONCLUSION: This study suggests that preoperative embolization could decrease surgery duration and blood loss, but emphasizes the importance of evaluating risks like nerve damage. However, the generalizability of these findings is restricted due to the diversity of available data.

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.

Contemporary Management of Jugular Paragangliomas With Neural Preservation.

OBJECTIVES: Management of jugular paragangliomas (PGL) has evolved toward subtotal resection (STR). The purpose of this study is to analyze neural preservation and adjuvant treatment for long-term local control. STUDY DESIGN: Retrospective chart review. SETTINGS: Tertiary neurotology practice. SUBJECTS AND METHODS: Adults undergoing surgical treatment of jugular PGL between 2006 and 2019. Patients, disease, and treatment variables were collected retrospectively. Single predictor logistic regression was used to ascertain predictors of regrowth or need for salvage radiation. RESULTS: A total of 41 patients (median age, 47 years; 76% female) were identified. Most patients presented with advanced-stage disease (Glasscock-Jackson stage III-IV = 76%). Subtotal resection (STR) was performed in 32 (78%) patients. Extended STR (type 1) was the most commonly performed conservative procedure (n = 19, 59%). Postoperative new low cranial neuropathy (LCN) involving CN X and XII was rare (n = 3 and n = 1, respectively). Seventeen patients (41%) underwent postsurgical therapy for tumor regrowth or recurrence, including 15 patients who underwent adjuvant (n = 4) or salvage (n = 11) radiation. Overall tumor control of 94.7% was achieved at a mean follow-up of 35 months. All patients treated with combined modality treatment had local control at last follow-up. Logistic regression identified no single predictor for postsurgical radiation treatment or salvage-free survival. CONCLUSION: Management of jugular PGL with a conservative approach is safe and effective with a low rate of new LCN deficit. Active surveillance of residual tumor with salvage radiation for growth results in excellent long-term tumor control.

Paraganglioma yugular bilateral: reporte de un caso y revisión de la literatura / Bilateral jugular paraganglioma: case report and review of the literature

Resumen El paraganglioma (PG) es una neoplasia infrecuente originada de las células paraganglionares, embriológicamente derivadas de la cresta neural. Se localizan en la cabeza, base de cráneo, cuello, mediastino, abdomen y pelvis. La mayor parte de los PG muestran un curso clínico benigno, sin embargo, algunos casos pueden mostrar un comportamiento biológico agresivo con invasión local y metástasis a distancia. Un avance significativo en patología molecular ha sido el reconocimiento que el 30%-40% de estas neoplasias presentan alteraciones genéticas. Se han descrito más de 45 genes involucrados, incluyendo mutaciones de la línea germinal succinato deshidrogenasa. Actualmente se recomienda hacer test genético a todos los portadores de PG incluyendo los de presentación esporádica. El PG más frecuente se ubica en la glándula suprarrenal llamado feocromocitoma. El diagnóstico definitivo se realiza con histología, sin embargo, el estudio imagenológico puede entregar una aproximación diagnóstica certera. Debido a la aceptación actual que todos los PG tienen potencial metastásico, el concepto de PG benigno y maligno ha cambiado a uno de estimación de riesgo de metástasis, aunque no existe un esquema único aceptado para tal efecto. El tratamiento considera la cirugía, la radioterapia, la observación y terapias combinadas. Dado el lento crecimiento de este tipo de neoplasia y las potenciales complicaciones de la terapia quirúrgica, la observación es una opción especialmente para pacientes añosos dejando las otras opciones para pacientes más jóvenes. En este trabajo se presenta un caso de paraganglioma yugular bilateral gigante tratado con radioterapia de intensidad modulada incluyendo una revisión bibliográfica pertinente.

Abstract Paraganglioma (PG) is a rare neoplasm derived from paraganglionic cells of the neural crest. They are located in the head, skull base, neck, mediastinum, abdomen and pelvis. Most PGs show a benign clinical course, however, some cases may show aggressive biological behavior with local invasion and distant metastasis. A significant advance in molecular pathology has been the recognition that 30%-40% of these neoplasms present genetic alterations; more than 45 genes have been described, including mutations of the germline succinate dehydrogenase. Currently it is recommended to make genetic test to all patients with PG, including sporadic presentation. The most frequent PG is located in the adrenal gland called pheochromocytoma. The definitive diagnosis is made with histology; however, the imaging study can provide an accurate diagnostic approach. It is now accepted that all PG have a metastatic potential, therefore the concept of benign or malignant has been changed to a metastasis risk stratification approach however no single scheme is been widely used. The treatment considers surgery, radiotherapy, observation and combination therapies. Given the slow growth of this type of neoplasia and the potential complications of surgical therapy, observation is an option especially for elderly patients leaving the other options for younger patients. In this work we present a case of giant bilateral jugular paraganglioma treated with intensity modulated radiation therapy, including a pertinent literature review.

Complete embolization of jugular paragangliomas by direct puncture. Technical note.

Objective: Intra-arterial embolization of jugular paragangliomas is an established endovascular technique. Intratumoral embolization by direct puncture has been proposed, prior to surgical treatment or radiosurgery to reduce the risk of cranial nerve deficits. Methods: We examined the technical aspects of two patients with jugular paragangliomas embolized with liquid embolic agent by direct puncture of the lesion, as sole treatment. Results: Two patients with jugular paragangliomas presented with lower cranial nerve deficits. The first patient showed an extended lesion (55-mm) and was treated with partial intra-arterial embolization plus direct puncture and injection of Squid 18 and a second staged embolization by direct puncture and filling of the remainder of the lesion. The second patient with a smaller jugular paraganglioma (33-mm) was treated by single embolization by direct puncture of the tumor and injection of Squid 12 and Squid 18 obtaining complete filling of the lesion. No procedural complications were observed. Both patients showed no residual and initial improvement of the neurological deficits. Conclusion: The intratumoral embolization by direct puncture of jugular paragangliomas, under accurate radiological control is a safe procedure, and complete exclusion of the lesion can be obtained in selected cases. A staged particle embolization of the lesion by direct puncture can be proposed for large lesions. Only further studies with larger series and long-term follow-up will be able to define, if this strategy can be curative avoiding additional surgical or radio-surgical treatment.

Surgery, radiotherapy or a combined modality for jugulotympanic paraganglioma of Fisch class C and D.

OBJECTIVES: To identify the risks associated with surgery, radiotherapy or a combined treatment approach for Fisch class C and D jugulotympanic paraganglioma, in order to develop an individualised approach for each patient depending on Fisch class, age, mutation presence, tumour size growth rate and presenting symptoms. DESIGN: A retrospective multicenter cohort study with all patient records of patients with a head and neck paraganglioma in the Radboudumc, Nijmegen and the St. Elisabeth Hospital, Tilburg, the Netherlands. MAIN OUTCOME MEASURES: Local control, cranial nerve damage, complications, function recovery. RESULTS: We found highest local control rates after tumour debulking with postoperative radiotherapy in case of residual tumour growth, referred to as the combined treatment group, (100%; n = 19), which was significantly higher than the surgical group (82%; n = 17; P = 0.00), but did not differ from the radiotherapy group (90%; n = 29). There were significantly less complications in the radiotherapy group, when compared to surgery (63 vs 27%; P = 0.002) and the combined group (44 vs 27%; P = 0.016). Furthermore,: using a logistic regression model, we found that pretreatment tumour growth was a negative predictor for post-treatment cranial nerve function recovery (OR = 50.178, P = 0.001), reducing the chance of symptom recovery (67.3% vs 35.7%) post-treatment. CONCLUSIONS: Radiotherapy should be the treatment of choice for the elderly. For younger patients, tumour debulking should be considered, with potential radiotherapy in case of residual tumour growth.

Dural arteriovenous fistula associated with a glomus jugulare tumour presenting with only pulsatile tinnitus.

We present the second known case of a dural arteriovenous fistula (DAVF) associated with a glomus jugulare tumour in a 66-year-old man and the first with a presenting symptom of pulsatile tinnitus. The tumour occluded the left internal jugular vein at the bulb. Our patient opted for monitoring, but the tinnitus progressed and became debilitating, prompting him to proceed with embolisation of the tumour. Angiography revealed a DAVF of the left transverse sinus with retrograde flow. Embolisation of 80% of the tumour did not relieve symptoms. The patient returned for embolisation of the DAVF. Occlusion of the DAVF achieved symptomatic relief. A quandary develops during a procedure when the surgeon discovers that another intervention could satisfy the patient, while the patient is under anaesthesia. The higher flow in the DAVF likely causes the tinnitus in those with a patent sigmoid sinus, and embolisation of the DAVF alone could achieve relief.

Results of a systematic literature review of treatment modalities for jugulotympanic paraganglioma, stratified per Fisch class.

OBJECTIVE: Key for successful jugulotympanic paraganglioma management is a personalised approach aiming for the best practice for each individual patient. To this end, a systematic review is performed, evaluating the local control and complication rates for the different treatment modalities stratified by the broadly accepted Fisch classification. DESIGN: A systematic literature review according to the PRISMA statement was performed. A detailed overview of individual treatment outcomes per Fisch class is provided. MAIN OUTCOME MEASURES: Local control, cranial nerve damage, complications, function recovery. RESULTS: Eighteen studies were selected, resembling 83 patients treated with radiotherapy and 299 with surgery. Excellent local control was found post-surgery for class A and B tumours, and risk of cranial nerve damage was <1%. For class C1-4 tumours, local control was 80%-95% post-surgery (84% post-radiotherapy), and cranial nerve damage was found in 71%-76% (none post-radiotherapy; P < .05). There was no difference in treatment outcomes between tumours of different C class. For class C1-4De/Di tumours, local control was 38%-86% (98% post-radiotherapy; P < .05) and cranial nerve damage/complication rates were 67%-100% (3% post-radiotherapy; P < .05). C1-4DeDi tumours showed lesser local control and cranial nerve damage rates when compared to C1-4De tumours. CONCLUSIONS: An individual risk is constituted for surgery and radiotherapy, stratified per Fisch class. For class A and B tumours, surgery is a suitable treatment option. For class C and D tumours, radiotherapy results in lower complication rates and similar or better local control rates when compared to the surgical group.

Acquired Vascular Tumors of the Head and Neck.

Vascular neoplasms of the head and neck present with a wide spectrum of signs and symptoms. Diagnosis requires a high index of suspicion and is usually made after tumors are large enough to be visually apparent or cause symptoms. This article discusses the most common acquired benign and malignant vascular tumors, with an emphasis on their evaluation and treatment.

Initial radiographic tumor control is similar following single or multi-fractionated stereotactic radiosurgery for jugular paragangliomas.

OBJECTIVE: To evaluate radiographic tumor control and treatment-related toxicity in glomus jugulare tumors treated with stereotactic radiosurgery (SRS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic referral center. PATIENTS: Glomus jugulare tumors treated with SRS between 1998 and 2014 were identified. The data analysis only included patients with at least 18months of post-treatment follow up (FU). INTERVENTION: Patients were treated with either single fraction or fractionated SRS. MAIN OUTCOME MEASURE: Patient demographics and tumor characteristics were assessed. Radiographic control was determined by comparing pre and post treatment MRI, and was categorized as no change, regression, or progression. RESULTS: Eighteen patients were treated with SRS, and 14 met inclusion criteria. Median age at treatment was 55years (range 35-79), and 71.4% of patients were female. 5 patients (35.7%) received single fraction SRS (dose range 15-18Gy), and 9 (64.3%) fractionated therapy (dose 3-7Gy×3-15 fractions). Median tumor volume was 3.78cm(3) (range 1.15-30.6). Median FU was 28.8months (range 18.6-56.1), with a mean of 31.7months. At their last recorded MRI, 7 patients (50%) had tumor stability, 6 (42.9%) had improvement, and 1 (7.1%) had progression. Disease improvement and progression rates in the single fraction group were 40% and 0%, and in the multiple-fraction group, 44.4% and 11.1%, respectively. There was no statistically significant difference in disease improvement (p=0.88) or progression (p=0.48) rates between groups (unpaired t-test). CONCLUSIONS: At a median follow up of 28months, both single fraction and fractionated SRS appear to have comparable radiographic tumor control outcomes and toxicity profiles.

Nonparaganglioma jugular foramen tumors.

This article discusses the epidemiology, presentation, and diagnostic work-up of nonparaganglioma jugular foramen tumors, and the management options and predicted outcomes. Paragangliomas are the most common jugular foramen tumors, but other nonparagangliomas are important to consider in a differential for jugular foramen tumors. This article specifically focuses on jugular foramen schwannomas, meningiomas, metastatic disease, and regional pathologies that may extend to the jugular foramen, such as endolymphatic sac tumors, chordomas, and chondrosarcomas. Operative approaches to these tumors are also reviewed.

Successful Onyx embolization of a giant glomus jugulare: case report and review of nonsurgical treatment options.

BACKGROUND: Otorrhagia is an uncommon but severe symptom of patients with large glomus jugulare tumors that erode through the tympanic membrane. In this case report we describe the use of transarterial embolization for long-term palliative management of otorrhagia in a patient with an unresectable glomus jugulare tumor. CASE DESCRIPTION: A 53-year-old woman presented with intermittent otorrhagia 10 years after subtotal resection of a glomus jugulare tumor. Follow-up magnetic resonance imaging showed progressive enlargement of the tumor with significant extension into the posterior fossa. Resection was thought to be impractical; therefore, transarterial embolization was offered as a palliative measure to help reduce the frequency and severity of bleeding episodes. RESULTS: Long-term control of otorrhagia was achieved after three rounds of intra-arterial embolization. In round one, the tumor was embolized from multiple external carotid artery feeding branches by the use of polyvinyl alcohol particles. In round two, the internal carotid artery was sacrificed by embolizing the cavernous and petrous segments with coils. In round three, persistent feeders from the cervical internal carotid artery were embolized with Onyx. In 6 years of clinical follow-up, the patient has had no otorrhagia or new neurological deficits. Serial magnetic resonance imaging revealed there has been no significant interval tumor growth. CONCLUSION: Long-term control of otorrhagia from glomus jugulare tumors can be safely achieved by intravascular embolization with Onyx.

Jugular and vagal paragangliomas: Systematic study of management with surgery and radiotherapy.

BACKGROUND: The definitive treatment for head and neck paraganglioma (PG) is surgical excision. Unfortunately, surgery, particularly of vagal paraganglioma (VPG; "glomus vagale") and foramen jugulare ("glomus jugulare") tumors, may be complicated by injuries to the lower cranial nerves, a high price to pay for treatment for a benign tumor. Alternatively these tumors may be followed without treatment, or irradiated. The purpose of this review was to compare the existing evidence concerning the efficacy and safety of surgery, external beam radiotherapy (EBRT), and stereotactic radiosurgery (SRS), for jugular paragangliomas (JPGs) and VPGs. METHODS: Relevant articles were reviewed using strict criteria for systematic searches. Forty-one surgical studies met the criteria which included 1310 patients. Twenty articles including 461 patients treated with EBRT, and 14 radiosurgery studies comprising 261 patients were also evaluated. Results were compared between treatment modalities using analysis of variance (ANOVA) tests. RESULTS: A total of 1084 patients with JPGs and 226 VPGs were treated with different surgical procedures. Long-term control of the disease was achieved in 78.2% and 93.3% of patients, respectively. A total of 715 patients with JPG were treated with radiotherapy: 461 with EBRT and 254 with SRS. Control of the disease with both methods was obtained in 89.1% and 93.7% of the patients, respectively. The treatment outcomes of a JPG treated with surgery or radiotherapy were compared. Tumor control failure, major complication rates, and the number of cranial nerve palsies after treatment were significantly higher in surgical than in radiotherapy series. The results of SRS and EBRT in JPGs were compared and no significant differences were observed in tumor control. Because only 1 article reported on the treatment of 10 VPGs with radiotherapy, no comparisons with surgery could be made. Nevertheless, the vagus nerve was functionally preserved in only 11 of 254 surgically treated patients (4.3%). CONCLUSION: There is evidence that EBRT and SRS offer a similar chance of tumor control with lower risks of morbidity compared with surgery in patients with JPGs. Although the evidence is based on retrospective studies, these results suggest that surgery should be considered only for selected cases, but the decision should be individual for every patient.

Oncologic outcome in surgical management of jugular paraganglioma and factors influencing outcomes.

BACKGROUND: The purpose of this study was to identify the factors that may influence the management outcome in patients with jugular paragangliomas. METHODS: The surgical records of 121 cases of jugular paraganglioma (Fisch classifications C and D) were reviewed. RESULTS: The average follow-up was 88 months. Intracranial extension (ICE; Fisch classification De and Di) constitutes 55.4% of the cases. Two cases had a malignant jugular paraganglioma. Complete tumor resection was achieved in 81.8% of the cases, and there was evidence of recurrence in 4.0% from this group. Surgical tumor control was achieved in 96% of cases. Perioperative complications consisted mainly of cerebrospinal fluid leakage in 1.6% of the cases. The lower cranial nerve (CN) was preserved in 63% of the patients mainly in the cases without ICE. CONCLUSION: The infratemporal fossa approach type A allows for complete tumor resection with low perioperative morbidity and recurrence rates. The significant influential factors were the severity of ICE and internal carotid artery involvement.

Facial and lower cranial neuropathies after preoperative embolization of jugular foramen lesions with ethylene vinyl alcohol.

OBJECTIVE: To report 3 unique cases of cranial neuropathy after super-selective arterial embolization of jugular foramen vascular tumors with ethylene vinyl alcohol. STUDY DESIGN: Clinical capsule report. SETTING: Three tertiary academic referral hospitals. PATIENTS: Three patients who underwent superselective arterial embolization (SSE) of head and neck paragangliomas with ethylene vinyl alcohol are described. One individual was treated with primary SSE, whereas the remaining tumors were treated with preoperative SSE followed by surgical extirpation within 72 hours. All patients were found to have new cranial nerve deficits after SSE. RESULTS: One patient with isolated complete cranial nerve VII palsy demonstrated partial return of function at 8 months. One individual experienced cranial nerve VII, X, and XII palsies and demonstrated partial recovery of function of the involved facial nerve after 19 months. One subject experienced ipsilateral cranial nerve X and XI palsies after SSE and recovered full function of the spinal accessory nerve within 1 week but failed to demonstrate mobility of the ipsilateral true vocal fold. CONCLUSION: We present the first report documenting facial and lower cranial neuropathies after super-selective embolization of head and neck paragangliomas with EVA. Although it is difficult to draw conclusions from this small number of cases, it is plausible that the use of ethylene vinyl alcohol during SSE may result in a higher risk of permanent cranial neuropathy than the use of other well-established and more temporary agents. Knowledge of the arterial supply to the cranial nerves can help the clinician to choose the embolization agent that will provide maximal occlusion while minimizing the risk of complications.

Devascularization of head and neck paragangliomas by direct percutaneous embolization.

Preoperative transarterial embolization of head and neck paragangliomas using particulate agents has proven beneficial for decreasing intraoperative blood loss. However, the procedure is often incomplete owing to extensive vascular structure and arteriovenous shunts. We report our experience with embolization of these lesions by means of direct puncture and intratumoral injection of n-butyl cyanoacrylate (NBCA) or Onyx. Ten patients aged 32-82 years who were referred for preoperative embolization of seven carotid body tumors and three jugular paragangliomas were retrospectively analyzed. Intratumoral injections were primarily performed in four cases with multiple small-caliber arterial feeders and adjunctive to transarterial embolization in six cases with incomplete devascularization. Punctures were performed under ultrasound and injections were performed under roadmap fluoroscopic guidance. Detailed angiographies were performed before and after embolization procedures. Control angiograms showed complete or near-complete devascularization in all tumors. Three tumors with multiple small-caliber arterial feeders were treated with primary NBCA injections. One tumor necessitated transarterial embolization after primary injection of Onyx. Six tumors showed regional vascularization from the vasa vasorum or small-caliber branches of the external carotid artery following the transarterial approach. These regions were embolized with NBCA injections. No technical or clinical complications related to embolization procedures occurred. All except one of the tumors were surgically removed following embolization. In conclusion, preoperative devascularization with percutaneous direct injection of NBCA or Onyx is feasible, safe, and effective in head and neck paragangliomas with multiple small-caliber arterial feeders and in cases of incomplete devascularization following transarterial embolization.

First clinical experience in applying XperGuide in embolization of jugular paragangliomas by direct intratumoral puncture.

PURPOSE: The purpose of this study is to introduce a novel image-guided technique utilized in the embolization of jugular paraganglioma tumors, using preoperative diagnostic scans and planning together with perioperative X-ray fluoroscopy in a combined image. METHODS: A lesion center and a skin entry point on the patient are selected and connected with a straight line, which resembles the most ideal lesion access trajectory to be followed during the needle insertion. The skin entry point and the corresponding line location are selected such that it avoids the impenetrable bones and vital anatomical structures. Two viewing incidence angles are defined to guide the cranial needle insertion: the entry view tangent to the planned trajectory, and the progression view perpendicular to the path. RESULTS: The proposed method was applied in two patients with jugular paragangliomas in order to navigate needles to the lesion location and subsequently embolize the tumors. The perioperative registration took less than 8 s. Using this method, it was possible to guide the needle within 5 mm of the planned path. CONCLUSION: The fluoroscopic needle navigation, overlaid on the corresponding soft tissue of the underlying anatomy, combined with a planned path, has been shown to be an accurate and efficient tool for needle guidance. The patient pose varied between the preoperative data and the fluoroscopy guided intervention, but this did not hinder the procedure.