DOI: 10.33962/roneuro-2022-001 Multimodal treatment of glomus jugular tumours. Case series and literature review F. Stoica, G. Popescu, Francesca Paslaru, Anamaria Gheorghiu, A.C. Paslaru, M. Apostol, M.C. Zaharia, R.M. Gorgan Romanian Neurosurgery (2022) XXXVI (1): pp. 9-13 DOI: 10.33962/roneuro-2022-001 www.journals.lapub.co.uk/index.php/roneurosurgery Multimodal treatment of glomus jugular tumours. Case series and literature review F. Stoica1, G. Popescu1, Francesca Paslaru1, Anamaria Gheorghiu1, A.C. Paslaru2,3, M. Apostol1, M.C. Zaharia1, R.M. Gorgan1,2 1 4th Neurosurgical Department, “Bagdasar Arseni” Clinical Emergency Hospital, Bucharest, ROMANIA 2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, ROMANIA 3 Department of Genetics, “Dr. Victor Gomoiu” Children’s Clinical Hospital, Bucharest, ROMANIA ABSTRACT Glomus jugulare tumours are extremely rare, slow-growing, hypervascular tumours that arise within the jugular foramen of the temporal bone and frequently involve the lower cranial nerves. We performed a retrospective study for patients treated between January 2005 and December 2019, reviewing clinical and radiological data for 91 cases of glomus jugulare tumours. Data were available for 91 patients presenting with 96 tumours. Surgery was 1st intention of treatment for 13 cases, the endovascular approach was 1st intention for 6 cases and GKRS was primarily performed in 72 cases. Combined treatment options were used in 19 cases. The median age at the time of treatment was of 57 years. The tumour volume varied between 0.5 and 73.4 cm3 with a median value of 8.3 cm3. For the cases treated with GKRS, the peripheral dose ranged between 8 and 35 Gy on the 35% to 65% isodose, with a median of 14 Gy on the 45% isodose. The average follow-up was 38 months with a maximum of 94 and consisted of contrast-enhanced MRI every six months in the first year after the procedure and every 1 to 2 years afterwards. Overall tumour control rate was of 95.6% using multimodal treatment options for glomus jugulare tumours. Multimodal treatment for glomus jugulare tumours offers the patient the chance for the best possible outcome and long-term survivability. Individual treatment approach for this kind of very rare head and neck tumour (0,6% of all head and neck tumours) is recommended to choose the best risk-versus-benefit treatment option. BACKGROUND Glomus jugulare tumor is a benign neuroendocrine tumor that arises from the jugular foramen. This tumor is characterized by a slow- growing pattern. Paragangliomas, also known as chemodectomas represent benign tumors with the origin from neural crest derivates also known as the parangalia [1],[2 ],[3 ]. These tumors are highly vascularised. They can receive blood supply from both from the external carotid artery and internal carotid artery. The localization of Keywords multimodal, jugular tumours, glomus Corresponding author: G. Popescu “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania george_popescu39@yahoo.com” Copyright and usage. This is an Open Access article, distributed under the terms of the Creative Commons Attribution Non–Commercial No Derivatives License (https://creativecommons .org/licenses/by-nc-nd/4.0/) which permits non- commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of the Romanian Society of Neurosurgery must be obtained for commercial re-use or in order to create a derivative work. ISSN online 2344-4959 © Romanian Society of Neurosurgery First published March 2022 by London Academic Publishing www.lapub.co.uk http://www.lapub.co.uk/ 10 F. Stoica, G. Popescu, Francesca Paslaru et al. these tumors can widely vary, from carotid bifurcation to the auricular branch of the vagus nerve. The most frequent localization is the carotid body, accounting for almost half of the tumors [5],[6] whereas glomus jugulare tumors represent 24% of them [6]. Even though they are benign tumors, the symptomatology can be the cause of the mass effect [2]. Usually, these tumors are diagnosed in the fourth to sixth decade of life, with a moderate female predilection. Most of the glomus jugulare tumors are isolated lesions but around 20% of them present hereditary components [4]. The inherited tumors are usually bilateral and the onset of the symptoms is reported to be earlier than the onset symptomatology of the sporadic tumors. The reported malignancy of these tumors is less than 5% [2]. Around 25% of the paragangliomas remain silent and are incidentally discovered. The symptoms caused by these tumors depend on their location. Lower cranial nerves impairment is reported in more than 10% of patients [8]. The most common neurological deficits reported are tongue deviation, hoarseness, facial palsy, dysphagia, and shoulder weakness [2],[7],[8]. Additionally, patterns of cranial nerve palsies were described and these include [12]: • Vernet syndrome that represents motor paralysis of cranial nerves IX, X and XI; [9] • Collet- Sicard syndrome described as the palsy of cranial nerves IX,X,XI and XII; [10] • Horner syndrome – oculosympathetic palsy. [11] Due to its slow-growing pattern and the complex anatomy of the skull base and neck, observation of the patient is considered a good treatment alternative. In more than 60% of the cases, tumor volume remains stable or decrease in size [14]. However, if the tumor tend to be symptomatic, surgical excision or stereotactic radiosurgery will be take into account. CASE SERIES We performed a retrospective study for patients treated between January 2005 and December 2019, reviewing clinical and radiological data for 91 cases of glomus jugulare tumors. Data were available for 91 patients presenting with 96 tumors. Surgery was the treatment of choice for 13 cases, endovascular embolization was performed as first intention treatment for 6 cases and GKRS was primarily performed in 72 cases. Figure 1. Distribution of the treatment option Combined treatment options were used in 19 cases (1 surgery with GKRS, 18 endovascular with GKRS). 44 glomus jugulare tumors were identified on the right side, and 47 on the left side. In the study group, we had 23 male patients and 63 female patients. 11 patients were in the 15-39 age group while 80 patients were older than 40 yrs. The median age at the time of treatment was of 57 years. The tumor volume varied between 0.5 and 73.4 cm3 with a median value of 8.3 cm3. Figure 2. Gender distribution of the patients For the cases treated with GKRS, the peripheral dose ranged between 8 and 20 Gy on the 35% to 65% isodose, with a median of 14 Gy on the 45% isodose. The average follow-up was 38 months with a maximum of 94 and consisted of contrast-enhanced MRI every six months in the first year after the procedure and every 1 to 2 years afterward. Overall GENDER DISTRIBUTION Male 25% Female 75% Treatment approach 3, 14% 6, 7% 72, 79% Surgery Endovascular GKRS 11 Multimodal treatment of glomus jugular tumours Reccurence Gamma Knife Radiosurgery 4 7 2 Emboliz ation 6 Open surgery 7 1 3 0 10 20 30 40 50 60 70 80 Reccurence Cases tumor control rate was 95.6% using multimodal treatment options for glomus jugulare tumors. Figure 3. Tumour localisation Table 1. Most common comorbidities Comorbidities were noted in 37 patients (40.6%) and consisted of lower cranial nerves deficits (26.4%), dizziness, tinnitus, partial or complete hearing loss in 21.9% of cases, 2 hemorrhages, 2 secondary hydrocephalus, and 1 hemiparesis. 23 patients (24.3%) presented recurrences: 13 after surgery, 6 after embolization, and 4 after GKRS. However, the mortality rate was 0. Figure 4. Recurrence cases based on the therapeutical approach CASE 1 The first case is represented by a female patient of 53 years old, whose symptoms are vertigo, hearing loss, and pulsating tinnitus. Soon it is discovered the typical aspect of “salt and pepper” for a glomus tumor with temporal localization, millimetric extracranial extension into jugular vein lumen and damage to the structures of the inner ear. 9 years after GKRS, a cerebral MRI was performed, which showed that the irradiated tumor volume has been reduced in circumferential dimensions, with a homogeneous intake of contrast substance ("densified" appearance due to sclerosis and obliteration of intratumoral blood vessels) without adverse reactions due to irradiation. No new neurological deficits were recorded after GKRS. Figure 5. Preoperative aspect of the tumour Figure 6. Postoperative aspect after Gamma Knife Radiosurgery COMORBIDITY Lower cranial nerves deficits Dizziness Tinnitus Hearing impairment Hemorrhages Hydrocephalus Hemiparesis Tumour localisation 52% 48 % Right Side Left Side 12 F. Stoica, G. Popescu, Francesca Paslaru et al. CASE 2 The second case is represented by a 62 years old female patient, whose symptoms onset with injury to multiple cranial nerves (VII, VIII, IX, XI, XII). The diagnosis was represented by a large glomic tumor with an important intracranial component with a mass effect on the brainstem. A cerebral MRI was performed 4 years post GKRS, showing a marked reduction in the size of the irradiated tumor, especially in the intracranial component, with a significant decrease in the mass effect, without perilesional reactive edema. No new neurological deficits were recorded. 18 months after irradiation, a complete remission of facial paresis has been noticed and other cranial nerves neurological status remained stationary. Figure 7. Preoperative aspect of the tumour Figure 8. Postoperative aspect after Gamma Knife Radiosurgery CASE 3 For the third case, we have a 35 years old male patient, who presented with glomic tumor located in the temporal bone, onset with hearing disorders (hearing loss and pulsating tinnitus). 6 years after GKRS, a periodic follow-up MRI has been performed. the inferior recurrence in the lumen of the jugular vein was identified outside the irradiation field with a volume of 4.6 cm3, asymptomatic. The decision is made in order to irradiate the recurrence with 14 Gy on 47% isodose. Figure 9. Preoperative aspect before Gamma Knife Radiosurgery Figure 10. The reccurence aspect, 6 years afte GKRS DISCUSSIONS The best treatment option for glomus jugulare tumors is yet to be debated. Due to their localization, surgical treatment does not represent the gold standard because of the complex anatomy of the region, high rates of morbidity, subtotal resection, and the alternative behavior of the tumors that could be very aggressive in some cases. In 2003, Roberto Pareschi et al [15] described their experience in the surgical treatment of glomus jugulare tumors. 42 patients with glomus jugulare tumors were identified, 3 of them previously undergone surgery for this pathology, and 3 patients presented bilateral temporal lesions. The otoscopic evaluation revealed in 80% of the patients the typical red middle ear mass. 70% of the cases had no preoperative cranial nerve deficit. 37 seven patients were elected for surgical intervention. In 33 cases, infratemporal fossa approaches were used and in 4 cases, conservative jugulopetrosectomy was performed, in order to preserve the facial nerve. In 20% of the cases, cranial nerves IX and X were injured. No recurrence after total resection was reported. An extensive dissection of the posterolateral skull base is required for surgery of glomus jugulare tumors [15]. Even though cranial nerve preservation is an 13 Multimodal treatment of glomus jugular tumours extremely important goal in the surgical approach, in 22% of the cases facial nerve is sacrificed [15]. The authors concluded that the focus should drift away from total resection to increasing the quality of life of the patient, a philosophy that our clinic shares. Only 14% percent of our cases were surgically treated, in order to avoid the decrease in the quality of patient`s life. Endovascular treatment is an alternative treatment approach for patients with glomus jugulare tumors. In 2017, Kocur et al [17] presented their experience and the outcome of embolization in 3 cases of glomus jugulare tumors. They described the technical difficulty of achieving complete obliteration of the glomus jugulare tumors and concluded that increased risk of revascularization is not beneficial compared to the diminished clinical symptoms. In our clinic, only 6 endovascular treatments were performed. A promising approach for this pathology is represented by radiosurgery. Due to the high degree of accuracy, rapid radiation dose falloff at the periphery of the target tumor, and their high precision, radiosurgery became a popular treatment choice. In their meta-analysis, Guss et al [13] included 19 studies, compounding 335 glomus jugulare patients. They reported a reduced or unchanged tumoral volume after radiosurgery, sustained by imagistic findings. Clinical control was reported as improved or unchanged after radiosurgery in 95% of the cases. The authors emphasized the effectiveness of this treatment option. In our clinic, 72 patients benefited from radiosurgery. 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