Endolymphatic Sac Tumors Research Articles

SURG-46. ENDOLYMPHATIC SAC TUMORS: A CASE REPORT AND REVIEW OF THE LITERATURE

Abstract Endolymphatic sac tumors are rare, histologically benign tumors that pose a danger of local bony destruction. Definitive treatment is complete surgical resection but the use of subsequent radiotherapy remains controversial and is typically used for residual or recurrent disease. Additionally, these tumors are associated with von-Hippel-Lindau (VHL) syndrome and are present in 10-30% of patients with this autosomal dominant disorder. We present the case of a 69 year-old woman who presented with cranial nerve 7 and 8 palsies that had started in the 1990s and was found to have a left CPA mass. She underwent pre-operative embolization followed by 2 stage craniotomy and post-operative radiotherapy. Testing for the VHL mutation was negative.

Surgical Management and Prognostic Factors for Endolymphatic Sac Tumor: A Single-Institute Experience with a Systematic Review

OBJECTIVETo evaluate the clinical features, surgical outcomes, and predictors of progression-free survival (PFS) in patients with Endolymphatic Sac Tumors (ELSTs). METHODSThis retrospective study analyzed 15 cases from Beijing Tiantan Hospital and 237 from literature (1988-2023), focusing on patients with pathologically confirmed intracranial or skull ELSTs who had comprehensive treatment and follow-up records. Univariate and multivariate Cox regression analyses were employed to identify factors influencing PFS. RESULTSCases from our institute comprised 10 males and 5 females with an average age of 39.1 years. Among these, 86.7% underwent gross total resection (GTR). During the follow-up period, two patients (13.3%) were lost to follow-up. After a mean follow-up of 74.9 months, one patient experienced recurrence and another died from unrelated causes. A review of literature identified 237 additional patients, including 134 females (56.5%), with an average age of 39.8 years; 22.8% of these patients had von Hippel-Lindau disease. The GTR rate was 69.2%. After a mean follow up of 53.2 months, 33 recurrences occurred, and the median PFS was 48 months. Additionally, eight patients died during the follow-up period, none of the deaths were attributed to ELSTs. Multivariate analysis identified GTR (HR 0.279, 95% CI 0.086-0.903, p = 0.033) as a significant protective factor against recurrence among the pooled cases. CONCLUSIONSGTR is crucial for improving PFS in ELST patients, emphasizing the need for advanced surgical techniques and long-term follow-up due to potential recurrences.

Surgical Outcomes in Patients with Endolymphatic Sac Tumors: A Single-Center Experience of 29 Patients.

To analyze the clinical features and surgical outcomes of patients with endolymphatic sac tumors (ELSTs). Single institution retrospective cohort study. The clinical data of 29 patients with 30 ELSTs who underwent surgery were retrospectively reviewed. Information on patient demographics, tumor size and grade, intraoperative blood loss volume, hearing and facial nerve outcomes, and follow-up data was collected and analyzed. The main symptoms were hearing loss in 26 ELSTs (86.7%) and tinnitus in 17 (56.7%). Twenty-four (80%) ELSTs were in advanced stages (Grade III). The median tumor volume was 6.35 cm3. The median intraoperative blood loss volume was 300 mL. Facial nerve function was well preserved in 21 patients. Among all patients with Grade III tumors, 12 patients underwent tension-free anterior facial nerve rerouting, and 11 patients (91.7%) maintained good facial nerve function postoperatively (HB I and HB II). Only one patient exhibited permanent vocal cord paralysis, and no patients experienced cerebrospinal fluid (CSF) leakage postoperatively. Gross total resection was achieved in 22 patients (73.3%), 5 patients (16.7%) experienced tumor recurrence, and 3 (10%) had residual tumors. Most ELSTs tend to be diagnosed in the advanced stage. Tension-free anterior facial nerve rerouting could maximally preserve facial nerve function. The intraoperative blood loss volume was associated with tumor size and stage. Tumor recurrence tends to occur at the posterior edge of the petrosal bone, internal auditory canal, and surface of the posterior fossa. Given the relatively high recurrence rate of ELSTs, long-term follow-up is recommended. 4 Laryngoscope, 2024.

Endolymphatic sac tumor with von hippel-lindau disease: report of a case

Endolymphatic sac tumor with von hippel-lindau disease: report of a case

Difficulties in Differentiation of Endolymphatic Sac Tumor That Extends Into Pontocerebellar Angle from Metastatic Tumors

Endolymphatic Sac Tumor is a local aggressive tumor that grows slowly, associated with Von-Hippel-Lindau disease and originated from endolymphatic canal. A 64-year-old male patient with VHL disease admitted to the neurosurgery department of our hospital and presented pain behind the ear and loss of sensation on the cheek. Cranial magnetic resonance imaging revealed an aggressive tumor located in the middle ear and left acoustic canal and extending to the pontocerebellar angle that eroded the mastoid and temporal bones. Histopathological examination of the lesion revealed a simple cuboidal epithelium forming glandular and papillary structures. The patient diagnosed with endolymphatic sac tumor as the presence of the morphological findings, positive staining with immunohistochemical markers such as Vimentin, NSE, EMA, PAX8, Cytokeratin 7. Our case showed neuroectodermal origin, which is even rare for von Hippel-Lindau disease, and has been discussed with histopathological findings and differential diagnosis.

68 Ga-DOTANOC PET/CT in 2 Siblings With Von Hippel-Lindau Disease.

Von Hippel-Lindau disease is a rare multisystem disorder that shows autosomal dominant inheritance. It is a cancer syndrome that is characterized by the development of a variety of benign and malignant tumors-CNS hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, adrenal pheochromocytomas, and epididymal cystadenomas. Here we present the 68 Ga-labeled DOTANOC scans of 2 siblings who show an interesting spectrum of findings consistent with Von Hippel-Lindau disease.

A rare clinical case of a labyrinthine lesion: an endolymphatic sac tumor

Endolymphatic sac tumors are rare neoplasms originating from the endolymphatic epithelium of the intraosseous part of the endolymphatic duct and sac, typically characterized by slow growth and local destructive changes. We present a case of an endolymphatic sac tumor in a 28-year-old man who consulted an otoneurologist with complaints of progressive hearing loss and dizziness attacks and was referred for a CT scan of the temporal bones and MRI of the inner ear with delayed contrast enhancement. The data of otoneurological and radiological examinations before and after surgical treatment and the results of surgical treatment with histological verification of the tumor are presented. The objective of this case presentation is to demonstrate the usefulness of CT and MRI methods in detecting an endolymphatic sac tumor, to compare the results of otoneurological and radiological examinations and intraoperative and histological data followed by surgery. Radiological examination revealed a neoplasm of the right temporal bone with typical imaging characteristics of endolymphatic sac tumor. Surgery was performed, the mass was removed completely, and the endolymphatic sac tumor was histologically verified. Radiologic presentation includes a typically located area of bone destruction in the petrous part of the temporal bone in the area of the vestibular aqueduct, possibly with the spread of the tumor into the cerebellopontine angle, with a heterogeneous structure, with uneven contrast enhancement. Due to the rarity of this pathology, diagnosis in the early stages is often difficult, and for the correct interpretation of radiologic findings in patients with hearing loss and dizziness, knowledge of the normal anatomy of the temporal bone and awareness of rare variants of its lesions are of key importance. Timely examination of patients with suspected temporal bone lesions and correct diagnosis are the key to successful treatment and maintaining the quality of life in this group of patients.

Management of Pregnancy in a Case of Endolymphatic Sac Tumour as a Part of Von Hippel–Lindau Syndrome Complex: A Case Report and Review of Literature

Management of Pregnancy in a Case of Endolymphatic Sac Tumour as a Part of Von Hippel–Lindau Syndrome Complex: A Case Report and Review of Literature

Iatrogenic inner ear dehiscence associated with lateral skull base surgery: a systematic analysis of drilling injuries and their causal factors.

Drilling injuries of the inner ear are an underreported complication of lateral skull base (LSB) surgery. Inner ear breaches can cause hearing loss, vestibular dysfunction, and third window phenomenon. This study aims to elucidate primary factors causing iatrogenic inner ear dehiscences (IED) in 9 patients who presented to a tertiary care center with postoperative symptoms of IED following LSB surgery for vestibular schwannoma, endolymphatic sac tumor, Meniere's disease, paraganglioma jugulare, and vagal schwannoma. Utilizing 3D Slicer image processing software, geometric and volumetric analysis was applied to both preoperative and postoperative imaging to identify causal factors iatrogenic inner ear breaches. Segmentation analyses, craniotomy analyses, and drilling trajectory analyses were performed. Cases of retrosigmoid approaches for vestibular schwannoma resection were compared to matched controls. Excessive lateral drilling and breach of a single inner ear structure occurred in 3 cases undergoing transjugular (n=2) and transmastoid (n=1) approaches. Inadequate drilling trajectory breaching ≥1 inner ear structure occurred in 6 cases undergoing retrosigmoid (n=4), transmastoid (n=1), and middle cranial fossa approaches (n=1). In retrosigmoid approaches the 2-cm visualization window and craniotomy limits did not provide drilling angles to the entire tumor without causing IED in comparison to matched controls. Inappropriate drill depth, errant lateral drilling, inadequate drill trajectory, or a combination of these led to iatrogenic IED. Image-based segmentation, individualized 3D anatomical model generation, and geometric and volumetric analyses can optimize operative plans and possibly reduce inner ear breaches from lateral skull base surgery.

Surgical Management of Endolymphatic Sac Tumor: A Systematic Review and Meta-Analysis.

The aim of our study was to report rates of facial nerve palsy and residual tumor following surgical intervention and subsequent tumor recurrence in patients with endolymphatic sac tumors. A systematic literature review of preoperative assessment and surgical management is also included. Studies including patient/s affected by sporadic or von Hippel-Lindau disease related endolymphatic sac tumors, reporting levels of facial nerve function, residual and recurrence pathology following a surgical procedure, were considered. Data were combined for proportional meta-analysis, and the selected studies' methodological quality was also evaluated. Overall 34 papers, including 202 subjects (209 cases of endolymphatic sac tumors) were analyzed. Pooled proportion rate (95% CI) of overall facial nerve palsy was 39.7% (28.2-51.9) and residual tumor was 16.5% (10.3-23.7) after surgical procedure. Pooled proportion rate (95% CI) of tumor recurrence was 14.0% (9.7-19.3) during a mean follow-up period of 49.7 months (8-136). Our results showed that preoperative facial nerve function is impaired in almost 30% of patients with endolymphatic sac tumors. Surgical management of endolymphatic sac tumor may cause a worsening of facial nerve function in a low percentage of treated subjects. Residual and/or recurrence of endolymphatic sac tumors are not rare events, and follow-up strategies should be designed accordingly.

What a Neurosurgeon Should Know About the Endolymphatic Sac: Part 2 – Diagnosis and Management of the Endolymphatic Sac Tumors

Abstract Objective This article is divided into three parts. In the second part of this review, the authors focus on describing the endolymphatic sac tumor and presenting illustrative cases. Methods A review of previous studies, from 1957 to 2021, from basic and translational research using human and animal endolymphatic sac (ES) tissue or cells, as well as other reviews on this theme. Results The ES is an inner ear structure, which is responsible for the homeostatic regulation, as well as endolymphatic fluid volume control, immune response etc. One of the possible alterations of the ES is the ELST, a low-grade malign neoplasm that originates from the epithelium of the endolymphatic duct and sac. The clinical presentation of the ELST includes hearing loss, tinnitus, headache, and vertigo. The diagnosis in the early stages is rare, given that this group of symptoms is very similar to other, more common, diseases such as the Meniere syndrome. Its diagnosis is made by computed tomography (CT), magnetic resonance imaging (MRI), immunohistochemistry, and confirmed by histopathology. However, none of these examinations are part of the pathological guidelines for ELST. The treatment for ELST in the early stages has a high rate of success. Conclusion The ELST is a very difficult diagnosis due to its presentation. Furthermore, the interactions between ELST and the Von Hippel-Lindau disease usually result in a more aggressive condition. Despite the difficulty of the diagnosis, doing it early increases the chances of successful treatment.

전정수도관 확장 증후군 환자에서 발견된 내림프낭 종양 1예

An endolymphatic sac tumor (ELST) is a tumor of neuroectodermal origin. Although several cases have been reported in Korea, it is known to be very rare. Clinically, it grows slowly but shows an aggressive pattern accompanied by bone destruction pathologically. As the tumor grows, it shows symptoms due to endolymphatic hydrops such as hearing loss, tinnitus, and dizziness. In this paper, we report a case in which an ELST was found in a patient suffering from profound sensorineural hearing loss, tinnitus, and dizziness, who turned out to be an enlarged vestibular aqueduct syn-drome.

The Diagnosis and Management of Advanced Endolymphatic Sac Tumor.

Endolymphatic sac tumor (ELST) is a group of low-grade malignant tumors originating from the endolymphatic sac of the inner ear. It is rare in the clinic and has the biological characteristics of slow growth and local aggression. Due to the lack of specificity in the clinical manifestations of patients with ELST, many cases have entered the advanced stage at the time of diagnosis. However, there are still great challenges in the treatment of advanced ELSTs. Here, the authors describe a case of advanced ELST, which relapsed after 2 operations. This time, the authors chose the transotic approach for tumor resection, which achieved the goal of complete resection of the tumor, and the patient recovered smoothly after surgery. There were no surgical complications and no tumor recurrence after the follow-up. Through literature review and our own experience, the authors suggest that complete surgical resection is the first choice for both primary and recurrent advanced ELSTs. The choice of a reasonable surgical approach is the key to ensuring complete resection of the tumor, while preoperative angiography and embolization, fine treatment of important structures during surgery, and postoperative long-term follow-up are equally important for patients with advanced ELST to obtain a good prognosis.

VON HIPPEL-LINDAU DISEASE, DESCRIPTION, GENETICS, MOLECULAR BASIS, CLASSIFICATION AND MANIFESTATIONS OF THE DISEASE

Introduction: Von Hippel-Lindau disease (VHL) is autosomal dominant tumor syndrome that debuts mostly in young adults , patients with this disease are linked to the triggering of various types of benign and malignant neoplasms in multiple locations, systems and organs, in particular affecting more the nervous system and other internal organs. Approximately this tumor syndrome shows an incidence rate of 1 in 36,000 live births with a penetrance greater than 90%. The molecular basis of VHL disease is the impairment of VHL protein function and the consequent clustering of hypoxia-inducible factors with subsequent consequences on cell differentiation and metabolism. Objective: to present current information related to Von Hippel-Lindau disease, description, genetics, molecular basis, classification and manifestations of the disease. Methodology: a total of 33 articles were analyzed in this review, including review and original articles, as well as clinical cases, of which 26 bibliographies were used because the other articles were not relevant to this study. The sources of information were PubMed, Google Scholar and Cochrane; the terms used to search for information in Spanish, Portuguese and English were: Von Hippel-Lindau, VHL, tumor suppressor gene, pheochromocytoma, hemangioblastomas. Results: VHL has an incidence of approximately 1 in 36,000 live births, with a penetrance of over 90%. These present tumors are initiated by inactivation of biallelic VHL and are related to pathologic activation of hypoxic gene response pathways. Conclusions: Von Hippel-Lindau disease is an autosomal dominant disorder that is generated by mutations in the VHL tumor suppressor gene. Within the field intrafamilial variation may evidence correctly shaped genotype-phenotype connections for renal cancer and pheochromocytoma risks. Visceral cysts (renal, pancreatic and epididymal) are frequent, however organ function involvement is rare. They usually occur with hemangioblastomas of the central nervous system and retina, as well as renal cancers. Unusually it includes non-functioning pancreatic endocrine cancers, adrenal and extra-adrenal pheochromocytomas, endolymphatic sac tumors, as well as head and neck paragangliomas. KEYWORDS: Von Hippel-Lindau, VHL, gene, suppressor, tumor, pheochromocytoma, hemangioblastomas

메니에르병 유사증상을 동반한 내림프낭에 발생한 콜레스테롤 육아종 1예

The endolymphatic sac tumor is a very rare neurological tumor. This could be accompanied with symptoms of Meniere’s disease, such as sensorineural hearing loss, tinnitus, dizziness. A 48-year-old man presented with right side fluctuating hearing loss lasting more than 10 years and intermittent vertigo. Magnetic resonance imaging (MRI) revealed mild enlargement with abnormal high signal intensity on T1-weighted at endolymphatic sac. The patient underwent right labyrinthectomy and surgical tumor resection. During surgery, reddish mass of filling retrofacial air cell nearby common crus was observed and histologic examination was performed. The mass was connected to the endolymphatic sac. Histopathological diagnosis is cholesterol granuloma. After 10 weeks of the surgery, vertigo had disappeared. At 7 years of postoperative follow-up, there was no recurrence of previous symptoms.

Resection of endolymphatic sac tumor by tension-free anterior rerouting of the facial nerve and by tunnel tamponade in inferior petrosal sinus: a case report

本文报道1例并发于VHL综合征的内淋巴囊肿瘤（endolymphatic sac tumor，ELST）。患者，男，42岁，因“左耳听力下降4个月”就诊，伴搏动性耳鸣、眩晕。耳内镜示左耳鼓膜完整，鼓膜后下象限见红色新生物膨出，MRI提示肿瘤位于后颅窝，累及颈静脉孔、内听道，增强后明显强化。基因检测结果显示：VHLc.486C>G， p.Cys126Trp，VHL基因3号外显子486位点C碱基错义突变为G碱基，126位的半胱氨酸被色氨酸取代。选择经颞下窝径路、面神经无张部分前移位及岩下窦隧道填塞技术完整切除肿瘤，术后无脑脊液漏，病理确诊为内淋巴囊肿瘤，术后1周顺利出院。患者出院1年复查显示面神经及后组颅神经功能正常，未见肿瘤复发。.

RARE CASE PRESENTAETION: VON HIPPLE LINDAU SYNDROME

Introduction: Von Hippel-Lindau syndrome (VHL) is autosomal dominant hereditary syndrome due to germline mutations of the tumor suppressor gene VHL, located on short arm of chromosome 3. 80% have a positive family history and about 20% of cases are de novo. Various multiple benign and malignant tumors occur affecting multiple organ system, central nervous system, kidneys, adrenals, pancreas, and reproductive system. Common manifestations include including retinal hemangioblastomas (HBs), central nervous system (CNS) HBs, endolymphatic sac tumors, pancreatic neuroendocrine tumors, pancreatic cystadenomas, pancreatic cysts, clear cell renal cell carcinomas, renal cysts, pheochromocytomas, paragangliomas, and epididymal and broad ligament cystadenomas. Confirmation of diagnosis is done by genetic testing in clinically and radiologically suspicious patient. A male patient of Case Report: age 30 years presented with cerebellar symptoms 2 year ago and MRI is done MRI reveal cerebellar and spinal hemangioblastoma. Patient is operated for cerebellar hemagioblastoma and histologically confirmed. On follow up study b/l renal cell carcinoma, pancreatic cyst and neuroendocrine tumor is found. VHL is a disease Conclusion: with no cure. Regular follow-up with necessary to follow the previous lesions and detect any newly developed VHL-associate tumors.

Imaging manifestations of von Hippel-Lindau disease: an illustrated guide focusing on abdominal manifestations.

Von Hippel-Lindau (VHL) disease is a monogenic autosomal dominant disorder with germline mutations of the VHL anti-oncogene on the short arm of chromosome 3 (3p25-26). It affects 1:36,000-50,000 individuals, with a penetrance greater than 90% at 65 years of age. Although of variable onset and presentation, with pleiotropism even among members of the same family who share a specific mutation, VHL disease usually manifests initially in young adults. It predisposes to the development of benign and malignant tumors of the central nervous system (CNS) and visceral organs. The clinical diagnosis of VHL disease can be made in the following circumstances: a) in patients with a family history of the disease and at least one of the tumors characteristic of it (e.g., retinal or CNS hemangioblastomas, clear cell renal cell carcinoma, pancreatic neuroendocrine tumors, and endolymphatic sac tumors); b) in patients with two or more CNS hemangioblastomas; c) or in patients with a retinal or CNS hemangioblastoma plus at least one visceral tumor characteristic of the disease, excluding renal and epididymal cysts. Imaging plays an important role in the diagnosis and follow-up of patients with VHL disease. This pictorial essay presents characteristic images of abdominal manifestations of VHL disease-related tumors that all radiologists should be aware of.

Von Hippel–Lindau (VHL) disease and VHL-associated tumors in Indian subjects: VHL gene testing in a resource constraint setting

BackgroundVon Hippel–Lindau (VHL) syndrome is a familial cancer syndrome caused by mutations in VHL gene. It is characterized by the formation of benign and malignant tumors like retinal angioma, cerebellar hemangioblastoma, spinal hemangioblastoma, renal cell carcinoma, pheochromocytoma, pancreatic and renal cysts, and endolymphatic sac tumors. Germline mutations in VHL gene have also been reported in isolated VHL-associated tumors. VHL gene is a small gene with 3 coding exons and can be easily tested even in a resource constraint setting.ObjectiveTo describe clinical presentation and estimate the diagnostic yield of in VHL and VHL-associated tumors.MethodsThis is a descriptive study in a hospital setting. Here, we describe the clinical and molecular data of 69 patients with suspected VHL or having VHL-associated tumors. Sanger sequencing of coding sequences and conserved splice sites of VHL gene were done in all patients. Multiplex ligation-dependent probe amplification (MLPA) of VHL gene to detect large deletions/duplications was performed for 18 patients with no pathogenic sequence variations.ResultsAmong tumor types at presentation, pheochromocytoma was seen in 49% (34/69), hemangioblastoma was seen in 30% (21/69), and renal cell carcinoma was seen in 7% (5/69). Rest had other tumors like paraganglioma, endolymphatic sac papillary tumors, cerebellar astrocytoma and pancreatic cyst. Seven patients (10%) had more than one tumor at the time of diagnosis. Pathogenic variations in VHL gene were identified in 31probands by Sanger sequencing; 18 were missense, 2 nonsense and 2 small indels. A heterozygous deletion of exon 3 was detected by MLPA in one patient among 18 patients for whom MLPA was done. Overall, the molecular yield was 46% cases (32/69). Family history was present in 7 mutation positive cases (22%). Overall, 11 families (16%) opted for pre-symptomatic mutation testing in the family.ConclusionsMutation testing is indicated in VHL and VHL-associated tumors. The testing facility is easy and can be adopted easily in developing countries like India. The yield is good, and with fairly high incidence of familial cases, molecular testing can help in pre-symptomatic testing and surveillance.

Impact of an Endolymphatic Sac Tumor on Subjective and Objective Audiovestibular Function.

This study reports subjective and objective audiovestibular function in patients diagnosed with an endolymphatic sac tumor (ELST), to evaluate the clinical implication of vestibular testing in ELST patients. Retrospective cohort study. Tertiary referral center/university hospital. Five patients diagnosed with unilateral ELST. Subjective and objective audiovestibular tests; pure-tone average; speech discrimination score; the Video Head Impulse Test; the cervical vestibular evoked myogenic potential test; the caloric irrigation test; the Speech, Spatial and Qualities of Hearing Scale; the Tinnitus Handicap Inventory; and the Dizziness Handicap Inventory. Findings and characteristics of both subjective and objective audiovestibular functions. The mean pure-tone average and the mean speech discrimination score were 49 dB HL and 68% on the tumor ear and 13 dB HL and 99% contralaterally. The mean Speech, Spatial and Qualities of Hearing Scale score was 84, and the mean Tinnitus Handicap Inventory score was 64. Caloric testing showed a mean unilateral weakness of 80%. The Video Head Impulse Test of the lateral semicircular canal revealed refixation saccades on all tumor ears and an average gain value of 0.75 on the tumor ear versus 0.94 contralaterally. No cervical vestibular evoked myogenic potentials were elicited on the tumor side, whereas all but one was elicited contralaterally. The average Dizziness Handicap Inventory score was 47. A characteristic pattern of abnormal caloric findings, refixation saccades, and normal vestibulo-ocular reflex gain alongside sensorineural hearing loss on the tumor ear was identified. Asymmetric sensorineural hearing loss in any patient should lead to objective vestibular evaluation to strengthen not only a targeted tumor surveillance strategy and the indication for imaging, but also the design of vestibular rehabilitation. In addition, vestibular findings may guide the choice of surgical approach.