Endolymphatic sac tumor
Endolymphatic sac tumor (ELST) is a non-metastasizing low-grade adenocarcinoma of endolymphatic sac origin. It is also known as Heffner tumour, low-grade adenocarcinoma of endolymphatic sac origin and aggressive papillary middle ear tumor.
Endolymphatic sac tumors may present as sporadic or may be associated with Von Hippel-Lindau disease. 1).
The tumor affects adults of both sexes 2).
Patients generally present with hearing loss, tinnitus and vertigo.
The clinical prodrome is prolonged. Presenting signs and symptoms most often relate to the involvement of cranial nerves V-VIII 3).
Imaging studies reveal large, enhancing, destructive tumors with a generous vascular supply 4).
ELSTs present as locally destructive lesions with characteristic computed tomography imaging features. Histologically, they show papillary, cystic or glandular architectures. Immunohistochemically, they express keratin, EMA, and variably S100 and GFAP. Currently, it is recommended that, given its rarity, ELST needs to be differentiated from other entities with similar morphologic patterns, particularly other VHL-associated neoplasms such as metastatic clear cell renal cell carcinoma (ccRCC) 5).
The definitive diagnosis requires a combination of clinical features, radiological finding, and pathological correlation 6).
Intraoperatively, the tumors are bloody, fibrous, and adherent to surrounding structures. Various surgical approaches in combination or in series may be used. Preoperative embolization may be helpful. The role of adjunctive radiation is unclear. Aggressive papillary middle ear tumors are histologically benign tumors with clinically destructive behavior. However, it appears that aggressive surgical management affords prolonged survival with minimal worsening of cranial nerve deficits 7).
Pre-operative embolization of the vessels supplying the tumor may reduce blood loss during surgical excision. Radiotherapy could be considered for any residual tumor 8)
Chang et al. demonstrated a difficult case of endolymphatic sac tumor and how it is managed via transcanal endoscopic assisted technique, with a discussion of the feasibility of transcanal approach to lateral skull base tumor 9).
Forty-six tumors from 42 patients were independently analyzed. The overall tumor control rate was 67.4%. When analyzing patients in which tumor was present at the time of radiation, external beam radiation controlled 9 of 19 tumors (47.4%) while stereotactic radiosurgery controlled 14 of 18 tumors (77.8%). The effect size of 30.4% favors stereotactic radiosurgery, but the wide confidence interval (-4.4 to 57.4%) limits what conclusions can be drawn. Radiation for ELST remains controversial and more long-term data is needed 10).
In accordance with PRISMA guidelines a systematic literature search of the Ovid Medline, Embase, Scopus, Cochrane Library, and clinicaltrails.gov databases was performed in August 2017.
Twenty-two studies met inclusion criteria and report ELST outcomes following radiation therapy. Additional data on tumor size, previous surgery, radiation modality, and radiation dosing was collected.
The methodological quality was independently assessed by three reviewers. The included studies were small, heterogeneous case reports with a low level of evidence, and several sources of bias.
The primary outcome was tumor control following radiation, defined as no growth. A comparative analysis of external beam versus stereotactic radiation was performed.
Forty-six tumors from 42 patients were independently analyzed. The overall tumor control rate was 67.4%. When analyzing patients in which tumor was present at the time of radiation, external beam radiation controlled 9 of 19 tumors (47.4%) while stereotactic radiosurgery controlled 14 of 18 tumors (77.8%). The effect size of 30.4% favors stereotactic radiosurgery, but the wide confidence interval (-4.4 to 57.4%) limits what conclusions can be drawn. Radiation for ELST remains controversial and more long-term data is needed 11).
Nineteen ELST cases were studied. Immunohistochemistry (18/19) and single nucleotide polymorphism microarray testing was performed (12/19). A comparison with the immunophenotype and copy number profile in RCC is discussed. Patients presented with characteristic bone destructive lesions in the petrous temporal bones. Pathology of tumors showed characteristic ELST morphology with immunoexpression of CK7, GFAP, S100, PAX-8, PAX-2, CA-9 in the tumor cells. Immunostained for RCC, CD10, CK20, chromogranin A, synaptophysin, TTF-1, thyroglobulin, and transthyretin were negative in the tumor cells. Molecular testing showed loss of 3p and 9q in 66% (8/12) and 58% (7/12) cases, respectively. Immunoreactivity for renal markers in ELST is an important diagnostic caveat and has not been previously reported. In fact, renal markers are currently recommended in order to rule out metastatic RCC although the PAX gene complex and CA-9 have been implicated in the development of the inner ear. Importantly copy number assessment of ELST has not been previously reported. Loss of 3p (including the VHL locus) in ELST suggests similar mechanistic origins as ccRCC 12).
Chang et al. demonstrated a difficult case of endolymphatic sac tumor and how it is managed via transcanal endoscopic assisted technique, with a discussion of the feasibility of transcanal approach to lateral skull base tumor 13).
A 63 yr old lady who presented with left sided facial palsy. Since the tumour was highly vascular and required preoperative embolization, initial clinicoradiological diagnosis was Jugulotymphanic paraganglioma. Histopathology showed features of Endolymphatic sac tumour, which was confirmed by immunohistochemistry. Since this tumour is locally aggressive low grade adenocarcinoma, the diagnosis is difficult in advanced cases where there is erosion of petrous temporal bone or the lesion shows extension into cerebellopontine angle as in our case. Since the association of this tumour with VHL disease is well established, it is important to screen all the patients of VHL disease for this lesion and also all the patients of ELST should be screened for other lesions of VHL disease to aid in early diagnosis and treatment. The case is presented here for its rarity and difficulty in initial diagnosis 14).
A twenty-five-year-old female presented with a five-year history of chronic ear discharge left-sided facial weakness, and recent onset of ataxia.
The unusual clinical presentation made management challenging, in large part due to profuse bleeding. Pre-operative embolization of the vessels supplying the tumor may reduce blood loss during surgical excision. Radiotherapy could be considered for any residual tumor.
The patient was diagnosed with an endolymphatic sac tumor of sporadic origin which presented at the cerebellopontine angle and was managed with a multidisciplinary approach 15).
A 54-year-old man presented with right-sided ear pain associated with dizziness and hearing loss. The radiological diagnosis was in favor of acoustic neurinoma. Surgical excision was performed and the diagnosis of the endolymphatic sac tumor was made 16).
A 65-year-old patient underwent GKRS of an unresectable, recurrent ELST. Tumor volumetric analysis showed an almost 15% increase in tumor volume in the 4 months between the pre-GKRS magnetic resonance imaging (MRI) and the stereotactic MRI (s-MRI) at treatment. Follow-up MRI at 12 and 20 months showed a significant decrease in local tumor volume, decreased contrast enhancement and no perifocal edema. The patient’s general and neurological status remains stable to the present day.
In the present case, GKRS was effective in the management of a recurrent ELST over the course of 20 months. Because of ELSTs recurrence potential, long-term follow up is required. The present case, as well as previous reports, might suggest a possible salvage/adjunctive role of radiosurgery in the management of ELST. Further studies are deemed necessary 17).
Two additional cases and discuss the clinical, radiologic, histologic, and operative features 18).