A Rare Case of Endolymphatic Sac Tumour: Clinical, Radiological, Pathological and Immunohistochemical Findings with Review of Literature

Abstract

Endolymphatic sac tumour (ELST) is a rare low grade malignant epithelial tumour of the petrous temporal bone, thought to arise from papillary epithelium of the endolymphatic sac. They may occur sporadically or in association with Von-Hippel Lindau disease. ELST is extremely rare neoplasm with benign histopathological appearance and clinically destructive behaviour. Because of the rarity of this tumour, it can easily be confused with other tumours such as paraganglioma, middle ear adenoma, metastatic carcinomas or choroid plexus papilloma. We report here a rare case of ELST with review of literature and discuss the differentiating features of ELST from its mimickers, showing a papillary configuration.

Introduction

Endolymphatic sac tumour (ELST) is a rare, locally aggressive hypervascular tumour of papillary architecture which arises from the endolymphatic sac in the posterior petrous bone. Hassard et al. in 1984, described the first case of endolymphatic sac tumour as papillary cystic neoplasm arising in the petrous bone [1]. Since that time, only 200 cases are reported in the literature. It is synonymous with Heffner tumour [2] and low grade adenocarcinoma of endolymphatic sac origin (LGAES), according to the recent World Health Organization classification of Head and Neck tumours [3]. Here we report a case of Endolymphatic sac tumour in 50 year old female who presented with left-sided facial paralysis.

Case Report

A 50 year old woman presented in ENT department with left-sided facial paralysis and left lower eyelid drooping with other complaints of hearing disturbances, tinnitus in left ear, giddiness & headache for one month. Patient had no other significant past or family history. Otoscopic findings were normal. Magnetic resonance imaging (MRI) of Brain with contrast showed a well defined extra-axial, predominantly solid mass, measuring 5.5 × 3.8 × 3.4 cm, in left cerebellopontine(CP) angle region, broad based to petrous temporal bone. It showed hypointense signals in T1W and heterogeneously isointense signals in T2W/FLAIR sequences with moderate homogenous contrast enhancement. Anteriorly, lesion infiltrated the left petrous apex, mastoid air cells and left clivus and protruded in the left sphenoid sinus. Petrous segment of left Internal Carotid Artery and 7-8th nerve complexes were engulfed by the lesion with permeation in the internal acoustic meatus and inner ear structures on the left side causing compression on left sigmoid sinus and Internal Jugular Vein. Medially, the lesion compressed the left lateral surface of pons, middle cerebellar peduncle and left cerebellar hemisphere. Radiological differential diagnosis were aggressive Meningioma and Schwannoma (Fig. 1).

Fig. 1.

a On T1W image (axial view), lesion appears Hypointense. b On T2W image (axial view), lesion appears Isointense. c On FLAIR image (axial view), lesion appears bright. d On Post Contrast study (sagittal view), lesion shows enhancement

Patient underwent left retromastoid, suboccipital craniotomy with surgical resection of the mass and tissue was sent for intraoperative frozen section. Microscopic examination showed predominantly cystic or glandular structures lined by a single layer of low cuboidal epithelial cells having uniform, bland nuclei with pale eosinophilic cytoplasm. Cystic glandular spaces were filled with colloid like material, similar to thyroid tissue. Cellular pleomorphism and mitosis were minimal and necrosis was absent. Based on the morphological findings, provisional diagnosis was Metastatic Follicular Carcinoma of Thyroid (Fig. 2). Clinical evaluation of Thyroid & Prolactin hormones was done and they were found to be within normal limits. Remaining tissue was received for histopathological examination. Histopathological findings correlated with the microscopy of the frozen section and further immunohistochemistry was advised for exact histogenesis.

Fig. 2.

Histopathology of Endolymphatic sac tumour: a Cystic or glandular structures with colloid like material (HE,10x). b Follicular pattern, with occasional colloid filled follicles resembling the thyroid parenchyma, are present (HE, 40x). c, d Glandular structures lined by cuboidal epithelial cells showing relatively uniform nuclei and pale eosinophilic cytoplasm. Cellular pleomorphism and mitosis are minimal (HE,40x)

Immunohistochemistry showed positive reactivity with AE1, Cytokeratin 7, Epithelial Membrane Antigen (EMA), Vimentin & Neuron Specific Enolase (NSE). It was negative for Thyroglobulin, Thyroid Transcription Factor 1 (TTF-1), Carcinoembryonic Antigen (CEA), Synaptophysin and Chromogranin. The Ki-67 immunostain showed a proliferation index of < 1% (Fig. 3). Based on morphological, radiological & IHC findings, the tumour was diagnosed as ELST. On follow up, postoperative MRI revealed no residual tumour.

Fig. 3.

Immunohistochemistry. a Diffuse positive AE1 staining (40x). b Diffuse positive Vimentin staining (40x). c Tumour cells showing positivity with NSE (40x). d Tumour cells showing very low MIB-1 index (< 1%) (10x)

Discussion

In 1984, Hassard et al. first described ELST during an endolymphatic sac decompression for Meneire’s disease as the tumour arising from the endolymphatic sac [1]. The origin of endolymphatic sac tumours remained controversial for many years. In 1988, Gaffey et al. called these lesions as aggressive papillary middle ear tumours (APMET) [4]. In 1989, Heffner speculated that this tumour arises in the endolymphatic sac because of its same anatomic location and histological appearance to that of normal endolymphatic sac [2]. In 1990, Benecke et al. described nine cases of aggressive temporal tumours with similar pathological and clinical features [5]. Recent studies have confirmed the cell of origin of these tumors as papillary endothelium of the endolymphatic sac [6]. WHO Tumour classification has recognized it as low grade malignant tumour of temporal bone. Since first described in 1984, only approximately 200 cases are reported in the literature [7]. The majority of ELST are sporadic while around 3–16% of patients have an autosomal dominant inherited disorder, VHL disease. The association of VHL disease with endolymphatic sac tumour was first reported in 1988 by Eby et al. [7]

The age at presentation ranges from 4 to 85 years with a mean age of 52 years in sporadic cases and 31 years in VHL disease patients with a slight female preponderance [3]. Patients characteristically present with unilateral sensorineural hearing loss, tinnitus, otalgia, otorrhea, vertigo,ataxia, and facial nerve paresis [8]. In our case, patient presented with similar characteristic clinical findings.MRI findings are characteristic, with tumour centred on petrous bone with lytic temporal bone lesion causing compression of the adjacent brain structures. ELSTs usually have a heterogeneous appearance. Multiple high-signal intensity foci on both T1- and T2-weighted images indicate the presence of haemorrhage within tumour [9].

Microscopically, ELST show two main growth patterns. In most cases tumour shows papillary configuration with thin fibrovascular core lined by cuboidal to low columnar cells. Other pattern show predominantly cystic glandular architecture containing colloid like material and sparse stroma, with cysts lined by a single layer of cuboidal epithelium, as seen in our case. Nuclear atypia and mitosis is minimal [3].

ELST typically stain positive for Cytokeratins, EMA, Vimentin, and Periodic acid Schiff and show variable positivity for S100, NSE, Synaptophysin, Chromogranin A and GFAP. Specific markers for metastases including PAX-8, Thyroglobulin and Prostate Specific Antigen are negative [10]. The histopathological differential diagnoses of ELST include paraganglioma, choroid plexus papilloma, papillary ependymoma, middle ear adenoma, and metastatic carcinoma of the thyroid, kidney and prostate [9].

Paragangliomas of the middle ear are cytologically benign and demonstrate papillary architecture and focal nesting pattern having cuboidal cells with eosinophilic cytoplasm. They are positive for chromogranin and synaptophysin. ELST is usually negative for neuroendocrine markers. Choroid Plexus Papilloma may be histologically similar to ELST, but it originates in the ventricle and does not invade bone. In case of Ectopic Choroid Plexus Papilloma, positivity with Transthyretin helps to aid in differentiation from ELST. Papillary Ependymoma is usually ventricular in location and shows pseudorosettes and pseudopapillae lined by single and multiple layers of cuboidal cells. Tumour cell processes are GFAP positive, in contrast with ELST. ELST can be mistaken for Middle Ear Adenoma, which are non papillary tumours, confined to middle ear & mastoid and rarely show bone destruction.

Papillary pattern of ELST may mimic Metastatic Papillary carcinoma of Thyroid, which can be differentiated by TTF-1 and Thyroglobulin markers. Predominantly cystic glandular pattern may resemble Metastatic Follicular carcinoma of Thyroid but ELST is negative for thyroid markers. Metastatic Prostatic Carcinoma in male show reactivity with PSA. Occasional clear cell changes with vascularity in ELST may resemble Metastatic Renal cell carcinoma, which is differentiated with the aid of IHC.

Surgery remains the treatment of choice for ELST. However, total excision of the tumour is often not possible due to its aggressive growth pattern. Local recurrencecan occur years after surgery which can be further managed by the use of adjuvant radiotherapy [8].

Conclusion

ELSTs are exceeding rare tumours with indolent course and should be considered in the differential diagnosis of tumours of CP angle region particularly when associated with a history of unilateral hearing loss and/or facial nerve involvement, temporal bone destruction and papillary architecture.

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The authors declare that they have no conflicts of interest.

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