Clinicopathologic study of endolymphatic sac tumor (ELST) and differential diagnosis of papillary tumors located at the cerebellopontine angle

Abstract

We investigated the clinicopathologic features and immunophenotypes of 10 cases of endolymphatic sac tumor (ELST) and compared them with other papillary tumors, including eight cases of choroid plexus papilloma (CPP), three cases of atypical choroid plexus papilloma (ACPP), two cases of papillary ependymoma (PE), three cases of papillary meningioma (PM) and two cases of metastatic carcinoma (MC) the at cerebellopontine angle (CPA). The age at onset of ELST ranged from 13 to 39 years. The male-to-female ratio was 1:1. The clinical presentations were primarily ear-related symptoms. The temporal bones showed extensive destruction. Histologically, the important characteristics for differential diagnosis with CPP, which is most similar to ELST, include the quantity of blood vessels, the nuclei location at apical surface of the papillary, clear cytoplasm cells sometimes with visible vacuoles, psammoma bodies and dura or bone invasion. Immunohistochemistry stains for AE1/AE3, cytokeratin CK)5/6, epithelial membrane antigen, CK8/18, S-100, and synaptophysin are helpful in diagnosis of ELST. In ELST, ultrastructure of uniform 2 μm vesicles in cytoplasm was seen, and gene analysis also showed missense mutation in exon 3. This study indicates that the above histological features combined with immunohistochemistry findings are important for making the correct diagnosis. Gene analysis should be used in patients without medical history to exclude von Hippel-Lindau disease.

CAIX and pax-8 Commonly Immunoreactive in Endolymphatic Sac Tumors: A Clinicopathologic Study of 26 Cases with Differential Considerations for Metastatic Renal Cell Carcinoma in von Hippel-Lindau Patients

“…The differential diagnosis histologically includes metastatic ccRCC, papillary thyroid carcinoma or follicular thyroid carcinoma, while choroid plexus papilloma, papillary ependymoma, papillary meningioma, paraganglioma and even middle ear adenoma are less frequently considered [56]. Centering of the tumors within the cerebellopontine angle, tumors with psammoma bodies and whorling, along with unique immunohistochemistry findings (such as CK5/6, synaptophysin, progesterone receptors) help to exclude the less common considerations of choroid plexus papilloma, papillary ependymoma and papillary meningioma.…”

Molecular characterisation of sporadic endolymphatic sac tumours and comparison to von Hippel–Lindau disease‐related tumours

“…Summarising information from 27 publications and our own data, genetic and clinical information of 158 VHL‐disease‐related ELSTs and 21 sporadic ELSTs was available (Table S4) [3, 6–11, 19–38]. VHL‐disease‐related ELSTs affected 31 females and 20 males (NA = 107), sporadic ELSTs 11 females and 10 males.…”

“…They may even expand into the posterior fossa representing a rare differential diagnosis for tumours of the cerebellopontine angle; e.g., Roche et al [2] found one ELST for every 300 vestibular schwannomas. They may be misdiagnosed as reactive and inflammatory processes, plexus tumours or metastases from thyroid, lung or clear cell renal carcinomas [1, 3–5].…”

“…ELST can occur sporadically; however, about one third of cases arise in von Hippel–Lindau (VHL) disease, a cancer susceptibility syndrome characterised by genetic alterations in the VHL tumour suppressor gene at chromosome location 3p25.3 [1]. Molecular data on ELSTs are sparse, due to the rarity of the disease; only single tumours or small series have been subjected to genetic analysis [3, 6–10]. So far, sequencing approaches exclusively focused on the detection of genetic alterations in VHL .…”

Current Treatment of Endolymphatic Sac Tumor of the Temporal Bone

“…Thus, particularly in patients with clinical manifestations simulating Ménière's disease, the endolymphatic sac region must be carefully examined in order not to miss an ELST [25]. ELSTs may be sporadic or associated with von Hippel-Lindau (VHL) disease which is attributable to inactivation of a tumor suppressor gene on the short arm of chromosome 3, and inherited as an autosomal dominant trait with variable expression [1,14,15,20,[26][27][28][29][30][31][32][33][34][35][36][37]. VHL predisposes patients to multiple hemangioblastomas of the retina or central nervous system as well as tumors and cysts in various organs, including renal cell carcinoma, pheochromocytoma, paraganglioma, ELST, epididymal cystadenoma, and pancreatic serous cystadenoma or neuroendocrine tumors [1].…”