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Aggressive papillary tumor of the middle ear: a true entity or an endolymphatic sac neoplasm?


Aggressive papillary tumors of the middle ear are rare, and their true origin is not clear. We describe the clinical, radiologic, genetic, and histopathologic features of a papillary epithelial tumor filling the middle ear of a 68-year-old woman. Imaging revealed no evidence of petrous temporal bone apex involvement, nor did genetic studies demonstrate the yon Hippel-Lindau mutation. A literature search revealed 24 previously reported cases of such a papillary epithelial tumor of the middle ear. All except 2 cases demonstrated apical petrous temporal bone invasion on imaging, and it has been suggested that they arose from a primary endolymphatic sac tumor, which has a similar papillary epithelial histology. Substantial numbers of cases of papillary epithelial tumors involving the middle ear are reported to be associated with yon Hippel-Lindau disease, as are known cases of endolymphatic sac tumor. This is the third reported case of papillary epithelial tumor of the middle ear that does not show apical petrous temporal bone invasion on imaging, suggesting that such neoplasms do not always arise from a primary in the endolymphatic sac.


Aggressive papillary tumors of the middle ear are rare. It has been suggested that these tumors mayarise from a primary papillaryendolymphatic sac tumor (ELST) because of the frequency of their concomitant petrous temporal bone involvement, (1) the similarity of the histopathologic appearances, (2) and the association of some tumors of both regions with von Hippel-Lindau (VHL) disease. (3-9) We present the third case in which, to our knowledge, there was no invasion of the petrous temporal bone.

Case report

A 68-year-old woman presented with an 18-month history of otalgia, hearing loss, and an offensive-smelling discharge from her right ear. Otoscopy revealed a polypoid growth emanating from a right central tympanic membrane perforation. The facial nerve was intact. Pure-tone audiometry showed a severe mixed hearing loss on the right. Nasoendoscopy was normal.

A biopsy of the polyp was taken under topical local anesthesia. Histology revealed inflammatory tissue with no unusual features. Computed tomography (CT) of the temporal bones showed a soft-tissue opacity filling the right middle ear but no erosion of the apical portion of the petrous temporal bone (figure 1). The cochlea and semicircular canals were intact, and there was no dilatation of the endolymphatic duct. A provisional diagnosis of active mucosal chronic of it is media was made.

The patient was managed with topical antibiotics and steroids. She underwent a second polypectomy under local anaesthesia 6 months later. Histology again confirmed inflammatory tissue. Since her ear remained active after 1 year, the patient agreed to undergo a cortical mastoidectomy and tympanoplasty. Operative findings were free fluid and a soft, greyish vascular mass filling the mastoid segment of the middle ear. The ossicular chain and all bony structures were intact. Postoperative recovery was uneventful.

Histopathology revealed an aggressive papillary tumor of the middle ear (figure 2, A). The tissue was composed of papillary epithelial outgrowths with a fibrovascular stroma and an epithelial covering that was cuboidal to columnar (figure 2, B). Immunohistochemical staining showed expression of pancytokeratin AE/AE3, which confirmed the epithelial nature of the neoplasm. Expression of glial fibrillary acidic protein was weak, and the presence o f Ki-67 protein demonstrated a low proliferation rate (figure 2,C). Genetic studies demonstrated that the patient did not have the VHL gene mutation or deletions on the short arm of chromosome 3.


The patient had no further intervention and remains symptom-free 12 months postoperatively (figure 3), without signs of recurrence on clinical examination or magnetic resonance imaging (MRI).


A papillary epithelial tumor filling the middle ear and invading the adjacent petrous temporal bone has been called a "primary aggressive papillary tumor of the middle ear" by Gaffey et al. (10) This is a rare tumor. We reviewed the literature on such a primary neoplasm, selecting only those cases in which there was definite evidence of middle ear involvement by the neoplasm. We found 24 reported cases, involving 17 female and 7 male patients. (3,4,11-23) This is considerably fewer than the 46 literature cases of primary aggressive papillary tumor of the middle ear referred to by Gaffey et al, (3) because of the care we took to select only those cases with bona fide involvement of the middle ear.

The range of age at diagnosis in the group we selected was 16 to 55 years, with a median age of 33 years. The present case represents the oldest at presentation, at 68 years of age. In many of the cases, however, the patient had already suffered symptoms for some years, subsequently ascribable to the tumor when the diagnosis was made, so that the real age at onset may be considerably younger than is suggested. In the present case, the true diagnosis was not apparent from the first two biopsies, and the histopathologic findings after the patient's mastoidectomy were unexpected.

In all of the previously reported cases except 2, there was extensive invasion of the apical portion of the petrous temporal bone, demonstrated as lytic lesions by CT. (20-21) In some cases, the tumor reached the cerebellopontine angle or invaded the cerebellum. (10)

It has been suggested that aggressive papillary middle ear tumors with involvement of the temporal bone may arise from a primary papillary ELST. (1) The endolymphatic sac develops from the otocyst and lies between the internal auditory canal and sigmoid sinus. ELSTs show two histopathologic patterns: colloid-filled cysts or a papillary pattern. (2) Because of the position of the endolymphatic sac, ELSTs primarily invade the petrous temporal bone and may extend into the posterior cranial fossa. (1) There is always bony erosion or dilatation of either the endolymphatic sac or vestibular aqueduct on CT in patients with ELST. MRI characteristically shows a mixture of hyperintense and isointense foci on T2-weighted images, with a heterogenous enhancement pattern. (24) Middle ear invasion is probably a late occurrence in the growth of this neoplasm.

Increasing evidence points to an association between both aggressive papillary tumors of the middle ear and ELST with VHL disease. VHL is a genetic abnormality on the short arm of chromosome 3 inherited as an autosomal-dominant trait. It predisposes patients to multiple hemangioblastomas of the central nervous system, pheochromocytomas, renal cysts, renal cell and other carcinomas, and pancreatic cysts.

Manski et al found radiologic evidence of ELST in 11% of 121 patients with VHL. (5) Gaffey et al found that 15% of 46 patients reported in the literature with aggressive papillary middle ear/temporal bone tumors had VHL. (3) Four reports have demonstrated the VHL mutation in patients with ELST. (6-9) One report demonstrated the VHL mutation in a patient with an aggressive papillary middle ear tumor, (4) but in our patient, genetic studies did not demonstrate this mutation.



The frequency of petrous temporal bone involvement, the similarity of the histopathologic appearances, and me association of some tumors of both regions with VHL disease support the possibility that aggressive papillary middle ear tumors may arise from a primary papillary ELST. However, an origin in the middle ear in some cases of this neoplasm has not been definitely excluded. Both in our case and 2 others reported, there was no involvement of the petrous temporal bone at all. (20-21) MRI in our case also did not demonstrate dilatation of the endolymphatic sac, supporting the possibility that aggressive papillary tumors of the middle ear may be an entity separate from the ELST. In a description of the pathologic changes of an aggressive papillary tumor of the middle ear in an autopsy temporal bone, widespread deposits of tumor were found at inner ear sites, but no mention was made of involvement of the endolymphatic sac or duct. (19)

Whatever the site of origin of this rare tumor, it should be recognized that a papillary epithelial tumor of the middle ear may be an aggressive neoplasm, in contrast to the nonpapillary adenoma of the middle ear, which is common and benign. (25) The present case raises the possibility that aggressive papillary tumors of the middle ear may be a separate entity from ELST. In view of the association of some cases of aggressive papillary middle ear tumors with VHL, consideration should be given to performing genetic studies for the VHL gene mutation in all patients with this neoplasm.


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James R. Tysome, MA, MRCS; Jonny Harcourt, MA, FRCS; Manish C. Patel, FRCR; Ann Sandison, FRCPath, Leslie Michaels, MD, FRCPath

From the Department of Otolaryngology-Head and Neck Surgery (Mr. Tysome, Mr. Harcourt), the Department of Radiology (Dr. Patel), and the Department of Histopathology (Dr. Sandison), Charing Cross Hospital; and the Department of Histopathology, University College (Prof. Michaels), London, U.K.

Corresponding author: Mr. James R. Tysome, 33 Burney St., London, SEI0 8EX, UK. Phone: 44-780-371-0935; fax: 44-163-482-5055; e-mail:
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Author:Tysome, James R.; Harcourt, Jonny; Patel, Manish C.; Sandison, Ann; Michaels, Leslie
Publication:Ear, Nose and Throat Journal
Article Type:Case study
Geographic Code:4EUUK
Date:Jul 1, 2008
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