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Neuroendocrine adenoma of the middle ear (NAME).


Neuroendocrine adenoma of the middle ear (NAME) is a rare tumor. We report a case of NAME, the clinical and pathologic findings of which illustrate the biologic behavior of adenomatous tumors of the middle ear and their relationship with rare carcinoid tumors of the middle ear. A 29-year-old man presented with a history of recurrent otitis media, right conductive hearing loss, and aural fullness. The tumor was removed in its entirety. Otolaryngologists should be familiar with this unusual but important entity.


Neuroendocrine adenoma of the middle ear (NAME) is the latest label of many that have been applied to a distinctive, rare tumor of the middle ear since its earliest published mention by Treitel in 1898. (1) Until recently, controversy over its histologic origin and debate concerning its appropriate designation have led to inappropriate diagnosis of this lesion as ceruminoma, ceruminous adenocarcinoma, ectopic salivary gland tumor, adenocarcinoma, and other entities. Derlacki and Barney in 1976 described the tumor as adenomatous to account for its glandular appearance but atypical biologic behavior, (2) and further studies have appreciated its neuroendocrine differentiation. (3-5) The clinical and pathologic findings in our patient illustrate the biologic behavior of adenomatous tumors of the middle ear and their relationship with rare carcinoid tumors of the middle ear.

Case report

A 29-year-old elementary school music teacher with a history of six to seven episodes of otitis media over the previous 2 years presented with right conductive hearing loss and aural fullness that had progressed over the preceding year. Until 2 years earlier, he had never experienced any difficulties with his ears. He had undergone tympanostomy tube placement for recurrent otitis media shortly before he was referred to our clinic, at which time a middle ear mass was observed and biopsied. Pathology was thought to be consistent with a ceruminous adenoma. He denied true vertigo, although he had experienced occasional disequilibrium during the previous few years. He denied otorrhea, tinnitus, and otalgia.

Examination of the patient's tympanic membrane revealed a myringotomy incision on the right with a white, fleshy mass protruding through the opening, which appeared to be contiguous with a mass seen through the posterior half of the tympanic membrane. The mass partially obscured complete evaluation and assessment of the malleus.

A computed tomography (CT) scan was obtained, revealing a soft-tissue density adjacent to the promontory (figure 1). It filled the sinus tympani and was adjacent to the pyramidal eminence. The mass was directly adjacent to the round window and filled the oval window. No definite signs of erosion of the ossicles were visible, although the mass surrounded the incus, part of the malleus, and extended into Prussak's space without eroding the scutum. The mass projected into the epitympanum but did not persist at the level of the aditus ad antrum.

The patient underwent a tympanomastoidectomy. Facial nerve electromyographywas performed throughout the procedure, and there was no evidence of facial nerve injury or malfunction. Tympanomeatal flap elevation afforded adequate access to the middle ear. The ear canal was intact and not involved with the tumor. The mass was encountered low in the hypotympanum, filling the sinus tympani. Its location and the patient's age rendered the diagnosis of ceruminous adenoma unlikely, and protein expression confirmed that the mass was a NAME tumor.


The tumor was dissected easily from the sinus tympani. However, it was firmly attached to the tympanic membrane at the level of the umbo, requiring resection of the portion_of the tympanic membrane that was in contact with the tumor. Firm tissue below the stapes passed through the obturator foramen and could not be dissected easily. Therefore, total stapedectomy was performed. Tumor involvement of Jacobson's canal required division of the Jacobson's nerve. The mass did not extend into the attic, nor did there appear to be promontorybone involvement. The tumor was removed in its entirety.

Samples were taken from distinct regions of the tumor and prepared as frozen sections. The specimens were described grossly as irregular, pinkish or brownish-tan soft-tissue fragments. Fibrous tissue samples from the stapes margin consisted of cells with small, hyperchromatic nuclei and mildly to moderately pink cytoplasm. Cells from the middle ear mass (MEM) were arranged in a sheet-like architecture with small trabeculae projecting from most of the lesion. Focally, the cells had a slightly larger nucleus than those from the stapes margin, with euchromasia and a moderate amount of pink cytoplasm. Stromal tissue surrounding the semicircular bone formed gland lumina, which differed from the trabecular pattern seen elsewhere, and included two cell types, A and B (figure 2). Type A (mucinous, luminal) cells were observed to have attenuated, less-well-seen cytoplasm, while type B (neuroendocrine, basal) cells had more ample eosinophilic cytoplasm. Paraffin sections of the MEM and stapes included cells that were immunoreactive with pancytokeratin, a marker expressed by all neoplastic cells. Immunohistochemically, differential expression of luminal cells with markers CK7 and epithelial membrane antigen, and in particular, basal cell expression of chromogranin (figure 3), further support findings more consistent with NAME than the diagnosis of ceruminous adenoma made previously at another institution.



NAME tumors occur in approximately equal distribution in both sexes. Age at presentation ranges from 14 to 80 years, (6) with an average of approximately 37 years. (7) Patients present clinically with progressive unilateral conductive hearing loss, tinnitus, and a feeling of fullness or stuffiness in the ear; pain and vertigo may or may not be present? Facial nerve involvement and bony erosion or destruction appear to indicate a poorer prognosis. (8) Radiographic imaging reveals a soft-tissue density in the middle ear that may encase the ossicles without destroying them. Because these tumors are relatively uncommon, their clinical manifestations are often misread and attributed to other causes. Differential diagnosis of such middle ear masses includes ceruminous adenoma, ceruminous adenocarcinoma, parotid pleomorphic adenoma, meningioma, paraglioma, and other abnormalities.

Adenomas of the middle ear were described first in 1976 by Derlacki and Barney. (2) They felt the histologic appearance of the tumors was most consistent with an origin from columnar or cuboidal epithelium, with limited nonmucous secretoryactivity. Previous observation of an increase in secretory cells--particularly mucinous cells and cells with dark, secretory granules--with occasional gland formation in cases of serous otitis media led to their hypothesis that these neoplasms arise from middle ear epithelium.


In another study, Hyams and Michaels proposed that adenomas originated from the mucosal epithelium of the middle ear. (9) Their hypothesis was derived from their perceiving tumor cells in the surface epithelial layer and invasion of the underlying stromal layer.

The earliest paper mentioning neuroendocrine differentiation of the tumors, by Murphy et al in 1980, made the observation that carcinoid tumors resembled adenomatous tumors. (10) The authors suggested that the benign appearance and biologic behavior of many reported adenomatous tumors of the middle ear might indicate unrecognized carcinoid differentiation. Fayemi and Toker also noted the similarity in appearance between primary adenocarcinoma of the middle ear and carcinoid. (11)

Whether carcinoid tumors and middle ear adenomas represent separate entities has been debated. At the time of Torske and Thompson's 2002 review, (7) there had been only one published case of metastatic middle ear mass, (12) which they attributed to radiation-induced malignant transformation to support the probability of the tumors being the same entity. However, the etiology of neurosecretory cells in the middle ear is still unknown, as these cells have not been identified in normal or inflamed middle ear mucosa. (3) In the most recent review, Ramsey et al (13) did not negate the similarities between carcinoid tumors and middle ear adenomas, but they countered with data from two cases with metastases after surgical removal without additional therapies, suggesting that metastases strongly support the argument that carcinoid tumors should be considered low-grade malignancies (3) and separate entities from adenomas.

Based on cytoplasmic argyrophilia and ultrastructural and immunocytochemical findings, McNutt and Bolen theorized that adenomatous tumors illustrate both mucinous and neuroendocrine differentiation. (3) Wassef et al further suggested the derivation of neuroendocrine cells from the multipotential basal cells of middle ear epithelium, which would acquire mixed mucous and/or neuroendocrine features during neoplastic transformation. (4) Their data indicate a potential endodermal origin for tumors of the middle ear mucosa, similar to that of other bidirectionally differentiated tumors.

Similarly, speculation by Amble et al of a stromal derivation suggests possible neural crest origin. (5) Neural crest cells give rise to parts of the ossicle chain and the three principal paraganglia found within the middle ear. These are the tympanic glomus, the jugular glomus, and the satellite glomus of Arnold-Cruveilhier. Owing to the middle ear's limited histologic variety, the clinical presentation, and the staining characteristics of the tumors in their study, Amble et al believed it likely that these tumors of possible glomus tissue origin might differentiate into carcinoid tumors, and rarely into adenomas or adenocarcinomas or mixtures thereof.

Benecke et al identified two distinct histopathologic and clinical patterns in neuroendocrine adenomas: mixed and papillary. (8) (Our patient presented with mixed type.) Pleomorphic variability was characteristic of the mixed pattern, with many architectural variants present in all tumors in this category. Glandular spaces, trabeculae, ribbons, cords, sheets, and nests have all been observed. Nuclei were mostly uniform and mitoses were rare. Although Benecke et al claimed bony involvement of all tumors, a more recent study by Torske and Thompson found only rare instances of nonextensive bone erosion. (7)

Clinically, mixed tumors are confined to the middle ear and mastoid; they rarely involve the otic capsule or facial nerve, and they may be misdiagnosed as chronic otitis media. In contrast, papillary neoplasms extend into the petrous apex and mayinvolve the posterior and/ or middle cranial fossa and the facial nerve. Papillary patterned tumors have been referred to as low-grade adenocarcinomas for their more invasive nature. (7)

Surgical management is the standard of care for middle ear masses. En bloc resection, including involved parts of the ossicular chain, has been shown to effect clinical cure. Cases that involved the ossicles, but whose treatment did not include their removal, resulted in an 18 to 22% recurrence rate. (7,13,14) Patients who underwent subsequent surgeries to completely remove remnants of remaining tumor had good clinical outcomes. Radiation therapy is not recommended for these tumors as their clinical manifestations are a result of mass effect and they have very little malignant potential. (15)


A rare pathologic entity, the NAME can be differentiated from other tumors of the middle ear by histologic and immunohistochemical features. Histologic analysis after the surgical procedure will establish the diagnosis. The treatment of choice is complete surgical resection without additional therapy. Although these are slow-growing tumors with low metastatic potential, recurrence is possible. Therefore, long-term follow-up is needed.


(1.) Treitel L. Uber das Carcinom des Ohres. Z Ohreheilk 1898;33: 152-64.

(2.) Derlacki EL, Barney PL. Adenomatous tumors of the middle ear and mastoid. Laryngoscope 1976;86(8):1123-35.

(3.) McNutt MA, Bolen JW. Adenomatous tumor of the middle ear. An ultrastructural and immunocytochemical study. Am J Clin Pathol 1985;84(4):541-7.

(4.) Wassef M, Kanavaros P, Polivka M, et al. Middle ear adenoma. A tumor displaying mucinous and neuroendocrine differentiation. Am J Surg Pathol 1989;13(10):838-47.

(5.) Amble FR, Harner SG, Weiland LH, et al. Middle ear adenoma and adenocarcinoma. Otolaryngol Head Neck Surg 1993;109(5):871-6.

(6.) Ayache S, Braccini F, Fernandes M, Homassin JM. Adenoma of the middle ear: A rare and misleading lesion. Otol Neurotol 2002;23(6):988-91.

(7.) Torske KR, Thompson LD. Adenoma versus carcinoid tumor of the middle ear: A study of 48 cases and review of the literature. Mod Pathol 2002;15(5):543-55.

(8.) Benecke JE, Noel FL, Carberry JN, et al. Adenomatous tumors of the middle ear and mastoid. Am J Otol 1990; 11 (1):20-6.

(9.) Hyams VJ, Michaels L. Benign adenomatous neoplasm (adenoma) of the middle ear. Clin Otolaryngol Allied Sci 1976; 1(1):17-26.

(10.) Murphy GF, Pilch BZ, Dickersin GR, et al. Carcinoid tumor of the middle ear. Am J Clin Pathol 1980;73(6):816-23.

(11.) Fayemi AO, Toker C. Primary adenocarcinoma of the middle ear. Arch Otolaryngol 1975;101(7):449-52.

(12.) Mooney EE, Dodd LG, Oury TD, et al. Middle ear carcinoid: An indolent tumor with metastatic potential. Head Neck 1999;21 (1):72-7.

(13.) Ramsey MJ, Nadol JB Jr., Pilch BZ, McKenna MI. Carcinoid tumor of the middle ear: Clinical features, recurrences, and metastases. Laryngoscope 2005;115(9):1660-6.

(14.) Thompson LD. Neuroendocrine adenoma of the middle ear. Ear Nose Throat J 2005;84(9):560-1.

(15.) Gunduz M,Yamanaka N, Saito T, et al. Middle ear adenoma with neuroendocrine differentiation. Auris Nasus Larynx 2000;27(1):73-6.

Karen Leong, MD; Marian M. Haber, MD; Venu Divi, MD; Robert T. Sataloff, MD, DMA, FACS

From the Department of Otolaryngology--Head and Neck Surgery (Dr. Leong, Dr. Divi, and Dr. Sataloff) and the Department of Pathology (Dr. Haber), Drexel University College of Medicine, Philadelphia.

Corresponding author: Robert T. Sataloff, MD, 1721 Pine St., Philadelphia, PA 19103. Phone: (215) 732-6100; fax: (215) 545-3374; e-mail:
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Author:Leong, Karen; Haber, Marian M.; Divi, Venu; Sataloff, Robert T.
Publication:Ear, Nose and Throat Journal
Article Type:Case study
Geographic Code:1USA
Date:Apr 1, 2009
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