Key points

Overview

Adenomatous tumors are an uncommon cause of a middle ear mass. The first description of middle ear adenoma as a distinct pathologic entity was by Hyams and Michaels in 1976, who described a series of 20 glandular middle ear neoplasms that did not resemble paraganglioma or salivary gland tumor. In the same year, Derlacki and Barney reported on 3 additional cases with similar histopathology. Murphy and colleagues in 1980 then described a middle ear tumor with related pathologic features but additionally having histochemical and ultrastructural evidence of neuroendocrine differentiation, labeling it carcinoid. Other investigators have subsequently reported similarly behaving middle ear tumors using the term neuroendocrine adenoma. Recent histopathologic evidence suggests that such labels may represent a spectrum of 1 common pathologic entity. In contrast, other researchers still posit that middle ear adenoma and carcinoid are distinct biological neoplasms.

The commonality to all adenomatous middle ear tumors is the presence of both epithelial and neuroendocrine elements. Immunohistochemical staining shows 2 distinct patterns of staining; one for cytokeratin markers within the glandular components of the tumor and another for neuroendocrine markers in the stromal regions. Similarly, electron microscopy can be used to reveal ultrastructural features within adenomatous tumors that confirm the presence of these opposing cell types.

Most adenomatous middle ear tumors show indolent biological behavior, with a benign histologic appearance and slow local growth. More aggressive histologic patterns may also sometimes be observed, although uncertainty exists as to whether this predicts an increased risk of local invasiveness, recurrence, and/or metastasis. Examples have been cited of locally invasive tumors that appear histologically benign as well as neoplasms that contain infiltrative/dysplastic cellular morphologies but do not show clinical invasiveness. Because of the rarity of adenomatous middle ear tumors, along with uncertainties in classification and differences in biological behavior, rigid protocols for management of these tumors are lacking.

Overview

Adenomatous tumors are an uncommon cause of a middle ear mass. The first description of middle ear adenoma as a distinct pathologic entity was by Hyams and Michaels in 1976, who described a series of 20 glandular middle ear neoplasms that did not resemble paraganglioma or salivary gland tumor. In the same year, Derlacki and Barney reported on 3 additional cases with similar histopathology. Murphy and colleagues in 1980 then described a middle ear tumor with related pathologic features but additionally having histochemical and ultrastructural evidence of neuroendocrine differentiation, labeling it carcinoid. Other investigators have subsequently reported similarly behaving middle ear tumors using the term neuroendocrine adenoma. Recent histopathologic evidence suggests that such labels may represent a spectrum of 1 common pathologic entity. In contrast, other researchers still posit that middle ear adenoma and carcinoid are distinct biological neoplasms.

The commonality to all adenomatous middle ear tumors is the presence of both epithelial and neuroendocrine elements. Immunohistochemical staining shows 2 distinct patterns of staining; one for cytokeratin markers within the glandular components of the tumor and another for neuroendocrine markers in the stromal regions. Similarly, electron microscopy can be used to reveal ultrastructural features within adenomatous tumors that confirm the presence of these opposing cell types.

Most adenomatous middle ear tumors show indolent biological behavior, with a benign histologic appearance and slow local growth. More aggressive histologic patterns may also sometimes be observed, although uncertainty exists as to whether this predicts an increased risk of local invasiveness, recurrence, and/or metastasis. Examples have been cited of locally invasive tumors that appear histologically benign as well as neoplasms that contain infiltrative/dysplastic cellular morphologies but do not show clinical invasiveness. Because of the rarity of adenomatous middle ear tumors, along with uncertainties in classification and differences in biological behavior, rigid protocols for management of these tumors are lacking.

Clinical presentation

Adenomatous middle ear tumor typically presents as a nonspecific middle ear mass ( Fig. 1 ). The mean age of presentation is the fifth decade (range, 14–80 years) with no gender preference. Hearing loss was the most common presenting symptom (86.3%) in a review of 94 previously published cases of middle ear glandular neoplasms, with most being conductive in nature. Other reported symptoms included aural fullness (33%), tinnitus (27.6%), otalgia (15%), otorrhea (11.4%), and facial weakness (11%). Facial nerve palsies associated with middle ear tumors have been reported by Krouse and colleagues and Torske and Thompson. There was no nerve infiltration by tumor in any of these cases. Instead, the palsies were thought to be related to anatomic abnormalities or local pressure from the tumor with facial canal bone dehiscence. Gross facial nerve invasion has been described in 1 case of middle ear carcinoid and presumed in another case, as reported by Ramsey and colleagues.

Otomicroscopy of a right ear shows a middle ear mass medial to an intact tympanic membrane.

( Courtesy of Matthew Carlson, MD, Rochester, MN.)

Regional and/or systemic symptoms may occasionally be associated with adenomatous middle ear tumors. There has been a case reported of middle ear carcinoid metastatic to ipsilateral cervical lymph nodes. Also of note, a carcinoid tumor of the middle ear associated with carcinoid syndrome was described in 1980 by Farrior and colleagues and in 1987 by Latif and colleagues. In the latter report, the patient presented with systemic signs and symptoms including diarrhea, abdominal cramps, skin flushing, and bronchoconstriction.

Diagnosis

The differential diagnosis of middle ear masses is extensive and includes chronic otitis media, cholesteatoma, mucosal adenoma, ceruminous adenoma, carcinoid, paraganglioma, adenoid cystic carcinoma, pleomorphic adenoma, meningioma, schwannoma, retrotympanic vascular masses, endolymphatic sac tumor, schneiderian-type mucosal papilloma, lipoma, and epidermoid. Adenomatous middle ear tumors can be distinguished based on several imaging and histologic characteristics.

Imaging

Preoperative evaluation includes use of computed tomography (CT) and MRI to delineate tumor features. CT highlights a nonspecific opacity with possible extension to the tympanic cavity and mastoid ( Fig. 2 ). The ossicles are generally embedded in the mass without ossicular or bony erosion or destruction. No characteristic differences between benign and malignant adenomatous middle ear tumors are detectable on CT.

Axial ( A ) and coronal ( B ) CT images of a middle ear adenoma, showing a nonspecific middle ear mass with ossicular chain involvement.

( Courtesy of Dr David S. Haynes, Nashville, TN.)

MRI may be helpful in cases with extension to the posterior or middle cranial fossa. On MRI, tumors are isointense to hyperintense relative to white matter on T1-weighted images, and avidly enhance with gadolinium administration ( Fig. 3 ). On T2-weighted images, tumors approximate the signal intensity of gray matter.

Axial ( A ) and coronal ( B ) T1-weighted magnetic resonance images of a middle ear adenoma, showing an enhancing middle ear mass.

( Courtesy of Matthew Carlson, MD, Rochester, MN.)

As previously noted, paraganglioma is an important consideration in the differential diagnosis of adenomatous middle ear tumors. Bierry and colleagues presented several radiologic and clinical findings to help discriminate between these disorders; the investigators included carcinoid and noncarcinoid tumors under the term middle ear adenoma. They concluded that although middle ear adenomas and glomus tympanicum both appear as tissular lesions with significant enhancement on CT and MRI, only glomus tumors have specific clinical features such as pulsatile tinnitus, a close relationship between tumor and Jacobson nerve or its branches, and vascular blush on angiography. In contrast, adenomatous middle ear tumors are clearly separate from the Jacobson nerve and its branches, and although they show contrast enhancement, they have unimpressive angiographic findings. The study discussed use of conventional angiography in differentiating tumor types, but not CT or magnetic resonance angiography.

Evaluation of patients with suspected metastases (neck mass, systemic symptoms) should include imaging of the neck, chest, and abdomen. Octreotide scanning has been successfully used for localizing undetected primary or metastatic gastroenteropancreatic carcinoid disease with a sensitivity of 80% to 90%, but is not well established in middle ear carcinoid and is limited to a single 2004 case report by Nikanne and colleagues. Postoperative octreotide scan was used in this case because of a positive tumor margin near the eustachian tube; slight immediate postoperative uptake was thought to be caused by inflammation and repeat scan 4 months later was within normal limits. The investigators concluded that octreotide scanning is a sensitive method for follow-up in cases of both middle ear carcinoid recurrence and metastases. No studies have assessed the use of diagnostic and preoperative octreotide scanning for these tumors.

Pathogenesis

The precursor cell for adenomatous middle ear tumors is unclear. Hyams and Michaels postulated an origin for middle ear adenoma from surface epithelium mucosa, as did Derlacki and Barney. It has also been suggested that middle ear adenomas develop from displaced or trapped embryonic rests of glandular cells in middle ear mucosa, and some investigators have suggested that these embryonic cells are of neural crest origin.

Other reports have deemphasized the relationship between middle ear adenoma and neuroendocrine tumors, maintaining that they are separate entities. The middle ear does not contain enterochromaffin cells, which normally give rise to carcinoid tumors in the lung and gastrointestinal tract, nor does it contain other cells with neuroendocrine features. One potential explanation put forth by Torske and Thompson is that an undifferentiated, pluripotent stem cell may give rise to an adenomatous middle ear tumor with both epithelial and neuroendocrine components.

Carcinoids are rare in the middle ear and mastoid. The tumor occurs predominantly in the small intestine, and, when these lesions develop in the head and neck region, most arise in the larynx. The first case of middle ear carcinoid was reported in 1980 by Murphy and colleagues and in 2005 Chan and colleagues found approximately 40 cases of documented middle ear carcinoid in the English literature. Carcinoid has historically been considered a distinct neoplasm given its reported metastatic potential. However, recent studies have used pathologic features to suggest that middle ear adenoma and carcinoid may represent different stages of differentiation of the same tumor. Hence many investigators currently view these tumors as a single primary low-grade glandular neoplasm, with more specific identification based on immunohistochemical markers and presence or absence of metastases.