Ceruminous gland tumors arise in the external auditory canal (EAC) from specialized glands that are closely related to apocrine glands,  which are found in the axillae, anogenital area, areolae, and eyelids (glands of Moll). These external ear glands contribute material that combines with sebaceous gland products and desquamated epithelial cells to produce a waxy substance known as cerumen (from Latin cēra “wax”). 
Like other apocrine-related glands, including mammary tissue, ceruminous glands are composed of an inner secretory layer of cells and an outer myoepithelial layer of cells. The glands drain into larger ducts, which, in turn, drain into hair follicles that populate the EAC. 
Tumors that likely derive from the ceruminous glands include benign tumors, such as ceruminous adenoma, ceruminous pleomorphic adenoma, and ceruminous syringocystadenoma papilliferum, as well as malignant tumors, such as ceruminous adenocarcinoma, adenoid cystic carcinoma, and, mucoepidermoid carcinoma. [4, 5, 6, 7]
Pathophysiology and Etiology
Between 1000 and 2000 ceruminous glands, along with sebaceous glands and associated hair follicles, typically occupy the outer, cartilaginous portion of the external auditory canal (EAC), with a few present in the auricular skin.  The remaining majority of the ear canal contains a thin layer of epithelium lining dense bone and contains no adnexal structures.
On the basis of histologic similarities and distribution pattern, the histogenesis for most of the benign (adenoma, pleomorphic adenoma, and syringocystadenoma papilliferum) and malignant (adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma) glandular tumors arising in the EAC is in all likelihood the ceruminous glands or their embryologic anlage. Ectopic salivary gland tissue has been suggested as another possible origin, [8, 9] though ectopic salivary gland tissue in the EAC has never been reported.
As expected, given the anatomic arrangement, tumors believed to derive from ceruminous glands are present almost exclusively in the EAC. Similar tumors from nearby parotid glandular tissue may extend into the EAC, most notably pleomorphic adenomas, adenoid cystic carcinomas, and mucoepidermoid carcinomas, [10, 11] but despite their indistinguishable histologic features, these are considered primary salivary gland neoplasms with secondary involvement of the auditory canal.
Ceruminous glands do not normally populate the middle ear, nor have ectopic ceruminous glands within the middle ear been reported. [12, 13] However, numerous cases reported as ceruminous adenoma and ceruminoma arising in the middle ear are found in the literature. [14, 15, 16, 17, 18, 19, 20, 21, 22]
Some of these reports were the result of confusing terminology, in that several different tumor types were originally categorized as ceruminoma, a term that should probably not be used. Many of these reported middle ear tumors might have been better classified as middle ear adenoma or as neuroendocrine adenoma of the middle ear (NAME), tumor types that are believed to arise from the epithelium of the middle ear rather than from ceruminous glands. 
Ceruminous tumors of the EAC have also been reported to extend into the adjacent middle ear, [6, 24] a phenomenon that further complicates the issue. In short, the possibility of a true ceruminous gland–related adenoma arising in the middle ear is controversial, and such a diagnosis should be approached with caution. [4, 8, 25]
The ultimate cause for these tumors remains unknown. Ceruminous pleomorphic adenoma development after protracted chronic otitis media has been reported [26, 27] ; the causal relationship between the 2 conditions is unknown. The concurrence of otitis media and ceruminous gland–related tumor development has also been reported in animals. 
No studies of the ceruminous gland–related tumors using molecular techniques or analyzing their genetic basis have been identified in the literature.
Although the true incidence of ceruminous gland tumors is difficult to determine, it is clear that such tumors are uncommon, if not rare. Squamous cell carcinomas and basal cell carcinomas are the most common external ear tumors; far fewer tumors are derived from glandular elements. [29, 30] Studies suggest that even if the site is restricted to tumors of the external auditory canal (EAC), glandular tumors are much less common (though these studies focused on carcinomas and did not record the presence of benign tumors). [31, 32, 33]
Ceruminous tumors have been reported in patients as young as 12 years and as old as 92 years. [34, 8] The mean age for patients with the most common benign tumor, ceruminous adenoma, is the sixth decade.  Ceruminous pleomorphic adenomas are less common than ceruminous adenomas; the mean age for affected individuals is also in the sixth decade. [26, 27, 35, 36]
Ceruminous adenomas and pleomorphic adenomas have been reported in both sexes. The sex distribution for ceruminous adenomas is nearly 50-50.  A few more cases of ceruminous pleomorphic adenoma have been reported in men than in women, but the overall number of cases is too small to suggest a statistically significant difference. [4, 26, 27, 35, 36]
Syringocystadenoma papilliferum is an uncommon benign tumor that is most often found on the scalp and face but has been found in the EAC on rare occasions (15 cases identified in the literature); it has been reported to arise in both men and women at this site. [37, 38, 39, 40]
The mean age for patients with the most common malignant ceruminous gland tumor, adenoid cystic carcinoma, may be slightly younger than that for patients with benign tumors, with a mean age more often reported in the fifth decade; this tumor is more frequently reported in females. [41, 42, 43, 44]
Thirty-four patients with a diagnosis of ceruminous adenocarcinoma involving the EAC have been identified from the English literature, with an age range of 26-89 years and an average age of 54 years, including 18 males and 11 females (demographic information was not available for 5 patients). [34, 45, 9, 46, 47, 48] A few additional cases of ceruminous adenocarcinoma involving the EAC have also been identified in the non-English literature. [49, 50, 51, 52, 53, 54]
Five patients (ages 28, 41, 58 and 62 y) with mucoepidermoid carcinoma involving the EAC have been identified from the English literature, [6, 55, 56, 57] including 1 male and 3 females (demographic information was not provided for the fifth patient). Rare cases of mucoepidermoid carcinoma involving the EAC have also been reported in the non-English literature. [58, 59]
The most common presenting symptoms for the benign ceruminous lesions are the presence of a mass and hearing changes. Other less common presenting symptoms include discharge, pain, and paralysis. [4, 8] The reported duration of symptoms ranges from zero, as some patients are asymptomatic at presentation, to as long as 40 years. 
The largest series of ceruminous adenomas to date reported an average symptom duration of 16 months.  Curiously, women had a longer mean symptom duration than men did (23.3 vs 13.3 mo), and tumors on the left side had a longer mean duration than those on the right (17.9 vs 13.9 mo); however, the authors noted that because of the limited number of cases, the statistical significance of these findings is uncertain.
Adenoid cystic carcinomas more often manifest with pain, otorrhea, and cranial nerve palsy. [8, 6, 44] The occurrence of pain in association with an external auditory canal (EAC) mass appears to be especially worrisome.
The largest series of EAC adenoid cystic carcinomas to date noted an average symptom duration of 2 years. Although the number of cases was small and the statistical significance of the findings uncertain, the authors suggested that a longer presence of symptoms before diagnosis appeared to be related to the likelihood of recurrence. 
Of the 5 cases of mucoepidermoid carcinoma identified in the English literature, 1 patient presented with “slight left-sided otalgia” associated with masses,  2 presented with painless masses, [6, 57] and in the remaining 2, the presenting symptoms were not described. [6, 55]
The following are considered in the differential diagnosis of ceruminous gland tumors of the external auditory canal:
Because of the nature of the surgical excision procedure, ceruminous adenoma specimens may be received in fragments. However, on the basis of reports of intact specimens  and clinical examinations,  these appear as polypoid masses covered by a nonulcerated epithelium. The largest series of these tumors to date reports a mean size of 1.1 cm and a range of 0.4-2.0 cm.  Adenomas have also been reported as being grossly cystic. 
The few reports of ceruminous pleomorphic adenomas describe them as having a gross appearance similar to that of ceruminous adenomas (polypoid mass) and being comparable (though generally slightly larger) in size. [4, 26, 27]
Adenoid cystic carcinoma may also appear as a polypoid mass, but additional ominous descriptors include epithelial ulceration, associated granulation tissue, and poor demarcation from the surrounding tissue. 
The gross features of the few reported mucoepidermoid carcinomas in the English literature are not well described.
Ceruminous adenomas are circumscribed but unencapsulated lesions with infrequent surface involvement. The tumors demonstrate variable architectures, including the formation of small closely approximated glands, areas of cystic dilatation, solid cellular proliferation, and papillary arrangements.
Similar to the native ceruminous glands and other apocrine-related structures, ceruminous adenomas are composed of 2 cell types. The first type consists of luminally placed cuboidal to low-columnar epithelial cells with eosinophilic cytoplasm that frequently contain small luminal tufts commonly referred to as apical caps or decapitation secretion (see the image below). These tufts are typical of apocrine-related glands.
The epithelial cells also contain the gold- to brown-colored ceroid pigment that distinguishes these lesions as related to cerumen-producing glands. The epithelial cells are surrounded by a layer of myoepithelial cells (the second cell type) with less apparent cytoplasm and a smaller hyperchromatic nucleus. Immunohistochemical studies differentially label these 2 cell types (see Immunohistochemistry).
The few reported ceruminous pleomorphic adenomas are described in much the same way as the pleomorphic adenomas that commonly occur in salivary glands. These tumors contain a prominent chondroid to myxoid stromal component admixed with epithelial and myoepithelial components (see the image below). The epithelial cells may form small tubules as well as small solid clusters of cells in varying patterns.
The tubules contain both epithelial and myoepithelial cells. Small collections of myoepithelial cells free in the stroma may also be seen. Mitotic figures are not easily identified, but features such as decapitation secretion and ceroid pigment may be seen in the epithelial component of the lesion [4, 26] ; these features are not typically described in pleomorphic adenomas from other sites.
Syringocystadenoma papilliferum appears as a mass extending from the overlying surface epithelium to expand the underlying tissues with cystic glandular structures that contain numerous papillary projections. The bilayered epithelium lining these complex structures is composed of inner cells that demonstrate prominent eosinophilic cytoplasm with occasional luminal tufts (decapitation secretion) and outer cells with less apparent myoepithelial cells. Characteristically, the papillary fibrovascular cores harbor numerous plasma cells.
Morphologically, ceruminous adenoid cystic carcinomas are essentially identical to the similar tumors arising in salivary glands, though one case series identified pigments similar to that seen in benign ceruminous glands within some of the tumors.  The tumors are composed of epithelial cells arranged in a variety of patterns. The classic pattern consists of a cribriform architecture with clusters of cells interrupted by cystlike spaces that may contain mucinous, slightly basophilic or eosinophilic material (see the following image).
The classic pattern may be admixed with areas of tubule formation or areas of solid cellular growth. Perineural invasion is a characteristic and diagnostically helpful feature of adenoid cystic carcinomas arising in the salivary glands, and this appears also to be true of ceruminous gland–related tumors. 
Salivary gland adenoid cystic carcinomas are assigned a histologic grade on the basis of the relative amount of solid growth present: greater amounts of solid growth correlate with a worse prognosis.  This association with solid growth may also be relevant in ceruminous adenoid cystic carcinomas, but even in the largest series,  the number of cases was too small to provide statistically significant support for this contention.
Ceruminous adenocarcinomas display a range of histologic features. The better-differentiated varieties demonstrate variably irregular gland formation with evidence of ceruminous gland derivation; these lesions may be difficult to differentiate from ceruminous adenomas. Features used to differentiate adenocarcinomas from adenomas include stromal invasion with associated stromal response, significant infiltrative growth, perineural invasion, cellular pleomorphism, prominent nucleoli, significant mitotic activity, atypical mitoses, and necrosis. [4, 8]
The less well differentiated examples of ceruminous adenocarcinomas demonstrate increasingly irregular gland formation and are often composed of small clusters of cells with minimal gland formation. The poorly differentiated lesions also demonstrate more marked cytologic atypia, including cellular and nuclear pleomorphism, and show increased mitotic activity. On the basis of these characteristics, Dehner and Chen classified ceruminous adenocarcinomas into low-grade and high-grade varieties. 
The limited number of reports of mucoepidermoid carcinoma in the literature describe histologic features indistinguishable from those of the much more common mucoepidermoid carcinomas that arise in the salivary glands. [55, 56, 57] The histologic hallmark of mucoepidermoid carcinomas is the presence of at least 3 cell types in varying proportions: mucous cells, epidermoid cells, and intermediate cells (see the image below).
Mucous cells have a conspicuous amount of clear cytoplasm and a peripherally displaced nucleus; they either line cystic spaces or may be present within areas of solid growth. Epidermoid cells are polygonal cells with eosinophilic cytoplasm; at times, they resemble squamous cells, though widespread features of squamous differentiation are absent. Intermediate cells demonstrate cytologic features in between the other types, with a variable amount of eosinophilic cytoplasm. Some observers also include clear cells as a fourth type typically seen in these lesions. 
The histologic appearance of any individual mucoepidermoid tumor varies not only according to the proportions in which these different cell types are present but also according to the amount of cystic spaces relative to the amount of solid growth. The number of mucoepidermoid carcinomas arising in the external auditory canal (EAC) that have been reported in the literature is too small to establish statistically significant prognostic grading criteria.
Uniform grading criteria also have not been established for mucoepidermoid tumors arising in the salivary glands; however, the proposed systems include the percentage of cystic component, the frequency of mitotic figures, nerve invasion, tumor necrosis, and the presence of cellular/nuclear atypia.  Other findings, including vascular invasion and the overall pattern of invasion, have been suggested as well. 
Ceruminous adenomas demonstrate labeling of the luminal cells with cytokeratin 7 and labeling of the myoepithelial cells with S100, cytokeratin 5/6, and P63 (nuclear labeling). [4, 22] The few reports of immunohistochemical studies performed in ceruminous pleomorphic adenomas describe similar labeling of the epithelial and myoepithelial components. [26, 64]
A single report of syringocystadenoma papilliferum with distinct epithelial (cytokeratin) and myoepithelial labeling (S100) has been published  ; interestingly, this case was associated with a ductal carcinoma, and the authors reported loss of myoepithelial labeling in the invasive component.
The immunohistochemical attributes of the other primary ceruminous gland–related tumors have not been defined in the literature.
Tumor Spread and Staging
No staging system designed specifically to classify primary glandular tumors arising in the external auditory canal (EAC) currently exists. A system for staging squamous cell carcinoma of the EAC has been proposed by a group that includes several members from the University of Pittsburgh School of Medicine.  Given the lack of a system focused on glandular tumors, some authors have applied this University of Pittsburgh system to the description of ceruminous malignancies. [43, 56]
The University of Pittsburgh system stages squamous cell carcinoma of the EAC as follows  :
T1: Tumor limited to the EAC without bony erosion or soft-tissue extension
T2: Tumor with limited EAC bony erosion (not full thickness) or radiographic evidence of limited (< 0.5 cm) soft-tissue involvement
T3: Tumor eroding the osseous EAC with limited (< 0.5 cm) soft-tissue involvement or tumor involving the middle ear/mastoid or patients presenting with facial paralysis
T4: Tumor eroding the cochlea, petrous apex, medial wall of the middle ear, carotid canal, jugular foramen, or dura or with extensive (>0.5 cm) soft-tissue involvement
Nodal involvement (N1): Poor prognostic indicator sufficient for classification as stage III (in association with T1 disease) or stage IV (with T2, T3, T4)
Distant metastasis (M1): Classified as stage IV
Prognosis and Predictive Factors
For the benign ceruminous gland tumors, complete excision is considered curative. However, the anatomic constraints of the external ear canal (EAC) may make complete excision difficult, and residual disease or recurrences of these benign tumors has been reported. In the largest series of benign tumors to date, 4 of 40 patients had either recurrent or residual tumor in subsequent excisions, 1 of them 4 years after the initial diagnosis; none of the patients in this study had evidence of disease at the last follow-up. 
Pleomorphic adenomas arising in salivary gland tissue are well known to recur after incomplete excision,  and at least 3 cases of recurrent ceruminous pleomorphic adenoma occurring in the EAC have been reported.  One of these recurrent cases first occurred in a 15-year-old girl in whom areas of “severe atypism and some mitotic activity” were noted, suggesting a more aggressive lesion. 
Like similar lesions at other locations in the head and neck, adenoid cystic carcinoma of the EAC has a slowly progressive course, often recurring many years after the original diagnosis.
The larger studies to date show 7 of 21 patients,  7 of 16,  5 of 10,  and 10 of 22  with no evidence of disease at last follow-up, though it is important to note that with multiple reports of a first recurrence many (>10) years after diagnosis, even these nonreassuring survival figures may present an overly optimistic impression. A predilection for metastasis to the lungs was noted in 2 of these series. [41, 44] A case of contralateral metastasis to the brain has been reported. 
As a consequence of these reports, initial aggressive treatment has been advocated for these patients. [34, 44] As noted (see Microscopic Findings), histologic features such as tumor grade and perineural invasion correlate with the recurrence of adenoid cystic carcinoma at other sites, but the number of cases in the EAC is too small to provide statistically significant evidence at this site.
Ceruminous adenocarcinoma also appears to have an aggressive course, with both local and distant recurrences in a significant number of reported cases.  Although it may be tempting to entrust the histologic grade with prognostic significance, once again, the number of reported cases is simply too small to yield statistically significant guidance. As with ceruminous adenoid cystic carcinoma, an aggressive initial treatment strategy has been promoted. 
Of the 5 cases of mucoepidermoid carcinoma of the EAC identified in the literature, 2 patients experienced recurrences, 1 of whom had no evidence of disease approximately 9 years after initial diagnosis and 1 of whom was lost to follow-up,  One patient had persistent disease at 18 months,  and the remaining 2 patients had no evidence of disease at 29 and 24 months, respectively. [56, 57]
A single case of adenocarcinoma arising in association with a syringocystadenoma papilliferum in the EAC has been reported in the literature.  The 49-year-old male patient showed no evidence of disease 20 months after resection.