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Ceruminous glands are modified sweat glands, confined to the skin lining of the cartilaginous part of the external auditory meatus. Tumours arising from these glands are extremely rare. Confusion exists regarding the nomenclature 'ceruminoma' and controversies prevail on the standard way of management. Treatment often involves a multidisciplinary approach, requiring reconstruction after extensive surgical resection. A case report of adenoid cystic carcinoma of ceruminous glands is presented along with discussion of the various pathological types and a review of management.

A case of lipomatous pleomorphic adenoma in the ceruminous gland is reported. A 69-year-old Japanese woman presented with a mass in the posterior wall of the cartilaginous external auditory canal. Light microscopic examination revealed a well-circumscribed tumor composed of tubular structures with apocrine secretion and ceroid deposition, extensive mature adipocytes, and spindle-shaped myoepithelial cells in the myxoid and fibrous stroma. This case demonstrates the peculiar location of a lipomatous pleomorphic adenoma in the external auditory canal.

WOS: 000233995700005 PubMed: 15968569 Pleomorphic adenoma of the external auditory canal is a rare disease. It is considered to derive from the ceruminous glands. The objective of this study is to familiarize the clinician with the clinical presentation and treatment of this disease. We report the case of a 58-year-old woman. Complete resection should be applied for cases in which magnetic resonanace imaging (MRI) and computerize tomography (CT) examination indicate no erosion in the bone and cartilage tissue. The patient should be seen regularly for recurrence.

The histological features of 124 ceruminous gland tumors from canine and feline biopsy submissions were reviewed. The tissues, which represented submissions from private veterinary practices and a veterinary college, included ceruminous gland adenocarcinomas and adenomas as well as a single, mixed ceruminous gland adenocarcinoma. A majority of the masses from both dogs and cats were identified as malignant processes.

The clinical and pathological features of glandular tumours of the external auditory meatus are presented. Their heterogenous clinical and pathological features make the collective term ‘ceruminoma’ ambiguous andmisleading. The spectrum of pathological behaviour and histological features demonstrated by these interesting tumours necessitate a broader classification system. In our hospital 32 patients presented with tumours of the external auditory meatus over a 30-year period, of which seven were glandular in origin. A review of the histology of these glandular tumours enabled us to reclassify them as adenoma, cylindroma, adenoid cystic carcinoma or ceruminous adenocarcinoma. Together with the less common mucoepidermoid carcinoma and pleomorphic adenoma this subdivision forms a basis for a more meaningful classification system with prognostic and therapeutic implications specific to each tumour type. The term ‘ceruminoma’ should no longer be used unqualified.

We present the case of a 38-year-old man with an adenoid cystic carcinoma originating from the ceruminous glands of the external ear canal. The patient subsequently presented with a contralateral brain mass that was also diagnosed as adenoid cystic carcinoma. To our knowledge, contralateral metastasis to the brain of a patient with an adenoid cystic carcinoma of the ceruminous glands has not been reported previously. This rare neoplasm should be considered in the differential diagnosis of poorly differentiated carcinomas metastatic to the central nervous system in patients with occult malignant neoplasms.

Afive-year-old boy was referred to our department with intermittent serous otorrhea due to a recurrent mass in his right external auditory canal (EAC). When the patient was four years of age, this lesion had been removed at another hospital. Histologically, the lesion was consistent with a ceruminoma. No other symptoms or signs were reported. A 0.6-cm pink-reddish, condyloma-like mass that bled easily was localized in the superior wall of the EAC at the level of the bone-cartilage junction (Fig 1). The tympanic membrane was normal. Computed tomography revealed no deep extension of the lesion. The lesion was removed completely via a transmeatal approach, and no histological involvement of the cartilaginous or bony EAC was detected. Histopathology revealed a well-differentiated, localized neoplasm with papillary proliferation of glands similar to normal ceruminous glands. This pattern was diagnosed as adenoma of the ceruminous glands (ceruminoma). At the one-year follow-up, the patient was tumor free. The institutional review board of Sapienza University approved this article.

Human beta-defensin-1 (hBD-1) and human beta-defensin-2 (hBD-2) antimicrobial peptides present in the cerumen, which is composed of exfoliated epithelial keratin and gland secretion, might provide the first line of defense against microbes in external auditory canal (EAC) skin.Cerumen (earwax) plays a primary role in protecting the EAC skin and tympanic membrane. Even though the protection by antimicrobial peptides present in the skin secretion has been well established, little is known about the intrinsic role of the peptides in the EAC skin and cerumen. The aim of this study was to examine the presence of important antimicrobial peptides, hBD-1 and hBD-2, in the cerumen and EAC skin.Cerumen was collected from 20 healthy adults, and the EAC skins were obtained from 12 patients who underwent middle ear surgery with canaloplasty. The presence of hBD-1 and hBD-2 was analyzed using immunohistochemistry and Western blotting.In the immunohistochemical study of the EAC skin, expression of hBD-1 and hBD-2 was observed in both the epithelium and the glands. The presence of hBD-1 and hBD-2 peptides in the cerumen was confirmed by Western blotting.

In general, tumors of the external auditory canal (EAC) are quite uncommon, and glandular tumors comprise only a minority of these tumors. Tumors of the ceruminous gland are infrequent in the EAC. Ceruminous adenocarcinoma is a malignant subtype of ceruminous gland neoplasm, 1 which is an exceedingly rare malignant tumor of the EAC. The true incidence and biological behavior of these tumors is still obscure, owing not only to the rarity of these tumors but also to ambiguous tumor nomenclature. The dearth of knowledge about this disease entity leads to difficulty in establishing the formulation of definitive treatment plans.

Ceruminous adenocarcinoma is a rare malignant tumor arising from the ceruminous gland of the external auditory canal ceruminous gland. Usually it displays no specific clinical symptoms or signs, so most reported cases have involved an advanced tumor and the treatment results have been disappointing. It is important to make an early diagnosis to improve the treatment's outcome. We present the case of a 54-year-old female patient with a 1-year history of feeling blockage in her left ear. Otoscopic examination revealed an aural polyp arising from the cartilaginous ear canal's anterosuperior wall. A wide local excisional biopsy was performed, and the pathologic result was a ceruminous adenocarcinoma. We were able to detect the tumor early, and en bloc resection was possible in the form of a partial temporal bone resection.

p63, a recently identified homologue of the p53 protein, is expressed consistently in basal cells of several human multilayered epithelia. In this study, expression of p63 was determined in 31 primary cutaneous glandular carcinomas, including sebaceous, perianal (hepatoid) gland, apocrine and ceruminous carcinomas, as well as their adjacent normal skin. Similar to humans, p63 is a reliable marker for basal and myoepithelial cells in canine epidermis, cutaneous appendages and malignant apocrine and ceruminous gland neoplasms. In sebaceous carcinomas, not only basal cells, but also some sebocytes, showed nuclear staining for p63. Most mature epithelial cells in perianal gland carcinomas exhibited strong p63 expression. Based on these findings, basal/myoepithelial cells could be involved in the oncogenesis of these tumours and p63 might be used as a diagnostic marker in these lesions.

A 40-year-old man was referred to us with a 1-year history of worsening deafness in his left ear. He was assumed to have ceruminous accumulation, such that his ear canal was occluded with black wax. Otoscopy showed a smooth, black mass blocking the left ear canal. The operator could not see or manoeuvre beyond the mass, which seemed to be rooted anteroinferiorly. CT confi rmed a soft-tissue lesion eroding through the anterior meatal wall into retromandibular, but not parotid, tissue. Moreover, neck palpation showed left cervical lymphadenopathy. Ultrasonography confi rmed pathological nodes, and fi ne-needle aspiration cytology confi rmed metastatic malignant melanoma. The patient chose lateral temporal bone resection, superfi cial parotidectomy, selective neck dissection, and postoperative radiotherapy. Although rare, malignant melanoma of the external ear canal is especially dangerous, because detection is delayed due to its hidden location. Melanoma thicker than 4 mm has a very poor prognosis, and ear canal melanomas are typically thicker than that. Black wax is not typical of ceruminous gland secretions, therefore, the presence of material resembling black wax should be viewed as an ominous sign. Malignant melanoma of the external ear canal

The distribution of complex glycoconjugates and antimicrobial substances in the ceruminous glands of the horse (Equus przewalskii f. dom., type: pony) was studied using carbohydrate histochemical and immunohistochemical methods. The epithelial cells and luminal secretion of these glands exhibited considerable amounts of glycoconjugates with various saccharide residues, such as alpha-D-mannose, alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine and sialic acid, including O-acetylated sialic acid. Several sugars (alpha-D-mannose, alpha-L-fucose, and beta-D-galactose) were also detectable in the secretion of sebaceous glands present. Additionally, lysozyme and the peptide group of beta-defensins are demonstrated as products of the apocrine ceruminous glands and sebaceous glands. The results obtained are discussed with regard to the functional significance of the glandular secretions. It is suggested that the complex carbohydrates, lysozyme and beta-defensins found in the ceruminous gland secretions are involved in the function of cerumen as a general antimicrobial protective agent in the external auditory canal.

The localization and chemical nature of complex carbohydrates in the ceruminous glands of the Japanese miniature (Shiba) goat were studied using light and electron microscopic histochemical methods, particularly lectin histochemistry. The epithelial cells and luminal secretion of the caprine ceruminous glands contained large amounts of neutral and smaller amounts of acidic glycoconjugates with different terminal sugars (alpha- d-mannose, alpha-L-fucose, alpha-N-acetyl-D-galactosamine, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid). Several sugars (alpha-L-fucose, beta-D-galactose, beta-N-acetyl-D-glucosamine, and N-acetyl-neuraminic acid) were also detectable in the secretion of the sebaceous glands. The results obtained are discussed with regard to the specific function of the glandular secretion mixture. The complex glycoconjugates found in the ceruminous gland secretion may control viscoelasticity of and bacterial proliferation within the cerumen in order to protect the external auditory canal against physical damage or microbial attacks.

Ceruminous gland tumours are infrequent lesions of the external auditory canal (EAC). Controversy still exists about nomenclature, classification, tissue of origin, and accurate diagnosis of these tumours. We present three cases of ceruminous gland tumours, including benign eccrine cylindroma, ceruminous adenoma, and adenoid cystic carcinoma. Superficial biopsy led to an initial erroneous diagnosis of adenocarcinoma in the latter. All cases were positive for cytokeratin and S-100 protein, supporting a ceruminous gland origin. The benign eccrine cylindroma should be included in the ceruminous gland tumour classification. A wide excisional biopsy should be performed in every EAC lesion. The terms ‘ceruminoma’ and ‘cylindroma’ should be avoided.

As glândulas ceruminosas são glândulas apócrinas modificadas encontradas na região profunda da derme que reveste a porção cartilaginosa do meato acústico externo. Os tumores originados dessas glândulas são raros. Existem controvérsias em relação ao termo ceruminoma, que nos parece impróprio. Na verdade, esses tumores são atualmente classificados como adenoma, adenocarcinoma, carcinoma adenóide cístico e adenoma pleomórfico. Relatamos o caso de uma mulher de 39 anos, apresentado-se com cefaléia, hipoacusia e zumbidos à direita, além de vertigem e náuseas. A TC de crânio evidenciou tumoração do ouvido médio, invadindo os limites ósseos e cartilaginosos, com extensão intracraniana. Foi submetida a cirurgia, com exérese parcial do tumor, seguida de radioterapia (6000 cG). A histologia mostrou tratar-se de carcinoma adenóide cístico de glândulas ceruminosas. A paciente apresentou no pós-operatório paralisia facial periférica à direita, mantendo os déficits anteriores. Após um ano da cirurgia encontra-se estável clinicamente. Ceruminous glands are modified apocrine glands, confined to the skin lining of the cartilaginous part of the external auditory meatus. Tumors arising from these glands are rare. Controversy exists regarding the term "ceruminoma". Actually this neoplasia should be classified as adenoma, adenocarcinoma, adenoid cystic carcinoma and pleomorphic ceruminous adenoma. We report a 39-year-old woman first seen at Santa Casa of Belo Horizonte, in 1998, presenting with headache, nausea, vertigo, hearing loss and tinitus on the right for the past two years. CT scan showed a tumor eroding cartilaginous and bony limits with intracranial invasion. She was submitted to multidisciplinary treatment with surgery followed by radiotherapy (6000 cG). Histology showed a ceruminous adenoid cystic carcinoma. The patient manifested a right peripherical facial palsy and had no recovery of the previous deficits. After one year from surgery she is clinically stable.

Ceruminous gland tumors are infrequent lesions of the external auditory canal (EAC). Controversy exists regarding several aspects of these tumors. In this report we presented a case of 63 years old woman with an 8-year history of a painless mass in the left EAC. Physical examination showed a skin-covered mass, occupying all its lumen. First superficial biopsy led to an initial erroneous diagnosis of papilloma. Local wide resection of the lesion was performed one month later. Histological examination revealed a lesion composed of solid nests and papillomatous and cystic glands surrounded by a hyaline sheath. Immunohistochemically, two different cell layers were demonstrated: a luminal epithelial cell layer with positive staining with cytokeratin 7 (CK7) and an outer myoepithelial cell layer, with positive staining with actin and S-100 protein. The proliferative index (Ki-67) was very low. The diagnosis was ceruminous gland adenoma. Two years after the operation, the patient is in good health and with normal ultrasound and laboratory results. We believe that conservative surgery seems to be ideal treatment in case of ceruminous adenoma.

A mixed tumor with apocrine differentiation seen in the external auditory canal of a 39 year old male is reported. The well demarcated polypoid tumor showed proliferation of elongated gland-like or duct-like structures lined by two rows of epithelial cells, occasionally accompanied by foci of keratinization. There were fat cells in the myxoid stroma, in which no chondroid elements were seen. This neoplasm is considered to have arisen from the ceruminous gland, the modified apocrine gland of the skin.

Specimens from five cases of adenoid cystic carcinoma of the external auditory canal were studied by immunohistochemical staining, and findings were compared with those from adjacent non-neoplastic tissues containing ceruminous glands. In the ceruminous gland, cytokeratin showed diffuse positive staining, while myoepithelial cells were stained for smooth muscle actin, desmin, S-100 protein and vimentin. The epithelial markers used were cytokeratin, carcinoembryonic antigen and secretory component and stained at various densities the inner cells of the tubular component and duct-lining cells in the cribriform component of tumor tissues. In contrast, the muscular markers, smooth muscle actin and desmin, and the mesenchymal marker, vimentin, were positive in the outer cells of the tubular component and in the cyst-lining cells of the cribriform component. S-100 protein immunoreactivity showed paradoxical results; positive findings occurred in the myoepithelial cells of the ceruminous glands and in the inner cells of the tubular component and duct-lining cells of the cribriform component of the tumor. Present findings demonstrate that adenoid cystic carcinoma of the external auditory canal had dual epithelial and myoepithelial differentiation and can mimic the ceruminous glands of the auditory canal.

Ceruminous glands should no longer be regarded as purely apocrine glands, but as apoeccrine glands with both apocrine and eccrine modes of secretion. We present two cases of pleomorphic adenoma of ceruminous glands, among the rarest of such tumours. The use of such terms as ‘ceruminoma’ and ‘hidradenoma’ should finally be abandoned, and ‘ceruminous gland tumour’ used instead as a generic term. Classification should be based on Wetli's prototype (adenoma, pleomorphic adenoma, adenoid cystic carcinoma and adenocarcinoma), with the addition of benign eccrine cylindroma and syringocystadenoma papilliferum; the inclusion of mucoepidermoid carcinoma should await full validation. Wide local excision is necessary for all tumours, with only follow-up for histologically benign neoplasms. Malignant tumours need early aggressive surgery and radiotherapy. If marginal invasion cannot be assessed histologically, then adenoma and adenocarcinoma cannot be distinguished and we suggest that the tumour be reported as ‘of uncertain malignant potential’. Long-term studies are needed to confirm or refute the view that all ceruminous gland tumours are potentially malignant.

Ceruminous gland tumors (ceruminomas), which usually involve the external auditory canal, are rare. A case of ceruminoma invading the temporal bone and histologically proven to be papillary adenoma is presented. The tumor recurred and invaded intracranially after subtotal removal and was finally diagnosed as adenocarcinoma. The importance of early diagnosis and radical treatment is stressed.

Tumors of the ceruminous glands may involve the auricular and preauricular skin and thus should be included in the differential diagnosis of neoplasms involving these areas. A rational decision as to the management of ceruminous gland tumors depends on the precise histologic classification of these tumors and the extent of involvement. We present seven patients with tumors of the ceruminous glands: ceruminous adenoma in one, ceruminous adenocarcinoma in three, and adenoid cystic carcinoma in three. The literature is reviewed with respect to signs and symptoms, pathology, and therapy.

Human ceruminous glands have been examined for the presence of adrenergic nerves using the histofluorescence method according to Falck and Hillarp, and immunohistochemistry for the presence of peptidergic nerves. The effect of adrenaline, alpha- and beta-blockers have been tested in vivo. No adrenergic or peptidergic nerves could be seen innervating the ceruminous glands. In spite of that, the glands reacted to local administration of adrenaline. This adrenaline effect could be blocked by alpha-blockers but not by beta-blockers. The cerumnious glands seem to possess alpha-adrenergic receptors, possibly capable of reacting with circulating catecholamines.

Currently available morphometric methods provide useful information on the three-dimensional properties (such as volume, surface, etc.) of biological structures. These methods, however, do not reveal how the same structures are spatially organized within the cell. A sum of problems, which concern mainly the definition of shape and location of the sectioned structures, does not allow the three-dimensional representation of the organelle arrangement from a quantitative analysis of sections. Following a different approach, this study considers the topographic relationship between ten distinct subcellular structures: nucleus, Golgi, ribosomes, mitochondria, lysosomes, lipid droplets, secretory granules, and apical, lateral, and basal plasmalemma. The analysis of associations from 2 X 2 tables calculated for each pair of structures and the pattern of multiple associations obtained by clustering methods provide a useful description of the spatial relationship among different cell compartments. The results of the investigation carried out in parallel on seven human exocrine glands (pancreas, parotid gland, submandibular gland, lacrimal gland, ceruminous gland, ampulla of the vas deferens, and seminal vesicle) allow an immediate evaluation of the method and a comparative analysis of the cytologic organization of secreting cells of human exocrine glands.

Three patients with ceruminomata were treated by radiation therapy, surgery or a combination of both of them. One patient was treated by surgery followed by radiation treatment and then, after recurrence of the tumor, by radical surgery, and another patient treated by surgery only, are free from disease six and five years respectively. One patient treated by incomplete radiation therapy only, has had recurrence of the tumor three months later, but after a full treatment by Cobalt teletherapy is free from recurrence four months later. Surgery is considered the treatment of choice; however, radiation therapy may be indicated when the tumor, either primary or recurrent, has extended beyond limits of surgical resection, or because of distant metastases, due to the patient's general condition precluded surgery, or finally, when surgery is refused.

Tumors of ceruminous gland origin in the external auditory canal are rare in man. A case is described in which such a tumor presented as an invasive vascular temporal bone neoplasm, mimicking a glomus jugulare tumor. Light and electron microscopic study of this tumor confirmed a diagnosis of ceruminous gland adenocarcinoma. Tumors of ceruminous gland origin appear to have a distinctive clinical behavior by virtue of their unique anatomical location in the external auditory canal. Our experience with this case establishes another clinical picture characterizing the histologic type of ceruminoma designated as a ceruminous gland adenocarcinoma. We feel that the generic term "ceruminoma," with its implied histologic subgroups, is useful to the clinician when he encounters a tumor arising from the modified sweat glands of the external auditory canal.

The secretory portion of the apocrine sweat gland of the human external auditory meatus which is also called the ceruminous gland was observed by transmission and scanning electron microscopy. The secretory glandular cells contain a well developed smooth endoplasmic reticulum and Golgi apparatus. Cisternae of rough endoplasmic reticulum are often closely applied to large round mitochondria. These large mitochondria have no relationship to the secretory granules. Near the concave surface of the Golgi lamellae several tubules can be found. In these golgi-associated tubules a dark substance may accumulate to form specific large dense granules. Many less dense droplets or vacuoles may appear in these dark prosecretory granules and become liberated from their surface. Vacuoles formed in this manner then migrate to the apical cell surface and often discharge their contents into the gland lumen by the mechanism of exocytosis. Also, some of these vacuoles may be released into the lumen by the pinching off of small protrusions of cytoplasm, that is, they are released by the so-called apocrine secretory mechanism. Acid phosphatase activity was demonstrated not only in the dark prosecretory granules but also in clear vacuoles situated at the apical end of the cell and in the gland lumen. Such a histochemical finding may indicate that the secretory substance of the apocrine sweat gland may contain hydrolytic enzymes derived from lysosomes, which are the prosecretory granules of this gland, and these enzymes may play a role in dissolution and break down of the material extruded into the lumen by apocrine secretion. Apocrine secretory process of various sizes were observed on the luminal surface with the scanning electron microscope.

✓ Patients with adenocarcinoma of the ceruminous gland arising in the middle ear have a typical syndrome consisting of unilateral hearing loss, otalgia, facial paresis, and a middle-ear mass. Adjacent cranial nerves also may be affected. Some patients may have an ipsilateral cerebellar ataxia if the lesion extends into the cerebellopontine angle and compresses the cerebellar hemisphere. Obstructive hydrocephalus may occur secondary to obstruction of the aqueduct or fourth ventricle. The initial clinical findings may be those of a jugular foramen syndrome. These lesions are usually slow-growing and may be associated with a very prolonged clinical course. Although the tumors are rare, the physician should be aware of their existence if proper care is to be given.

• Primary adenocarcinoma of the middle ear is rare. It may or may not be associated with chronic suppurative otitis media. After the exclusion of a primary site elsewhere, the tumor should be managed by surgery and postoperative radiotherapy, especially if tumor excision is incomplete. We report a case in which primary papillary adenocarcinoma developed in the middle ear, possibly due to aberrant ceruminous gland elements. The findings prior to histologic examination were unusual in that they were consistent with a tumor of the glomus tympanicum or glomus jugulare. (Arch Otolaryngol101:702-705, 1975)

A case of adenoid cystic carcinoma of a ceruminous gland in the external auditory meatus, treated by local excision, is presented.

Sixteen patients with a rare tumor, adenoid cystic carcinoma (ACC) involving the external auditory canal, have been studied. Clinically, most patients complained of ear pain, often of several years duration. On physical examination, a mass or a nodule usually was identified in the ear canal. In most cases, treatment consisted of a wide surgical resection of the auditory canal and adjacent structures. Histologically, these neoplasms had the same appearance as ACC originating in salivary glands. In eight cases, the tumor was confined to the ear canal wall and unquestionably arose in this area, probably within the ceruminous glands. When incompletely excised, these lesions usually recurred locally. Nine patients had a total of 26 local recurrences. Most recurrences were found within two years of the preceding treatment, but the interval in some cases was long, ranging up to 14 years. Of the 16 patients, seven had no evidence of recurrence following surgical resection, two were living with recurrent, unresectable tumor, five had died of disease, one had died of other causes, and one was lost to follow-up. Some patients died of tumor after a prolonged clinical course with multiple recurrences. Death usually was caused by intracranial extension by the tumor, or by pulmonary metastases. Radiotherapy did not appear to cure the lesion, but probably resulted in palliation. An increased incidence of recurrent, unresectable tumor or of death from the neoplasm correlated with the following histologic features: demonstration of tumor on the lines of surgical excision, involvement of the parotid gland, extension into bone, perineural invasion and local recurrence of tumor.

Light and electron microscopic features of a case of ceruminous adenocarcinoma are presented and compared to normal ceruminous glands. A survey of the literature disclosed 4 types of ceruminoma: adenoma, adenocarcinoma, adenoid-cystic carcinoma, and mixed tumor. The pathogenesis and histologic features of each type are discussed. Because biologic activity varies with the histologic pattern, and because of the greater frequency of malignancy as compared to other cutaneous apocrine tumors, it is recommended that the generic term “ceruminoma” be retained for apocrine tumors arising in the external auditory canal.

Introduction : External auditory canal is a cul-desac. This is lined by stratified squamous epithelum which is continous distally with the skin of pinna and proximally with the epithelial covering of tympanic membrane. The skin of external auditory canal has three appendages e. g; ceruminous glands, sebaceous gland and hair. Tympanic membrane is characterized by the absence of the appendages but in the bony canal these are restricted to a few small hairs and sebaceous glands scattered along the superior wall (Maximow and Bloom, 1925. Ceruminous glands are mostly found in the cartilaginous ear canal but few of these may be found on the auricle. It is said that there are 10002000 ceruminous glands on average in each ear (Maxinmow and Bloom 1952). Histologically, the ceruminous gland is, in all respects similar with the apocrin.sweat gland of human

The medical literature in general, and the otology journals in particular, abound in studies on the etiology, classification and treatment of otitis externa, but only a few investigators have studied the physiology of the ceruminous gland (1, 2). The marked histologic resemblance between the ceruminous gland in the human ear canal and the apocrine gland in the axilla of man is well known. The apocrine gland in the axilla has recently received due attention and much has been learned of its physiology (3, 4). By reason of these studies we are now in a better position to understand some of the pathologic processes occurring in this gland (5). We felt that similar investigations into the physiologic processes of the ceruminous gland might not only illuminate the relationship of these two glands but might also provide a fresh approach to the problem of otitis externa.

Cerumen gland tumors are unusual clinical and pathological entities. Three cases seen at the San Francisco Veterans Administration Hospital from 1958 to 1969 are presented in this paper with a review of the literature on the subject. The typical clinical appearance is a skin-covered mass in the external meatus with little in the way of otologic symptoms. Histologically, adenomas, adenocarcinomas, and adenoid cystic carcinomas are seen. Adenomas are not locally aggressive, but the carcinomas exhibit a potential for local invasion and distant metastasis. The treatment of choice is wide surgical excision because of the known tendency for these lesions to recur.

Histologic study reveals that, at least morphologically, the ceruminous gland of the human external auditory canal is an apocrine sweat gland (1). It has apocrine secretory cells lining a rather large lumen which apparently acts as a reservoir to hold preformed secretion until the proper stimulus causes contraction of the myoepithelial sheath and consequent emptying of the gland. Recent studies on the physiology of the ceruminous gland have shown that adrenergic drugs such as epinephrine or nor-epinephrine can cause this gland to pour its secretion out onto the skin (2). However, to date, there has been little anatomic study of the innervation of these glands (3). Furthermore new histo-chemical technics (4) permit the demonstration of cholinergic fibers in the skin. In the present study we have shown the presence of nerve fibers about the tubules of the ceruminous gland and have indirect histochemical evidence that these fibers are adrenergic in character. METHOD Biopsies were obtained from the ear canal of four subjects, two males and two females, who were under general anesthesia for major surgery of the ear. (a) Silver staining: The modified Bielschowski stain (5) was used to demonstrate nerve fibers about the glands. Biopsy material was fixed in 10 % formalin before sectioning and deparaffmization. The sections were washed three times in distilled water and then placed in 20 % silver nitrate for one hour. After a quick rinse in distilled water, they were transferred to a 20 % solution of silver nitrate which had been filtered after adding fresh ammonium hydrate drop by drop until the precipitate dissolved. The sections were then washed two times in distilled water and transferred to neutral 10% formalin for one minute. After again washing in distilled water they were toned in gold chloride solution (1 gram of gold chloride to 500 ml. water), and then fixed in sodium thiosulfate (5 grams in 100 ml. water) for one to two minutes. Finally the sections were dehydrated and mounted. (b) Choli nest erase staining: Other excised skin specimens were stored in the deep freeze ( - 1 to - 2°C.) until used (within 72 hours). Frozen sections were cut at 10 micra and placed on glass slides. These sections were then carried through the histochemical method of Koelle, using the latest modifications de- 219 220 THE JOURNAL OF INVESTIGATIVE DERMATOLOGY scribed for the localization of specific and non-specific cholinesterase activity (3). This method provides four sets of slides for the identification of the enzymes as follows : Slides A, which reveal sites of both specific and non-specific cholinesterase activity. Sections of this group were incubated for 45, 75 or 120 minutes at 37.5°C. in a medium containing 0.004 M acetylthiocholine, 0.004 M copper glycinate, 0.04 M MgCl2, 0.01 M sodium maleate buffer (pH 6.0) and 24% Na2S04 saturated with copper thiocholine. Under these conditions, thiocholine which is liberated at the sites of cholinesterase activity as a result of enzymatic hydrolysis of the substrate, is precipitated as a white copper mercaptide. This is subsequently converted to black copper sulfide by immersion in ammonium sulfide. Slides B, which stain sites of specific cholinesterase activity alone. This was accomplished by preliminary incubation of these sections in 1010 M diiso-propylfluorophosphate (DFP) in 24% Na2S04 solution at room temperature for 30 minutes. At this concentration, DFP selectively inhibits non-specific cholinesterase activity. The slides were then treated as were slides A. Slides C, which demonstrate sites of non-specific cholinesterase activity alone. These sections were incubated in a medium similar to that for slides A, but containing 0.004 M butrylthiocholine as substrate for the non-specific cholinesterase. Slides D, for the detection of other esterases and the non-enzymatic adsorption of copper ions. These sections were first treated wTith DFP, then incubated with butrylthiocholine. Fig. 1. Argyrophilic nerve fibers supplying the secretory tubules of a ceruminous gland in man. Note numerous fine beaded dark lines which are the terminal nerve fibrillae. A larger myelinated fiber is seen in the central part of the picture. Magnification 1920X. ADRENERGIC INNERVATION OF APOCRINE GLAND OF HUMAN EAR CANAL 221 Alternate sections were lightly counterstained with eosin or with hematoxylin and eosin. RESULTS On examination of the slides stained with silver, one can discern fine argyro-philic fibers around many of the ceruminous gland tubules. These are interpreted as nerve fibers. The histologic sections which have been stained for specific and non-specific cholinesterase activity reveal no evidence of these enzymes around the tubules of the ceruminous glands. Control specimens of skin from the arm showed abundant specific cholinesterase staining about the eccrine sweat gland tubules. DISCUSSION The slides that have been stained with silver leave little doubt that the ceruminous glands are supplied by nerves. The physiologic data would suggest that these nerves belong to the autonomic nervous system and are motor fibers. The absence of cholinesterase around the tubules of the ceruminous glands indicates that the nerves supplying it are not cholinergic. This is in agreement with the finding that acetylcholine is not an effective stimulus for the ceruminous gland (2). We are therefore led to postulate that fibers of the autonomic nervous system innervate the ceruminous gland, and that these fibers are adrenergic in nature. This is the same finding as for the axillary apocrine gland. SUMMARY Special histologic studies.have revealed that there are nerve fibers coursing about the human ceruminous glands, and that they are probably adrenergic motor fibers of the autonomic nervous system.

Glandular neoplasms represented 14% of primary tumors of the external and middle ear at the University of Minnesota. Although the collective term "ceruminoma" has been used in the past, four distinctive histopathologic patterns were recognized among our 12 cases: adenoma (four cases), pleomorphic adenoma (one case), adenoid cystic carcinoma (two cases) and adenocarcinoma (five cases). The prognosis correlated with these subgroups. A thorough review of the English literature also tended to support the rationale for the subclassification of so-called ceruminomas. The prevailing histogenetic view is that these tumors are derived from the modified apocrine glands of the auditory canal, the ceruminous glands. In some instances, these tumors may originate from ectopic salivary gland tissue.

Neoplasms in the external auditory canal (EAC) of ceruminous gland origin have been generally classified under the title of ceruminoma, which is inaccurate and misleading. There have emerged four distinct types of ceruminous gland tumors of the EAC. They are 1. ceruminous adenoma, 2. adenoid-cystic carcinoma, 3. ceruminous adenocarcinoma, and 4. pleomorphic adenoma (mixed tumor). The natural course and clinical approach to these tumors can be determined by accurate histopathologic evaluation. This paper presents 10 cases of tumors of glandular origin in the EAC, 4 cases being ceruminous adenomas, 3 cases being adenoid-cystic carcinomas, 2 cases being ceruminous adenocarcinoma, and 1 case of pleomorphic adenoma (mixed tumor). In reviewing these cases as well as those in the literature, a number of recommendations are suggested: 1. Identifying a tumor of the glandular structures of the EAC solely as a ceruminoma is no longer acceptable without accompanying histologic specificity. 2. Early wide excisional biopsy is imperative for diagnosis. 3. The signs and symptoms of the tumor do not always correlate with the histopathologic diagnosis and subsequent clinical behavior of these tumors. 4. Ceruminous adenoma and pleomorphic adenoma are benign tumors and are best treated only by wide local excision. 5. Adenoid-cystic carcinoma and ceruminous gland adenocarcinoma are pernicious, malignant tumors which are best treated, in general, by an initial aggressive wide en bloc surgical resection or, if there is extension to the middle ear and temporal bone, by resection of the temporal bone and contiguous structures. 6. Postoperative irradiation has an essential role in managing these malignant tumors. 7. Five year survival rates for the malignant tumors do not reflect the biological behavior pattern of "late" local and distant recurrence and metastasis.

A case of extramammary Paget's disease of the external ear canal in association with ceruminous gland carcinoma is presented. Extramammary Paget's disease is not uncommonly seen in regions where apocrine glands are prevalent, with or without underlying apocrine gland carcinoma. This is the first case, to our knowledge, of this association in the external ear canal.

Ceruminous gland tumours are uncommon in the dog and this paper reports a case of two such tumours which arose in either ear of a 12 year old male long-haired Dachshund. Histologically, one tumour was a ceruminous adenoma and the other a rare ceruminous mixed tumour of borderline malignancy.

A man 44 years of age had a ceruminous gland tumor originating in the external auditory canal. A follow-up of 12 years showed the deliberate invasive nature of the tumor, which invaded the petrous bone and actually penetrated intracranially. The tumor was repeatedly treated by surgical excision and irradiation. At present, the patient has been in good condition for two successive years. As far as we are aware, only two comparable case histories have been reported in the literature. The present case may illustrate the fact that a tumor resembling the normal ceruminous gland should be considered as potentially malignant. Consequently, the term "ceruminoma" should be avoided.

Thirty-seven cases of ceruminous gland tumors of the external auditory-canal are presented. These are rare tumors, each of which has different clinical characteristics. Six adenomas are reported which are benign and require only local excision for long-term cure. Two muco-epidermoid carcinomas, a type not previously reported, are presented. The muco-epidermoid carcinoma tends to iecur locally and radical excision is necessary for control. The most common glandular tumor of the external auditory canal is the adenoid cystic carcinoma. Twenty-four are reported. Pain is the hallmark of this tumor. The long clinical course ultimately results in death if the tumor is not radically removed at the earliest possible time. Radiation is ineffective. Treatment recommended is (1) wide excision of the external auditory canal, (2) extensive radical mastoidec-tomy, and (3) total parotidectomy and mandibular condylectomy. Five cases of adenocarcinoma are presented. Four were dead from local invasion and distant metastasis within four years, and the fifth was lost to follow-up. Careful histologie evaluation and classification of the type of tumor is necessary to predict the natural history and select the proper treatment. Local excision is curative for the benign adenoma. For the three types of carcinoma described, the surgeon must not hesitate to do the radical operation for the early lesion, because it is in the early stages that the opportunity to produce the cure exists.

THE LINING of the external acoustic meatus is lined with skin that is continuous with the auricle. The part of this skin covering the cartilaginous portion of the meatus (8 mm long) contains hair follicles, sebacous glands, and modified sweat glands or ceruminous glands. In the longer bony portion, the aforementioned skin structures are absent. Arising from the narrow confines of the cartilaginous portion and corresponding histologically to the ceruminous glands, a special form of tumor, the "ceruminoma," has been described. Relatively common in lower animals, especially the dog and the cat, tumors of ceruminal gland origin are rare in man. This report is a clinicopathological assessment of ceruminomata, based on a review of the literature 1-6 and experience with two previously unreported cases of ceruminoma treated at the University of Michigan Medical Center. Report of Cases Case1.—A 71-year-old white woman was first seen at the University of Michigan