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American Cocker Spaniels (ACSs) develop aural ceruminous gland hyperplasia and ectasia more often than dogs of other breeds. Data on the cause and development of these breed characteristic histopathological changes are lacking. We performed video-otoscopic examinations and dermatological work-up on 28 ACSs, obtained aural biopsies from each dog and assessed the statistical associations between the presence of ceruminous gland hyperplasia and ectasia and disease history, clinical or microbiological findings and underlying cause of otitis externa (OE). Histological lesions of ceruminous gland hyperplasia and ectasia were observed in aural biopsies from 6/13 clinically healthy ears and 13/15 ears with OE from 19/28 examined dogs. Nine of 28 dogs had histologically normal ceruminous glands (odds ratio [OR] 6.2, 95% confidence interval [CI] 1.1-36.6). Bacterial growth in microbiological culture of aural exudate (OR 14.1, 95% CI 2.1-95.3) was associated with ceruminous glandular changes, whereas previous history of OE, cutaneous findings or underlying allergies were not. Pedigree analysis and a genome-wide association study (GWAS) were performed on 18 affected and eight unaffected dogs based on histopathological diagnosis. While the GWAS indicated a tentative, but not statistically significant, association of ceruminous gland hyperplasia and ectasia with chromosome 31, a larger cohort is needed to confirm this preliminary result. Based on our results, ceruminous gland hyperplasia and ectasia may also precede clinical signs of OE in ACSs and a genetic aetiological component is likely Further studies with larger cohorts are warranted to verify our preliminary results. (C) 2021 The Authors. Published by Elsevier Ltd.

Ceruminous gland adenocarcinomas are uncommon malignant neoplasms arising from the ceruminal glands of the external ear canal. They include three variants: ceruminous adenocarcinoma (not otherwise specified, NOS), ceruminous adenoid cystic carcinoma, and ceruminous mucoepidermoid carcinoma. The clinicopathological details of these neoplasms have been described; however, due to their scarcity, their cytological features in humans have not been documented before. The objective of this study was to investigate the cytological, histological, and immunocytochemical features of a ceruminous gland adenocarcinoma with pleural effusion. We performed effusion cytology on a 57-year-old man who was diagnosed with ceruminous adenocarcinoma (NOS) 8 months earlier and found pleural metastases. The cytology revealed features similar to those seen via tissue pathology, such as irregular glandular architecture with dual cell populations and a solid pattern of tumour cells. Although ceruminous adenocarcinoma (NOS) is rare, recognising its cytology is important to eliminate it as a differential diagnosis.

Ceruminous adenocarcinoma is a malignant subtype of ceruminoma. Ceruminous gland tumors of the external auditory canal (EAC are rare neoplasm, and less than 150 cases have been reported to date. These tumors encompass a wide variety of histological presentations with different malignant potential. A 51-year-old woman presented with one month history of a right side otalgia. Physical examination showed an irregular surface elevation on the anterior portion of the right EAC and a normal tympanic membrane. Histologic examination revealed adenoid cystic carcinoma. After radiation therapy, lateral temporal bone resection, total parotidectomy and split thickness skin graft were performed. The diagnosis was confirmed as a ceruminous adenocarcinoma. At the last follow-up at 10 months, there was no evidence of recurrence. Ceruminous adenocarcinoma of the EAC is a rare malignant neoplasm and as definitive diagnosis is sometimes not provided until surgery, a biopsy must be performed in every EAC lesion. Combined radical surgery and radiation is the mainstay of therapy. (Korean J Otolaryngol 2004;47:1311-4)

Given the limited source of human external auditory canal (EAC) skin, animal experiments remain an important approach for studying functional EAC reconstruction. However, differences between humans and animals in terms of the general EAC structure, histological characteristics of EAC skin, and cell markers of its specific glands in cartilaginous EAC skin remain unknown. We compared the characteristics of the EAC between humans and large animals, as a basis for appropriate animal model selection. Temporal bone computed tomography was used to compare the EACs of humans, goats, pigs, and dogs. EAC skin samples were harvested and their histological characteristics evaluated. The skin's ultrastructure and the histological structure of specific glands and cell markers related to cell phenotype and function were further identified. The EAC structure in goats was similar to that in humans in terms of diameter, length, and cartilaginous segment ratio of the EAC, while that of pigs and dogs differed markedly. Furthermore, histological evaluation showed that there were abundant ceruminous and sebaceous glands in the goat's cartilaginous skin, while dogs and pigs showed notably fewer of these glands in cartilaginous skin than humans. Nevertheless, ceruminous glands in all species studied showed similar expression of cell biomarkers and secretion function. Goats might have advantages in terms of surgery and reconstruction of the functional EAC skin compared to dogs and pigs and can be a useful candidate for ceruminous gland cell sources.

Ceruminous glands are modified apocrine glands located in the external auditory canal (EAC). Neoplastic lesions arising from these glands are rare in humans and constitute a major differential diagnosis for glandular neoplasms of the EAC. Due to anatomic restrictions, benign and malignant neoplasms present with similar symptoms and to some extent even comparable radiologic features, particularly when the tumors are localized. Biopsies are frequently limited by small size, fragmentation and improper anatomic and architectural orientation, thereby hampering our ability to appreciate the relationship of peripheral edges of the tumor to the surrounding tissue. Benign and malignant tumors may also have overlapping histomorphologic features, which further magnifies the challenges in accurate diagnosis and management strategies. This article summarizes the salient clinical, radiologic and histologic features of common ceruminous gland tumors, in addition to discussing features that can aid in differentiating ceruminous tumors from other EAC tumors and to distinguish benign from malignant entities.

Ceruminous adenoma (CA) is a rare, benign tumor of the ceruminous gland found in the cartilaginous part of the external auditory canal (EAC). The tumor is diagnosed on histopathology and shows a characteristic dual population of luminal epithelial cells and basal myoepithelial cells. However, CA can be diagnosed on fine-needle aspiration cytology (FNAC) prior to surgery and the cytopathologist should be well aware of its cytological findings to avoid any misdiagnosis. The tumor shows an excellent prognosis with possible recurrence and malignant transformation. The present case emphasizes the cytological features of CA, which have been scantily described in the literature and highlights the role of cytopathologists in preoperative diagnosis.

The 2017 fourth edition of the World Health Organization Classification of Tumours, specifically as it relates to the ear (Chap. 9), has several changes. Importantly, the number of entities has been significantly reduced by omitting tumors or lesions if they do not occur exclusively or predominantly at this site or if they are discussed in detail elsewhere in the book. These entities include: embryonal rhabdomyosarcoma, osteoma, exostosis, angiolymphoid hyperplasia with eosinophilia, Schneiderian papilloma, inverted papilloma, lipoma of the internal auditory canal, hemangioma, hematolymphoid tumors, and secondary tumors. Paraganglioma was included in the neck chapter. New entries include otosclerosis and cholesteatoma, while refinements to nomenclature, classification and criteria were incorporated into the ceruminous gland tumors and epithelial tumors of the middle and inner ear. Specifically, the middle and inner ear were combined, as practical limitations of origin and imaging make a definitive separation artificial. The classification reflects the state of current understanding for these uncommon entities, with this update only highlighting selected entities that were the most significantly changed.

The present study was designed to characterize and diagnose different spontaneously occurring canine neoplasms using conventional and advanced diagnostic techniques. Fifty eight tumour samples were collected from dogs irrespective of their sex, breed, age and were grouped in three categories viz. mammary, skin and visceral tumours. Location wise overall occurrence of tumours was highest in skin (50%) followed by visceral organs (25.86%) and mammary gland (24.13%). Cytological diagnosis from 30 freshly incised tissues revealed 14 benign and 16 malignant cases. Histopathological diagnosis (n=58) evinced 1 (1.72%) benign mammary tumour (carcinoma-in situ); 13 (22.41%) malignant mammary tumours (mixed carcinoma-4, tubular carcinoma-4, tub- ulopapillary carcinoma-3, comedocarcinoma-1 and poorly differentiated carcinoma-1); 12 (20.68%) benign skin tumours (perianal gland adenoma-5, trichoblastoma-4, trich of olliculoma-1, tricholemmoma-1 and haemangioma-1); 17 (29.31%) malignant skin tumours (fibrosarcoma-6, mast cell tumour-3, apocrine adenocarcinoma-3, haemangiopericytoma-1, perianal gland adenocarcinoma-1, chondrosarcoma-1, melanoma-1, poorly differentiated carcinoma-1); 9 (15.51%) benign visceral tumours (oral papilloma-4, sertoli cell tumour-1, angioleiomyoma-1, ceruminous gland adenoma-1, ameloblastic fibro-odontoma-1, haemangioma-1); and 6 (10.34%) malignant visceral tumours (haemangiosarcoma-4, round cell sarcoma-1 and vaginal haemangiopericytoma-1). Immunohistochemistry was performed in 30 tumours for various molecular markers, viz. F8, SMA, Desmin, S-100, HER2 and ER. All mammary tumours were found negative for ER and HER2, whereas fibrosarcoma and haemangiosarcoma were found positive for SMA and F8, respectively. Real time PCR was employed to study the overexpression of ERBB2 gene in tumour tissues. Over expression of ERB-B2 was found only in skin fibrosarcoma (10 fold) and apocrine adenocarcinoma (112 fold).

A case of aural carcinoma with chondroid metaplasia at metastatic foci in an 8-year-old male pug is described. Multiple metastases in both lungs and the right submandibular, parotid, retropharyngeal, cervical and prescapular lymph nodes were detected. Histologically, the skin of the right ear canal appeared to be diffusely infiltrated by cords and nests of neoplastic epithelial cells, showing multifocal contiguity with the overlying hyperplastic squamous epithelium. Most of the carcinomatous cells were arranged in a glandular-like pattern, with formation of lumens containing epithelial cells attached to the peripheral cell layer by elongated intercellular bridges. Scattered foci of keratinization with central accumulations of compact, laminated keratin were also observed, and histochemical stains failed to detect mucinous secretory material. Even though histological and histochemical findings were compatible with a diagnosis of acantholytic squamous cell carcinoma, CAM5.2 immunostaining was detectable in the majority, although not all, neoplastic cells, confirming a diagnosis of poorly differentiated ceruminous gland carcinoma. Pulmonary metastatic nodules revealed multifocal areas of cartilaginous metaplasia with apparent transition of carcinomatous cells to chondroid cells, showing nuclear atypia and focal cytokeratin immunostaining. Carcinomatous cells surrounding chondroid areas also revealed focal vimentin and S100 immunoreactivity. Histological evidence of transition between the two components, as well as the presence of intermediate cells displaying both epithelial and mesenchymal immunohistochemical features, strongly indicated a final diagnosis of carcinosarcoma, in which chondrosarcomatous elements were derived from carcinoma cells.

Background Ceruminal gland carcinomas are rare neoplasms confined to the skin lining the cartilaginous part of the external auditory canal. Design Retrospective. Results The patients included 11 men and 6 women, aged 33–82 years (mean, 59.5 years). Patients presented clinically with a mass of the outer half of the external auditory canal (n = 14), hearing changes (n = 5), drainage (n = 4), or paralysis of the facial nerve (n = 3). The polypoid masses ranged in size from 0.5 to 3 cm in greatest dimension (mean, 1.8 cm). Histologically, the tumors demonstrated a solid to cystic pattern, composed of an infiltrating glandular to cribriform arrangement of epithelial cells. Histologic features included a dual cell population (although not the dominant histology), increased cellularity, moderate to severe nuclear pleomorphism, irregular nucleoli, increased mitotic figures (mean, 3/10 HPF), including atypical forms, and tumor necrosis (n = 2). Tumors were divided into three types of adenocarcinoma based on pattern of growth and cell type (ceruminous, NOS [n = 12], adenoid cystic [n = 4], mucoepidermoid [n = 1]). CK7 and CD117 highlighted the luminal cells, while S1-00 protein showed a predilection for the basal cells of ceruminous and adenoid cystic carcinomas. Metastatic adenocarcinoma or direct extension from salivary gland neoplasms are the principle differential considerations. Surgical resection was used in all patients with radiation used in four patients. Eleven patients were alive or had died of unrelated causes without evidence of disease (mean, 11.2 years); six patients had died with disease (mean, 4.9 years), all of whom had developed local recurrence. Conclusion Ceruminous-type carcinomas, with the exception of ceruminous mucoepidermoid carcinoma, all demonstrated a dual cell population of basal myoepithelial-type cells and luminal apocrine cells. The specific histologic sub-type does not influence the long-term patient outcome.

A 6-year-old, castrated male Shiba-inu displayed a mass showing invasive growth in the external auditory canal of the left ear. Histologically, the tumor mass predominantly comprised spindle-shaped neoplastic cells, arranged in solid nests admixed with irregular tubulo-acinar structures, lined by cuboidal to polygonal neoplastic cells. Neoplastic cells had extensively infiltrated into deep tissues. No bone formation or chondroid matrix was observed in the tumor stroma. Both types of neoplastic cells showed nuclear atypia and high mitotic activities. Luminal epithelial elements were immunohistochemically positive for pan-cytokeratin and cytokeratin 8. Spindle-shaped cells showed intense immunoreactivity for vimentin, pan-cytokeratin and α-smooth muscle actin, indicating that spindle-shaped cells retained the original histological characteristics of myoepithelial cells. These findings were consistent with a diagnosis of ceruminous gland carcinoma with malignant proliferation of acinar epithelial and myoepithelial tumor cells, which rarely occurs in dogs. Following resection with wide surgical margins, no recurrence or metastases have been observed as of 6 months postoperatively.

In this study, we examined the prevalence, pathology, and epidemiology of tumors in free-ranging island foxes occurring on three islands in the California Channel Islands, USA. We found a remarkably high prevalence of ceruminous gland tumors in endangered foxes (Urocyon littoralis catalinae) occurring on Santa Catalina Island (SCA)--48.9% of the dead foxes examined from 2001-2008 had tumors in their ears, and tumors were found in 52.2% of randomly-selected mature (≥ 4 years) foxes captured in 2007-2008, representing one of the highest prevalences of tumors ever documented in a wildlife population. In contrast, no tumors were detected in foxes from San Nicolas Island or San Clemente Island, although ear mites (Otodectes cynotis), a predisposing factor for ceruminous gland tumors in dogs and cats, were highly prevalent on all three islands. On SCA, otitis externa secondary to ear mite infection was highly correlated with ceruminous gland hyperplasia (CGH), and tumors were significantly associated with the severity of CGH, ceruminous gland dysplasia, and age group (older foxes). We propose a conceptual model for the formation of ceruminous gland tumors in foxes on SCA that is based on persistent, ubiquitous infection with ear mites, and an innate, over exuberant inflammatory and hyperplastic response of SCA foxes to these mites. Foxes on SCA are now opportunistically treated with acaricides in an attempt to reduce mite infections and the morbidity and mortality associated with this highly prevalent tumor.

The ceruminous glands in the skin of the human external auditory canal are modified apocrine glands, which, together with sebaceous glands, produce the cerumen, the ear wax. Cerumen plays an important role in the protection of the ear canal against physical damage and microbial invasion. We studied the morphology of the glandular cells by light and electronmicroscopy. Antimicrobial and cytoskeletal components of the ceruminous glands were investigated by immunohistochemical methods. Numerous antimicrobial proteins and peptides are present in the ceruminous glandular cells: beta-defensin-1, beta-defensin-2, cathelicidin, lysozyme, lactoferrin, MUC1, secretory component of IgA. These data indicate a crucial role in the innate host defense against diverse pathogens. The apocrine secretion mechanism is a special mode of secretion by which the apical part of the cell cytoplasm surrounded by a membrane is pinched off. We could show that the presence of actin filaments, CK 19 and CK 7, seems to play a role in the pinching-off mechanism. Finally, we showed the secretion of lipid vesicles from the ceruminous gland. We could extend the number of detected antimicrobial peptides and proteins in human ceruminous glandular cells that protect the surface of the external auditory meatus. In addition, we detected proteins involved in the apocrine secretion mode of the ceruminous gland.

BACKGROUND: The cytologic diagnosis of ear canal tumors is difficult or impossible by swab alone because cell exfoliation may be poor and neoplastic cells may be masked by associated inflammation. Fine-needle biopsy (FNB) can be used to obtain a higher yield of cells for diagnosis. OBJECTIVE: The purpose of this study was to assess the efficacy and diagnostic value of FNB and cytologic examination in providing an accurate diagnosis of masses growing in the external ear canal of cats. METHODS: Cytologic specimens from masses in the external ear canal, taken under inhaled, general anesthesia, were classified into 4 groups: 1) ceruminous gland hyperplasia or adenoma, 2) ceruminous gland adenocarcinoma, 3) inflammatory polyps, and 4) other neoplastic and non-neoplastic masses. Cytopathologic diagnoses were compared with the final histopathologic diagnoses, and indices of diagnostic test accuracy (sensitivity, specificity, likelihood ratios, diagnostic-odds ratios) were calculated. RESULTS: Twenty-seven masses (from 25 cats, including 2 cats affected bilaterally) were included in the study. The results showed good correspondence between cytologic and histologic diagnoses with an overall agreement index (kappa) of.74, a diagnostic odds ratio of 22, and 100% (27/27) agreement in the diagnosis of inflammatory polyps versus neoplasia (both benign and malignant). CONCLUSIONS: FNB cytopathology of external ear masses in the cat was sufficiently accurate for distinguishing inflammatory polyps from neoplasia. For differentiation of benign proliferation and malignant neoplasia, however, histopathologic confirmation is recommended.

Background: Ceruminous gland neoplasms are rare neoplasms. To date, a large clinicopathologic study of benign ceruminous gland neoplasms has not been reported. Design: Forty-one cases of ceruminous gland adenomas diagnosed between 1970 and 2000 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemical analysis was performed (n = 21), and patient follow-up was obtained (n = 40). Results: The patients included 22 men and 19 women, 24 to 85 years of age (mean, 54.2 years). Patients presented clinically with a painless mass of the outer half of the external auditory canal (n = 33) or with hearing changes (n = 11). Symptoms were present for an average of 16.3 months. The polypoid masses affected the external auditory canal only and ranged in size from 0.4 to 2 cm in greatest dimension (mean, 1.1 cm). Histologically, the tumors demonstrated glands and small cysts lined by a tubuloglandular proliferation of inner ceruminous cells (cerumen-secreting epithelium with decapitation secretion) subtended by a spindled to cuboidal myoepithelial layer. A hyalinized stroma created an infiltrative pattern of growth; surface involvement (n = 8) was seen. Tumors were divided into ceruminous adenoma (n = 36), ceruminous pleomorphic adenoma (n = 4), and syringocystadenoma papilliferum (n = 1) types. The luminal cells were strongly and diffusely immunoreactive with CK7, while the basal cells were highlighted with CK5/6, S-100 protein, and p63. CDI 17 highlighted the luminal cells preferentially. The proliferation markers revealed a low index. Adenocarcinoma and middle ear adenoma are the principal differential consideration. Surgical excision was used in all patients. Four patients developed a recurrence due to incomplete excision. All patients were without evidence of disease at the last follow-up: alive (n = 28, mean 16.3 years) or dead (n = 12, mean 11.8 years). Conclusion: Ceruminous gland adenomas are the most common external auditory canal tumors. They demonstrate a dual cell population of basal myoepithelial-type cells and luminal ceruminous (ceruminal) cells. Cerumen pigment, CK7, and p63 can help to distinguish this tumor from other neoplasms that occur in the region. Complete surgical excision results in an excellent long-term clinical outcome.

Objective—To compare pathologic changes of the horizontal ear canal associated with chronic severe otitis externa between Cocker Spaniels and dogs of other breeds. Design—Retrospective study. Animals—80 dogs with severe otitis externa that required total ear canal ablation with lateral bulla osteotomy. Procedure—Medical records were reviewed for breed, sex, and age at time of surgery. Histologic specimens from the horizontal ear canal were evaluated by a single examiner for overall tissue response pattern and scored for sebaceous gland hyperplasia, ceruminous gland hyperplasia, ceruminous gland ectasia, fibrosis, pigment-laden macrophages, and osseous metaplasia. Results—48 of 80 (60%) dogs were Cocker Spaniels. Thirty-five of 48 (72.9%) Cocker Spaniels had a predominately ceruminous tissue response pattern; only 9 of 32 (28.1%) dogs of other breeds had the same pattern. Other breeds most commonly had a pattern dominated by fibrosis (n = 13 [40.6%]); fibrosis was the predominant pattern in only 4 of 48 (8.3%) Cocker Spaniels. Discriminant analysis and K-means clustering of 4 histopathologic criteria correctly classified 75% of the dogs as Cocker Spaniels or all other breeds. Conclusions and Clinical Relevance—Cocker Spaniels are at increased risk for chronic severe otitis externa requiring total ear canal ablation with lateral bulla osteotomy, indicating that earlier and more aggressive management of the primary otitis externa and secondary inflammation is warranted in this breed. Cocker Spaniels with chronic severe otitis externa have distinct differences in pathologic characteristics of the horizontal ear canal, compared with other breeds. (J Am Vet Med Assoc 2002;221: 1000–1006)

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.

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.

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.

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.

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.

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.

• 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.

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.

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.