Ceruminous adenocarcinoma: A rare tumor of the external auditory canal

We report two cases of high-grade ceruminous adenocarcinoma, one presenting as a crusted, exophytic skin lesion encircling the lobule of the left auricle, a previously unreported presentation for this entity. Ceruminous adenocarcinoma is a malignant subtype of ceruminoma. The term "ceruminoma" embraces a heterogeneous group of glandular tumours of the external auditory canal (EAC) that vary markedly according to histology, clinical behaviour, and prognosis. We review the pathology, epidemiology, clinical presentation, recommended investigations, and approach to treatment for ceruminous adenocarcinoma.

Case Reports

Case 1

A 60-year-old woman presented to the otolaryngology clinic with a nodule of 2 years duration in the left preauricular area. She reported no symptoms associated with the lesion, until the preceding 6 months, when she noted crusting, tenderness, and numbness in the lobule of the left ear.

Figure 1

Figure 2

Physical examination revealed a crusted, exophytic, 3-cm mass extending anteriorly and posteriorly around the lobule of the left ear. Otoscopic examination of the external auditory canal and tympanic membrane was normal bilaterally. Facial motor and sensory functions were intact, except for paraesthesia of the left lobule on light touch testing. Oral cavity, oropharynx, larynx, neck, and thyroid examinations were normal. Pulmonary, cardiac, and abdominal examinations were also unremarkable.

Past medical history was significant for hypertension, hypercholesterolemia, non-insulin-dependent diabetes, recovered stroke, hypothyroidism, panic attacks, and major depression. She reported heavy use of alcohol and tobacco.

Open biopsy of the lesion suggested a poorly differentiated adenocarcinoma, possibly of salivary origin. As the patient refused intravenous contrast, nonenhanced computed tomography (CT) of the neck confirmed a mass in the superficial aspect of the left parotid gland, with infiltration of the subcutaneous fat, skin, and adjacent lobules. There was no evidence of neck lymphadenopathy or osseous destruction (Fig. 1).

The patient underwent superficial parotidectomy, excision of preauricular skin, partial auriculectomy, and functional neck dissection at levels II and III. The patient received postoperative radiotherapy.

Histology revealed a poorly differentiated adenocarcinoma involving the skin and subcutaneous tissues surrounding the lobule. The tumour ulcerated the perilobular skin, invaded the parotid gland, and undermined the skin of the proximal external auditory canal. There was extensive perineural and lymphatic/vascular space invasion. The malignant cells were arranged as irregular glands, as small nests, or in single file. They showed marked nuclear pleomorphism, with frequent mitoses and areas of confluent tumour necrosis. There was a dense desmoplastic response. Many of the tumour cells were noted to have abundant eosinophilic cytoplasm with gland formation. The tumour cells appeared to be of apocrine differentiation, and this was confirmed by the presence of apical snouts in some of the cells. The findings were consistent with a diagnosis of high-grade ceruminous adenocarcinoma (Figs. 2 and 3).

Case 2

A 65-year-old man presented with a 15-month history of recurrent pain in the left ear, complicated by intermittent vertigo and progressive left-sided hearing loss over the preceding 12 months.

Past medical history was significant for a recovered left-sided stroke, left-sided Bell's palsy that resulted in facial paralysis, and hypercholesterolemia.

Physical examination of the left external auditory canal revealed a discharge of foul-smelling serous fluid and a nontender nodule arising from the posteroinferior wall. The left tympanic membrane and right ear examination were normal. There was no palpable cervical lymphadenopathy. Examination of the nose, oral cavity, hypopharynx, and larynx was unremarkable. Other than previous idiopathic, left-sided Bell's palsy, examination of cranial nerves and cerebellar function was normal.

Biopsy of the nodule revealed an adenocarcinoma undermining the squamous epithelium lining the external auditory canal, with focal ulceration. The tumour was composed of individual or fused glands with small areas of necrosis. The tumour cells had abundant granular eosinophilic cytoplasm and showed occasional apical snouts or blebs, indicating decapitation-type secretion and consistent with cells of apocrine derivation. There were moderate nuclear pleomorphism and occasional mitoses. The surrounding tissue was desmoplastic with mixed acute and chronic inflammation. Overall, the histologic features were in keeping with a high-grade ceruminous adenocarcinoma.

Figure 3

Audiologic assessment revealed a profound leftsided sensorineural hearing loss. Magnetic resonance imaging of the head revealed an enhancing, infiltrative lesion involving the petrous bone, areas of the temporal squama, and the superficial and deep parotid glands. The lesion bulged anteriorly into the temporomandibular joint and posteriorly into the posterior fossa as an extradural mass. Involvement of the jugular bulb, distal sigmoid sinus. and foramen ovale was noted.

Because of the extensive involvement of the temporal bone, the patient was judged inoperable. He underwent a palliative course of radiotherapy and received only sympatomatic pain treatment with acetaminophen with 30mg codeine thereafter. At the 1-year follow-up, invasion of the left middle ear was confirmed by biopsy. At the 2year follow-up, the patient suffered partial left vocal cord paralysis secondary to tumour impingement of the vagus nerve and was treated with left thyroplasty with moderate success. Computed tomography at this time showed a marked destructive process of the left middle ear with extension into the posterior cerebral fossa, internal auditory canal, proximal internal artery canal, left margin of the foramen magnum, occipital condyle, and hypoglossal canal. The patient was lost to follow-up.

Discussion

The term "ceruminoma" encompasses a group of tumours of the EAC, which, despite the prognostic implications of the suffix -oma, may or may not exhibit benign clinical behaviour. A clinically more relevant classification based on light and electronic microscopy, clinical behaviour, and response to therapy has resulted in the division of the group "ceruminoma" into four categories: (1) ceruminous adenoma, (2) ceruminal gland pleomorphic adenoma, (3) ceruminal gland adenoid cystic carcinoma, and (4) ceruminous adenocarcinoma.1 This system is in keeping with conventional nomenclature, wherein adenoma describes benign and carcinoma malignant behaviour and facilitates selection of proper therapy.2 A fifth entity not adequately defined by these categories was later described: mucoepidermoid carcinoma of the ceruminal gland.3 The term "ceruminoma" thus denotes a heterogeneous group of entities that varies markedly in histology, clinical behaviour, and prognosis.

Ceruminomas are rare; they represented only 13% of tumours in one series of 92 primary neoplasms of the external and middle ear.2 As of 1995, at most 100 histologically confirmed cases of ceruminoma were reported in the English literature.4 Malignant tumours outnumber benign 2.5 to 1, with an average presenting age of 44 years for malignant and 57 years for benign growths. Ceruminomas affect both sexes equally.' Adenoid cystic carcinoma is the most common type of ceruminoma, followed by ceruminous adenoma, pleomorphic adenoma, adenocarcinoma, and mucoepidermoid carcinomas The cartilagenous EAC is the usual primary site for these tumours; however, cases of ceruminoma arising from the osseous canal and the middle ear have been reported.6,7 The rarity of this tumour and the consequent lack of meaningful experience by most otolaryngologists in its diagnosis and management make this topic worthy of review.

Ceruminous adenocarcinoma can be classified as low or high grade depending on the degree of cytologic and architectural atypia.4,8 Retention of features of normal ceruminous gland, mild nuclear pleomorphism, and few mitotic figures typify low-grade adenocarcinomas. High-grade adenocarcinomas extensively infiltrate the surrounding tissues as irregular glands and sheets of overtly malignant cells. They show marked nuclear pleomorphism and abundant mitotic figures and may exhibit little or no evidence of apocrine derivation.8 Ceruminous adenocarcinomas may contain foci of adenoid cystic carcinoma or other tumour patterns.4 It is of interest that a lack of glandular differentiation in high-grade neoplasms may obscure their histogenesis. The presumption is that ceruminous glands are the progenitors of all types of ceruminomas; cytologic evidence, however, is inconclusive. Mills et al. proposed ectopic salivary gland tissue as an alternative source, particularly for adenoid cystic carcinoma, on the argument that (1) adenoid cystic carcinomas of the EAC are morphologically identical to those of salivary gland origin, (2) adenoid cystic carcinoma is the most common malignant tumour of the minor salivary glands, and (3) primary adenoid cystic carcinoma of the skin is rarely malignant.4 Wetli et al.'s ultrastructural study of a ceruminous adenocarcinoma found histologic features consistent with an eccrine (as opposed to apocrine) origin.1 A more recent ultrastructural, immunohistochemical, and lectin histochemical study of a lowgrade adenocarcinoma, however, reported features consistent with an apocrine origin.9 It is clinically important that low-grade adenocarcinoma, by virtue of its well-differentiated histology, may be indistinguishable from a ceruminous adenoma. The pathognomonic finding for the malignant type is stromal invasion and desmoplasia; a sufficient tissue sample must therefore be obtained to diagnose adenocarcinoma.1

The incidence of ceruminous adenocarcinoma is obscured by the absence of cohort studies on this disease. Wethe et al. reviewed all 52 reported cases of ceruminoma up to 1972 and reported 9 cases of ceruminous adenocarcinoma.1

Ceruminous adenocarcinoma exhibits a prolonged subclinical phase, often lasting years, before presentation, as in our cases.10,11 Clinical symptoms usually comprise a sensation of blockage in the EAC with or without hearing loss; the presence of pain or tinnitus suggests superinfection and invasion.2,8 Otoscopic examination usually demonstrates a nodule covered by normal skin, with or without otorrhea, hemorrhage, lymphadenopathy, or cranial nerve palsies.8,10 Tuning fork tests and pure-tone audiometry may show conductive hearing loss on the affected side.5 Ceruminous and pleomorphic adenomas, by contrast, present as painless nodules with or without hearing loss.8 Our second case exemplifies this classic presentation of ceruminous adenocarcinoma. Our first case of ceruminous carcinoma, however, did not present within the EAC but encircled the lobule, unlike the prototypic clinical presentation. This presentation confused the initial diagnosis (which was poorly differentiated adenocarcinoma, possibly of salivary gland origin) and illustrates an important point. Disease in the cartilagenous canal may spread easily through the cartilage and the fissures of Santorini into the area of the parotid gland and surrounding lymphatics.2 This anatomic relationship should be kept in mind with lesions presenting in the preauricular area.

Investigations include temporal bone CT scan to determine the extent of the lesion and the presence of osseous invasion and to exclude extrapetrosal disease, such as a meningeal or parotid tumour bulging into the EAC.10 Metastasis from primary lung, breast, or kidney cancer is more common and should be excluded clinically and radiologically.8,11

Combined surgery and radiation is the mainstay of therapy.4 Garin et al. recommend bypassing preliminary biopsy for immediate large excision of the lesion on the basis that this would not only treat benign lesions but would also provide large tissue samples to diagnose malignant variants (of particular importance in low-grade adenocarcinoma for which identifying invasion is the distinguishing feature from adenoma). Moreover, small histologic samples may yield false negatives.10 Hicks, in a survey of the literature, advocated wide en bloc excision of the EAC, surrounding bone and associated cartilage, mastoid, middle ear, parotid and contingent muscle, lymphatics, and nerve structures, with preservation of the facial nerve for tumours involving the EAC.2 For tumours of the middle ear and temporal bone, with or without facial nerve involvement, he recommended subtotal temporal bone resection with modifications and nerve grafting. Removal of dura, parotid gland, and ascending ramus of the mandible and upper neck dissection may be performed, if necessary. Although radiotherapy is of little benefit on its own, it should always follow surgery.z2,11 Radical neck dissection should be performed if the jugulodigastric nodes or parotid gland is positive on frozen section at the time of surgery.2 Ceruminous adenocarcinoma may metastasize to the lung, liver, and kidney, and resection of solitary metastases has been recommended by some investigators.4,8

Wide surgical margins must be taken as high recurrence rates have been reported. Of the 15 reports of ceruminous adenocarcinoma reviewed by Hicks, 5 reported recurrence between the 1-month and 10-year follow-up, 3 reported death from disease between the 2- and 5-year follow-up, 2 reported no follow-up, and 7 reported no recurrence within 3 months to 8 years follow-up.2 Recurrence has been attributed to the technical difficulty of primary clearance and the frequency of perineural invasion.1,3,8,11,12 One report described a well-differentiated ceruminous adenocarcinoma that recurred intracranially after a 7-year follow-up period free of disease."3 Our second case similarly demonstrates the potential for intracranial invasion. Given the frequent and often late recurrence of this tumour, postoperative follow-up must be for at least 5 years; lesser duration is insufficient.2,14

Ceruminous adenocarcinoma is a malignant subtype of ceruminoma, a class of glandular tumour of the EAC that varies markedly in histology and clinical behaviour. Although clinical presentation of this tumour has hitherto consisted of an intrameatal mass, otolaryngologists should remain cognizant of the intimate relationship between the EAC and the parotid gland and the potential for ceruminomas to present as crusting dermatologic lesions in this region.

References

References

Wetli CV, Pardo V, Millard M. Tumors of ceruminous glands. Cancer 1972; 29:1169-1178.

Hicks GW. Tumors arising from the glandular structures of the external auditory canal. Laryngoscope 1983; 3:326-340. Pulec JL. Glandular tumors of the external auditory canal. Laryngoscope 1977; 87:1601-1612.

References

4. Mills RG, Douglas-Jones T, Williams RG. "Ceruminoma-a defunct diagnosis." J Laryngol Otol 1995; 109:180-188.

5. Hasan SA, Ahmad KN. Ceruminous gland tumour. J Indian Med Assoc 1986; 84:308-309.

6. Stone HE, Lipa M, Bell RD. Primary adenocarcinoma of the middle ear. Arch Otolaryngol 1976; 101:702-705.

7. Yamamoto E, Keisaku T, Mori K. Ceruminous adenoma in the osseous external auditory canal. J Laryngol Otol 1987; 101:940-945.

8. Dehner LP, Chen KTK. Primary tumours of the external and middle ear. Arch Otolaryngol 1980; 106:13-19.

9. Nadasy T, Kemeny E, Gyongy M. Adenocarcinoma of the ceruminous glands: ultrastructural, immunohistochemical

References

and lectin histochemical studies. Acta Morphol Hung 1991; 39:157-165.

10. Garin P, Degols JC, Delos M. Benign ceruminous turnouts of the external auditory canal. J Otolaryngol 1999; 28:99-101. 11. Iqbal A, Newman P. Ceruminous gland neoplasia. Br J Plast Surg 1998; 51:317-320.

12. Cankar V, Crowley H. Tumors of ceruminous glands: a clinicopathological study of 7 cases. Cancer 1964; 17:67-75.

13. Hageman MEJ, Becker A. Intracranial invasion of a ceruminous gland tumor. Arch Otolaryngol 1974; 10:395-397.

14. Wagenfeld DJH, Keane T, Van Nostrand AWP. Primary carcinoma involving the temporal bone. Analysis involving twenty-five cases. Laryngoscope 1980; 9:912-919.