Ceruminous Adenocarcinoma with Extensive Parotid ,Cervical and Distant Metastases –
1
Case Report and Review of Literature
2 3 4
Jih-Chuan Jan, M.D.1, Ching-Ping Wang, M.D.1, Po-Cheung Kwan, M.D.2, Shang-Heng Wu, 5
M.D.3, Hui-Fen Shu, M.D.4 6
7 8
From the Department of Otolaryngology-Head and Neck Surgery1 and Pathology2, Taichung 9
Veterans General Hospital, and the Department of 3Otolaryngology and 4Pathology, 10
Fong-Yuan Hospital, Taiwan, ROC 11
China Medical University, Taiwan 12
National Yang-Ming University, Taiwan 13
14
Address for correspondence Dr. Ching-Ping, Wang, Department of Otolaryngology, Taichung 15
Veterans General Hospital, Taichung City, Taiwan, Tel: 886-4-23592525 ext. 5401, Fax: 16 886-4-23596868, E-mail: [email protected] 17 18 Word counts 2052 19
Abstract 20
We report a case of high-grade ceruminous adenocarcinoma in a 47-year-old male. The tumor 21
initially presented as a five millimeter nodular mass on left external auditory canal (EAC). 22
Consequently, extensive intraparotid and neck lymph nodes metastasis occurred and axillary 23
lymph nodes metastases developed several months later. To our knowledge, extensive neck 24
and distant lymph node metastasis of a patient with a ceruminous adenocarcinoma has not 25
been reported previously. We also believe that this case represents the first report of lymph 26
nodes metastasis to level V of neck and axilla from cancer of external ear canal. We present 27
our experiences in dealing with this rapidly progressing malignant tumor. The clinical features, 28
pathology, and treatment are described and relevant literatures have been reviewed. 29
30
Key words: Ceruminous gland, Adenocarcinoma, External auditory canal, Metastasis 31
Introduction 32
In general, tumors of the external auditory canal (EAC) are quite uncommon, and glandular 33
tumors comprise only a minority of these tumors. Tumors of the ceruminous gland are 34
uncommon in the external auditory canal. Ceruminous adenocarcinoma is a malignant 35
subtype of ceruminous gland neoplasm1, which is an exceedingly rare malignancy of the 36
external auditory canal. The true incidence and biological behavior of these tumors is still 37
obscure not only owing to the rarity of these tumors but also due to ambiguous tumor 38
nomenclature. The dearth of knowledge about this disease entity leads to difficulty in 39
establishing the formulation of definitive treatment plans. 40
41
Most ceruminous adenocarcinomas behave as moderately aggressive, slow-growing tumors 42
with local invasion. Regional lymph nodes and distant metastasis are rare.2, 3 On reviewing of 43
literatures; only one case of lung metastasis has been reported.4 Most recurrences are local 44
recurrence, and the recurrence rate can be quite high in spite of treatment with aggressive 45
multimodal managements. Here we present a case ceruminous adenocarcinoma that shows as 46
a 5 mm nodular lesion but with rapid progression with extensive intraparotid and neck lymph 47
nodes, including level V, metastases. We also believe that this case represents the first report 48
of lymph nodes metastasis to level V of neck and axilla from cancer of external ear canal. 49
Case report 50
A 47-year-old male, with underlying irregular hypertension medically controlled, smoked 51
cigarettes and drank socially for decades. He suffered from increased left ear discharge for 52
one month and visited a local hospital for help. On physical examination, he was found to 53
have a 5 mm sized nodular lesion arising from the anteroinferior wall of left external ear canal. 54
The left tympanic membrane and the other ear were normal. No obvious neck 55
lymphadenopathy or palpated parotid mass was found. Examination of the nose, nasopharynx, 56
oral cavity, oropharynx, larynx, and hypopharynx was unremarkable. Computerized 57
tomography (CT) scan of temporal bone demonstrated a 5 mm sized nodular lesion with soft 58
tissue density in the left external auditory canal but no sign of bone destruction or erosion 59
(Figure 1). There was no notable abnormality in the middle, inner ear or in the internal 60
auditory canal. The patient underwent a trans-canal wide excision and the histopathological 61
examination of the specimen provided a diagnosis of high-grade adenocarcinoma. 62
On histological examination, the ear canal tumor measured 5 × 6 mm2 with normal 63
ceruminous gland nearby. The tumor undermined the squamous epithelium lining the 64
external auditory canal via subepithelial invasion (Figure 2). On high-power field, the tumor 65
cells were shown as cuboidal to polygonal cells, with eosinophilic cytoplasm, and large, 66
round-to-ovoid, hyperchromatic, vesicular nuclei. The nucleoli were conspicuous. The cancer 67
cells were disposed in irregular glands or solid sheets, separated by bands of fibrous tissue. 68
(Figure 3) Focal areas of tumor invasion into lymphatic channel and epidermis were 69
demonstrated. The dense desmoplastic response in the stroma was evident. 70
Three weeks after surgery, several tender masses were found on his left neck. Then he was 71
referred to our hospital. During the hospitalization, a series of studies were arranged. 72
Otoscopic examination of the external auditory canal showed no evidence of local recurrence 73
or obvious residual tumor. A thorough search for other primary sites of adenocarcinoma, 74
including gastroscopy, colonoscopy, CT scan of lung, and whole body PET scan revealed 75
negative for other malignancy. Another CT of head and neck showed several ring-like 76
enhancing nodular lesions with a central necrosis over left parotid gland, carotid space and 77
posterior triangle of left neck (Figure 4). Fine needle aspiration of level V lymph node of the 78
left neck yielded a suspected metastatic adenocarcinoma. The patient underwent a left total 79
parotidectomy with facial nerve preservation and left radical neck dissection. The pathology 80
reported a high grade metastatic adenocarcinoma. Tumor metastasized to intraparotid lymph 81
nodes (4/5), and to cervical lymph nodes (level I: 6/6, level II: 23/24, level III: 16/16, level IV 82
15/15, level V: 14/14) with extranodal invasion. Nearly all the intra-parotid and cervical 83
lymph nodes were violated by cancer cells, which were histologically compatable with 84
previous EAC tumor. The presence of extranodal invasion was found 85
86
Neoadjuvant chemoradiation was administrated post-operatively with 5-FU, MTX, 87
Epirubicin, and Cisplatin in divided 12 doses and radiation with 7000 cGy in 35 fractions. 88
Unfortunately, a lump was palpated over his left axilla 6 months later after completion of 89
chemoradiation. Excisional biopsy of axillary lymph nodes revealed high grade metastatic 90
adenocarcinoma. After discussion with the patient and his family, he was transferred back to a 91
local hospital for palliative treatment. 92
Discussion 93
Malignant tumors arising from the glandular structures of the external auditory canal are rare. 94
On reviewing of literatures, several origins of EAC adenocarcinomas have been reported, 95
including ceremonious gland2, sebaceous gland5, direct invasion from parotid gland6, and 96
distant metastasis from other glandular tissues.7-9 We believe that this case is a tumor of 97
ceruminous adenocarcinoma. First of all, the tumor was located deep in the cartilaginous 98
segment of the EAC; this corresponds to the distribution of the ceruminous glands rather than 99
sebaceous glands.10 On pathological view, the normal glandular structures of specimen show 100
no resemblance to the sebaceous gland. Secondly, the tumor presented ear canal mass as an 101
initial symptom. The CT scan and physical examination did not show a lesion within the 102
parotid gland. Several weeks later, another CT scan of head and neck demonstrated multiple 103
nodular lesions located in the parotid gland but with an intact external ear canal wall. These 104
pictures are not compatible with a parotid cancer with ear canal invasion. On pathologically 105
reviewing the parotid specimen, the diseases are in intraparotid lymph nodes rather than 106
parenchyma of gland. Thirdly, although several authors have reported ear canal tumors as a 107
distant metastatic cancer 7-9, there is not any evidence of other primary sites for 108
adenocarcinoma during one year follow-up period. We conclude that the ear canal tumor 109
should be a primary ceruminous adenocarcinoma. 110
111
Most ceruminous adenocarcinomas behave as moderately aggressive, slow-growing tumors 112
with local invasion. Regional lymph nodes and distant metastasis are rare.3 This case shows a 113
rapid course of disease progression via neck lymph node metastasis rather than by local tissue 114
infiltration or destruction. Ceruminous adenocarcinoma may occur in any grade depending on 115
the degree of cytological and architectural atypia.11 The ability of malignant neoplasms to 116
invade adjacent normaltissues is fundamental to the neoplastic process. On pathologic view, 117
the tumor cells show high-grade maligancy and evidences of lymphatic permeations, focal 118
invasion into epidermis and desmoplasticresponses. Desmoplasticresponses are results of a 119
complex interactionbetween the host and invading neoplasm, comprising fibroblasts,various 120
inflammatory cells, proliferating vascular structures,as well as normal parenchymal cells 121
undergoing atrophy at theinvasive edge.These may explain the circumstances of extensive 122
lymph nodes metastases; even though the primary lesion is quite small. 123
To date, no specific data is available on cervical lymph node metastasis patterns for these 124
tumors. Concerning the anatomic relationship, the routes of lymphatic drainage should be to 125
the nodes anterior, posterior, and inferior to the auricle, with the inferior nodes draining to the 126
subparotid and subdigastric nodes. On other high grade malignancies of EAC, such as 127
squamous cell carcinomas, lymph nodes metastases are commonly seen in parotid, level II 128
and III.3 On reviewing previously reports of regional spray pattern of external ear 129
malignancies, there is no case showing metastasis to the posterior triangle nodes.12Our case 130
showed extensive lymph nodes metastasis from parotid to level II to V. Consequently, we 131
recommend that whenever neck dissection is considered for external ear malignancy, level V 132
neck dissection may be considered 133
The treatment modality of ceruminous adenocarcinoma is not yet well-established. Combined 134
surgery and irradiation is advocated by most authors presently. Hicks, in survey of the 135
literature, advocated wide en bloc excision of the EAC, surrounding bone and associated 136
year follow up. The role of chemotherapy in ceruminous adenocarcinomas has not yet been 143
evaluated. In our case, the chemotherapy of 5-FU, MTX, Epirubicin, and Cisplatin did not 144
prevent the patient from distant metastasis. 145
The actual long-term disease-free survival rates after such aggressive multimodal therapies 146
are not clear at present; further experience after treatment will provide further information for 147
long-term disease control. 148
149
Reference 150
1. Wetli CV, Pardo V, Millard M, et al. Tumors of the ceruminous gland. Cancer 151
1972;29:1169-78. 152
2. Soon SL, Bullock M, Prince ME. Ceruminous adenocarcinoma: a rare tumour of the 153
external auditory canal. J Otolaryngol 2001;30 (6) 373-7 154
3. Joseph Chang CY, Cheung SW. Tumors of the Ear and Temporal Bone. Auditory canal: 155
glandular tumors. Philadelphia: Lippincott WW, 2000 156
4. Turner HA, Carter H, Neptune WB. Pulmonary metastases from ceruminous 157
adenocarcinoma (cylindroma) of external auditory canal. Cancer. 1971 158
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5. Ray J, Schofield JB, Shotton JC, Al-Ayoubi A. Rapid invading sebaceous carcinoma of 160
the external auditory canal. J Laryngol Otol. 1999 Jun;113(6):578-80 161
6. Choi JY, Choi EC, Lee HK, Yoo JB, Kim SG, Lee WS. Mode of parotid involvement in 162
external auditory canal carcinoma J Laryngol Otol. 2003 Dec; 117 (12): 951-4 163
7. Michaelson PG, Lowry TR. Metastatic renal cell carcinoma presenting in the external 164
auditory canal. Otolaryngol Head Neck Surg. 2005 Dec;133(6):979-80. 165
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external auditory canal. J Laryngol Otol. 1994 Sep;108(9):808-10. Review. 167
Laryngol Otol. 1995 Mar;109(3):180-8. 174
12. Lee D,Nash M,Har-El G. Regional spread of auricular and periauricular cutaneous 175
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179
Figure 1. Axial CT revealing a 5 × 6 mm2 mass over left external ear canal. 180
Figure 2. External auditory canal tumor, low-power view. The tumor was mainly situated in 181
the subepithelium with bulging into the external auditory canal. Note the normal glandular 182
structure in the upper left-head corner. (Hematoxylin and eosin stain, × 10) 183
Figure 3. Malignant cell exhibiting cellular atypia, nuclear pleomorphism, and eosinophilic 184
cytoplasm. The tumor cells were arranged in an irregular glandular pattern. (Hematoxylin and 185
eosin stain, × 400) 186
Figure 4. Axial CT showing multiple ring-like enhancing nodular lesions with a central low 187
density over left parotid gland and multiple enlarged lymph nodes with central necrosis over 188
the carotid space and posterior triangle of the left neck. 189
