J Oral Maxillofac Surg 59:1502-1505, 2001
Epithelial-Myoepithelial Carcinoma of the Palate: A Case Report Yuko Inoue, DDS,* Jouji Nomura, DDS, PhD,† Masanori Hashimoto, DDS,‡ and Toshiro Tagawa, DDS, PhD§ Neoplasms of salivary gland origin are histologically diverse. The overlapping microscopic features shared by many of the tumors, benign and malignant, frequently pose a diagnostic challenge. Several salivary gland neoplasms that were previously considered benign are now recognized as malignant. An example of such a case is the epithelial-myoepithelial carcinoma (EMC). Epithelial-myoepithelial carcinoma is an uncommon neoplasm, which was officially classified by the World Health Organization (WHO) in 19911 as a salivary gland malignancy. Previously, the tumor was referred to by a variety of names that reflected its domination by clear cells. The tumor represents fewer than 0.5% to 1% of all salivary gland neoplasms.2-4 It arises most frequently in the parotid gland,1,2,5 but occurs only rarely in minor salivary glands. We present a case of EMC that originated in a minor salivary gland in the palate.
Report of Case A 66-year-old woman consulted the Department of Oral and Maxillofacial Surgery in May 1998 with the chief complaint of gingival pain of 1 year’s duration in the right maxillary molar region. The patient noted swelling and ulceration 1 month before the current consultation. However, she had not sought treatment before this time, until her dentist suggested an oral and maxillofacial surgery consultation. The past medical and family histories were noncontributory. On examination there was no facial asymmetry or any sign of neuroparalysis or any other obvious abnormality.
Received from the Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Mie University, Mie, Japan. *Junior Resident. †Lecture. ‡Research Fellow. §Professor and Chief. Address correspondence and reprint requests to Dr Inoue: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, Mie University, 2-174 Edobashi, Tsu, Mie 514-8507, Japan; e-mail:
[email protected] © 2001 American Association of Oral and Maxillofacial Surgeons
0278-2391/01/5912-0023$35.00/0 doi:10.1053/joms.2001.28295
Oral examination revealed a relatively well-defined, nearly circular, concave ulcer measuring 2 ⫻ 2 cm that extended from the gingiva in the edentulous right maxillary molar region to the adjacent palatal mucosa. The ulcer borders were not indurated. The surface was erythematous and smooth, with some telangiectasia evident. There was no regional lymphadenopathy (Fig 1). A panoramic radiograph showed resorption of the alveolar bone in the region of the ulcer; there was no apparent invasion of the maxillary sinus (Fig 2). Computed tomography revealed destruction of the maxillary alveolar bone without apparent invasion of the adjacent pterygoid muscle. A biopsy was performed, and a diagnosis of EMC was established. Microscopic examination revealed a glandular neoplasm characterized by an unencapsulated proliferation of doublelayered duct-like structures. The latter were composed of an inner layer of eosinophilic, cuboidal duct-lining cells and an outer layer of clear cells that abutted the fibrous stroma (Figs 3, 4). Although there were no mitoses, invasion of nerve and blood vessels was observed. Immunohistochemistry showed anti ␣-smooth muscle actin antibody (a marker for smooth muscle) positivity in cells of the outer ductal layer; cells of the inner ductal layer were positive for antikeratin antibody. In addition, positive staining for antiglial fibrillary acidic protein antibody was detected in cells of the inner ductal layer, whereas anti-S-100 protein antibody was detected in outer ductal layer cells (Fig 5). Subsequent gallium and technetium scintigraphy revealed no evidence of metastasis. Therefore, a right partial maxillary resection was performed. There was no evidence of residual tumor in the surgical margins. The postoperative course was uneventful, and the patient was discharged from the hospital 2 months after the surgical procedure. At a recent 2-year postsurgical follow-up visit, there was no evidence of recurrence or of metastasic disease.
Discussion In the past, salivary gland tumors composed mainly of clear cells were referred to by various names, including tubular solid adenoma,6 cystic adenoma,7 adenomyoepithelioma, and clear cell adenoma.8,9 The term epithelial-myoepithelial carcinoma was originally proposed by Donath et al in 1972.10 In 1991, the WHO applied the term EMC selectively after reclassification according to novel histologic and clinical profiles of tumors that had been collectively termed “adenocarcinoma” in the past.
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FIGURE 1. Initial presentation of a depressed ulcer with telangiectasia.
Epithelial-myoepithelial carcinoma is malignant salivary gland neoplasm that is characterized by a biphasic tubular structure that consists of duct-lining cuboidal cells in the inner layer and clear cells in the outer layer.1 However, the proportion of each component can vary. Clear cells with a sheet-like growth pattern are dominant in some cases,1 whereas in other cases there are exclusively solid clear cells without obvious ductal formation.11 Batsakis et al3 classified EMC into 3 subtypes: 1) a predominantly clear-cell type without duct formation, 2) a spindle myoepithelial-cell type, and 3) a predominantly ductal epithelial-cell type. Others12 divide EMC into 2 subtypes: 1) a tubularcribriform type characterized by a double-layered tubuloductal structure and 2) a solid type dominated by clear cells. In the present case, the tumor showed features consistent with both EMC of the spindle myoepithelial-cell type and EMC of the tubular-cribriform type because it contained double-layered tubular structures composed of cells that were slightly less clear than those characteristic of the other subgroups. Other microscopic features of EMC include periodic acid-Schiff (PAS) positivity of the clear cells, with corresponding negativity on diastase digestion; markedly PAS-positive basement membrane, with minimal cellular atypia; infrequent mitoses; and a tendency to
FIGURE 2. Panoramic radiograph showing lytic destruction of alveolar bone in right posterior maxilla (arrows).
FIGURE 3. Photomicrograph showing double-layered duct-like structures. (Hematoxylin & eosin stain, original magnification ⫻50.)
exhibit ductal differentiation.12,13 These generally benign features account for why this tumor had been previously regarded as an adenoma. However, there is often evidence of nerve and blood vessel invasion, and both recurrences and metastases are frequently reported. The solid type of EMC tends to be more invasive than the tubular-cribriform type.12 In recurrent cases, clear cells predominate and mitoses and atypia are prominent.11 Electron microscopic and other studies suggest that EMC arises from intervening ductal precursor cells with the capacity to differentiate into both myoepithelial cells and ductal epithelial cells.10,14 This hypothesis is also supported by reports of tumors containing transitional cells with characteristics of both ductal epithelial and myoepithelial cells15 and by re-
FIGURE 4. Photomicrograph showing an inner layer of eosinophilic cuboidal duct lining cells and an outer layer of clear cells abutting the surrounding fibrous stroma (Hematoxylin & eosin stain, original magnification ⫻100). Inset, Neural invasion. (Hematoxylin & eosin stain, original magnification ⫻100.)
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FIGURE 5. A, Positive staining with ␣-smooth muscle actin antibody in the outer ductal cell layer (⫻60). B, Positive staining with anti-keratin antibody in the inner ductal cell layer (⫻100).
ports of recurrent tumors that display a shift from bilaminar to unilaminar growth.16,17 Epithelial-myoepithelial carcinoma has been reported to represent about 1%,3 0.5%,2 and 0.48%4 of all salivary gland tumors, respectively. The most common site of occurrence is the parotid gland (73.5% to 80%).1-3,14 In minor salivary glands, EMC represents between 5% and 6.2%3 of all salivary gland tumors. It is more frequently found in females, with the maleto-female ratio reported to be 1:1.5,2 1:1.7,3 and 1:2,5,14 respectively. The age at onset has been reported as being from 60 to 79 years,1 and 61.3 years,14 61.7 years,2 62.0 years,5 and 68 years4 in other reports. The recurrence rate is comparatively high, ranging from 31.3% to 43%.2-5,14 This may be partly because EMC often appears histologically benign, and this can result in incomplete excision. Metastasis to regional cervical lymph nodes has been reported at rates of 17.9%3 and 19.6%,2 respectively. There have been distant metastases to the kidney, lung, and brain18 at rates of between 7.53 and 9.8%,2 respectively. Because of the tumor’s propensity to locally invade nerves and blood vessels, resection with a wide margin to prevent recurrence and metastasis is recommended. Epithelial-myoepithelial carcinoma can be lethal if there is distant metastasis, with reported mortality rates of 6%5 and 15.2%.2 Thus, although the tumor is commonly considered to be a low-grade malignant neoplasm, it does not behave like a low-grade malignancy given its tendency to metastasize and its associated mortality rates. Therefore, the postoperative course should include close clinical follow-up, including a metastatic work-up.
The differential diagnosis of EMC includes clear cell-dominated tumors, such as clear cell myoepithelioma, acinic cell carcinoma, mucoepidermoid carcinoma, and metastatic clear cell tumors. Because a denoid cystic carcinoma (ACC) also can show doublelayered duct-like structures, it can be mistaken for EMC. To distinguish EMC from ACC, immunostaining is useful,11 because it may otherwise be difficult to differentiate EMC from ACC, not only because ACC also shows double-layered ductal structures similar to those seen in EMC, but also because EMC can have cribriform nest pattern with glandular spaces and pseudocysts similar to those seen in ACC.1 Although there is positive reactivity for S-100 protein in the inner ductal cell layer in ACC, only the outer ductal cell layer is S-100 positive in EMC.19,20 With ACC, the 10-year survival rate is 50%,1 and the mean length of survival is 35.4 months when tumors measure 2cm or less.21 The dismally poor prognosis of ACC as compared with EMC requires that careful attention be paid to the key features that distinguish these 2 distinct malignancies from one another.
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