A Case of Mucoepidermoid Carcinoma with Clear Cell Components Occurring in Retromolar Region

Nobuharu Yamamoto1), Yukio Watabe1), Masashi Iwamoto1), Kenichi Matsuzaka2) and Takahiko Shibahara1)

1) Department of Oral and Maxillofacial Surgery, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan

2) Department of Clinical Pathophysiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan

Received 12 April, 2013/Accepted for publication 20 September, 2013

Abstract

Mucoepidermoid carcinomas in the minor salivary glands usually originate in the palatine gland, and their occurrence in the retromolar region is rare. We report a rare case of mucoepidermoid carcinoma with clear cell components occurring in the retromolar region. The patient was a 63-year-old woman referred to our hospital with the chief complaint of a painless mass in the right retromolar region initially found during treatment at a local dental clinic. The 20210-mm mass was well-defined, elastic, and flexible. The surface of the mucosa was healthy. The mass was clinically diagnosed as a gingival benign tumor in the right retromolar region. There were no significant findings in the patient’s medical history. The tumor was resected under local anesthesia. Histopathology revealed that squamoid cells, undifferentiated intermediate cells, and clear cells were dominant, with mucus-producing cells in some areas. A mucoepidermoid carcinoma with clear cell components was diagnosed. There were no signs of recurrence or metastasis at 15 months postoperatively and the patient’s progress has been satisfactory. Because the tumor was a painless, slow-growing mass, it was clinically diagnosed as a benign tumor of the gingiva, and resection was performed under local anesthesia without performing a biopsy. However, even if a mass in the retromolar region is clinically diagnosed as a benign tumor, the course of treatment should be decided after performing fine-needle aspiration cytology, taking into consideration the possibility of mucoepidermoid carcinoma.

Key words: Mucoepidermoid carcinoma — Clear cell — Retromolar region — Salivary gland tumor

Case Report

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Bull Tokyo Dent Coll (2014) 55(1): 25–31

Introduction

Named by Stewart et al.22) in 1945, a muco-epidermoid carcinoma is a salivary gland

ductal epithelium-derived tumor composed of mucus-producing, squamoid, and interme-diate cells. Among the major salivary glands, it occurs most frequently in the parotid gland

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(about 80%), and is rare in the submandibular (approximately 10%) and sublingual glands (approximately 5%). In the minor salivary glands, mucoepidermoid carcinomas mainly derive from the palatine gland, but are also found in the tongue, oral floor, gingiva, and buccal mucosa1). Development in the retro-molar or buccal regions, or inside the jaw bone, however, is rare9,10). Histologically, they are classified as follows: well-differentiated (low- grade malignancy), moderately-differentiated (intermediate-grade malignancy), and poorly differentiated (high-grade malignancy)1,8). One report has shown that poorly-differentiated (high-grade) mucoepidermoid carcinomas are rare, and that the well-differentiated type (low- grade malignancy) predominates, especially in tumors developing in the minor salivary glands13).

Here, we report a case of an mucoepider-moid carcinoma with clear cell components that showed a comparatively low degree of differentiation and originated in the retro-molar salivary gland.

Case

In November 2010, a 63-year-old woman visited a nearby dental clinic, where a mass was detected in the right retromolar region during treatment. She was subsequently referred to our hospital for a more detailed examination. Her chief complaint was a mass in the right retromolar region. Here medical history showed no remarkable findings.

Her facial appearance was symmetrical. She reported no pain, and no swelling was observed in the right submandibular lymph nodes. A 20210-mm, well-defined, elastic, mobile, and painless mass was observed in the right retromolar region. No fluctuation was observed on palpation, and the mucosa was healthy (Fig. 1). Magnetic resonance imag-ing revealed a well-defined, 1028210-mm mass in the right submandibular retromolar region with a smooth periphery (Fig. 2). The mass was isointense to muscle on T1W1 and heterogeneous hyperintense on T2W1 (Fig.

2b). Although it was close to the mandible, there appeared to be no evidence of bone destruction (Fig. 2a) and a benign tumor was suspected.

When the patient first visited our hospital, the mass was clinically diagnosed as gingival benign tumor in the right retromolar region. At the first medical examination in November 2010, surgical resection was recommended, but due to the patient’s own decision, she stopped coming to the hospital. In November 2011, the patient revisited our hospital, with the size of the mass showing no change. In January 2012, the mass was resected under intravenous anesthesia as an outpatient pro-cedure. An electrotome was used to incise only the epithelial layer of the entire periphery of the mass and surgical scissors to dissect the mass cleanly. The lesion was covered with a capsule and showed no adhesion to the lingual nerve or blood vessels (Fig. 3). The entire tumor was resected and a 3-0 nylon thread used to suture the resected area. The resected lesion was 20215-mm; it was covered with a capsule, had an asymmetrical and uneven surface, and was solid but elastic on the inside.

Histopathological findings (Figs. 4a, 4b) predominantly revealed squamoid (arrow A), undifferentiated intermediate, and clear cells

Yamamoto N et al.

Fig. 1 Oral image obtained at second visit

Well-defined, flexible, 20210-mm mass was observed in right retromolar region. Surface mucosa was healthy.

27Mucoepidermoid Carcinoma with Clear Cell Components

(arrow B); mucus-producing cells were also observed in some areas. Therefore, the tumor was diagnosed as a clear cell variant of mucoepidermoid carcinoma. Histochemistry with mucicarmine revealed positive staining for mucus-producing cells (Figs. 5a, 5b); stain-

ing with PAS revealed positive staining for glycogen inside the cells. Staining was positive for keratin and negative for S-100 or GFAP. In addition, because the labeling index of Ki-67 was low, the growth potential was determined to be low. At 15 months postoperatively, no

Fig. 2 Preoperative MRI image

a, b: 1028210-mm mass in right submandibular retromolar region was well-defined with smooth periphery. a: Mass was close to mandible, but no clear evidence of bone destruction. b: Mass was isointense to muscle on T1W1 and heterogeneous hyperintense T2W1.

Fig. 3 Inside oral cavity and resected specimen postoperatively

Tumor was easily resected. It comprised 20215-mm mass, covered with capsule; it had asymmetrical and uneven surface, and was elastic. When tumor was cut in center, inside was solid and yellow in color.

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sign of recurrence or metastasis has been observed (Fig. 6).

Discussion

Mucoepidermoid carcinomas, originally known as mucoepidermoid tumors, are benign. Nevertheless, cases of recurrence and metas-

tasis have been reported8,18), and in the 1991 WHO Classification18) of Tumors, they were classified as mucoepidermoid carcinoma. In the 2005 WHO Classification1), they were classified into three different types depend-ing on the correlation between the cell distri-bution ratio and degree of malignancy: well- differentiated (low-grade malignancy), in which more than 50% of the tumor is comprised

Fig. 5 Histochemical staining

Mucicarmine-positive mucus-producing cells (arrow) were observed sporadically or agglomerated in some areas.

Fig. 4 H-E staining

a: Tumor was formed of fibro-connective tissue lined with parakeratotic stratified squamous epithelium (arrow A). Tumor cells were lined with incomplete thin capsule. They were lobular, solid, and had fine layer of fibro-connective tissue, forming cobblestone appearance in subepithelial connective tissue layer. Atypical glandular cavities of various sizes had formed in parenchyma of tumor. Tumor cells were small and displayed following wide range of characteristics: circular nucleus, eosinophilic cells in dense cobblestone arrangement, and clear cells (arrow B). b: In addition, there were spindle-shaped cells, larger cells that appeared to have mucus inside, and concentric formed crystalloids. Cell nuclei had deeply-stained nuclear chromatin, hyper-trophied nuclear body, and cellular atypia, with an increased N/C rate. Clear cell variant of mucoepidermoid carcinoma was diagnosed based on the following findings: squamoid, undifferentiated intermediate, and clear cells were dominant, with mucus-producing cells seen in some parts.

Yamamoto N et al.

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of parenchymal, mucus-producing cells and differentiated squamoid cells; moderately- differentiated (intermediate-grade malignancy), in which it is made up of an increasing number of intermediate cells with partial proliferation of cellularity in mucus-secreting and squamoid cells; and poorly-differentiated (high-grade malignancy), in which 10% or less of the tumor comprises mucus-producing cells, along with moderately- and poorly- differentiated squamoid cells. It has been reported that, usually, the poorly-differentiated type is rare in mucoepidermoid carcinoma1,22), especially for those developing in the minor salivary glands, and the well-differentiated type is predominant13). The susceptible age is 30 to 60 years (average age of 44 years), and it is seen slightly more frequently in women than in men8).

The clinical findings in the present study revealed a slow-growing, painless mass. Because the clinical diagnosis was a benign tumor, resection was carried out with only local anesthesia and no biopsy. The histopatho-logical findings, however, revealed only a few mucus-producing cells, with squamoid, undifferentiated intermediate, and clear cells

dominating. In addition, there was only very little evidence of cyst formation, so it was diagnosed as the clear cell variant of muco-epidermoid carcinoma according to the WHO Classification18). Nonetheless, the possibility of a transition from clear cell components to clear cell variant was recognized. A post-operative whole body PET-CT scan revealed no sign of new tumor formation, including renal metastases. The disease duration of mucoepidermoid carcinoma is reported to be between 8 days to 34 years, with an average of 22 months2). However, in the present case, disease duration was 1 to 2 years. Such mucoepidermoid carcinomas with clear cell components, a type of mucoepidermoid car-cinoma, are rare in the salivary glands11). For other sites, the clear cell variant of mucoepi-dermoid carcinomas is very rare, although there are some reports on the clear cell variant of mucoepidermoid carcinomas in the pharynx12,19) and oral cavity17,20,21). Further-more, in addition to in mucoepidermoid carcinoma, the clear cell type appears to occur predominantly in renal cell cancer, thyroid tumor, acinar cell carcinoma, eosino-philic cell carcinoma, ameloblastoma, and odontogenic tumor. Therefore, care should be taken in arriving at a diagnosis6,21). Ogawa et al.16) reported a case of a clear cell variant containing a very large number of clear cells observed in the right mandibular molar region, and pointed out three factors as indicative of the clear cell variant of muco-epidermoid carcinoma: 1) the proliferation of solid clear cells; 2) the presence of mucous cells; and 3) the carcinoma not being a metastatic tumor derived from a clear cell carcinoma. Moreover, they also suggested that the source of the clear cells might be epi-dermoid cells with glycogen accumulation in the cytoplasm. The clear cells in the present case also showed a positive PAS reaction, sug-gesting the presence of glycogen. In addition, the clear cells were mucicarmine-negative, with only the mucus-producing cells being mucicarmine-positive. Therefore, a diagnosis of mucoepidermoid carcinoma with clear cell components was established.

Fig. 6 Inside oral cavity at 15 months postoperatively

Tissue was completely epithelized with healthy mucosa; there have been no signs of local recurrence, indicating good progress.

Mucoepidermoid Carcinoma with Clear Cell Components

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In terms of the postoperative prognosis with mucoepidermoid carcinoma, Kajiyama et al.9) reported that recurrence was not seen with the low-grade malignancy type, but was 42.9% with the high-grade malignancy type. The survival rate is relatively good, reported as 69.4% by Mese et al.14) and 86% by Monoo et al.15). Meanwhile, the prognosis and malig-nancy of mucoepidermoid carcinomas with clear cell components remains unknown. It has been suggested that the clear cell variant of mucoepidermoid carcinoma will show rela-tively low differentiation or high malignancy if the source of the clear cells is squamous cells20). However, one study found no correla-tion between the prognosis and differentiation type in mucoepidermoid carcinoma7). The histologic grading of the tumor in the present study was carried out in line with that in earlier studies3,5) and revealed that 1) sacculation was less than 20%; 2) no nerve invasion; 3) no necrosis; 4) no more than 5 images of mitotic transformation (at 102magnification); and 5) no anaplasia. Furthermore, because the labeling index of Ki-67 was low, the tumor was considered to be low-grade, indicating a good prognosis.

Twenty-three cases of mucoepidermoid carcinoma have been treated at our hospital over the last 20 years, between 1993 and 2012. The distribution in the body was as

follows: 11 cases in the palate (48%); 5 in the retromolar region (22%); 2 in the oral floor (9%); 2 in the lower lip (9%); and 1 each in the maxillary sinus, maxillary bone, and buccal region (4%)(Table 1). Occurrence in the retromolar region is known to be rare6,7). However, Gnepp and Heffner4) reported that the retromolar region was the second most common site after the palate. This was also the case at our hospital, with most occurring in the palate. This clearly indicates a relatively high rate of occurrence in the retromolar region.

At 15 months postoperatively, there have been no signs of recurrence or metastasis. Further, long-term follow-up is required, how-ever. Mass lesions in the retromolar region may be clinically diagnosed as benign tumors, but the possibility of mucoepidermoid carcinoma cannot be ignored. Therefore, the results of fine needle aspiration cytology should also be considered in deciding on the course of treatment.

Conclusion

We have reported a case of mucoepider-moid carcinoma with clear cell components occurring in the retromolar region of a 63- year-old woman. The findings were discussed in reference to the literature.

Acknowledgements

The authors would like to thank Professor Jeremy Williams, Tokyo Medical University, for his assistance with the English of the manuscript.

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Tokyo Dental College Chiba Hospital

Investigation year 1993–2012

Case No. 23

Site (%)

Palate 11 (48%)

Retromolar region 5 (22%)

Floor of mouth 2 (9%)

Lower lip 2 (9%)

Maxillary sinus 1 (4%)

Maxillary bone 1 (4%)

Buccal region 1 (4%)

Table 1 Clinical statistics on mucoepidermoid carci-noma at this college

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Reprint requests to: Dr. Nobuharu Yamamoto Department of Oral and Maxillofacial Surgery, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan E-mail: nyamamot@tdc.ac.jp

Mucoepidermoid Carcinoma with Clear Cell Components