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

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

Case Report

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

Introduction ductal epithelium-derived tumor composed of mucus-producing, squamoid, and interme- Named by Stewart et al.22) in 1945, a muco- diate cells. Among the major salivary glands, epidermoid carcinoma is a salivary gland it occurs most frequently in the parotid gland

25 26 Yamamoto N et al.

(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 retromolar 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 1,8) differentiated (high-grade malignancy) . One Fig. 1 Oral image obtained at second visit report has shown that poorly-differentiated Well-defined, flexible, 20210-mm mass was (high-grade) mucoepidermoid carcinomas are observed in right retromolar region. Surface rare, and that the well-differentiated type (low- mucosa was healthy. grade malignancy) predominates, especially in tumors developing in the minor salivary glands13). Here, we report a case of an mucoepider- 2b). Although it was close to the mandible, moid carcinoma with clear cell components there appeared to be no evidence of bone that showed a comparatively low degree of destruction (Fig. 2a) and a benign tumor was differentiation and originated in the retro suspected. molar salivary gland. When the patient first visited our hospital, the mass was clinically diagnosed as gingival benign tumor in the right retromolar region. Case At the first medical examination in November 2010, surgical resection was recommended, In November 2010, a 63-year-old woman but due to the patient’s own decision, she visited a nearby dental clinic, where a mass stopped coming to the hospital. In November was detected in the right retromolar region 2011, the patient revisited our hospital, with during treatment. She was subsequently the size of the mass showing no change. In referred to our hospital for a more detailed January 2012, the mass was resected under examination. Her chief complaint was a mass intravenous anesthesia as an outpatient pro- in the right retromolar region. Here medical cedure. An electrotome was used to incise only history showed no remarkable findings. the epithelial layer of the entire periphery Her facial appearance was symmetrical. of the mass and surgical scissors to dissect She reported no pain, and no swelling was the mass cleanly. The lesion was covered with observed in the right submandibular lymph a capsule and showed no adhesion to the nodes. A 20210-mm, well-defined, elastic, lingual nerve or blood vessels (Fig. 3). The mobile, and painless mass was observed in entire tumor was resected and a 3-0 nylon the right retromolar region. No fluctuation thread used to suture the resected area. The was observed on palpation, and the mucosa resected lesion was 20215-mm; it was covered was healthy (Fig. 1). Magnetic resonance imag- with a capsule, had an asymmetrical and ing revealed a well-defined, 1028210-mm uneven surface, and was solid but elastic on mass in the right submandibular retromolar the inside. region with a smooth periphery (Fig. 2). The Histopathological findings (Figs. 4a, 4b) mass was isointense to muscle on T1W1 and predominantly revealed squamoid (arrow A), heterogeneous hyperintense on T2W1 (Fig. undifferentiated intermediate, and clear cells Mucoepidermoid Carcinoma with Clear Cell Components 27

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.

(arrow B); mucus-producing cells were also ing with PAS revealed positive staining for observed in some areas. Therefore, the tumor glycogen inside the cells. Staining was positive was diagnosed as a clear cell variant of for keratin and negative for S-100 or GFAP. In mucoepidermoid carcinoma. Histochemistry addition, because the labeling index of Ki-67 with mucicarmine revealed positive staining was low, the growth potential was determined for mucus-producing cells (Figs. 5a, 5b); stain- to be low. At 15 months postoperatively, no 28 Yamamoto N et al.

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.

Fig. 5 Histochemical staining Mucicarmine-positive mucus-producing cells (arrow) were observed sporadically or agglomerated in some areas.

sign of recurrence or metastasis has been tasis have been reported8,18), and in the 1991 observed (Fig. 6). WHO Classification18) of Tumors, they were classified as mucoepidermoid carcinoma. In the 2005 WHO Classification1), they were Discussion classified into three different types depend- ing on the correlation between the cell distri- Mucoepidermoid carcinomas, originally bution ratio and degree of malignancy: well- known as mucoepidermoid tumors, are benign. differentiated (low-grade malignancy), in which Nevertheless, cases of recurrence and metas- more than 50% of the tumor is comprised Mucoepidermoid Carcinoma with Clear Cell Components 29

dominating. In addition, there was only very little evidence of cyst formation, so it was diagnosed as the clear cell variant of mucoepidermoid 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- Fig. 6 Inside oral cavity at 15 months postoperatively cinoma, are rare in the salivary glands11). For Tissue was completely epithelized with healthy mucosa; other sites, the clear cell variant of mucoepi- there have been no signs of local recurrence, indicating dermoid carcinomas is very rare, although good progress. there are some reports on the clear cell variant of mucoepidermoid carcinomas in the pharynx12,19) and oral cavity17,20,21). Further- of parenchymal, mucus-producing cells and more, in addition to in mucoepidermoid differentiated squamoid cells; moderately- carcinoma, the clear cell type appears to differentiated (intermediate-grade malignancy), occur predominantly in renal cell cancer, in which it is made up of an increasing thyroid tumor, acinar cell carcinoma, eosino- number of intermediate cells with partial philic cell carcinoma, ameloblastoma, and proliferation of cellularity in mucus-secreting odontogenic tumor. Therefore, care should and squamoid cells; and poorly-differentiated be taken in arriving at a diagnosis6,21). Ogawa (high-grade malignancy), in which 10% or et al.16) reported a case of a clear cell variant less of the tumor comprises mucus-producing containing a very large number of clear cells cells, along with moderately- and poorly- observed in the right mandibular molar differentiated squamoid cells. It has been region, and pointed out three factors as reported that, usually, the poorly-differentiated indicative of the clear cell variant of muco type is rare in mucoepidermoid carcinoma1,22), epidermoid carcinoma: 1) the proliferation especially for those developing in the minor of solid clear cells; 2) the presence of mucous salivary glands, and the well-differentiated cells; and 3) the carcinoma not being a type is predominant13). The susceptible age is metastatic tumor derived from a clear cell 30 to 60 years (average age of 44 years), and carcinoma. Moreover, they also suggested that it is seen slightly more frequently in women the source of the clear cells might be epi than in men8). dermoid cells with glycogen accumulation in The clinical findings in the present study the cytoplasm. The clear cells in the present revealed a slow-growing, painless mass. Because case also showed a positive PAS reaction, sug- the clinical diagnosis was a benign tumor, gesting the presence of glycogen. In addition, resection was carried out with only local the clear cells were mucicarmine-negative, anesthesia and no biopsy. The histopatho with only the mucus-producing cells being logical findings, however, revealed only a mucicarmine-positive. Therefore, a diagnosis few mucus-producing cells, with squamoid, of mucoepidermoid carcinoma with clear cell undifferentiated intermediate, and clear cells components was established. 30 Yamamoto N et al.

Table 1 Clinical statistics on mucoepidermoid carci- follows: 11 cases in the palate (48%); 5 in noma at this college the retromolar region (22%); 2 in the oral Tokyo Dental College floor (9%); 2 in the lower lip (9%); and 1 each Chiba Hospital in the maxillary sinus, maxillary bone, and Investigation year 1993–2012 buccal region (4%)(Table 1). Occurrence in 6,7) Case No. 23 the retromolar region is known to be rare . 4) Site (%) However, Gnepp and Heffner reported that Palate 11 (48%) the retromolar region was the second most common site after the palate. This was also Retromolar region 5 (22%) the case at our hospital, with most occurring Floor of mouth 2 (9%) in the palate. This clearly indicates a relatively Lower lip 2 (9%) high rate of occurrence in the retromolar Maxillary sinus 1 (4%) region. Maxillary bone 1 (4%) At 15 months postoperatively, there have Buccal region 1 (4%) been no signs of recurrence or metastasis. Further, long-term follow-up is required, however. Mass lesions in the retromolar region may be clinically diagnosed as benign tumors, but In terms of the postoperative prognosis the possibility of mucoepidermoid carcinoma with mucoepidermoid carcinoma, Kajiyama cannot be ignored. Therefore, the results of et al.9) reported that recurrence was not seen fine needle aspiration cytology should also with the low-grade malignancy type, but was be considered in deciding on the course of 42.9% with the high-grade malignancy type. treatment. 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- Conclusion nancy of mucoepidermoid carcinomas with clear cell components remains unknown. It We have reported a case of mucoepider- has been suggested that the clear cell variant moid carcinoma with clear cell components of mucoepidermoid carcinoma will show rela- occurring in the retromolar region of a 63- tively low differentiation or high malignancy year-old woman. The findings were discussed if the source of the clear cells is squamous in reference to the literature. cells20). However, one study found no correlation between the prognosis and differentiation type in mucoepidermoid carcinoma7). The Acknowledgements histologic grading of the tumor in the present study was carried out in line with that in earlier The authors would like to thank Professor studies3,5) and revealed that 1) sacculation was Jeremy Williams, Tokyo Medical University, less than 20%; 2) no nerve invasion; 3) no for his assistance with the English of the necrosis; 4) no more than 5 images of mitotic manuscript. 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 References good prognosis. Twenty-three cases of mucoepidermoid 1) Barnes L, Eveson JW, Reichart P, Sideansky D (Eds) (2005) World Health Organization Clas- carcinoma have been treated at our hospital sification of Tumours, Pathology and Genetics over the last 20 years, between 1993 and Head and Neck Tumours, pp.219–220, IARC 2012. The distribution in the body was as Press, Lyon. Mucoepidermoid Carcinoma with Clear Cell Components 31

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