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1 Kor J Oral Maxillofac Pathol 2013;37(6): 연구개소타액선에발생한투명세포선암종의증례보고 강경림 1), 김조은 2), 조영아 1), 윤혜정 1), 이재일 1), 홍삼표 1), 홍성두 * 1) 서울대학교치의학대학원구강병리학교실 1), 구강악안면방사선학교실 2) <Abstract> Clear Cell Adenocarcinoma of the Soft Palate: a Case Report Kyung Rim Kang 1), Jo Eun Kim 2), Young Ah Cho 1), Hye Jung Yoon 1), Jae Il Lee 1), Sam Pyo Hong 1), Seong Doo Hong 1) Department of Oral Pathology 1) and Department of Oral and Maxillofacial Radiology and Dental Research Institute 2), School of Dentistry, Seoul National University Clear cell adenocarcinoma (CCA) is a rare malignant neoplasm of salivary gland that represents only 1% of all salivary gland tumors. CCA is histopathologically characterized by monotonous, glycogen-rich, round to ovoid clear cells intermixed with hyalinized stroma. However, other salivary gland tumors such as mucoepidermoid carcinoma, acinic cell adenocarcinoma, oncocytoma, epithelial-myoepithelial carcinoma, and myoepithelial carcinoma should be ruled out to diagnosis CCA. We herein report a case of CCA involving the soft palate in a 56-year-old female. It is essential to consider CCA in the differential diagnoses of clear cell tumors. Key words:clear cell adenocarcinoma, Salivary Gland Neoplasms, Palate Ⅰ. 서론 투명세포선암종 (Clear cell adenocarcinoma) 은극히드물게발견되는타액선의악성종양이다. WHO에서는투명세포선암종을 H&E 염색에서투명하게보이는세포들로이루어진상피성종양으로정의하고있다 1). 발생비율은보고에따라차이가있으나전체타액선종양의약 1% 미만으로생각된다 2,3). 남녀에서비슷한비율로발생하며, 40대이후에주로발생한다. 호발부위는소타액선으로, 절반가량이구개부위에서발견된다 2,4). 조직학적으로는원형에서다각형에이르는투명한세포질을갖는세포들이 sheet, cord 혹은 nest 형태로배열되어있으며, 핵의다형성은매우드물게관찰된다. 세포 * Correspondence: Seong Doo Hong, Department of Oral Pathology, School of Dentistry, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, Korea. Tel: , hongsd@snu.ac.kr Received: Nov 11, 2013; Revised: Nov 14, 2013; Accepted: Nov 21, 2013 사이에서는유리화된기질 (hyalinized collagen stroma) 이종종발견되며, 이러한기질조직으로이루어진격벽에의해세포들이분리되어존재하는모습도관찰된다. 투명한세포질을갖는세포들은다양한종류의종양에서발견되므로, 감별진단이매우중요하다. WHO 역시투명한세포로구성된다른타액선종양들을모두배제함으로써투명세포선암종을최종진단할수있다고기술하고있다 1). 본연구에서는 56세여자환자의연구개에발생한투명세포선암종과그진단과정을보고하고자한다. Ⅱ. 증례보고 56세여자환자가연구개중앙에위치한병소의진단과치료를위하여서울대학교치과병원으로의뢰되었다. 병소는 4~5개월전에발생하였으며, 연구개에돌출되어있는직경 2 cm 가량의연조직종괴였다. 병소를인지할당시에는통증이없었으나최근간헐적통증이시작되었다고보고되었다.

2 환자는고혈압과당뇨병, 고지혈증으로투약중이었으며그외다른병력은없었다. 자기공명영상에서연구개중앙부에 cm의연조직종괴가관찰되었다. 종괴내부는다소불균일한양상으로 T2 강조영상에서높은신호강도를보였으며, T1 강조영상에서는낮은신호강도를보였다. 병소와주변조직과의경계는비교적명확하였으며, 구개골등의주위해부학적구조물로의침윤은관찰되지않았다 (Fig. 1). 임상적, 방사선학적소견을종합하였을때, 소타액선에발생한양성종양을의심할수있었으며, 다형성선종 (pleomorphic adenoma) 의임상진단하에절제술이시행되었다. 육안검사시검체는담황색의연조직종괴로, 수개의소엽 (lobule) 으로나뉘어있었으며, 표면은울퉁불퉁한양상으로뚜렷한피막은관찰되지않았다. 검체의단면관찰시, 내부에국소적인괴사부위가존재함을알수있었다 (Fig. 2). 현미경검사결과, 종괴는피막화되어있지않고주변조직과의경계가분명하지않았다. 종양조직은대부분투명한세포질을갖는종양세포들 (clear cell) 로구성되어있었다. 세포들은전체적으로시트형태의성장양상 (sheet-like growth pattern) 을이루며배열되어있었으나, nest 형태를이루면서성장하는부분도관찰되었다세포는원형에서다각형에이르는모양이었으며, 핵은호염기성을띠고세포질내에서한쪽으로치우쳐존재하였다 (Fig. 3A). 세포의유사분열및핵의다형성은거의관찰되지않았다. 종양세포사이에서유리화된아교섬유 (hyalinized collagen) 로이루어진기질 (stroma) 이관찰되었으며 (Fig. 3B), 특히섬유조직으로이루어진격벽 (fibrous septa) 이종양세포들사이에명확히존재하고있었다. 특수염색결과대부분의종양세포들이 periodic acid-schiff (PAS) 염색에서는양성, diastase-pas 에서는음성으로나타났으며 (Fig. 4), mucicarmine 염색에서도전체적으로음성소견을보였다. 면역조직화학검사에서는 cytokeratin 7과 p63에양성을보였으며, vimentin, S-100 및 smooth muslcle actin 염색에음성소견을보였다 (Fig. 5). Ⅲ. 고찰투명세포 (clear cell) 가나타나는종양의종류는매우다양하다. 악안면영역에서는타액선기원의많은종양들이투명 Fig. 1. Magnetic resonance images show a well-defined soft tissue mass in the soft palate with hyper-intense T2 (left) and low T1 (right) signal. Fig. 2. Grossly, the tumor exhibits irregular surface with no capsule and lobulating growth pattern. Focal necrosis is observed on the cut surface. 328

3 세포를 포함하고 있으며, 또한 치성 종양이나 전이 암종도 유 항상 감별하여야 할 필요가 있다. 일찍이 1966년 Jacobs 등이 사한 형태의 투명세포를 보일 수 있다. 따라서 이러한 종양들 신세포암의 하악골로의 전이를 보고한 바 있으며5), 유사한 을 감별진단 하는 것은 병리 의사들의 지속적인 관심사가 되 보고는 Quinn 등에 의해 계속되고 있다6). 악성흑색종 어 왔다. 특히, 투명세포가 관찰되는 대표적 종양인 신세포암 (malignant melanoma)의 일부도 투명세포를 포함한다. 그 중 종(renal cell carcinoma)의 악골 전이는, 악골의 원발 병소와 에서도 전이성 풍선세포흑색종(metastatic balloon cell Fig. 3. Histopathologic examination shows clear cells arranged in sheets (A). Hyalinized fibrous tissue separates the sheets of polygonal clear cells, which have eccentrically located nuclei. Few mitotic figures are seen (B). Fig. 4. PAS staining results before (A) and after (B) diastase treatment show the presence of cytoplasmic glycogen. Fig. 5. Immunohistochemical staining results. Tumor cells are positive for cytokeratin 7 (A) and p63 (B), and negative for vimentin (C), S-100 (D) or smooth muscle actin (E). 329

4 melanoma) 은큰투명세포혹은세포질내과립을함유한종양세포가특징으로, 전체병소가이들세포로만구성된경우도있다. 이들세포들은멜라닌색소를함유하고있지않아현미경상에서투명하게관찰되나 HMB45, S-100 염색등에서양성을보여종양세포들이멜라닌세포기원임을유추할수있다. 또한 PAS와 mucicarmine 염색에서음성을보여투명세포의세포질내물질들이당원 (glycogen) 이나점액이아님을알수있다 7). 조직학적으로투명세포를특징으로하면서타액선에서기원하지않는종양들중악안면영역에나타날수있는병소는대부분치성종양으로대표되는데, 석회화상피성치성종양 (calcifying epithelial odontogenic tumor), 투명세포치성암종 (clear cell odontogenic carcinoma) 등이이에해당한다 8). 그러나본증례는연구개에발생한것으로, 악골및치아와의연관성은관찰되지않았다. 따라서치성종양의일종인석회화상피성치성종양과투명세포치성암종의가능성이매우낮을것으로생각된다. 타액선기원의종양중투명세포를보이는것으로는점액표피양암종 (mucoepidermoid carcinoma), 선포세포암종 (acinic cell adenocarcinoma), 상피-근상피암종 (epithelial-myoepithelial carcinoma), 근상피암종 (myoepithelial carcinoma) 등이있다 9). 점액표피양암종은가장흔한대 소타액선의악성종양이며, 대개의점액표피양암종에서투명세포들은전체종양세포의 10% 가량을차지하나, 드물게는종양의상당부분을차지하기도한다 2,10). 이러한투명세포들의일부는점액을함유하고있어 mucicarmine 염색에서선명한붉은색으로관찰된다. 투명세포와동시에표피양세포 (epidermoid cell) 들도존재하는것이점액표피양암종의특징으로, 본증례에서는명확한표피양세포가관찰되지않았으며, 또한 mucicarmine 염색에투명세포들의세포질이염색되지않아점액표피양암종을배제할수있었다. 이와더불어최근의분자유전학적연구에따르면, 투명세포선암종에서 EWSR1-ATF1 gene fusion 이관찰된바있다 11). EWSR1-ATF1 fusion 은일반적으로점액표피양암종에서는발견되지않으므로, 투명세포선암종의감별진단에유용한도구가될수있다. 반면에점액표피양암종에서는 MECT1 과 MAML2 oncogene 의 fusion 이발견되었으며 12), 이는투명세포선암종에서발견되지않아감별진단을할수있는또다른 특징으로생각된다. 선포세포암종은타액선의선포와유사한분화를보이는악성종양으로종양세포는풍부한세포질과호염기성과립을보인다. 이들은주로당원으로 PAS 와 diastase- PAS 염색에모두양성을보이나 13) 본증례의투명세포들은이에모두염색되지않았으므로선포세포암종역시배제될수있었다. 상피-근상피암종의경우에도투명한세포들이관찰되나, 이러한투명세포들은호산성의입방세포형태로나타나는도관세포들을둘러싸며성장한다. 또한상피-근상피암종의투명세포들은근상피세포성분화를보이며, 도관구조가쉽게관찰되지않고투명한세포들이다수를이루어도면역조직화학검사를통하여근상피세포분화여부를확인할수있다. 본증례는세포질의양이적은일부종양세포들이 p63 염색에서양성을보여근상피세포와공통점이있었으나, 동시에 vimentin 음성을보였고도관세포의증식이전혀동반되어있지않았으므로상피-근상피암종을배제할수있었다. 마찬가지로근상피암종을구성하는종양세포들역시주로 vimentin에양성을보이므로배제가능하였다. 결론적으로투명세포선암종은극히드물게발생하는저등급의타액선악성종양으로임상적감별은매우어려우나병리의는항상투명세포선암종의가능성을염두에두어야할것이다. 이선암종은투명한세포질을특징적으로보이며따라서유사한특징의다른암종들과감별하여야할필요가있다. 특수염색과면역조직화학검사를통해진단에도움을받을수있으며분자병리학의발전으로유전자수준에서변이를찾아낼수있는방법도발견되었다. Ⅳ. 참고문헌 1. Barnes L EJ, Reichart PA, Sidransky D: World Health Organization classification of tumours. Pathology and genetics. Head and neck tumours. World Health Organization Ellis GL, Auclair PL: Atlas of Tumor Pathology: Tumors of the Salivary Glands. Washington, DC: Armed Forces Institute of Pathology Sicurella F, Stival P, Brenna A: Clear cell carcinoma of 330

5 minor salivary gland of the tongue. Acta Otorhinolaryngol Ital 2004;24: Milchgrub S, Gnepp DR, Vuitch F, et al: Hyalinizing clear cell carcinoma of salivary gland. Am J Surg Pathol 1994;18: Jacobs H, Ruben MP, Lyon J: Renal-cell carcinoma metastatic to the mandible and gingiva. Oral Surg Oral Med Oral Pathol 1966;22: Quinn JH, Kreller JS, Carr RF: Metastatic renal cell carcinoma to the mandible: report of case. J Oral Surg 1981;39: Mowat A, Reid R, Mackie R: Balloon Cell Metastatic Melanoma - an Important Differential in the Diagnosis of Clear-Cell Tumors. Histopathology 1994;24: Weinreb I: Hyalinizing clear cell carcinoma of salivary gland: a review and update. Head Neck Pathol 2013;7: Rodriguez MS, Reija MF, Rodilla IG: Primary clear cell carcinoma of parotid gland: Case report and review of literature. J Oral Maxillofac Pathol 2013;17: Auclair PL, Goode RK, Ellis GL: Mucoepidermoid carcinoma of intraoral salivary glands. Evaluation and application of grading criteria in 143 cases. Cancer 1992;69: Antonescu CR, Katabi N, Zhang L, et al: EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer 2011;50: Martins C, Cavaco B, Tonon G, et al: A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands. J Mol Diagn 2004;6: Eversole LR: On the Differential-Diagnosis of Clear-Cell Tumors of the Head and Neck. Oral Oncology 1993;29B:

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