[Salivary papillary cystic low-grade mucoepidermoid carcinoma and cystadenoma: a comparison of clinicopathological and genetic features].

Objective: To study the clinicopathologic and genetic features of papillary cystic low-grade mucoepidermoid carcinoma (LG-MEC) and cystadenoma. Methods: A retrospective review was performed on salivary gland tumor patients with papillary cystic architecture who presented to department of oral pathology, Peking University School and Hospital of Stomatology between January 2010 and June 2022. Among this cohort, there were 17 males and 17 females with a range age of 23-82 years [(55.6±14.6) years]. Diagnosis was confirmed by histological, immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) analysis. Finally, 15 papillary cystic LG-MEC and 19 cystadenoma patients were included in the present study. All patients were followed clinically and radiologically, and the duration of follow-up ranged from 1 to 141 months. Results: All neoplasms showed papillary proliferation with multilocular or giant cystic tumors. Papillary cystic LG-MEC was characterized by epidermoid cells, intermediate cell and mucous cells with multiple lining-layers. Papillary cystic LG-MEC had mild cellular atypia and a pushing infiltration. Cystadenoma was characterized by cuboidal, columnar and ciliated pseudostratified columnar lining epithelium. Squamous metaplasia, mucinous metaplasia and acidophilic degeneration could also be observed focally in cystadenoma. For IHC staining, papillary cystic LG-MEC showed diffusely and strongly positive for mucin 4 (MUC4) (15/15) and mucin 5 Subtype AC (MUC5AC) (4/15) in the epidermoid cells, intermediate cell and mucous cells. The epidermoid cells and intermediate cells were diffusely positive for p40 and p63. The Ki-67 index was about 10%-15% in LG-MEC. As a contrast, p40 (17/19) and p63 (14/15) were only detected in the basal cells of cystadenoma. Cystadenoma showed focal MUC5AC (4/19)expression and MUC4 (19/19)diffuse expression. In addition, the Ki-67 index was 5%-10% in cystadenoma. The MAML2 gene translocation was detected in 11 LG-MEC patients, but none in cystadenoma. Conclusions: The differential diagnosis points between papillary cystic LG-MEC and cystadenoma included the specific epidermoid cells, intermediate cells and mucus cells in LG-MEC, cell atypia, the pushing-infiltration pattern, diffuse expression of p40 and p63 in the lining epithelium, and a MAML2 gene rearrangement. The molecular test of MAML2 should be recommended to reduce missed LG-MEC diagnoses.目的： 探讨唾液腺乳头囊性低级别黏液表皮样癌（low-grade mucoepidermoid carcinoma，LG-MEC）与囊腺瘤的临床病理学和分子遗传学特征以鉴别诊断，避免误诊漏诊。 方法： 回顾性分析2010年1月至2022年6月北京大学口腔医学院·口腔医院口腔病理科收检的唾液腺标本，形态表现以乳头囊性结构为主的唾液腺肿瘤34例，男性17例，女性17例，年龄为（55.6±14.6）岁（23~82岁）。经组织学、免疫组化及原位荧光杂交检测，确诊为15例乳头囊性LG-MEC和19例囊腺瘤患者，并分别进行随访，随访时间1~141个月，观察患者有无复发。 结果： 34例唾液腺肿瘤镜下表现均以大囊或多囊乳头结构为主。乳头囊性LG-MEC具有特征性表皮样细胞、中间型细胞和多少不一的黏液细胞，衬里上皮层次不等，部分肿瘤细胞具有轻度异型性，范围较局限，但与周围组织界限不清，呈推挤性浸润。囊腺瘤衬里上皮呈立方、柱状或高柱状，部分呈假复层纤毛柱状，部分伴有黏液细胞化生、鳞状化生或嗜酸细胞化生。免疫组化染色结果显示，乳头囊性LG-MEC黏液细胞、中间型细胞和表皮样细胞均弥漫表达黏蛋白4（mucin4，MUC4）（15/15），4例弥漫表达黏蛋白5 AC亚型（mucin5 subtype AC，MUC5AC）；表皮样细胞和中间型细胞弥漫性表达p40（10/15）和p63（14/15）；Ki-67增殖指数为10%~15%。囊腺瘤组的基底细胞和黏液细胞化生均可表达MUC4（19/19）和MUC5AC（4/19），但MUC4呈弥漫性表达，MUC5AC呈灶性表达；仅在基底细胞中表达p40（17/19）和p63（19/19）；Ki-67增殖指数为5%~10%。荧光原位杂交检测显示11例乳头囊性LG-MEC存在MAML2基因断裂（11/15），囊腺瘤未检测到MAML2基因的断裂（0/19）。 结论： 唾液腺乳头囊性低级别LG-MEC具有表皮样细胞、中间型细胞和黏液细胞，细胞异型性略大于囊腺瘤，呈推挤性浸润的生长方式，p40和p63在衬里上皮中弥漫表达，存在MAML2基因断裂，在临床诊断中需重视与囊腺瘤的鉴别诊断，必要时建议辅助MAML2基因重排检测以减少误诊及漏诊。.