目的：探讨肺混合性鳞状细胞和腺性乳头状瘤（pulmonary mixed squamous cell and glandular papilloma,PMSGP）的临床病理特征,并分析该病的冷冻切片病理诊断要点及误诊原因。方法：收集2019年至2021年上海交通大学医学院附属瑞金医院经术后石蜡切片病理检查确诊为PMSGP的病例2例,并结合文献分析其临床病理特点及冷冻切片病理检查误诊的原因。结果：2例患者分别为74岁的女性及66岁的男性,均为体检发现肺占位,其中1例伴有胸闷胸痛,影像学检查均考虑为恶性肿瘤,行肺叶切除术。术中冷冻切片病理检查结果,1例考虑为黏液腺癌,1例考虑为PMSGP,但不能排除黏液表皮样癌。术后石蜡切片病理检查显示,2例患者的肿瘤体积分别为3.0 cm×2.5 cm×2.5 cm和1.7 cm×1.7 cm×1.6 cm,肿瘤细胞排列呈乳头状,表面被覆腺上皮及鳞状上皮,乳头轴心有较多炎症细胞,鳞状上皮有轻-中度不典型性,核分裂象罕见,无坏死。免疫组织化学检查示,2例患者的肿瘤组织中,腺上皮细胞表达CK7和TTF-1,黏液柱状上皮表达MUC5AC,鳞状上皮及基底细胞表达CK5/6、P63和P40,Ki-67仅在基底层高表达。2例荧光原位杂交（fluorescence in situ hybridization,FISH）检测均未发现MAML2基因重排。2例患者分别随访9个月及24个月,均无复发或转移。复习相关文献报道的39例PMSGP患者,冷冻切片病理检查的肿瘤性质误诊率高达52.6%,误诊原因主要为PMSGP与黏液表皮样癌及黏液腺癌等恶性肿瘤存在形态学交叉,且被覆鳞状上皮的不典型性在冷冻切片病理诊断时容易被放大。结论：PMSGP为肺部少见的良性肿瘤,术中冷冻切片病理检查误诊率高。冷冻切片中,PMSGP肿瘤的形态特征包括境界清楚,呈乳头状结构,乳头被覆鳞状上皮及腺上皮,基底细胞沿纤维血管轴心栅栏状排列,细胞排列有层次感,无异型性。

Objective: To discuss the clinicopathologic characteristics of pulmonary mixed squamous cell and glandular papilloma(PMSGP), and to analyze the key points for diagnosis and the causes of misdiagnosis of frozen section. Methods: Two cases of PMSGP diagnosed by pathology at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2019 to 2021 were enrolled, and the clinicopathologic and immunohistochemical characteristics and key points of frozen section diagnosis were analyzed based on literature review. Results: Two patients, a 74-year-old female and a 66-year-old male, were found to have pulmonary nodules in physical examination. One patient had chest tightness and pain. All nodules were considered as malignant tumors on imaging and lobectomy was performed. Frozen sections indicated one case was diagnosed as mucinous adenocarcinoma and the other diagnosed as PMSGP, but mucoepidermoid carcinoma could not be ruled out. In the paraffin section, the tumor sizes of 2 cases were 3.0 cm×2.5 cm×2.5 cm and 1.7 cm×1.7 cm×1.6 cm respectively. PMSGP displayed a papillary growth pattern lined by glandular epithelial cells and squamous cells. Inflammatory cells were observed along the papillary axis. Squamous epithelium could be mild to moderately atypical with rare mitosis and no necrosis. Immunohistochemistry examination showed that CK7 and TTF-1 were expressed in glandular epithelial cells, MUC5AC was expressed in mucinous columnar epithelial cells, squamous cells and basal-like cells expressed CK5/6, P63, P40 and Ki-67 was highly expressed only in the basal layer. MAML2 rearrangement was not detected in the 2 cases by FISH. No recurrence or metastasis was observed at 9 and 24 months of follow-up. A literature review of 39 cases showed that due to the morphological crossover with mucoepidermoid carcinoma and mucinous adenocarcinoma, and the atypical nature of the covered squamous epithelium was easily amplified in frozen section diagnosis, the misdiagnosis rate of PMSGP of tumor properties on frozen section is as high as 52.6%. Conclusions: PMSGP is a rare benign tumor of the lung, that has a high rate of misdiagnosis on frozen section. On frozen section, the tumor is well defined and has a papillary structure. The papilla is covered with squamous epithelium and glandular epithelium. Basal cells are arranged in a palisade pattern along the fibrovascular axis, and the cells are stratified without atypia. Mastering these characteristics helps to improve the diagnostic accuracy of frozen section.