肺混合性鳞状细胞和腺性乳头状瘤2例临床病理特征及冷冻切片病理诊断误诊分析

doi:10.16150/j.1671-2870.2022.04.010

摘要/Abstract

摘要：

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。

关键词: 肺肿瘤, 混合性鳞状细胞和腺性乳头状瘤, 冷冻切片病理检查, 误诊

Abstract:

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.

Key words: Tnmor of the lung, Mixed squamous cell and glandular papilloma, Pathological examination of frozen section, Misdiagnosis

中图分类号:

R541.7

车稳, 柳蒋书, 陈晓炎, 王朝夫, 袁菲, 王璇. 肺混合性鳞状细胞和腺性乳头状瘤2例临床病理特征及冷冻切片病理诊断误诊分析[J]. 诊断学理论与实践, 2022, 21(04): 476-481.

CHE Wen, LIU Jiangshu, CHEN Xiaoyan, WANG Chaofu, YUAN Fei, WANG Xuan. Pulmonary mixed squamous cell and glandular papilloma clinicopathological characteristics of 2 cases and misdiagnosis analysis of frozen section[J]. Journal of Diagnostics Concepts & Practice, 2022, 21(04): 476-481.

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参考文献 27

[1]	Borczuk AC, Cooper WA, Dacic S, et al. WHO Classifica-tion of Tumours of Thoracic Tumours[M]. 5th ed, Lyon(France): International Agency for Research on Cancer, 2021:37-40.
[2]	Flieder DB, Koss MN, Nicholson A, et al. Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature[J]. Am J Surg Pathol, 1998, 22(11):1328-1342. pmid: 9808125
[3]	Tryfon S, Dramba V, Zoglopitis F, et al. Solitary papillomas of the lower airways: epidemiological, clinical, and therapeutic data during a 22-year period and review of the literature[J]. J Thorac Oncol, 2012, 7(4):643-648. doi: 10.1097/JTO.0b013e3182468d06 pmid: 22425912
[4]	Noda N, Ebie Y, Matsumura M, et al. Comparison of detection specificity of nitrifying bacteria in biofilm using fluorescence in situ hybridization and in situ fluorescent antibody methods[J]. Water Sci Technol, 2003, 47(5):129-132.
[5]	Li F, He M, Li F, et al. Histologic characteristics and prognosis of lung mixed squamous cell and glandular papilloma: six case reports[J]. Int J Clin Exp Pathol, 2019, 12(9):3542-3548.
[6]	Lin DL, Xing XM, Ran WW, et al. Pulmonary peripheral glandular papilloma and mixed squamous cell and glandular papilloma frequently harbour the BRAF V600E mutation[J]. Histopathology, 2020, 76(7):997-1004. doi: 10.1111/his.14098 URL
[7]	汪小霞, 李锐, 冯潇, 等. 肺混合性鳞状细胞和腺性乳头状瘤临床病理学分析[J]. 中华病理学杂志, 2019, 48(4):318-321.
	Li R, Feng X, et al. Clinicopathological analysis of pulmonary mixed squamous cell and glandular papilloma[J]. Chin J Pathol, 2019, 48(4):318-321.
[8]	Iijima Y, Nakajima Y, Kinoshita H, et al. Mixed squamous cell and glandular papilloma of the lung: a case report and literature review in Japan[J]. Int J Surg Case Rep, 2020, 68:39-42. doi: 10.1016/j.ijscr.2020.02.021 URL
[9]	Yun JS, Kim DW, Choi YD, et al. Mixed squamous cell and glandular papilloma of the lung in a 64-year-old woman[J]. Korean J Thorac Cardiovasc Surg, 2014, 47(1):55-58. doi: 10.5090/kjtcs.2014.47.1.55 pmid: 24570869
[10]	Miyoshi R, Menju T, Yoshizawa A, et al. Expression of p16 Ink4a in mixed squamous cell and glandular papilloma of the lung[J]. Pathol Int, 2017, 67(6):306-310. doi: 10.1111/pin.12531 pmid: 28470939
[11]	Feng AN, Wu HY, Zhou Q, et al. Solitary endobronchial papillomas with false impression of malignant transformation: report of two cases and review of the literature[J]. Int J Clin Exp Pathol, 2015, 8(7):8607-8612.
[12]	刘荣美, 孟庆大. 肺混合性鳞状细胞和腺性乳头状瘤3例报道[J]. 诊断病理学杂志, 2018, 25(7):533-534.
	Meng QD. Pulmonary mixed squamous cell and glandular papilloma: a report of three cases[J]. Chin J Diagn Pathol, 2018, 25(7):533-534.
[13]	Yabuki K, Matsuyama A, Obara K, et al. A unique case of a huge mixed squamous cell and glandular papilloma of non-endobronchial origin with a peripheral growth[J]. Respir Med Case Rep, 2018, 24:108-112. doi: 10.1016/j.rmcr.2018.05.001 pmid: 29977775
[14]	Huo Z, Wu H, Li J, et al. Primary pulmonary mucoepidermoid carcinoma: histopathological and moleculargenetic studies of 26 cases[J]. PLoS One, 2015, 10(11):e0143169.
[15]	王征, 王恩华, 刘东戈. 肺原发性黏液性上皮源性肿瘤的病理诊断与鉴别诊断[J]. 中华肿瘤杂志, 2017, 39(1):1-6. pmid: 28104025
	Wang Z, Wang EH, Liu DG. Pathological diagnosis and differential diagnosis for primary pulmonary mucinous epi-thelial tumors[J]. Chin J Oncol, 2017, 39(1):1-6. doi: 10.3760/cma.j.issn.0253-3766.2017.01.001 pmid: 28104025
[16]	Chang JC, Montecalvo J, Borsu L, et al. Bronchiolar adenoma: expansion of the concept of ciliated muconodular papillary tumors with proposal for revised terminology based on morphologic, immunophenotypic, and genomic analysis of 25 cases[J]. Am J Surg Pathol, 2018, 42(8):1010-1026. doi: 10.1097/PAS.0000000000001086 pmid: 29846186
[17]	Ishikawa Y. Ciliated muconodular papillary tumor of the peripheral lung: benign or malignant?[J]. Pathol Clin Med (Byouri-to-Rinsho), 2002,20,964-965.
[18]	Kamata T, Sunami K, Yoshida A, et al. Frequent BRAF or EGFR mutations in ciliated muconodular papillary tumors of the lung[J]. J Thorac Oncol, 2016, 11(2):261-265. doi: 10.1016/j.jtho.2015.10.021 pmid: 26718882
[19]	Liu L, Aesif SW, Kipp BR, et al. Ciliated muconodular papillary tumors of the lung can occur in western patients and show mutations in bRAF and AKT1[J]. Am J Surg Pathol, 2016, 40(12):1631-1636. pmid: 27454941
[20]	Abe J, Ito S, Takahashi S, et al. Mixed squamous cell and glandular papilloma of the lung resembling early adenocarcinoma: A case report[J]. Ann Med Surg (Lond), 2016, 7:61-64. doi: 10.1016/j.amsu.2016.03.025 pmid: 27141302
[21]	Sasaki E, Masago K, Fujita S, et al. AKT1 mutations in peripheral bronchiolar papilloma: glandular papilloma and mixed squamous cell and glandular papilloma is distinct from bronchiolar adenoma[J]. Am J Surg Pathol, 2021, 45(1):119-126. doi: 10.1097/PAS.0000000000001573 URL
[22]	陈晓炎, 杨晓群, 袁菲, 等. 肺纤毛黏液结节性乳头状肿瘤2例临床病理分析及文献复习[J]. 诊断学理论与实践, 2018, 17(5):575-580.
	Yang XQ, Yuan F, et al. Pulmonary ciliated muconodular papillary tumor: clinical pathologic analysis of two cases and review of literature[J]. J Diagn Concepts & Pract, 2018, 17(5):575-580.
[23]	Popper HH, Wirnsberger G, Jüttner-Smolle FM, et al. The predictive value of human papilloma virus (HPV) typing in the prognosis of bronchial squamous cell papillomas[J]. Histopathology, 1992, 21(4):323-330. pmid: 1328017
[24]	Huang YL, Chang YL, Chen KC, et al. Mixed squamous cell and glandular papilloma of the lung: a case report of a novel mutation in the BRAF gene and coexistent HPV infection, possible relationship to ciliated muconodular papillary tumor[J]. Pathol Int, 2019, 69(2):104-109. doi: 10.1111/pin.12747 URL
[25]	Inamura K, Kumasaka T, Furuta R, et al. Mixed squamous cell and glandular papilloma of the lung: a case study and literature review[J]. Pathol Int, 2011, 61(4):252-258. doi: 10.1111/j.1440-1827.2011.02659.x pmid: 21418399
[26]	Tryfon S, Dramba V, Zoglopitis F, et al. Solitary papillomas of the lower airways: epidemiological, clinical, and therapeutic data during a 22-year period and review of the literature[J]. J Thorac Oncol, 2012, 7(4):643-648. doi: 10.1097/JTO.0b013e3182468d06 pmid: 22425912
[27]	Hayashi T, Tachibana S, Nakao K, et al. Solitary peripheral pulmonary squamous cell papilloma; diagnostic significance of 18F-fluorodeoxyglucose positron emission tomography findings[J]. Kyobu Geka, 2017, 70(4):309-312.

文献	病例数（男∶女）	年龄（中位年龄,岁）	肿瘤位置		最大径（cm）	分型		临床症状	随访
文献	病例数（男∶女）	年龄（中位年龄,岁）	左肺	右肺	最大径（cm）	中央	外周	临床症状	随访
Li等^[5]	6（4∶2）	39~67（53）	1	5	1.8~4.2	1	5	腹胀、食欲不振1例;咳嗽咳痰1例;体检发现4例	随访12~52个月（平均31个月）,其中1例术后11月胸部CT示双肺结节,考虑转移,其余均无复发转移
Lin等^[6]	5（2∶4）	55~70（60）	3	2	1.0~5.0	0	5	1例胸痛,1例胸痛及咳嗽,1例咳嗽及血痰,2例无症状	随访10~89个月（平均51.6个月）,均无复发转移
汪小霞等^[7]	5（0∶5）	42~59（48）	不详	不详	1.5~3.5	3	2	胸痛、胸闷、咳嗽咳白痰、痰中带血、发热	随访2~28个月,无复发转移
Iijima等^[8]	20（10∶10）	34~84（63.5）	10	10	0.9~3.0	8	12	不详	不详

文献	误诊率	冷冻病理诊断结果
Lin等^[6]	1/2	1例黏液表皮样癌,1例PMSGP
Iijima等^[8]	6/12	2例腺癌,2例腺鳞癌,1例黏液表皮样癌,1例鳞状细胞癌,5例乳头状瘤,1例无恶性证据
Yun等^[9]	1/1	腺癌
Miyoshi等^[10]	1/1	黏液表皮样癌不能除外
Feng等^[11]	0/1	倾向良性病变
本文	1/2	1例黏液腺癌,1例考虑PMSGP,但不除外黏液表皮样癌