目的：探讨肺纤毛黏液结节性乳头状肿瘤（ciliated muconodular papillary tumors,CMPT）的临床和病理组织学特征、免疫表型及鉴别诊断。方法：总结2例CMPT患者的临床病理资料,分析其临床表现、影像学特点、病理学特征及免疫表型,并结合相关文献进行探讨。结果：术中冷冻病理检查结果,1例患者诊断为微浸润性黏液腺癌,另1例考虑需鉴别CMPT与微浸润性黏液腺癌。术后石蜡组织显示其具有共同的特征性结构,肿瘤组织主要排列呈腺管状、乳头状结构,局部可呈贴壁状生长,也可形成微乳头状结构;肿瘤内及肿瘤周围肺泡腔内充满黏液,并形成黏液池;肿瘤间质常伴有淋巴细胞、浆细胞浸润;肿瘤由基底细胞、纤毛柱状细胞及黏液细胞3种细胞构成。3种肿瘤细胞均无异型性,无核分裂象,无肿瘤性坏死。免疫组织化学检查提示基底细胞表达P63及P40,部分表达TTF-1;纤毛柱状细胞及黏液细胞均表达CK7及MUC-1,部分或少数弱表达TTF-1、NapsinA、SP-A及P63,均不表达P40,少量纤毛细胞弱表达MUC5AC;3种细胞Ki-67均低表达。结论：肺CMPT是一种新近认识的少见肺肿瘤,其组织形态及免疫表型均具有特征性,3种肿瘤细胞的免疫组化表达不一致,但在影像学检查及术中冷冻病理检查中易被误诊为腺癌,确诊需要进行石蜡组织形态学观察和免疫组化标志检测。
Objective: To investigate the clinical manifestation, pathological feature, immunophenotype, differential diagnosis of ciliated muconodular papillary tumor. Methods: Clinical data from two cases of CMPT were collected, analyzed retrospectively, including clinical, pathologic features, imaging findings, immunophenotype. Results: In frozen section examination during operation, one case was diagnosed as minimally invasive mucinous adenocarcinoma, the other was considered as CMPT or minimally invasive mucinous adenocarcinoma. Histologic findings of paraffin embedded tissue sections revealed that the tumor consisted of papillary, glandular architecture, a minimal extent of micropapillary structure, discontinuous lepidic growth. There was abundant extracellular mucin surrounding the tumor, which formed pools of mucin, with chronic inflammatory cell infiltration in the stroma. The epithelial components of the lesion consisted of ciliated columnar cells, mucous cells, basal cells. The basal cells provided a scaffold in the ou-ter layer, the ciliated columnar cells, mucous cells intermingled at the surface of the glandular/papillary structures. All three types of cells showed no nuclear atypia, no mitotic figures. Tissue necrosis was not observed. The basal cells expressed P63, P40, while a subset of basal cells expressed TTF-1. Both ciliated columnar cells, mucous cells expressed CK7, MUC-1, whereas TTF-1, Napsin A, SP-A, P63showed a patchy moderate intensity staining, P40showed no staining. The ciliated columnar cells were focally positive for MUC5AC. All three types of cells showed a low Ki-67index. Conclusions: CMPT of lung is a newly defined, extremely rare tumor with characteristic histological findings, immunophenotype. There is a potential diagnostic pitfalls for CMPT because it is easily misdiagnosed as mucinous adenocarcinoma by imaging findings, in the frozen section examination. The accurate pathologic diagnosis depends on the morphologic characteristics of paraffin-embedded tissue section, immunohistochemical staining
[1] Ishikawa Y.Ciliated muconodular papillary tumor of the peripheral lung: benign or malignant?(in Japanese)[J]. Pathol Clin Med(Byaur-to-Rinsho),2002,20:964-965.
[2] Kamata T, Yoshida A, Kosuge T, et al.Ciliated mucono-dular papillary tumors of the lung: a clinicopathologic analysis of 10 cases[J]. Am J Surg Pathol,2015,39(6):753-760.
[3] 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.
[4] Lau KW, Aubry MC, Tan GS, et al.Ciliated muconodular papillary tumor: a solitary peripheral lung nodule in a teenage girl[J]. Hum Pathol,2016,49:22-26.
[5] Kon T, Baba Y, Fukai I, et al.Ciliated muconodular pa-pillary tumor of the lung: A report of five cases[J]. Pathol Int,2016,66(11):633-639.
[6] Ishikawa M, Sumitomo S, Imamura N, et al.Ciliated muconodular papillary tumor of the lung: report of five cases[J]. J Surg Case Rep,2016,2016(8):1-4.
[7] Chu HH, Park SY, Cha EJ.Ciliated muconodular papillary tumor of the lung:The risk of false-positive diagnosis in frozen section[J]. Hum Pathol Case Reports,2017,7:8-10.
[8] Kim L, Kim YS, Lee JS, et al.Ciliated muconodular papil-lary tumor of the lung harboring BRAF V600E mutation and p16INK4a overexpression without proliferative activity may represent an example of oncogene-induced senescence[J]. J Thorac Dis,2017,9(12):E1039-E1044.
[9] Hata Y, Yuasa R, Sato F, et al.Ciliated muconodular papillary tumor of the lung: a newly defined low-grade malignant tumor with CT findings reminiscent of adenocarcinoma[J]. Jpn J Clin Oncol,2013,43(2):205-207.
[10] Sato S, Koike T, Homma K, et al.Ciliated muconodular papillary tumour of the lung: a newly defined low-grade malignant tumour[J]. Interact Cardiovasc Thorac Surg,2010,11(5):685-687.
[11] Taguchi R, Higuchi K, Sudo M, et al.A case of anaplastic lymphoma kinase (ALK)-positive ciliated muconodular papillary tumor (CMPT) of the lung[J]. Pathol Int,2017, 67(2):99-104.
[12] Udo E, Furusato B, Sakai K, et al.Ciliated muconodular papillary tumors of the lung with KRAS/BRAF/AKT1 mutation[J]. Diagn Pathol,2017,12(1):62.
[13] Chuang HW, Liao JB, Chang HC, et al.Ciliated muco-nodular papillary tumor of the lung: a newly defined peripheral pulmonary tumor with conspicuous mucin pool mimicking colloid adenocarcinoma: a case report and review of literature[J]. Pathol Int,2014,64(7):352-357.
[14] Nakamura S, Koshikawa T, Sato T, et al.Extremely well differentiated papillary adenocarcinoma of the lung with prominent cilia formation[J]. Acta Pathol Jpn,1992,42(10):745-750.
[15] Imai T, Suga M, Kaimori M, et al.Peripheral pulmonary papillary adenocarcinoma with prominent cilia: report of a rare case that was difficult to diagnose preoperatively[J]. Acta Cytol,2010,54(5 Suppl):949-957.
[16] Nair AR, Samvedam S, Madathipat U, et al.Moderately differentiated peripheral adenocarcinoma of the lung with cilia[J]. Int J Surg Pathol,2014,22(6):540-543.
[17] Aida S, Ohara I, Shimazaki H, et al.Solitary peripheral ciliated glandular papillomas of the lung: a report of 3 cases[J]. Am J Surg Pathol,2008,32(10):1489-1494.
[18] Emerson LL, Layfield LJ.Solitary peripheral pulmonary papilloma evaluation on frozen section: a potential pitfall for the pathologist[J]. Pathol Res Pract,2012,208(12):726-729.
[19] Kaseda K, Horio H, Harada M, et al.Solitary glandular papilloma of the peripheral lung: a report of two cases[J]. World J Surg Oncol,2014,12:149.
[20] Tsuta K, Ishii G, Nitadori J, et al.Comparison of the immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma with mucin production, and mucinous bronchioloalveolar carcinoma of the lung characterized by the presence of cytoplasmic mucin[J]. J Pathol,2006,209(1):78-87.
[21] 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.
[22] Jin Y, Shen X, Shen L, et al.Ciliated muconodular papillary tumor of the lung harboring ALK gene rearrangement: Case report and review of the literature[J]. Pathol Int,2017,67(3):171-175.
