肺胶样腺癌4例临床病理分析及文献复习

doi:10.16150/j.1671-2870.2019.06.009

摘要/Abstract

摘要：

目的：探讨肺胶样腺癌（colloid adenocarcinoma, CA）的临床病理学特征、免疫表型、分子特征及鉴别诊断。方法：回顾性分析4例肺CA患者的临床病理资料,并结合相关文献进行探讨。结果：4例均为老年男性,年龄为61~67岁,中位年龄为64岁,其中3例有吸烟史,临床表现为乏力、咳嗽等非特异性症状,或因体检发现。肿瘤位于右肺上叶3例,右肺下叶1例。胸部CT检查提示病灶呈实性结节状或团块状。大体检查,3例为外周型,1例几乎占据整个肺叶,最大径为1.6~12.0 cm,切面呈灰白色,黏冻样,有光泽。光镜检查可见,肿瘤组织富含黏液,形成黏液池,肺泡间隔断裂。肿瘤细胞呈单个、簇状、条索状或微乳头状,漂浮于黏液池中,少量肿瘤细胞贴壁生长,4例肿瘤中3例可见微乳头成分。细胞呈杯状细胞或印戒细胞形态,中度异型,核分裂相少见。2例黏液池中可见少量砂砾体。免疫组织化学（免疫组化）检查结果显示,4例均表达CK7及MUC-1,1例表达CK20;3例表达TTF-1与NapsinA,其中1例两者均弥漫表达,2例两者均局灶表达;2例表达CDX-2、MUC-2及Villin;3例表达MUC5AC。4例中2例行分子检测,1例行EGFR、ALK及ROS1基因检测,未检测到基因改变;另1例行数字PCR检测,检测到KRAS外显子2基因突变。随访结果显示,3例伴微乳头结构的病例中,2例出现转移,其中1例病灶伴有少量实性成分者出现远处转移;另1例虽无微乳头结构,但肿瘤巨大,术后半年患者因肺部感染、呼吸衰竭死亡。结论：肺CA是一种少见的原发性肺腺癌,明确诊断依赖病理组织学检查及免疫组化检查,TTF-1及NapsinA阳性有助于原发性肺CA的诊断,当两者均阴性时要综合形态学、免疫表型及临床病史排除转移的可能性;大部分肺CA患者预后较好,但出现微乳头结构提示预后不佳。

关键词: 肺, 胶样腺癌, 微乳头, 砂砾体

Abstract:

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and differential diagnosis of colloid adenocarcinoma. Methods: The clinical and pathological data of 4 cases of pulmonary adenocarcinoma were retrospectively analyzed, and associated literature was reviewed. Results: All 4 patients were elderly men, aged 61-67 years, with a median age of 64 years. Three of them had a history of smoking. The clinical manifestations were non-specific symptoms such as fatigue and cough, or without symptoms. The tumors were located in right upper lobe in 3 cases and right lower lobe in 1 case; 3 cases were peripheral located and 1 case almost occupied the entire lobe. The maximum diameter was 1.6-12.0 cm. The cut surface was grayish white, jelly-like and shiny. Microscopically, the tumor showed abundant mucin pools which destroyed the walls of alveolar spaces. The tumor cells showed goblet or signet-ring morphology, with moderate nuclear atypia and low mitotic rate, presenting singly, in small clusters or micropapillary clusters. Tumor cells floated in the mucin pool and a small number of tumor cells might line the alveolar space. Psammoma bodies could be seen in 2 cases. Immunophenotyping showed that 4 cases expressed CK7 and MUC-1, 1 case expressed CK20, 3 cases expressed TTF-1 and NapsinA（1 diffuse and 2 focal）, 2 cases expressed CDX-2, MUC-2 and Villin, 3 cases expressed MUC5AC. Molecular detection showed KRAS mutation in one case. Conclusions: Pulmonary adenocarcinoma is rarely seen. The pathological diagnosis depends on histopathological examination and immunohistochemical staining. The differential diagnosis includes primary mucinous tumor of lung and metastatic mucinous adenocarcinoma. Most cases of pulmonary adenocarcinoma have a good prognosis, but the presence of non-colloid component, interstitial infiltration and micropapillary structure suggests a worse prognosis.

Key words: Lung, Colloid adenocarcinoma, Micropapillary, Psammoma body

中图分类号:

R734.2

许海敏, 陈晓炎, 张静, 王朝夫. 肺胶样腺癌4例临床病理分析及文献复习[J]. 诊断学理论与实践, 2019, 18(06): 649-654.

XU Haimin, CHEN Xiaoyan, ZHANG Jing, WANG Chaofu. Pulmonary colloid adenocarcinoma: Clinical pathological analysis of 4 cases and review of literature[J]. Journal of Diagnostics Concepts & Practice, 2019, 18(06): 649-654.

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参考文献 19

[1]	Travis WD, Brambilla E, Burke AP, et al. WHO Classification oftumours of the lung, pleura, thymus and heart[M]. Lyon: IARC Press, 2015:40-41.
[2]	Zenali MJ, Weissferdt A, Solis LM, et al. An update on clinicopathological, immunohistochemical, and molecular profiles of colloid carcinoma of the lung[J]. Hum Pathol, 2015, 46(6): 836-842. doi: 10.1016/j.humpath.2014.10.032 URL
[3]	Sonzogni A, Bianchi F, Fabbri A, et al. Pulmonary adenocarcinoma with mucin production modulates phenotype according to common genetic traits: a reappraisal of mucinous adenocarcinoma and colloid adenocarcinoma[J]. J Pathol Clin Res, 2017, 3(2):139-152. doi: 10.1002/cjp2.67 URL
[4]	Cha YJ, Shim HS, Han J, et al. Clinicopathologic ana-lysis of 10 cases of pulmonary colloid adenocarcinoma and prognostic implication of invasive micropapillary component[J]. Pathol Res Pract, 2018, 214(12):2093-2098. doi: 10.1016/j.prp.2018.10.014 URL
[5]	Masai K, Sakurai H, Suzuki S, et al. Clinicopathological features of colloid adenocarcinoma of the lung: A report of six cases[J]. JSurg Oncol, 2016, 114(2):211-215.
[6]	Rossi G, Murer B, Cavazza A, et al. Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special refe-rence to CDX-2 homeobox gene and MUC2 expression[J]. Am J Surg Pathol, 2004, 28(4):442-452. doi: 10.1097/00000478-200404000-00003 URL
[7]	Graeme-Cook F, Mark EJ. Pulmonary mucinous cystic tumors of borderline malignancy[J]. Hum Pathol, 1991, 22(2):185-190. pmid: 2001880
[8]	Moran CA, Hochholzer L, Fishback N, et al. Mucinous (so-called colloid) carcinomas of lung[J]. Mod Pathol, 1992, 5(6): 634-638.
[9]	Gao ZH, Urbanski S J. The spectrum of pulmonary mu-cinous cystic neoplasia : a clinicopathologic and immunohistochemical study of ten cases and review of litera-ture[J]. Am J Clin Pathol, 2005, 124(1):62-70. doi: 10.1309/52XXR6E6U0J2JX0F URL
[10]	Berger K L, Nicholson S A, Dehdashti F, et al. FDG PET evaluation of mucinous neoplasms: correlation of FDG uptake with histopathologic features[J]. Am J Roentgenol, 2000, 174(4):1005-1008. pmid: 10749239
[11]	Shim S S, Han J. FDG-PET/CT imaging in assessing mucin-producing non-small cell lung cancer with pathologic correlation[J]. Ann Nucl Med, 2010, 24(5):357-362. doi: 10.1007/s12149-010-0358-x URL
[12]	Miyake A, Okudela K, Matsumura M, et al. Update on the potential significance of psammoma bodies in lung adenocarcinoma from a modern perspective[J]. Histopatho-logy, 2018, 72(4):609-618.
[13]	Chang JC, Montecalvo J, Borsu L, et al. Bronchiolar adenoma: expansion of the concept of ciliated mucono-dular 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 URL
[14]	Chuang H W, Liao J B, Chang H C, et al. Ciliated muconodular 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. doi: 10.1111/pin.12179 URL
[15]	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.
[16]	Ye J, Findeis-Hosey JJ, Yang Q, et al. Combination of napsin A and TTF-1 immunohistochemistry helps in differentiating primary lung adenocarcinoma from metastatic carcinoma in the lung[J]. Appl Immunohistochem Mol Morphol, 2011, 19(4):313-317. doi: 10.1097/PAI.0b013e318205b059 URL
[17]	Rossi G, Cavazza A, Righi L, et al. Napsin-A, TTF-1, EGFR, and ALK status determination in lung primary and metastatic mucin-producing adenocarcinomas[J]. Int J Surg Pathol, 2014, 22(5):401-407. doi: 10.1177/1066896914527609 URL
[18]	Kalhor N. Colloid carcinoma of the lung: Current views[J]. Semin Diagn Pathol, 2014, 31(4):265-270. doi: 10.1053/j.semdp.2014.06.003 pmid: 25239272
[19]	Morita K, Nagashima A, Takemoto N, et al. Primary pulmonary mucinous (colloid) adenocarcinoma with postope-rative bone metastasis[J]. Ann Thorac Cardiovas Surg, 2014, 20(Suppl):677-681.

病例	性别	年龄（岁）	吸烟史	症状	体积（cm）	PET/CT	部位	手术方式	病理分期	随访
1	男	61	无	体检发现,无症状	1.6×1.6 ×1.5	代谢轻度增高	右肺上叶	肺段切除+纵隔淋巴结清除	ⅢA （T_1bN₂M₀）	术后34个月无复发及远处转移
2	男	67	有	咳嗽、咳痰,胸闷、气促	2.9×1.7 ×1.5	未查	右肺下叶	肺叶切除+纵隔淋巴结清除	ⅠA3 （T_1cN₀M₀）	术后半年发生骨转移及脑转移
3	男	66	有	体检发现,无症状	1.6×1.0 ×1.0	未查	右肺上叶	肺叶切除+纵隔淋巴结清除	ⅠA2 （T₁bN₀M₀）	术后31个月无复发转移
4	男	62	有	全身乏力半年余	12.0×11.0 ×8.0	代谢轻度增高	右肺上叶	肺叶切除+纵隔淋巴结清除	ⅢA （T₄N₀M₀）	术后半年因肺部感染、呼吸衰竭死亡

病例	TTF-1	NapsinA	SP-A	CK7	CK20	CDX-2	Villin	MUC-1	MUC-2	MUC5AC
1	-	-	-	+	-	-	-	F+	-	F+
2	F+	F+	-	+	-	+	F+	+	F+	+
3	+	+	-	+	-	-	-	+	-	+
4	F+	F+	F+	+	+	+	F+	F+	+	-