Liu B, Wu N, Shen Q, Shi S S, Zhang S S, Ru Y, Rao Q, Zhou X J
Department of Pathology, Suzhou Hospital, Nanjing Medical University, Suzhou 215001, China.
Department of Pathology, Nanjing Jinling Hospital, Nanjing 210002, China.
Zhonghua Bing Li Xue Za Zhi. 2018 Aug 8;47(8):603-608. doi: 10.3760/cma.j.issn.0529-5807.2018.08.007.
To evaluate the clinicopathologic characteristics of lung non-terminal respiratory unit (non-TRU) type adenocarcinoma. Seventy-two cases of lung non-TRU type adenocarcinoma that underwent complete resection and diagnosed at Departments of Pathology, Affiliated Suzhou Hospital of Nanjing Medical University and Nanjing General Hospital of the PLA from January 2005 to December 2016 were retrospectively studied. The histomorphological changes and precursor lesions were observed under microscope. The expression of lineage-specific markers and tumor stem cell markers was detected by immunohistochemistry (IHC). The major driver mutations of lung adenocarcinoma were tested by ARMS and directive gene sequencing. Non-TRU type adenocarcinomas were more commonly found in male (65.3%, 47/72), former or current smokers (68.1%, 49/72), the elder (mean 61 years old), central adenocarcinoma (75.0%, 54/72), tumors with necrosis (61.1%, 44/72) and higher grade (73.6%, 53/72). Histologically, non-TRU type adenocarcinoma displayed complex histomorphology and was often composed of large irregular gland-like and acinar pattern accumulating extracellular mucin, necrotic tumor cell debris and neutrophils, or invasive adenocarcinoma with mucin production. The tumor cells were composed of bronchial surface epithelial cells, mucinous column cells, polygonal cells and goblet cells. Eighteen (25.0%), 23 (31.9%) and 28 (38.9%) cases exhibited ciliated columnar cell metaplasia (CCCM), mucous columnar cell change (MCCC) and bronchiolar columnar cell dysplasia (BCCD) (precursor lesion of lung adenocarcinoma). IHC showed the expression of CK7 (100.0%, 72/72), TTF1 (12.5%, 9/72), Napsin A (5.6%, 4/72), MUC5AC (81.9%, 59/72), MUC5B (87.5%, 63/72), p53 (66.7%, 48/72), CK5/6 (12.5%, 9/72), p63 (18.1%, 13/72), CK20 (19.4%, 14/72) and CDX2 (16.7%, 12/72) in the tumor cells. The expression of tumor stem cell markers was detected in 43.1% cases (31/72) for CD44, 31.9% (23/72) for CD133, 58.3% (42/72) for β-catenin, 36.1% (26/72) for ALDH1, 12.5% (9/72) for GATA6, 20.8% (15/72) for SOX2 and 29.2% (21/72) for OCT4. The driver mutations were 26.4% (19/72) for KRAS, 2.8% (2/72) for EGFR and 1.4% (1/72) for EML4-ALK, and none for BRAF and ROS1. Non-TRU type adenocarcinoma is an uncommon subtype of lung adenocarcinoma with distinct clinicopathologic characteristics, histologic appearances, immunophenotype and molecular genetic alterations.
评估肺非终末呼吸单位（非TRU）型腺癌的临床病理特征。回顾性研究了2005年1月至2016年12月期间在南京医科大学附属苏州医院病理科和解放军南京总医院接受完整切除并确诊的72例肺非TRU型腺癌。在显微镜下观察组织形态学变化和前驱病变。通过免疫组织化学（IHC）检测谱系特异性标志物和肿瘤干细胞标志物的表达。通过ARMS和定向基因测序检测肺腺癌的主要驱动基因突变。非TRU型腺癌在男性中更常见（65.3%，47/72）、既往或当前吸烟者中更常见（68.1%，49/72）、老年人中更常见（平均61岁）、中央型腺癌中更常见（75.0%，54/72）、有坏死的肿瘤中更常见（61.1%，44/72）以及高级别肿瘤中更常见（73.6%，53/72）。组织学上，非TRU型腺癌表现出复杂的组织形态，常由大的不规则腺样和腺泡样结构组成，伴有细胞外黏液、坏死肿瘤细胞碎片和中性粒细胞聚集，或为产生黏液的浸润性腺癌。肿瘤细胞由支气管表面上皮细胞、黏液柱状细胞、多边形细胞和杯状细胞组成组成。18例（25.0%）、23例（31.9%）和28例（38.9%）表现出纤毛柱状细胞化生（CCCM）、黏液柱状细胞改变（MCCC）和细支气管柱状细胞发育异常（BCCD）（肺腺癌的前驱病变）。IHC显示肿瘤细胞中CK7（100.0%，72/72）、TTF1（12.5%，9/72）、Napsin A（5.6%，4/72）、MUC5AC（81.9%，59/72）、MUC5B（87.5%，63/72）、p53（66.7%，48/72）、CK5/6（12.5%，9/72）、p63（18.1%，13/72）、CK20（19.4%，14/72）和CDX2（16.7%，12/72）的表达。在43.1%的病例（31/72）中检测到肿瘤干细胞标志物CD44的表达，31.9%（23/72）的病例中检测到CD133的表达，58.3%（42/72）的病例中检测到β-连环蛋白的表达，36.1%（26/72）的病例中检测到ALDH1的表达，12.5%（9/72）的病例中检测到GATA6的表达，20.8%（15/72）的病例中检测到SOX2的表达，29.2%（21/72）的病例中检测到OCT4的表达。驱动基因突变中KRAS为26.4%（19/72），EGFR为2.8%（2/72），EML4-ALK为1.4%（1/72），BRAF和ROS1均无突变。非TRU型腺癌是肺腺癌的一种罕见亚型，具有独特的临床病理特征、组织学表现、免疫表型和分子遗传学改变。
