非小细胞肺癌新辅助治疗后手术切除标本的病理评估

Pathological assessment of non-small cell lung cancer resection specimens after neoadjuvant therapy

目的探讨对非小细胞肺癌新辅助治疗(新辅助化疗、新辅助靶向治疗及新辅助免疫联合化疗)后手术切除标木的病理评估。方法收集2000年1月至2020年3月同济大学附属上海市肺科医院接受新辅助治疗后手术切除肺癌标本113例分析并比较90例[腺癌26例,鱗状细胞癌(简称鳞癌)64例]新辅助化疗患者(化疗组)、13例(腺癌13例)新辅助靶向治疗患者(靶向组)及10例(腺癌4例,鳞癌6例)新辅助免疫治疗联合化疗的患者(免疫联合化疗组)手术切除标本的肿瘤消退反应组织学特征(坏死、炎性细胞浸润、胆固醇裂隙、泡沫细胞聚集、反应性肉芽肿及间质胶原纤维形成)的差异及病理缓解[明显病理缓解(MPR)及完全病理缓解(PCR)]状况:结果化疗组非小细胞肺癌、靶向组肺腺癌及免疫联合化疗组非小细胞肺癌均可见残存肿瘤细胞发生退行性变,异型性增加,肿瘤床内见不同程度的坏死、泡沫细胞聚集、胆固醇裂隙、炎性细胞浸润、反应性肉芽肿及间质胶原纤维形成。化疗组、靶向组及免疫联合化疗组三者之间肿瘤消退反应组织学特征差异均无统计学意义(P>0.05),但靶向组及免疫联合化疗组坏死所占的百分比最高10%及20%,而化疗组高达80%;1例免疫联合化疗组肺腺癌出现肿瘤消退床;免疫联合化疗组肿瘤床旁的非肿瘤肺实质内可有明®的淋巴细胞、浆细胞浸润及淋巴滤泡的形成。化疗组肺腺癌及鱗癌MPK率分別为35%(9/26)及64%(41/64);耙向组MPR比例为2/13;免疫联合化疗组肺腺癌及鱗癌MPR比例分别为2/4及2/6化疗组肺腺癌及鳞癌PCR率分別为11%(3/26)及3%(2/64);靶向组PCR比例0/13;免疫联合化疗组肺腺癌及鳞癌PCK比例分别为0/4及1/6结论非小细胞肺癌不同的新辅助治疗方式引起组织病理学变化存在形式及程度上的差异,化疗组可见较多的坏死,免疫联合化疗组可出现消退床,免疫联合化疗组肿瘤床旁的非肿瘤肺实质内可有明显的淋巴细胞、浆细胞浸润及淋巴滤泡的形成.

Objective To pathologically evaluate the surgically resected specimens of three different therapies(neoadjuvant chemotherapy,neoadjuvant targeted therapy and neoadjuvant immunotherapy combined with chemotherapy)for non-small cell lung cancer.Methods One-hundred and thirteen cases of post neoadjuvant therapy non-small cell lung cancer specimens were collected at Tongji University Affiliated Shanghai Pulmonary Hospital from January 2000 to March 2020.There were ninty patients receiving neoadjuvant chemotherapy(chemotherapy group;26 cases of adenocarcinoma and 64 cases of squamous cell carcinoma),13 patients receiving neoadjuvant targeted therapy(targeted group;13 cases of adenocarcinoma)and 10 patients receiving neoadjuvant immunotherapy combined with chemotherapy(immune combined chemotherapy group;4 cases of adenocarcinoma and 6 cases of squamous cell carcinoma).They were evaluated for histologic tumor regression responses(necrosis,inflammatory cell infiltration,cholesterol crystal deposition,foam cell infiltration,reactive granuloma and interstitial collagenous formation)and pathological responses[main pathological response(MPR)and complete pathological response(PCR)]_Results Chemotherapy group,targeted group and immune combined chemotherapy group all showed degenerative changes in residual tumor cells,increased atypia,various degrees of necrosis,foam cell aggregation,cholesterol cleft,inflammatory cell infiltration,and reactive granuloma in the tumor bed.Histologic characteristics of tumor regression reaction were not different between these three groups(P>0.05);the highest percentage of necrosis in the targeted group and immune combined chemotherapy group was only 10%and 20%,respectively,while that in the chemotherapy group was as high as 80%.One case of adenocarcinoma in immune combined chemotherapy group had tumor regression bed.The MPR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 35%(9/26)and 64%(41/64),respectively;the MPR ratio of targeted group was 2/13;the MPR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinoma in immune combined chemotherapy group were 2/4 and 2/6,respectively.The PCR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 11%(3/26)and 3%(2/64),respectively;the PCR ratio of targeted group was 0/13;the PCR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinomain immune combined chemotherapy group were 0/4 and 1/6,respectively.Conclusions Different neoadjuvant therapy may cause various histopathological changes in non-small cell lung cancer:more necrosis is noted in the chemotherapy group and regression bed frequently appears in the immune combined chemotherapy group.In the immune combined chemotherapy group,there are significant lymphoplasmacytic infiltration and lymphoid follicle formation in the lung parenchyma beside the tumor bed.