Maezawa Naoki, Tsuta Koji, Shibuki Yasuo, Yamazaki Shigeki, Maeshima Akiko M, Watanabe Shun-ichi, Matsuno Yoshihiro
Division of Clinical Laboratory, National Cancer Center Hospital, Tokyo, Japan.
Cancer. 2006 Dec 25;108(6):488-93. doi: 10.1002/cncr.22287.
Patients with noninvasive, small-sized primary adenocarcinomas of the lung have excellent prognosis after lobectomy. Several researchers have suggested that limited resection could be an acceptable alternative for these patients. Therefore, a preoperative or intraoperative judgment of invasiveness would be one of the critical determinants of the surgical procedure in each case. Cytopathologic findings that can distinguish invasive from noninvasive adenocarcinomas remain to be elucidated.
Imprint smears were obtained from 60 resected adenocarcinomas with nonmucinous bronchioloalveolar features. Thirteen cytologic factors were evaluated: the presence of necrosis, fibrovascular tissue, proportion of macrophages, the presence of large tumor cell clusters, nuclear grooves, nuclear overlapping, variation in nuclear size, chromatin pattern, presence of a nucleolus, intranuclear inclusions, multinucleated cells, spindle cells, and mitosis. Each factor was examined by univariate analysis for correlation with the presence of histopathologic invasion.
In the univariate analysis, 5 cytologic factors--presence of tumor cell clusters consisting of more than 50 tumor cells (P < .001), nuclear overlapping in more than 3 layers (P < .001), presence of nuclear grooves (P = .007), more than 3-fold variation in nuclear size (P < .001), and 1 mitotic cell per 1000 tumor cells (P = .035)--were associated significantly with invasion. Among these, nuclear overlapping in more than 3 layers (P = .003) and more than 3-fold variation in nuclear size (P = .005) were found to be independent predictive factors for invasion by multivariate analysis.
Using imprint smears, the presence of invasion in small-sized primary adenocarcinomas of the lung is predictable by the 2 above-mentioned cytologic findings. Imprint smear cytology may effectively aid intraoperative judgement of invasion in cases where frozen section histology is difficult to interpret.
肺原发性小尺寸非侵袭性腺癌患者肺叶切除术后预后良好。几位研究者提出，对于这些患者，有限切除可能是一种可接受的替代方案。因此，术前或术中判断侵袭性将是每个病例手术方式的关键决定因素之一。能够区分侵袭性和非侵袭性腺癌的细胞病理学表现仍有待阐明。
从60例具有非黏液性细支气管肺泡特征的切除腺癌中获取印片涂片。评估了13个细胞学因素：坏死、纤维血管组织、巨噬细胞比例、大肿瘤细胞团簇的存在、核沟、核重叠、核大小变化、染色质模式、核仁的存在、核内包涵体、多核细胞、梭形细胞和有丝分裂。对每个因素进行单变量分析，以确定其与组织病理学侵袭的相关性。
在单变量分析中，5个细胞学因素——存在由50个以上肿瘤细胞组成的肿瘤细胞团簇（P <.001）、3层以上的核重叠（P <.001）、核沟的存在（P =.007）、核大小变化超过3倍（P <.001）以及每1000个肿瘤细胞中有1个有丝分裂细胞（P =.035）——与侵袭显著相关。其中，多变量分析发现3层以上的核重叠（P =.003）和核大小变化超过3倍（P =.005）是侵袭的独立预测因素。
使用印片涂片，通过上述2种细胞学表现可预测肺原发性小尺寸腺癌的侵袭情况。在冰冻切片组织学难以解读的病例中，印片涂片细胞学可有效辅助术中侵袭判断。
