Thunnissen Erik, Beasley Mary Beth, Borczuk Alain, Dacic Sanja, Kerr Keith M, Lissenberg-Witte Birgit, Minami Yuko, Nicholson Andrew G, Noguchi Masayuki, Sholl Lynette, Tsao Ming-Sound, Le Quesne John, Roden Anja C, Chung Jin-Haeng, Yoshida Akihiko, Moreira Andre L, Lantuejoul Sylvie, Pelosi Giuseppe, Poleri Claudia, Hwang David, Jain Deepali, Travis William D, Brambilla Elisabeth, Chen Gang, Botling Johan, Bubendorf Lukas, Mino-Kenudson Mari, Motoi Noriko, Chou Teh Ying, Papotti Mauro, Yatabe Yasushi, Cooper Wendy
Amsterdam University Medical Center, Amsterdam, The Netherlands.
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York.
J Thorac Oncol. 2023 Apr;18(4):447-462. doi: 10.1016/j.jtho.2022.11.026. Epub 2022 Dec 9.
Since the eight edition of the Union for International Cancer Control and American Joint Committee on Cancer TNM classification system, the primary tumor pT stage is determined on the basis of presence and size of the invasive components. The aim of this study was to identify histologic features in tumors with lepidic growth pattern which may be used to establish criteria for distinguishing invasive from noninvasive areas.
A Delphi approach was used with two rounds of blinded anonymized analysis of resected nonmucinous lung adenocarcinoma cases with presumed invasive and noninvasive components, followed by one round of reviewer de-anonymized and unblinded review of cases with known outcomes. A digital pathology platform was used for measuring total tumor size and invasive tumor size.
The mean coefficient of variation for measuring total tumor size and tumor invasive size was 6.9% (range: 1.7%-22.3%) and 54% (range: 14.7%-155%), respectively, with substantial variations in interpretation of the size and location of invasion among pathologists. Following the presentation of the results and further discussion among members at large of the International Association for the Study of Lung Cancer Pathology Committee, extensive epithelial proliferation (EEP) in areas of collapsed lepidic growth pattern is recognized as a feature likely to be associated with invasive growth. The EEP is characterized by multilayered luminal epithelial cell growth, usually with high-grade cytologic features in several alveolar spaces.
Collapsed alveoli and transition zones with EEP were identified by the Delphi process as morphologic features that were a source of interobserver variability. Definition criteria for collapse and EEP are proposed to improve reproducibility of invasion measurement.
自国际癌症控制联盟和美国癌症联合委员会肿瘤TNM分类系统第八版以来，原发性肿瘤pT分期是根据浸润成分的存在和大小来确定的。本研究的目的是确定具有鳞屑样生长模式的肿瘤的组织学特征，这些特征可用于建立区分浸润性和非浸润性区域的标准。
采用德尔菲法，对切除的非黏液性肺腺癌病例进行两轮盲法匿名分析，这些病例具有假定的浸润性和非浸润性成分，随后对已知结果的病例进行一轮审阅者去匿名化和非盲法审阅。使用数字病理平台测量肿瘤总体积和浸润性肿瘤体积。
测量肿瘤总体积和肿瘤浸润体积的平均变异系数分别为6.9%（范围：1.7%-22.3%）和54%（范围：14.7%-155%），病理学家对浸润的大小和位置的解释存在很大差异。在国际肺癌研究协会病理委员会的成员展示结果并进行进一步讨论后，塌陷的鳞屑样生长模式区域的广泛上皮增殖（EEP）被认为是可能与浸润性生长相关的特征。EEP的特征是多层腔内上皮细胞生长，通常在几个肺泡腔内具有高级别细胞学特征。
通过德尔菲法确定塌陷的肺泡和具有EEP的过渡区是观察者间变异性的形态学特征来源。提出塌陷和EEP的定义标准以提高浸润测量的可重复性。
