237 Arguments for pulmonary AIS larger than 7 cm Introduction The prognosis of lung cancer is largely determined by its stage, with the diameter being one of the components of the TNM classification. Typically, the larger the tumor, the higher the stage79. However, if a large tumor has a complete non-invasive, in situ growth pattern, then the relationship between tumor size and prognosis is not applicable in theory. In the 2015 revision of non-small cell lung cancer by the World Health Organization (WHO), a new histologic classification for adenocarcinoma of the lung was proposed, wherein the term “bronchioloalveolar carcinoma” (BAC) was replaced by “adenocarcinoma in situ” (AIS) and “minimally invasive adenocarcinoma” (MIA) in cases with an invasive area smaller than 0.5cm. When completely resected, these entities both exhibit 100% recurrence-free survival 1 341. AIS is characterized by the growth of a monolayer of tumor cells along pre-existing alveolar structures in tumors that are 3cm or smaller, without invasive features316. Adenocarcinomas larger than 3 cm, with an invasive component exceeding 0.5cm are called lepidic predominant adenocarcinoma (LPA). So far, there is no category for non-invasive adenocarcinoma larger than 3 cm, since at the time of the 2015 revision no such cases were documented. The aim of this study was to explore the existence of AIS with a size greater than 7 cm. To this end we i) histologically analyzed in two cases the whole lobe, where initial histological sampling revealed AIS while on radiology a pneumonia-like pattern in nearly a whole lobe was present and ii) conducted a comprehensive search in a previous published pT3N0 cohort with adenocarcinomas > 7cm cm342 to identify potential cases with a pure in situ growth pattern. Materials and methods Two cases from separate institutes were included in this study, where the entire lobe was examined histologically due to the suspected presence of AIS. One from Vrije Universiteit medical center (VUmc), Amsterdam and one from San Raffaele Scientific Institute, Milan, Italy. Selected slides of both cases were besides hematoxylin and eosin (H&E) stainings, also stained with Elastin von Gieson (EvG) and cytokeratin 7 (CK7). Clinical data, including follow-up were obtained. In parallel an observational study was performed on a previous reported nationwide retrospective cohort of 683 patients, who underwent lung surgical resection for pT3N0M0 NSCLC (TNM 7th edition) from 2010 to 2013342. This study cohort gave us the opportunity to investigate our hypothesis that adenocarcinomas in situ larger than 3 cm might exist, especially if we could demonstrate their presence in cases with a diameter larger than 7 cm, related to adequate follow-up. Therefore, a subgroup of 112 cases was selected based on the combination of tumor diameter larger than 7 cm, and adenocarcinoma histology. A further selection 16
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