12 Chapter 1 In 2012 a reproducibility study on simple power point images of different adenocarcinoma subtypes showed that one group of pathologists consistently judged a subset of adenocarcinomas to be invasive (Invasive Group, ING), while another group of pathologists consistently judged the same subset to be non-invasive (non-ING)14. This clearly points toward a necessity for calibration or re-evaluation of the diagnostic criteria. The concept of “loose tumor tissue fragments” as a pattern of invasion in lung carcinoma has recently been proposed and is included in the 2015 WHO fascicle on the classification of lung tumors, and was specifically called ‘spread through air spaces” or STAS4. This inclusion is at least somewhat controversial, as an alternative explanation is that “loose tumor tissue fragments” represents an artifact. In the current WHO classification of lung cancer “STAS” is a criterium of invasion. The difference in consequences of both concepts warrants further research. The main function of staging lung cancer, is to determine the extent of disease at time of diagnosis, because of the associated prognosis. The staging system for cancers is based upon anatomic primary tumor characteristics, lymph node metastasis, and distant metastasis (TNM) at time of diagnosis and has been developed to predict survival outcome in cancer patients. Stage is the main denominator for treatment planning in patients with lung cancer NSCLC15. As for many other tumors, the descriptors of the T, N and M for NSCLC evolve with time. The most recent transition from the 7th (TNM7) to the 8th (TNM-8) editions dates in 201716 17 18. The accurate determination of the maximum diameter of the invasive part of the tumor is crucial for pathologists with regards to the T-descriptor. This is because the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) TNM classification system for NSCLC recommends that the measurement of the primary tumor’s size should be based only on its invasive components19. This emphasizes the need of precise and accurate diagnosis of a non-invasive (AIS and MIA) as opposed to an invasive carcinoma. Another aspect of staging is the examination of the response after neoadjuvant therapy in resection specimen. This may provide insight in the assessment of the efficacy of neoadjuvant treatment in NSCLC. Aim and outline of the thesis This thesis investigates three histopathological aspects in resected NSCLC specimens, relevant to diagnosis, prognosis, and staging. Firstly, we aimed to establish criteria for the pathologic response effect after neoadjuvant therapy by examining whether histopathological findings such as the percentage of tumor rest, proliferative activity, and morphometric properties may lead to a refinement in the prognosis of patients with NSCLC after chemoradiation therapy.
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