308 Appendices Summary This thesis is the result of the doctoral research of Dr. J.L.G. Blaauwgeers on various histopathological aspects in lung resections, removed for the treatment of non-small cell lung carcinoma, entitled “Histopathological aspects of resected non-small cell lung carcinoma, with emphasis on spread through air spaces and collapsed adenocarcinoma in situ.” The role of the pathologist in lung cancer is important in several ways. Firstly, in making a diagnosis of a lesion detected by imaging in the lung. It is important to determine whether it is a malignant tumor, then whether it is primary lung cancer, and then which variant it is. A diagnosis on tissue from another part of the body can confirm suspicion of metastases. With lung cancer variants, it is particularly important to distinguish between “non-small cell carcinoma” (NSCLC) and “small cell carcinoma.” In the case of non-small cell carcinoma, it is important to differentiate between squamous cell carcinoma and adenocarcinoma. With adenocarcinoma, it is also relevant to determine whether it is an invasive tumor or a precursor (in situ) carcinoma, and in the case of an invasive tumor, what the main, dominant growth pattern is. Both have an impact in terms of the patient’s prognosis. A non-invasive tumor does not metastasize, and the patient is cured after removal (resection), while some subtypes of invasive carcinoma, such as those with a solid or micropapillary growth pattern, have a potentially worse prognosis with a greater chance of metastases. A relatively recent described phenomenon, the presence of loose tumor cells in the air spaces (alveoli) of the lung (spread through air spaces, STAS), is interpreted as a new form of invasive growth and is thought to be related to an unfavorable prognosis. Although, incorporated in the WHO classification of pulmonary adenocarcinomas, its exact significance is still unclear. In addition to determining whether there is an invasive tumor and which variant it is, the pathologist also plays a role in evaluating tumors that are removed after pretreatment (neoadjuvant therapy). The assessment of the response to this pre-treatment is a determining factor for the further prognosis of the patient. This thesis investigates three aspects in lung resections with non-small cell carcinoma that are relevant for diagnosis, prognosis, and staging. Firstly, the pathological response after neoadjuvant therapy was examined. Secondly, research was conducted on the so-called “STAS” with the hypothesis that this phenomenon may be an artifact rather than a biological phenomenon. Thirdly, attempts were made to refine diagnostic tools that can help distinguish invasion from non-invasion in non-mucinous adenocarcinoma, with particular attention to the effect of collapsed lung tissue on tumor morphology. In chapter 2 of Part I, the histological changes after neoadjuvant therapy are described in a study cohort of 46 patients with a sulcus superior tumor who underwent chemoradiation followed by surgical resection. Complete pathological response was identified in 20 patients (43%) who underwent induction chemoradiotherapy. A
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