260 Chapter 17 pattern. The use of a cytokeratin 7 staining can be of great help in recognizing the regular pattern, especially in collapsed AIS / lepidic adenocarcinoma. Paradoxically, the effect of iatrogenic collapse on pulmonary parenchyma is until today not taken into account by most pathologists across the globe. The expectation management is needed: the pathologist should realize that curved alveolar walls lined with a monolayer of tumor cells with a lepidic seemingly papillary or acinar pattern is a distinct manifestation of AIS, if no other characteristics of invasion are present. Collapse at the cellular level The consequence of iatrogenic collapse is pressure on tumor cells. We demonstrated an increased average tumor cell height in severe iatrogenic collapsed AIS areas compared to less iatrogenic collapsed areas. The shift of some cellular content towards the apical side is plausible and a new finding. Associations of cytoplasmic and nuclear flexibility were reported in other disease states, such as small cell lung carcinoma59 60, large cell neuroendocrine carcinoma376 377 378, atypical carcinoid378, typical carcinoid 378 and basaloid squamous cell carcinoma379. A further extension of the cellular vulnerability is cytologically and histologically described as “smearing of the tumor cells”, “nuclear streaking”376, “crush artifact”379, “Azzopardi phenomenon”377. The small size and the flexibility of the tumor cells and alveolar walls with the lack of desmoplastic stroma make that these tumors are difficult to palpate. Collapse and tissue handling The two cohorts in our studies differed in a practical aspect, namely fixation procedure of the resection specimen. Tumor nodules of Milan cohort were cut perpendicular to pleural surface in 1-2 cm slices to allow formalin diffusion, while in the OLVG cohort, the resection specimens were subject to formalin perfusion by filling the lung with as much formalin as possible, through the bronchial tree, using the pressure of a formalin tap or a syringe with formalin. If necessary, transpleural injection with a formalin filled syringe is added. After 12-24 hours subsequent perpendicular cuts are made198. The different handling of specimens resulted in the following issues: i) more extensive iatrogenic collapse among Milan cases than in OLVG samples; ii) consequently higher difficulty in recognition of lepidic component and iii) more cases with delay in fixation as established by detached tumor cells. Nevertheless, in the selected samples the correlation coefficient obtained with Weibel’s method was almost the same in both cohorts: (-0.44 and -0.42). This suggests that elongation and morphological alterations of the tumor cells occurring in iatrogenic collapse is significantly related to amount of air, but independent from the fixation procedure. In Japan perfusion fixation is present in the national guideline281. It would be useful if other countries would adopt this approach too.
RkJQdWJsaXNoZXIy MTk4NDMw