312 Appendices invasion of lung adenocarcinoma using elastin and cytokeratin 7 staining to diagnose (collapsed) AIS more reliably and reduce variation between assessors of invasive patterns in small pulmonary adenocarcinomas was investigated. A total of 42 pathologists from 13 countries scored all 70 cases in the first 2 rounds, while 36 pathologists scored 41 non-unanimous cases in the 3rd round. The kappa values for rounds 1, 2, and 3 were 0.27, 0.45, and 0.62, respectively. A kappa score ranges from “0” to “1”. A score of 0 means that tossing a coin is as good, while a score of “1” shows perfect uniformity. This reproducibility study confirms the difficulty in assessing invasion in pulmonary adenocarcinomas on full histological sections, supporting the notion that pathologists worldwide are consciously incompetent in assessing invasion according to WHO criteria. Heatmap analysis showed differences and variation in the location and size of invasion. In contrast, the revised classification obtained a significantly higher kappa score in blind assessment (0.45) or coached assessment (0.62), demonstrating a substantial increase in competence. No recurrence was demonstrated in the group of patients with “no invasion” scores (100% survival). Additional support for these findings, for example, through biomarker research, could further support the results. According to the WHO, the non-invasive adenocarcinoma variant (AIS) has a maximum size of 3 cm. Given the above findings, it is theoretically possible for AIS to occur as a larger tumor. In Chapter 16, this hypothesis was investigated in the national subgroup of T3N0 NSCLC from Chapter 4. In the subgroup of 112 adenocarcinomas larger than 7 cm, three patients were identified in whom the tumors were assessed as non-invasive based on the available sections. Radiological correlation showed a pneumonia-like image in these cases. Strikingly, in potentially non-invasive cases, which were supported by elastin staining as papillary carcinoma, a solid tumor aspect was seen radiologically and pathologically. Two later additional case, not from the T3N0 cohort, in which the entire lung lobe was histologically evaluated with more than 300 and 130 tissue blocks, showed in the sections a non-invasive tumor in this entire lobe (both 16 cm). Follow-up showed no tumor recurrence. The study provides strong arguments for abandoning the diameter limit of 3 cm for AIS.
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