248 Chapter 16 Large sized AIS tumors have extensive growth of tumor cells with 20+μm height on alveolar walls. In pathophysiologic terms, this leads to a 20+ fold increase of the diffusion distance in the gas exchange of oxygen and carbon dioxide. Since large sized AIS tumors involve large alveolar surface areas, this effect might be measurable by a decrease in a diffusion test. We surmise that patients with this form of lung cancer may have a different clinical course than those with the more frequent form of invasive and palpable lung cancer. The blinded revision of the radiologic images did show an at least partly pneumonictype tumor morphology346 347 in all 7 possible in situ cases of the retrospective cohort. In two of these cases with papillary carcinoma, the tumor had a more predominant solid appearance with minor areas of surrounding (ground-glass) consolidation. One control patient with invasive carcinoma showed a pneumonic-type tumor morphology on CT-scan, which could be explained by a significant lepidic component accompanying otherwise clearly invasive carcinoma. All other invasive cases did not show pneumonic-type tumor morphology, but were all mainly solid masses. Pneumonic-type adenocarcinoma has been described as two different types: localized pneumonic-type lung adenocarcinoma (L-PLADC) and a diffuse variant (D-PLADC)348. The diffuse variant usually is a mucinous adenocarcinoma on histology Non-mucinous pneumonic-type adenocarcinomas seem rare349, 350, but this may also be due the fact they are not diagnosed as such. Our current study not only shows several cases that were consistent with PLADC on CT, but also were non-mucinous and noninvasive on histology. Some of the patients had a discrepancy regarding tumor diameter between imaging and gross examination on pathology, which is consistent with the difficult-to-see-andpalpate non-solid, spongy consistency of an in-situ carcinoma. Discrepancy between a suggested solid component on CT but absent invasive component on histology may be explained by in vivo tumor collapse279. Interestingly, two cases that initially were “possibly non-mucinous AIS” on H&E staining, were reclassified as papillary carcinoma based on elastin staining. Both showed a solid mass morphology on radiology, without significant pneumonia-like features. Visual inspection of the paraffin block after cutting the slides showed a clearly delineated tumor (Figure 1G). The fact that these orthogonal methods of radiology and gross aspect on the paraffin block points in the same direction is a strong support in the differential diagnosis between (collapsed) AIS and papillary carcinoma, and should probably be included in a modified classification. The limitations of this study include for the pT3N0 cohort, i) its retrospective nature, which prohibits re-examining the resection specimen, since the remaining resection specimen is not stored (which is standard procedure as soon as a few weeks after resection); ii) the number of available histologic slides per case is limited even for tumors that occupy a relatively large portion of a lobe; iii) we did not select cases that were reported as acinar adenocarcinoma as possible non-invasive cases, nor cases with multiple nodules in the same lobe, larger than 3 cm. So, we might have missed some
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