PMC:3135183 / 5387-9328 JSONTXT

{"project":"2_test","denotations":[{"id":"21789266-21252716-82904621","span":{"begin":2010,"end":2011},"obj":"21252716"},{"id":"T62030","span":{"begin":2010,"end":2011},"obj":"21252716"}],"text":"4. Results\n\n4.1. Macroscopic Findings\nThe initial wedge resection showed a slightly greyish thickening of the visceral and parietal pleura at gross inspection. An ulceration of the visceral pleura with adherent blood was recognized. Underneath the visceral pleura an irregular and poorly defined greyish consolidation of approximately 2 cm was seen. There were no other detectable masses present. There was no connection to large airways.\n\n4.2. Histological Findings\nMicroscopy revealed features of a diffusely growing discohesive carcinoma, exclusively growing in the alveolar interstitium, thus expanding it, while leaving the original alveolar architecture intact (Figure 2). There was local ulceration of the pleura, while, beyond this ulcer, the tumor formed a thick cake of discohesive tumor cells lining the pleural membrane (Figure 2(c)), with only focal, microscopic invasion into the fatty tissue of the parietal pleura.\nThe tumor consisted of atypical, moderately polymorphous, and irregularly shaped tumor cells with marked discohesiveness. They featured scant eosinophilic cytoplasm and irregularly contoured and hyperchromatic nuclei, often containing one or more prominent nucleoli (Figure 2(b)). There were many mitoses and apoptoses present, but necrosis was not observed. No squamous or glandular differentiation was observed, and mucin stains (PAS-D and alcian blue) were negative. Within the tumor, there were multiple small blood-filled clefts and blood lakes. Angioinvasion in medium-sized vessels, including an artery, was demonstrated (Figure 2(d)).\nOf note, the broadened alveolar septa were lined by markedly atypical epithelial cells, yet less atypical than the interstitial carcinoma (Figures 2(a) and 2(b)). The atypia of the lining cells extended beyond the tumor front, showing a sharp demarcation with normal type I pneumocytes (Figure 2(a)), a feature characteristic to nonmucinous adenocarcinoma in situ with lepidic growth pattern (former bronchioloalveolar carcinoma, BAC) [3].\n\n4.3. Immunohistochemical Findings\nThere was partial weak positivity for the keratin proteins CAM5.2 (Figure 2(e)), CK14, and CK19, and strong positivity for vimentin, CD99, and AE1/3. The tumor cells were nonreactive with EMA, CEA, MOC31, CK7, CK20, 34BE12, SP-A, and S100 and only mildly reactive with P53 and CD56. The neuroendocrine markers chromogranin and synaptophysin were negative. Calretinin, thrombomodulin, and D2-40, frequently positive in malignant epitheloid mesothelioma, were negative. Because of its high vascularity, angiosarcoma was considered in the differential diagnosis, but markers for vascular differentiation (CD31, CD34, factor VIII) were negative in the tumor cells. These markers did reveal the presence of a fine network of thin-walled vessels within the tumor, including many sinusoid-like vascular spaces. The tumor showed near-diffuse staining for TTF-1, varying from negative to strongly positive (Figure 2(f)). TTF-1 positive staining has to our knowledge not been described in angiosarcomas or mesotheliomas. On the basis of these findings, a histological diagnosis of poorly differentiated adenocarcinoma of the lung was made. Consistent with discohesive growth the tumor cells were negative for E-cadherin. Mib-1 was positive in most tumor cells, confirming high proliferative activity. Thyroglobulin was negative.\nThe atypical alveolar lining cells were uniformly and strongly positive for TTF-1, CAM5.2, CK7, CEA, EMA, beta-catenin, and surfactant A (Figures 2(e)–2(f)). There was a diffuse weak positivity for p53.\n\n4.4. Molecular Findings\nNo mutation in EGFR exons 19–21 and KRAS exons 1-2 could be detected (PCR and sequencing).\nThe second pleural resection showed an identical picture of pleural cake with only focal microscopic invasion. As no other lesions of the pleura were observed at surgery 10 days before, this finding supports the suspected rapid progression of the tumor.\n"}

{"project":"AnEM_full-texts","denotations":[{"id":"T8","span":{"begin":815,"end":831},"obj":"Multi-tissue_structure"},{"id":"T9","span":{"begin":894,"end":906},"obj":"Tissue"},{"id":"T10","span":{"begin":914,"end":929},"obj":"Multi-tissue_structure"},{"id":"T11","span":{"begin":935,"end":940},"obj":"Pathological_formation"},{"id":"T12","span":{"begin":1012,"end":1023},"obj":"Cell"},{"id":"T13","span":{"begin":1073,"end":1095},"obj":"Organism_substance"},{"id":"T14","span":{"begin":1141,"end":1147},"obj":"Cellular_component"},{"id":"T15","span":{"begin":1188,"end":1196},"obj":"Cellular_component"},{"id":"T16","span":{"begin":1293,"end":1301},"obj":"Cell"},{"id":"T17","span":{"begin":1305,"end":1314},"obj":"Cell"},{"id":"T18","span":{"begin":1412,"end":1417},"obj":"Pathological_formation"},{"id":"T19","span":{"begin":1445,"end":1450},"obj":"Organism_substance"},{"id":"T20","span":{"begin":1469,"end":1474},"obj":"Organism_substance"},{"id":"T21","span":{"begin":1512,"end":1519},"obj":"Multi-tissue_structure"},{"id":"T22","span":{"begin":1534,"end":1540},"obj":"Multi-tissue_structure"},{"id":"T23","span":{"begin":1597,"end":1611},"obj":"Multi-tissue_structure"},{"id":"T24","span":{"begin":1644,"end":1660},"obj":"Cell"},{"id":"T25","span":{"begin":1689,"end":1711},"obj":"Pathological_formation"},{"id":"T26","span":{"begin":1755,"end":1767},"obj":"Cell"},{"id":"T27","span":{"begin":1788,"end":1793},"obj":"Pathological_formation"},{"id":"T28","span":{"begin":1841,"end":1859},"obj":"Cell"},{"id":"T29","span":{"begin":1903,"end":1929},"obj":"Pathological_formation"},{"id":"T30","span":{"begin":1974,"end":2002},"obj":"Pathological_formation"},{"id":"T31","span":{"begin":2004,"end":2007},"obj":"Pathological_formation"},{"id":"T1","span":{"begin":519,"end":540},"obj":"Pathological_formation"},{"id":"T2","span":{"begin":569,"end":590},"obj":"Multi-tissue_structure"},{"id":"T3","span":{"begin":638,"end":646},"obj":"Multi-tissue_structure"},{"id":"T4","span":{"begin":713,"end":719},"obj":"Multi-tissue_structure"},{"id":"T5","span":{"begin":740,"end":745},"obj":"Pathological_formation"},{"id":"T6","span":{"begin":751,"end":756},"obj":"Pathological_formation"},{"id":"T7","span":{"begin":780,"end":803},"obj":"Cell"}],"text":"4. Results\n\n4.1. Macroscopic Findings\nThe initial wedge resection showed a slightly greyish thickening of the visceral and parietal pleura at gross inspection. An ulceration of the visceral pleura with adherent blood was recognized. Underneath the visceral pleura an irregular and poorly defined greyish consolidation of approximately 2 cm was seen. There were no other detectable masses present. There was no connection to large airways.\n\n4.2. Histological Findings\nMicroscopy revealed features of a diffusely growing discohesive carcinoma, exclusively growing in the alveolar interstitium, thus expanding it, while leaving the original alveolar architecture intact (Figure 2). There was local ulceration of the pleura, while, beyond this ulcer, the tumor formed a thick cake of discohesive tumor cells lining the pleural membrane (Figure 2(c)), with only focal, microscopic invasion into the fatty tissue of the parietal pleura.\nThe tumor consisted of atypical, moderately polymorphous, and irregularly shaped tumor cells with marked discohesiveness. They featured scant eosinophilic cytoplasm and irregularly contoured and hyperchromatic nuclei, often containing one or more prominent nucleoli (Figure 2(b)). There were many mitoses and apoptoses present, but necrosis was not observed. No squamous or glandular differentiation was observed, and mucin stains (PAS-D and alcian blue) were negative. Within the tumor, there were multiple small blood-filled clefts and blood lakes. Angioinvasion in medium-sized vessels, including an artery, was demonstrated (Figure 2(d)).\nOf note, the broadened alveolar septa were lined by markedly atypical epithelial cells, yet less atypical than the interstitial carcinoma (Figures 2(a) and 2(b)). The atypia of the lining cells extended beyond the tumor front, showing a sharp demarcation with normal type I pneumocytes (Figure 2(a)), a feature characteristic to nonmucinous adenocarcinoma in situ with lepidic growth pattern (former bronchioloalveolar carcinoma, BAC) [3].\n\n4.3. Immunohistochemical Findings\nThere was partial weak positivity for the keratin proteins CAM5.2 (Figure 2(e)), CK14, and CK19, and strong positivity for vimentin, CD99, and AE1/3. The tumor cells were nonreactive with EMA, CEA, MOC31, CK7, CK20, 34BE12, SP-A, and S100 and only mildly reactive with P53 and CD56. The neuroendocrine markers chromogranin and synaptophysin were negative. Calretinin, thrombomodulin, and D2-40, frequently positive in malignant epitheloid mesothelioma, were negative. Because of its high vascularity, angiosarcoma was considered in the differential diagnosis, but markers for vascular differentiation (CD31, CD34, factor VIII) were negative in the tumor cells. These markers did reveal the presence of a fine network of thin-walled vessels within the tumor, including many sinusoid-like vascular spaces. The tumor showed near-diffuse staining for TTF-1, varying from negative to strongly positive (Figure 2(f)). TTF-1 positive staining has to our knowledge not been described in angiosarcomas or mesotheliomas. On the basis of these findings, a histological diagnosis of poorly differentiated adenocarcinoma of the lung was made. Consistent with discohesive growth the tumor cells were negative for E-cadherin. Mib-1 was positive in most tumor cells, confirming high proliferative activity. Thyroglobulin was negative.\nThe atypical alveolar lining cells were uniformly and strongly positive for TTF-1, CAM5.2, CK7, CEA, EMA, beta-catenin, and surfactant A (Figures 2(e)–2(f)). There was a diffuse weak positivity for p53.\n\n4.4. Molecular Findings\nNo mutation in EGFR exons 19–21 and KRAS exons 1-2 could be detected (PCR and sequencing).\nThe second pleural resection showed an identical picture of pleural cake with only focal microscopic invasion. As no other lesions of the pleura were observed at surgery 10 days before, this finding supports the suspected rapid progression of the tumor.\n"}