PMC6702807_01
Axial computed tomography (CT) images. (a) A follow-up chest CT image obtained before left lobectomy shows a solid mass accompanied by infiltrative and reticular shadows, and the shadow of a suspected skip lesion (arrow) is also found near the mass. (b) Chest CT image obtained 1 month before partial resection of the right lung shows a widespread infiltrative shadow.
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A follow-up chest CT two months later showed expansion of the mass, and a shadow suspected to be a skip lesion was also found near the mass (Figure 1(a)). Moreover, the shadow gradually expanded over the course of 1 year (Figure 1(b)).
Left lung cancer. (a) Gross view shows an ill-defined gelatinous tumor with a diffuse pneumonia-like consolidation. Bar, 1 cm. (b) Columnar tumor cells with intracytoplasmic vacuoles reveal a papillary growth pattern. H&E stain, x200. (c) Multiple mucin-producing tumor cells. Alcian blue stain, x200. (d) Several tumor cells are positive for MUC 5AC. MUC 5AC immunostain, x200.
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Macroscopically, both tumors were ill-defined and gelatinous with a diffuse pneumonia-like consolidation (Figure 2(a)). Histopathologically, the majority of each tumor exhibited lepidic or papillary growth consisting of columnar tumor cells with varying amounts of intracytoplasmic mucins (Figures 2(b) and 2(c)). Multiple tumor cells were positive for MUC 5AC (Figure 2(d)).
Detachment of tumor cells in the primary site of left lung cancer. (a) Villous-shaped tumor cells project and separate into the alveolar space. H&E stain, x100. (b) Immunopositivity on the cell-cell borders is weakened as tumor cells project or separate. Annexin A2 immunostain, x400. (c) Tumor cells are negative, whereas the remaining alveolar epithelial cells are positive. TTF-1 immunostain, x400.
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The tumor cells were negative for TTF-1, whereas alveolar epithelial cells (AECs) were positive (Figures 3(c), 4(d), and 5(c)). Cytoplasmic positivity of those aggregates was increased compared with that of detached components (Figure 3(b)) of the primary lesion (Figure 4(c)).
Aerogenous metastasis of left lung cancer I. (a) Many isolated lesions are seen. H&E stain, x40. (b) Small tumor cell aggregates are attached to alveolar epithelial cells, forming a protrusion. Some of the alveolar epithelial cells have an obscure nucleus and are detached within the alveolar spaces. H&E stain, x400. (c) Tumor cell aggregates represent the immunopositivity near the cell surface with granular cytoplasmic positivity. Alveolar epithelial cells also show a weak positivity near the cell surface. Annexin A2 immunostain, x400. (d) Alveolar epithelial cells are positive. The arrangement of these cells is well kept; however, some show weakened immunopositivity. TTF-1 immunostain, x400.
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The tumor cells were negative for TTF-1, whereas alveolar epithelial cells (AECs) were positive (Figures 3(c), 4(d), and 5(c)). The results are shown in Figures 4(a)-4(d), 5(a)-5(c), and 6(a) and 6(b) (Figures 4(c), 5(b), and 6(b) show ANX A2 staining). Small tumor cell aggregates that were positive near the cell surface and within the cytoplasm were attached to AECs and surrounded them, forming a protrusion (Figure 4(c)). Cytoplasmic positivity of those aggregates was increased compared with that of detached components (Figure 3(b)) of the primary lesion (Figure 4(c)). AECs also showed weak positivity near the cell surface (Figure 4(c)). In the AECs surrounded by tumor cell aggregates, both obscure nuclei and the weakened positivity for TTF-1 were observed (Figure 4). Furthermore, some AECs separated into the air spaces (Figure 4).
Aerogenous metastasis of left lung cancer II. (a) Tumor cell aggregates adhere to the alveolar wall, and pseudoluminal gaps are seen inside the aggregates. H&E stain, x400. (b) Cytoplasmic-positive products accumulate in the lateral sides, especially on the underside, forming membranous positivity. Annexin A2 immunostain, x400. (c) Many alveolar epithelial cells disappear or are indistinct compared with those observed in Figure 4(d). TTF-1 immunostain, x400.
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The results are shown in Figures 4(a)-4(d), 5(a)-5(c), and 6(a) and 6(b) (Figures 4(c), 5(b), and 6(b) show ANX A2 staining). AECs disappeared, and pseudoluminal gaps were scattered inside the aggregates (Figure 5). At this stage, cytoplasmic-positive products accumulated on the lateral sides, especially the underside (Figure 5(b)). After that, as the tumor cells formed one layer along alveolar wall, the membranous positivity on the cell-cell borders became more distinct (Figure 6(b)).
Aerogenous metastasis of left lung cancer III. (a) Tumor cells arrange in one layer along the alveolar wall, and intracytoplasmic mucins are localized on the luminal sides. H&E stain, x400. (b) Distinct membranous positivity on the cell-cell borders is seen. Annexin A2 immunostain, x400.
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At this stage, cytoplasmic-positive products accumulated on the lateral sides, especially the underside (Figure 5(b)). After that, as the tumor cells formed one layer along alveolar wall, the membranous positivity on the cell-cell borders became more distinct (Figure 6(b)). In this process, intracytoplasmic mucins were translocated on the luminal sides (Figure 6(a)).