PMC4995526_01
High-resolution computed tomographic appearance of the chest 31 months after transplantation. The crazy paving appearance is consistent with recurrence of pulmonary alveolar proteinosis, and left dominance was seen from the beginning of recurrence.
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Nine months after the transplantation, she developed mild dyspnea and ground glass opacity that predominantly progressed in the left lung (Fig. 1).
Results of bronchoscopic analysis. (A) Bronchoalveolar lavage cells showing foamy alveolar macrophages (Diff-Quik stain). (B) Snapshot image of foamy alveolar macrophages under a scanning electron microscope. (C) FISH analysis demonstrated that 99% of the alveolar macrophages had XX sex chromosomes.
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Sixteen months after the lung transplantation, we obtained bronchoalveolar lavage fluid from the bilateral lungs and found bilateral recurrence of PAP (Fig. 2A and B). Fluorescence in situ hybridization (FISH) analysis demonstrated that more than 99% of the alveolar macrophages from both lungs did not harbor the Y chromosome, indicating that the phenotype of the alveolar macrophages had reversed to the recipient type in the bilateral lungs (Fig. 2C).
Histological examination of autopsied lungs. (A) The right lung, donated by the husband, and (B) the left lung, donated by the brother, showed accumulation of surfactant proteins (hematoxylin and eosin stain). (C) Chronic airway rejection that manifested as bronchiolitis obliterans was histologically confirmed (Elastica van Gieson stain). (D) Chronic vascular rejection was confirmed by C4d deposition on vascular endothelial cells (immunohistochemical stain).
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PAP findings were also predominant in the left lung. Pulmonary emphysema was seen only in the right lung (Fig. 3A and B). Chronic airway rejection, which was pathologically detected as bronchiolitis obliterans, and chronic vascular rejection with C4d deposition confirmed by immunohistochemistry were also found. (Fig. 3C and D).
Histological examination of autopsied lungs. (A, B) Granulomas and Aspergillus were detected (hematoxylin and eosin stain and Grocott's methenamine silver stain). Immunohistochemical analysis showed expression of the GM-CSF common beta receptor in right lung (C) and left lung (D) epithelial cells (arrow), but not alveolar macrophages (arrowhead).
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Furthermore, Aspergillus infection remained in both lungs despite intensive antifungal therapy (Fig. 4A and B). The GM-CSF common beta receptor was not expressed on alveolar macrophages but on hyperplastic alveolar epithelial cells in the bilateral lungs (Fig. 4C and D).