PMC5088546_01
Clinical course. Allo-PBSCT: allogeneic peripheral blood stem cell transplantation, BP: blood pressure, Cr: serum creatinine, CY: cyclophosphamide, CyA; cyclosporin A, MTX: methotrexate, TBI: total-body irradiation
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However, asymptomatic proteinuria and glomerular hematuria appeared during CyA tapering four months after PBSCT and persisted for six years without clinical manifestations of GVHD (Fig. 1).
Findings of the renal biopsy samples. In the renal biopsy samples, 40 glomeruli were observed, 6 of which had deteriorated (arrowheads in A; PAS stain 200x). The glomeruli showed mild hypertrophy and increased numbers of small capillary lumens with irregular thickening of the GBM (B: PAM stain 600x). The glomeruli also showed swollen endothelial cells in the glomerular capillaries (open arrowhead in C), double-contoured GBM (closed arrowhead in C), and mesangial cell proliferation (arrow in C) in the glomeruli (C: PAM stain 800x). CD34 staining revealed narrowing of the glomerular capillaries (D: CD34 stain 800x). In the glomeruli, a few CD3+T cells (arrows in E) were noted (E: CD3 stain 800x). According to the results obtained for the tubulointerstitium, slight infiltration of mononuclear cells (arrow in F), primarily CD3+T cells, was noted in the peritubular capillaries (arrow in G) and tubules (arrows in H) (F: PAS stain 600x; G, H: CD3 stain 600x). In interlobular arteries, irregular thickening of the intima was evident with edema and the accumulation of mucoid-like materials (arrow in I), without elastosis or cellular components (arrow in J). In addition, irregular thickening of the intima (arrow in K) was evident in arcuate arteries without elastosis (I: Hematoxylin and Eosin staining 600x; J, K: Elastic Masson-Goldner stain 600x)
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Light microscopy showed swelling of endothelial cells in glomerular capillaries, mesangial cell proliferation, and double-contoured glomerular basement membrane (Fig. 2A-C). CD34 staining revealed narrowing of the glomerular capillaries (Fig. 2D). A few CD3+ T cells were detected in the glomeruli (Fig. 2E). Furthermore, slight infiltration of mononuclear cells, primarily CD3+ T cells, was detected in the peritubular capillaries and tubules (Fig. 2F-H). In the interlobular and arcuate arteries, some irregular thick lesions were found in the intima with edema and an accumulation of mucoid-like materials without elastosis or cellular components (Fig. 2I-K).
Immunofluorescence findings. Focal and segmental irregular deposition of IgM, C3, and C1q was noted along the capillaries in the glomeruli. Pathologische Anatomie Leiden-endothelium (PAL-E) staining was positive along some glomerular capillaries. The deposition of C4d was evident on glomerular capillaries and on some peritubular capillaries.
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Under immunofluorescence microscopy, positive staining for IgM, C3, and C1q was noted along the glomerular capillaries (Fig. 3). Furthermore, the deposition of C4d was detected along the glomerular capillaries and partly on the peritubular capillaries (Fig. 3).
Electron microscopy findings. Swelling and morphological changes in the endothelial cells of glomerular capillaries (arrows) and mesangial interposition into the subendothelial space were detected (arrowhead).
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Electron microscopy revealed swelling of endothelial cells in the glomerular capillaries, mesangial proliferation, and interposition into the subendothelial space (Fig. 4).