PMC9149344_01
Light microscopy of a representative trephin shows (a, Giemsa stain, original magnification x200) slightly hyperplastic bone marrow, regular fat cell distribution, slightly hyperplastic and left-shifted granulopoiesis with complete maturation, some small and larger groups of erythropoiesis, scattered megakaryocytes (black arrows) as well as some rare lymphocytes and few plasma cell aggregates (red arrows). CD20 staining (b, original magnification x200) shows randomly distributed B-lymphocytes (yellow arrows), CD138 staining (c, original magnification x200) shows plasma cells both scattered (black arrows) and arranged in very small aggregates (red arrows). d (original magnification x200) shows Kappa restricted plasma cells irregularly scattered and organized in very small clusters (red arrows), polyclonal background. In total the degree of bone marrow, infiltration is approximately 15% (clonal and polyclonal plasma cells together). The lower panels under the black line demonstrate stable findings in a follow-up bone marrow biopsy after 30 months with a bone marrow infiltration of monoclonal plasma cells below 10% (e, Giemsa stain, original magnification x200: small plasma cell aggregates (red arrows). f CD20 staining, original magnification x200: scattered B-cells (yellow arrows). g CD138 staining, original magnification x200: scattered plasma cells (black arrow) and small plasma cell aggregates (red arrows). h Kappa stain, original magnification x200: small plasma cell aggregates (red arrows).
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F1
After CD 138 staining, histology revealed slightly increased plasma cells (up to 15% diffuse), partially arranged in aggregates monoclonal for kappa (shown in Fig. 1), with a slight polyclonal background for lambda, but without significant expression of CD56 or of CyclinD1. The degree of monoclonal plasma cell infiltration then was stable and could be quantified below 10% (Fig. 1).
Renal biopsy: Light microscopy (a: Hematoxylin-eosin-stain and b: Periodic acid-Schiff stain; original magnification, x200): The glomeruli show typical changes with mesangial proliferation, luminal cells and basal membrane splitting (see arrow marks). Tubulointerstitium with a focal tubulusatrophy, fibrosis, and a lymphocytic infiltration.
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F2
In the interstitium, in some parts acute tubular injury and more globally slight to moderate tubular atrophy and lymphoplasmacellular inflammation were present (shown in Fig. 2).
Renal biopsy: Immunofluorescence analysis with predominant positivity for IgG (a) with lesser IgA (b) and IgM (c) by coexpression of C1q (d) and C3c (e). (Original magnification, x200).
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F3
Immunofluorescence was positive for IgG and IgM with coexpression of C1q and C3c and was negative for IgA (shown in Fig. 3).
Electron microscopy: Dense microtubular deposits in parallel arrays from 30 to 50 nm as specific criteria for the diagnosis of ITG (see arrows marks) (Original magnification, x11,000 in the left panel and x8,900 in the right panel).
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F4
Finally, microtubules with a diameter of approximately forty-eight nanometer arranged in parallel bundles were shown by electron microscopy of separately stored material (shown in Fig. 4).
Time course of paraproteinemia by the kappa/lambda ratio of the free light chains (in blue, left vertical axis) and IgM-level (in green, right vertical axis). The 5 red arrows indicate the application of rituximab.
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F5
A transient decrease of IgM-level and the kappa/lambda ratio has been notified after application of rituximab therapy (shown in Fig. 5).