PMC9977547_01
Clinical course of the patient. The patient was referred to a nephrologist with a diagnosis of nephrotic syndrome at 76 years of age. The serum level of immunoglobulins was high in addition to massive urinary protein, and polyclonal gammopathy was identified. Before administration of prednisolone for the treatment of nephrotic syndrome, inguinal lymph node biopsy was performed. Nephrotic syndrome promptly responded to prednisolone and proteinuria improved along with decreased disease markers of Castleman's disease, such as IgG, IgA, C-reactive protein, serum IL-6, and plasma VEGF. During tapering of prednisolone, proteinuria transiently elevated. We performed renal biopsy to evaluate activity of renal involvement for decision making regarding long-term treatment. LN, lymph node; Ig, immunoglobulin; IL-6, interleukin-6; and VEGF, vascular endothelial growth factor.
CRIN2023-4926000.001.jpg
PMC9977547_01_CRIN2023-4926000.001.jpg
fig1
 Figure 1 indicates the clinical course of this case.
Lymph node pathology. Light microscopic appearance of inguinal lymph node obtained by needle biopsy reveals diffuse interfollicular plasma cell infiltration (hematoxylin and eosin staining (HE)) (a). As hyaline vascular proliferation was not evident, this case present plasma cell type of MCD. Immunohistochemistry reveals CD20-positive lymphocytes in the follicular region (b), while significant CD138-positive plasma cells exist in the interfollicular region (c).
CRIN2023-4926000.002.jpg
PMC9977547_01_CRIN2023-4926000.002.jpg
fig2
Immunohistochemistry revealed CD20-positive lymphocytes in the follicular region and significant CD138-positive plasma cells in the interfollicular region (Figure 2).
Renal biopsy findings. Periodic acid schiff (PAS) staining shows no obvious mesangial proliferation, crescent, or focal adhesions (a). Periodic acid methenamine silver (PAM) staining shows spikes and bubbling in the basement membranes (b). Electron microscopy reveals subepithelial and intramembrane deposits of homogenous sizes and stages and mild subendothelial enlargement (c). Immunofluorescent findings show marked granular deposit of IgG, IgA, and IgM, but no staining for complement (d). We examined depositions of IgG subclasses (e) and several MN-associated antigens as follows: phospholipase A2 receptor (PLA2R), thrombospondin type-1domain-containing 7A (THSD7A), neural epidermal growth factor-like 1 (NELL-1), and exostosin-1 (EXT-1) (f).
CRIN2023-4926000.003.jpg
PMC9977547_01_CRIN2023-4926000.003.jpg
fig3
No infiltration of inflammatory cells or mesangial cellular proliferation, crescents, or adhesions were noted (Figure 3(a)). Glomerular capillaries were diffusely and globally thickened and periodic acid methenamine silver staining showed spikes and bubbling in basement membranes (Figure 3(b)). II late to III, partially with stage IV, and mild subendothelial enlargement (Figure 3(c)). Immunofluorescent investigations showed marked granular deposition of IgG, IgA, and IgM along the glomerular basement membrane, but no staining for complement (Figure 3(d)). We further assessed IgG subclass and revealed positive staining for IgG4, while faintly stained in IgG1 and negatively stained in IgG2 and IgG3 (Figure 3(e)). Regarding antigen-specific antibody staining, deposition of phospholipase A2 receptor (PLA2R) was positive in this case, while any other representative antigen-specific antibodies were not stained (thrombospondin type-1domain-containing 7A, neural epidermal growth factor-like 1 and exostosin-1) (Figure 3(f)).
Radiological findings. Computed tomography of the chest before (a) and after treatment (b). Periaortic and lung hilar lymph nodes (two-headed arrow) appear reduced in size.
CRIN2023-4926000.004.jpg
PMC9977547_01_CRIN2023-4926000.004.jpg
fig4
The periaortic and lung hilar lymph nodes were reduced in size (Figure 4), as were the lymph nodes in the bilateral axillary and inguinal regions.
Subsequent clinical course of the patient. In the case, proteinuria was successfully controlled for 6 months with corticosteroid monotherapy after discharge from our hospital. During the process of tapering prednisolone, serum IgG titer began to increase, and polyclonal gammopathy appeared. The patient was referred to another hospital for induction of anti-IL-6 therapy, tocilizumab. The disease markers of MCD such as serum IL-6 and plasma vascular endothelial growth factor were not examined.
CRIN2023-4926000.005.jpg
PMC9977547_01_CRIN2023-4926000.005.jpg
fig5
The patient was referred to another hospital for induction of anti-IL-6 therapy (Figure 5).