In 2019, a 59-year-old man developed a generalized pruritic rash after being bitten by mosquitoes. He was hospitalized to our hospital in 2021 after receiving treatment with Chinese traditional medicine and angiotensin receptor blockers (ARBs), which did not significantly reduce proteinuria, and a urine analysis revealed urinary protein 3 + with bilateral lower extremities edema.
Serum creatinine (Scr) of 107 µmol/L, estimated glomerular filtration rate (eGFR) of 65.1 ml/min/1.73m2, albumin (ALB) of 32.3 g/L, urinary albumin-to-creatinine ratio (UACR) of 457.9 µg/mg, alkaline phosphatase (ALP) of 199 U/L, and lactate dehydrogenase (LDH) of 244 U/L were the laboratory results at the time of admission. Urinalysis showed protein 3+, erythrocytes 3+, and leukocytes 1+. Anti-neutrophil cytoplasmic antibodies (ANCAs), anti-nuclear antibodies (ANAs), anti-phospholipase A2 receptor (PLA2R) antibodies, anti-glomerular basement membrane (GBM) antibodies, serum M-protein, hepatitis B antibodies, hepatitis C antibodies, and syphilis spirochete antibodies were all negative.
Upon physical examination, there was minor edema in both lower extremities, a widely dispersed brown rash on the skin of the extremities and trunk, and slightly enlarged superficial lymph nodes palpable in the neck and axillae bilaterally.
Skin performanceBroad brown rash the size of a bean that is widely distributed across the trunk and limbs, especially the extremities, with nodules and discolored patches. There is a noticeable itching sensation, scrapes, and some cracked and crusted nodules along with the rash. (Fig. 1).
Fig. 1Scattered rash all over the body with crusting. Brown nodules on the limbs and trunk
Renal histologyA renal biopsy revealed sclerosis in one out of eight evaluated glomeruli. The remaining glomeruli exhibited mild proliferation of glomerular mesangial and stromal cells, diffuse thickening of the basement membrane with visible spike formation, significant inflammatory cell infiltration in the renal interstitium, and intimal thickening of small arteries. Eosinophilic deposits were observed in several areas. Immunofluorescence (IF) staining was specific for IgG, IgM, C3, and C1q, with IgG1 and IgG3 showing positive results. These granular deposits were positive for both λ-type and κ-type light chains, with no glomerular deposits of IgA, C4, FRA, ALB, PLA2R, or THSD7A detected. Electron microscopy revealed numerous electron-dense materials beneath the epithelial cells and within the basement membrane, along with diffuse podocyte process fusion (Fig. 2A). Immunohistochemistry (IHC) was positive for CD19, Cyclin D1, CD5, BCL2, and Ki-67 (Fig. 2B and C).
Fig. 2A. Light microscopy and IF of renal biopsies in SMN. (a) Mononuclear lymphocytes, plasma cells with large patchy and multifocal infiltration, and scattered eosinophilic infiltration were seen in the renal interstitium. (hematoxylin-eosin staining, Original magnification, ×200). (b) Mild segmental hyperplasia of glomerular mesangial cells and basement membranes. (hematoxylin-eosin staining, Original magnification, ×400). (c) Diffuse thickening of the glomerular basement membrane, with “spikes” formation. (Jones silver stain, Original magnification, ×400). (d) IF reveals diffuse granular staining along the GBM for IgG. (Original magnification, ×400). (e、f、g and h) IgG1 and IgG3 were positive, and IgG2 and IgG4 were not detected. B. IHC of infiltrating cells in MCL. (a and c) CD5 was positively expressed in a focal distribution under high magnification. (Original magnification, a ×200, c ×400). (b and d) Interstitial infiltrate positive staining for cyclin D1. (Original magnification, b ×200, d ×400). (e) Renal interstitium CD19 positive with diffuse distribution. (Original magnification, ×400). C. IHC of infiltrating cells in MCL. (a and c) CD5 was positively expressed in a focal distribution under high magnification. (Original magnification, a ×200, c ×400). (b and d) Interstitial infiltrate positive staining for cyclin D1. (Original magnification, b ×200, d ×400). (e) Renal interstitium CD19 positive with diffuse distribution. (Original magnification, ×400). D. Light microscopy and IHC of Lymph node biopsy. (a) Massive infiltration of disorganized small lymphocytes in the interstitium. (hematoxylin-eosin staining, Original magnification, ×200). (b) CD5 expression in lymph node interstitium with diffuse distribution. (Original magnification, ×200). (c) CD20 positive with diffuse distribution. (Original magnification, ×200). (d) Interstitial infiltrate positive staining for cyclin D1. (Original magnification, ×200)
Lymph node histologyMCL was identified by the massive infiltration of tiny cells with positive expression of CD5, CD19, CD20, CyclinD1, and PAX5. (Fig. 2D).
The patient’s urine output (UO) dropped to 800 ml/d between the first and third weeks following hospitalization, while the UACR rose to 953.6 µg/mg and the ALB level dramatically dropped. Using the results of renal biopsies and IHC, we determined that the patient had SMN in order to explain the reason for the patient’s ongoing proteinuria. The patient received a definitive diagnosis of MCL through lymph node biopsy. Bone marrow smear revealed abnormal lymphocytes in 10% and flow cytometry analysis of the bone marrow showed about 5.4% nucleated cells considered as abnormal mature B lymphocytes.
From the third week, he started chemotherapy with the BR regimen. For a total of twelve weeks, treatments were administered every four weeks. His kidney and liver function indices did not significantly change following the first round of chemotherapy, but there was a decrease in urine protein.
The patient discontinued chemotherapy in the eleventh week after finishing the third course, and no severe side effects were noted during the course of treatment. Despite the fact that his renal function parameters were similar to those at admission due to hypoalbuminemia, his UACR dropped to an all-time low of 397.4 ug/mg and stayed stable after that. The patient had routine check-ups, and his kidney and liver functions improved. He also had normal white blood cell, platelet, and hemoglobin levels, and normal UO with considerably less foamy pee. His Scr level was 94.6 µmol/L, eGFR was 75.8 ml/min/1.73m2, UACR was 283.6 µg/mg, and ALB level was 30.4 g/L at the time of the most recent follow-up. (Fig. 3).
Fig. 3Changes in clinical indicators over time. Note: The patient’s initial chemotherapy treatment is indicated by the black arrow, and the chemotherapy treatment’s conclusion is indicated by the red arrow
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