Clinicopathological features and individualized treatment of kidney involvement in B-cell lymphoproliferative disorder

Abstract

Background: Due to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is still unclear, and data on kidney prognosis is scarce.

Methods: We retrospectively reviewed the renal pathology profiles from January 2010 to December 2021, and 28 patients with B-cell LPD combined with intact renal biopsy data were included.

Results: There were 20 men and eight women aging 41 to 79 years at the time of renal biopsy (median age 62 years). According to hematological diagnosis, patients were classified into four groups: chronic lymphocytic leukemia (CLL) (group1, n=7), Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) (group 2, n=8; WM, n=6; LPL, n=2), Other non-Hodgkin's lymphomas (NHL) (group3, n=7; diffuse large B-cell lymphoma (DLBCL), n=2; mucosa-associated lymphoid tissue (MALT) lymphoma, n=4; Low grade B-cell lymphoma, n=1), and monoclonal gammopathy of undetermined significance/monoclonal gammopathy of renal significance (MGUS/MGRS) (group 4, n=6). Median serum creatinine (Scr) level was 129 (range,59-956) umol/L. Eight patients (29%) were presented with acute kidney injury (AKI), and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria (median protein excretion, 2.14 g/d), 11(39%) of whom had the nephrotic syndrome. Interstitial malignant infiltration was the most frequent renal lesion (n=6). Eight patients underwent immunohistochemistry of renal tissues, of which three patients (CLL, n=1; LPL, n=1; WM, n=1) had confirmed lymphoma infiltrates, and the infiltrating cells in the remaining five patients (CLL, n=1; MALT lymphoma, n=2; MGUS, n=2) were considered unrelated to lymphoma. The most common glomerular diseases were renal amyloidosis (n=4) and membranous nephropathy (n=4). Only 20 patients were treated, 13 of whom were treated with rituximab separately or in combination. The median follow-up time was 11 months. Of these, six had achieved hematological response, complete response in five cases. Eight had achieved renal response. At the end-of-study visit, four patients died and two progressed to end stage kidney disease (ESKD).

Conclusion: In conclusion, the clinicopathological spectrum of renal involvement in BLPD is diverse. Renal biopsy and immunohistochemistry are required for early diagnosis and prognostic assessment.

Keywords: Waldenström macroglobulinemia/lymphoplasmacytoid lymphoma; chronic lymphocytic leukemia; kidney involvement; lymphoproliferative disorders; monoclonal gammopathy of undetermined significance; non-Hodgkin’s lymphomas.

Figure 1

Flowchart of study participants. B-LPD, B-cell lymphoproliferative disorders; eGFR, estimated glomerular filtration rate; CKD, chronic kidney disease; ESRD, end-stage renal disease.

Figure 2

Kidney pathological finding. lymphocytic infiltration of the renal interstitium. (A) scattered atypical cells visible in the interstitium in one patient with LPL (PAS,original magnification×400). (B) diffuse and massive inflammatory cell infiltration in the interstitium in a patient with CLL (hematoxylin and eosin staining, original magnification×400), the infiltrating cells were positive for CD20 (C) and CD23 (D) by immunohistochemistry analysis (original magnification×200).

Figure 3

Morphologic features of membranoproliferative glomerulonephritis on renal biopsy of the patient with Waldenstrom’s macroglobulinemia. (A) Mesangial cells were severely proliferated and lobulated, and mesangial matrix was moderately increased. (asterisks; PAS, original magnification×400). (B, C) Deposits were observed in mesangial, subcutaneous and subepithelial areas (PASM. b, original magnification×400; c, original magnification×600). (D) Deposits stained with IgM in the mesangial area and para mesangial area by immunofluorescence (original magnification×400). (E, F) ByEM, electron-dense deposits were observed in the subendothelial, mesangial area and medial of basement membrane. Foot processes showed diffuse fusion (original magnification×2500). PAS, periodic acid–Schiff; PASM, periodic acid-silver metheramine; EM, electron microscopy.

Figure 4

Morphologic features of C3 glomerulonephritis with thrombotic microangiopathy on renal biopsy of the patient with MGRS. (A) Mesangial cells were severely proliferated and lobulated (PAS, original magnification×400). (B) Diffuse inflammatory cells infiltrate in the renal interstitium (PAS, original magnification×400). (C) Endothelial cell proliferation, capillary occlusion, visible microthrombosis, and basement membrane thickening were observed by PASM-Masson (original magnification×400). (D) Deposits stained with C3 in the mesangial area by immunofluorescence (original magnification×400). (E, F) By EM, TMA-like changes were observed in the glomerulus (original magnification×2500). MGRS, monoclonal gammopathy of renal significance; TMA, thrombotic microangiopathy; monoclonal gammopathy of undetermined significance.