Renal Diseases Associated with Hematologic Malignancies and Thymoma in the Absence of Renal Monoclonal Immunoglobulin Deposits

Abstract

In addition to kidney diseases characterized by the precipitation and deposition of overproduced monoclonal immunoglobulin and kidney damage due to chemotherapy agents, a broad spectrum of renal lesions may be found in patients with hematologic malignancies. Glomerular diseases, in the form of paraneoplastic glomerulopathies and acute kidney injury with various degrees of proteinuria due to specific lymphomatous interstitial and/or glomerular infiltration, are two major renal complications observed in the lymphoid disorder setting. However, other hematologic neoplasms, including chronic lymphocytic leukemia, thymoma, myeloproliferative disorders, Castleman disease and hemophagocytic syndrome, have also been associated with the development of kidney lesions. These renal disorders require prompt recognition by the clinician, due to the need to implement specific treatment, depending on the chemotherapy regimen, to decrease the risk of subsequent chronic kidney disease. In the context of renal disease related to hematologic malignancies, renal biopsy remains crucial for accurate pathological diagnosis, with the aim of optimizing medical care for these patients. In this review, we provide an update on the epidemiology, clinical presentation, pathophysiological processes and diagnostic strategy for kidney diseases associated with hematologic malignancies outside the spectrum of monoclonal gammopathy of renal significance.

Keywords: acute kidney injury; glomerulonephritis; hematologic malignancies; onconephrology.

Figure 1

Main glomerular disorders (MCD, TMA, mesangial proliferative GN and FSGS) occurring in association with hematological malignancies and thymoma. The most relevant associations are highlighted in blue in the Figure. cHL: Classical Hodgkin lymphoma; CLL: Chronic lymphocytic leukemia; FSGS: Focal and segmental glomerulosclerosis; HPS: Hemophagocytic syndrome; MDS: Myelodysplastic syndrome; MPN: Myeloproliferative neoplasms; NHL: Non-Hodgkin lymphoma; POEMS: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome; TAFRO: Thrombopenia, Anasarca, Fever, Reticulin myelofibrosis, and Organomegaly syndrome.

Figure 2

C-mip is selectively induced in HRS cells from patients with MCD occurring in association with cHL (A), whereas no expression is found on lymph node tissues from patients with cHL not associated with MCD (B).

Figure 3

Diffuse interstitial infiltration by chronic lymphoid leukemia cells (A), hematein eosin saffron ×20) positive for CD20 ((B), ×100) and CD5 ((C), ×200), whereas immunohistochemistry with anti-CD3 antibody is negative on tumoral cells (D), ×200).

Figure 4

Minimal interstitial infiltration (arrows) by few tumoral lymphocytes and plasma cells ((A), hematein eosin saffron ×100), displaying CD79a positivity ((B), ×100) and monotypic staining for IgM ((C), ×100, arrow) and lambda light chain ((D), ×100, arrows).

Figure 5

Monotypic plasma cell interstitial nephritis in a patient with multiple myeloma. Numerous interstitial plasma cells ((A), hematein eosin saffron ×100, arrow) with strong staining for CD38 ((B), ×100) and monotypic staining for kappa light chain ((C) ×100, arrow).

Figure 6

Thrombotic microangiopathy associated with POEMS syndrome. Glomerular enlargement with mesangium loosening, endothelial cell swelling ((A), Masson trichrome staining ×400) and double contours ((B), Jones methenamine silver, ×400, arrows).