A Rare Presentation of C3 Glomerulopathy As a Paraneoplastic Syndrome in a Patient with Leukemic Non Nodal Mantle Cell Lymphoma

Introduction

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma, accounting for approximately 6% of all lymphomas. The clinical presentation is divided into conventional and leukemic non-nodal (LNN). LNN presentation is 10-20% of cases and patients are commonly asymptomatic with involvement of bone marrow, peripheral blood and the spleen. Renal involvement in MCL is uncommon, and when present, it is typically due to direct infiltration. Paraneoplastic Glomerulonephritis (GN) are rare, particularly C3 GN, which is an immune complex-mediated kidney disease. We present a unique case of a 63-year-old male with MCL LNN who developed C3 GP as a paraneoplastic syndrome.

Case Presentation

A 63-year-old male presented with a 3-month history of systemic “B” symptoms, including fever, night sweats, and weight loss. Physical examination revealed significant splenomegaly. Laboratory findings showed leukocytosis with a white blood cell count of 16,600/μL with 58% of atypical lymphocytes in blood smear. Bone marrow flow cytometry confirmed the diagnosis of LNN MCL, characterized by CD5+, CD19+,CD20+, CD23+, CD200-, IgM+ cells.

During his initial evaluation, the patient also exhibited signs of nephrotic syndrome, including significant proteinuria (9.5 g/day), hypoalbuminemia, and peripheral edema. Within his serum laboratory workup, he presented with Hypocomplementemia of C3, with a light chain ratio of 1 mg/dL, serum protein electrophoresis showing an increase in alpha 1 and beta with a discrete monoclonal peak in gamma identified as IgG lambda by serum immunofixation. A renal biopsy was performed, revealing a diagnosis of C3 GN with severe interstitial fibrosis (60%) and moderate tubular atrophy (40%), confirmed by immunofluorescence and electron microscopy. The patient required hemodialysis support due to fluid overload. He received MCL treatment with Bruton tyrosine kinase inhibitor and bendamustine for 6 cycles, achieving resolution of symptoms and proteinuria associated with GN.

Discussion

C3G is a rare and complex glomerular disease resulting from dysregulation of the alternative complement pathway. Its association with hematologic malignancies, including MCL, is exceedingly rare. In a retrospective study of 30 patients with GN and MCL, only 3 patients were found to be associated with this GN, of which 2 showed improvement in GN with lymphoma treatment. There are no reported cases of MCL LNN associated with C3 GN.The pathophysiology is thought to involve aberrant production of monoclonal proteins or other factors by the malignant lymphocytes, leading to complement activation and glomerular damage.

In our case, the diagnosis of C3 GN as a paraneoplastic manifestation of MCL NLL was made based on the association of renal symptoms with the lymphoma diagnosis and the absence of other underlying causes of C3 GN. Despite the poor prognosis associated with this GN, our case responded to treatment with ibrutinib.

Conclusion

This case highlights the rare association of C3 GN with MCL, emphasizing the need for awareness among clinicians regarding potential paraneoplastic renal manifestations in patients with hematologic malignancies. Despite the poor prognosis associated with this glomerulonephritis, the case demonstrates that the glomerulopathy can improve with appropriate treatment, such as a Bruton tyrosine kinase inhibitor. Prompt recognition and appropriate management of such conditions are crucial for improving patient outcomes.

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No relevant conflicts of interest to declare.