The First Case of Lupus Nephritis Developing in a Patient With Mantle Cell Lymphoma
We present a case of lupus nephritis (LN) associated with mantle cell lymphoma (MCL) in a 74-year-old Japanese male patient. The patient developed acute renal dysfunction with severe proteinuria and hematuria. Laboratory examination showed positive results for anti–double-stranded DNA (anti-dsDNA) immunoglobulin G antibody. Renal biopsy examination revealed the coexistence of LN class IV-G (A) and the direct invasion of MCL cells into the kidney. To our knowledge, this is the first reported case of LN associated with MCL. Interestingly, although the patient presented with extranodal involvement of the kidneys and spleen, cells were positive for expression of the transcription factor SOX11, which is classically associated with nodal MCL.
Systemic lupus erythematous (SLE) is one of the most common autoimmune diseases characterized by loss of tolerance against nuclear autoantigens, lymphoproliferation, polyclonal autoantibody production, immune complex deposition, and multiorgan tissue inflammation.1 A meta-analysis first confirmed that SLE is a risk factor for non-Hodgkin lymphoma (NHL), especially diffuse large B-cell lymphoma, in 2005.2 However, no study to date has reported an association between SLE and MCL. Here, we report the first case of SLE associated with MCL.
A 74-year-old Japanese male patient presented with rapidly progressive renal dysfunction and massive proteinuria. Fifteen years before admission, he was diagnosed as having MCL and treated with cyclophosphamide, doxorubicin, vincristine, and prednisolone chemotherapy. His disease relapsed twice, and he received chemotherapy, which led to complete remission. Three months before admission, he visited another hospital because of rapid progression of general fatigue and edema. His renal dysfunction progressed aggressively, resulting in nephrotic syndrome, which prompted referral to our hospital.
On admission, physical findings were significant for severe edema of the face and extremities. Respiratory and cardiovascular findings were normal. Cervical, axillary, and inguinal lymph nodes were palpable, and splenomegaly was present. As shown in the Table 1, laboratory examination revealed further elevation of serum creatinine and blood urea nitrogen levels to 2.4 and 55 mg/dL, respectively. White blood cell count was 5.3 × 103/μL with 10% of peripheral abnormal lymphocytes. Urinalysis showed proteinuria and occult blood of 4+ and 3+, respectively. Urinary protein excretion (UPE) value was 8.4 g/g Cr. Serum and urine immunoelectrophoresis confirmed immunoglobulin Mλ (IgMλ) monoclonal gammopathy and Bence-Jones proteins, respectively (Fig. 1). Anti–double-stranded DNA IgG antibody and anti–single-stranded DNA IgG antibody levels were elevated to 71.0 and 350.6 U/mL, respectively. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) detected multiple lymphadenopathy, including cervical, axillary, mediastinal, abdominal para-aortic, iliac, and inguinal lymph nodes, and splenomegaly, as well as increased FDG uptake within the multiple lymph nodes and spleen (Fig. 2). As shown in Figure 3, a renal biopsy of 12 glomeruli revealed diffuse mesangial proliferation, endocapillary proliferation, cellular crescents, and interstitial infiltration of a nodular mass of medium-sized lymphoid cells with irregular nuclei. Two of the glomeruli showed global sclerosis. Immunofluorescence analysis revealed positive granular staining for IgG, IgM, C3, and C1q in the mesangium and capillary wall, with negative IgA and C4. Congo red staining showed negative results. Immunohistochemical analysis revealed a population of lymphoblasts that were strongly positive for CD5, CD 20, bcl-2, cyclin D1, sex-determining region Y-box 11 (SOX11), and Ki67. MIB-1 index was almost 10%. Bone marrow biopsy examination revealed diffuse infiltration by neoplastic lymphoma cells. Based on the clinicopathological and immunohistochemical findings, the diagnosis of SLE3 with LN class IV-G (A)4 associated with MCL5 was established.
The patient's clinical course is shown in Figure 4. At the time of admission to our hospital, 40 mg/d of oral prednisolone was started to target the LN, which was contributing to the rapid deterioration of renal function, proteinuria, and generalized edema.