A 47-year-old Caucasian male with a history of HCV infection (genotype 3A) and hypertension was admitted with complaints of shortness of breath, dyspnea on exertion, lower extremity edema, abdominal distention, and decreased urine output for the past two months. Physical examination revealed an elevated jugular venous pulse to 8-10 cm of water, bibasilar crackles, an S3 gallop, bilateral lower extremity edema, and hepatosplenomegaly. He was hypertensive with a blood pressure of 183/111 mmHg. Laboratory tests revealed pancytopenia, hypoalbuminemia, hypocomplementemia, cryoglobulinemia, elevated HCV PCR levels, an elevated creatinine level, and an elevated rheumatoid factor level (). Urine microscopy revealed dysmorphic red blood cells (RBC) in addition to white blood cell (WBC) and RBC casts. He was also found to have nephrotic range proteinuria (9.5 g in 24 hours).\nRetroperitoneal ultrasound only showed a small volume of ascites, 14 cm and 12 cm sized kidneys with no hydronephrosis. HCV-induced cryoglobulinemia was suspected and a kidney biopsy was performed.\nLight microscopy (LM): of the twenty-six glomeruli present, one glomerulus showed segmental sclerosis with capsular adhesion. The remaining glomeruli revealed diffuse endocapillary proliferation with lobular simplification and glomerular influx of monocytes, neutrophils, and even eosinophils (one glomerulus). Many glomeruli contained PAS-positive intracapillary coagula of cryoglobulin (), and small double contours were observed on silver stain. The interstitium contained sheets of lymphocytes in two foci and a lymphoid follicle with clear germinal center in another focus. Interstitial fibrosis, tubular atrophy, and arterial changes were minimal. One arteriole contained intraluminal cryoglobulin.\nImmunofluorescence microscopy (IF): eleven glomeruli were present in the specimen processed for IF and revealed the following findings: IgM, Kappa, and C3 (3+) granular staining along peripheral capillary loops (); IgG and Lambda (negative to trace) staining in the glomeruli. IgA, C1q, and Albumin were negative. Fibrinogen showed (1+) staining in some glomerular capillaries. Positive controls were satisfactory. As there was more than 2+ difference in intensity between Kappa and Lambda light chains, IgG, IgM, Kappa, and Lambda were repeated and the results of the second run were identical to the first run: presence of IgM with Kappa restriction was confirmed in the deposits.\nElectron microscopy (EM): endocapillary proliferation, mesangial interposition, and presence of subendothelial and subepithelial electron dense deposits were observed in the single glomerulus present for electron microscopy (). On high magnification, characteristic paired and curved organized deposits of cryoglobulin were identified. Occasionally, the deposits revealed a microtubular pattern. Foot processes were focally effaced.\nThe diagnosis of mCGN (with type III MPGN pattern) was rendered based on the presence of the following findings: features of MPGN (type III), intracapillary coagula of cryoglobulin (by LM), glomerular deposits of IgM with Kappa restriction (by IF), and organized deposits of cryoglobulins (by EM). The pathologist's suggestion regarding the possibility of an underlying B cell malignancy triggered further workup. Serum viscosity was within normal limits, but serum and urine protein electrophoresis revealed IgM monoclonal gammopathy. Computed tomography (CT) detected hepatosplenomegaly associated with retroperitoneal paraaortic lymph node enlargement. Bone survey did not reveal any lytic or blastic lesions; however, bone marrow biopsy results were consistent with bone marrow involvement by low-grade lymphoma, favoring Marginal Zone Lymphoma (MZL). Marrow biopsy showed multiple lymphoid aggregates in the background of trilineage maturing hematopoiesis. The lymphoid aggregates are composed of small-sized lymphoid cells without increased plasma cells or large atypical lymphoid cells. By immunohistochemistry studies, the lymphoid cells in the lymphoid aggregates are mostly PAX-5 and CD20 positive B cells. Plasma cells scattered in the marrow spaces are polyclonal and express both Kappa and Lambda. Flow cytometry detected about 3% of Kappa monoclonal B-cells expressing CD19, CD20, and CD22, but do not express CD5, CD10, or CD103. These findings support a diagnosis of marginal zone lymphoma rather than a lymphoplasmacytic lymphoma or hairy cell leukemia. The patient was initiated on a rituximab/dexamethasone-based regimen, which he tolerated well, with improvement of his renal function, urinary sediment, and proteinuria.\nDuring the course of his hospitalization, hematology and infectious disease were consulted and they favored treating with the above regimen and planned a trial of direct acting antivirals at a later stage. At the most recent follow-up, patient is being continued on the abovementioned therapy and is being monitored by oncology closely.
A 19-year-old male patient was admitted to the Nephrology Department of Ankara University Faculty of Medicine due to painless hematuria, bilateral renal masses, and acute kidney injury for further investigations. He was first evaluated at another center for hematuria. There was one episode of hematuria, which had subsided spontaneously. Abdominal ultrasonography had revealed bilateral diffuse renal masses and the patient was referred to our center for further examination.\nOn admission, there was no history of fever, weight loss, night ssweats and any other health problem. The patient’s physical examination findings were unremarkable. In particular, there was no peripheral lymphadenopathy or hepatosplenomegaly. Also the kidneys were not palpable. Laboratory tests revealed white blood cell count of 7.7x109/L, hemoglobin of 11.6 g/dL, platelet count of 315x109/L, serum blood urea nitrogen of 17 mg/dL, serum creatinine of 1.5 mg/dL (normal range: 0.5-0.9), serum uric acid of 7.6 mg/dL (normal range: 2.4-5.7), serum lactate dehydrogenase of 1042 U/L (normal range: 125-220), and serum ferritin of 749 ng/mL (normal range: 11-307). Erythrocyte sedimentation rate was 52 mm/h and C-reactive protein level was 27.5 mg/L (normal: <3). Urinalysis showed density of 1010, pH of 5.5, protein of 15 mg/dL, and glucose negative, and urine microscopy showed 4 leukocytes and 3 erythrocytes per high-power field. Viral serology tests were negative. C3 and C4 as well as quantitative immunoglobulin levels were all within normal limits with negative antinuclear antibody and anti-neutrophil cytoplasmic antibody tests. Urinary ultrasonography demonstrated bilaterally enlarged kidneys without obstruction (right: 16x8 cm, left: 15.5x8 cm) and numerous solid hypoechoic nodular cortical masses in both kidneys (largest of 6.5x5.5 cm in size, numerous variably sized masses) with perirenal and paraaortic multiple enlarged lymph nodes (largest <2.5 cm in size).\nContrast-enhanced computerized tomography (CT) scanning of the abdomen confirmed bilaterally enlarged kidneys, bilateral variably sized multiple hypodense renal masses, and paraaortic, paracaval multiple enlarged lymph nodes (). In addition, the liver was slightly enlarged with normal parenchyma while the size of the spleen and parenchyma was normal.\nThereafter, 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) was performed for staging and its role in the differential diagnosis. It was performed to examine the entire body, revealing an abnormal accumulation in the thyroid gland, anterior mediastinum, bilateral hilar, right parasternal lymph node, left subdiaphragmatic lymph node, bilateral renal cortices, and multiple abdominal paraaortic, paracaval, and aortocaval lymph nodes ( and ).\nA percutaneous tru-cut biopsy of the kidney was performed and histopathological examination showed extensive infiltration of the renal parenchyma by atypical lymphoid cells ( and ). Immunohistochemical studies demonstrated positive staining of the neoplastic cells for CD20, CD10, bcl-6 (, , , and ) and negative results for MUM1 () and Bcl-2. The ki-67 proliferation index of neoplastic cells was 80% (). EBER in situ hybridization was negative. A diagnosis of diffuse large B-cell non-Hodgkin lymphoma (NHL) was made. To exclude lymphoma involvement of the bone marrow, the patient underwent bone marrow biopsy and there was not bone marrow infiltration.\nSubsequently, the patient was transferred to the department of hematology for treatment and chemotherapy regimen as well; cyclophosphamide, adriamycin, vincristine, prednisolone, and rituximab (CHOP+R) were started. After a cycle of chemotherapy, the patient’s renal functions returned to normal.