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 50-year-old female with a past medical history significant for idiopathic thrombocytopenic purpura (ITP) presented with chief complaint of back pain for three weeks. Prior to her presentation, the patient was undergoing treatment for ITP wherein she had received four doses of weekly rituximab and recently completed a prednisone taper. A computed tomography (CT) scan of the abdomen and pelvis showed bilateral renal masses (6.6 x 4.2 cm on the right, 6.3 x 5 cm on the left) with upper para-aortic and right retro-crural lymphadenopathy (Figure ). Upon chart review, it was noted that the abdominal ultrasound done seven months prior to admission (for thrombocytopenia workup) was negative for renal masses. She was admitted for evaluation; laboratory workup showed white blood cell count 10.55 TH/uL, hemoglobin 12.3 g/dL, and platelet count 113 TH/uL. Her kidney function and liver function tests were normal. Lactate dehydrogenase was elevated at 763 IU/L (range 313-618). A CT guided biopsy of the left renal mass showed DLBL (Epstein-Barr virus (EBV) negative, fluorescent in situ hybridization (FISH) negative for MYC rearrangement, but 71% of interphase cells showed three copies of an intact MYC (8q24.1), 65% positive for rearrangement of BCL6, no BCL2 fusion). Bone marrow biopsy and flow cytometry were negative. Positron emission tomography (PET)/CT showed left supraclavicular and retroperitoneal lymphadenopathy (standardized uptake values (SUV) 10.8 and 15.7 respectively) with hypermetabolic bilateral renal masses (SUV 15.3 and 17.5 on right and left respectively) (Figure ). Lumbar puncture cytology was negative. Given these findings, she was staged IVB and received intrathecal methotrexate for central nervous system (CNS) disease prevention. The next day, the patient was started on dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (DA-REPOCH) chemotherapy regimen. She completed six cycles of DA-REPOCH and intrathecal methotrexate with no evidence of disease on repeat imaging (Figure ). She continues to follow up with oncology clinic for observation and is in complete remission at one year.