A 17-year-old female, without medical history, presented with a 15-day history of diplopia, nasal obstruction, and left orbital pain, associated with fever and night sweats. The physical examination found a left exophthalmos and bilateral cervical lymphadenopathy. T2-weighted orbital magnetic resonance imaging showed a left soft-tissue mass slightly hyperintense compared to muscle involving intra- and extraconal space responsible for an exophthalmos, with an extension to the left ethmoid sinus and the left nasal fossa. Biopsy of the nasal mass and histopathologic examination objectified a high-grade DLBCL (CD20+, Bcl2+, CD3-, and CD5-, with a Ki-67 proliferation index of 95%). In addition, the cerebrospinal fluid analysis was consistent with a central nervous system (CNS) involvement.\nBaseline18F-FDG PET/CT revealed intense18F-FDG uptake throughout the bilaterally enlarged renal parenchyma, on the soft tissue in the left orbit extending into the left nasal cavity, and on cervical and abdominal lymph nodes. Peritoneal nodules with diffusely increased18F-FDG and multiple hypermetabolic bones foci, including humeri, ribs, and pelvis uptake were also noted []. After 4 cycles of dose-adjusted EPOCH-rituximab, the patient was referred for18F-FDG PET/CT for response evaluation. The18F-FDG PET/ CT showed a total regression of renal lesions suggesting good response to therapy [].
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.