Thirty six-year-old male was presented with left tibial mass for the last 6 months. MRI showed contour irregularity and cortical thinning at the diaphysis of the left tibia and 1.5 cm severe periostal reaction at the same region. On follow-up, pathologic fracture of the left tibia occured. The intramedullary and soft tissue curettage of the left tibia, performed 3 months after the fracture, confirmed high grade diffuse large B-cell lymphoma. There is no past medical and genitourinary history. Laboratory analysis showed a normal complete blood count, normal urine analysis, and normal basic metabolic panel. Patient was reffered to our PET/CT unit for initial staging. FDG PET/CT scan showed a very intense FDG accumulation (SUVmax: 17.1) at the distal 2/3 of the left tibia extending to neighbouring soft tissue and proximal metaphysis of the left tibia which were compatible with primary disease involvement. Additionally, there was diffuse highly intense FDG uptake in the bilateral hyperplastic kidneys which was consistent with disease involvement (). The possibility of nephrotoxicity was excluded because of normal laboratory examination and no drug history.\nPatient underwent local external radiotherapy to the left tibia and systemic chemotherapy. Four months after the treatment, repeated FDG PET/CT scan revealed complete resolution of the renal lesions, indicative of complete remission. There was near-complete remission in the left tibia lesion. Middle part of left the tibial diaphysis which showed slightly increased FDG uptake in the fracture line was considered as an inflammatory process ().\nLiterature Review and Discussion\nNon-hodgkin lymphomas (NHL) are grouped as nodal and extranodal lymphoma according to their localization. Extranodal localization exists in 25%-40% of all NHL cases and can occur in any organ including gastrointestinal tract, head-neck, orbita, central nervous system, lungs, bones, breast, testis, thyroid and genitourinary system (). It may be multifocal involving two or more organs ().\nThe incidence of secondary renal involvement is about 3% (). Primary renal lymphoma (PRL) is even more uncommon, accounting for less than 1% of all lymphomas. PRL can occur as a solitary renal nodule or as an infiltrative renal disease. The most common presentation of PRL is acute renal failure, proteinuria, microscopic hematuria and renal enlargement. The prognosis of PRL is usually poor (). Early diagnosis is important for preserving renal function.\nPrimary lymphoma of bone is also a rare disease that represents less than 1% of all lymphomas, 5% of extranodal NHL and 3%-5% of all primary bone tumours (). NHL usually shows solitary bone involvement and mostly involves diametaphysis of long bones (). The most common manifestation of primary NHL of bone is frequent pathological fracture (). There are multiple imaging features of primary bone NHL, including a near-normal bone appearance, focal lytic lesion with geographic margins or a diffusely permeative lesion with bone destruction and soft-tissue involvement (). Although CT scan can discriminate trabecular destruction, periosteal reaction, sequestration and extraosseos lesions in patients with bone involvement, it may not differentiate malign and benign bone tumours. In such cases, more advanced imaging techniques such as magnetic resonance imaging (MRI) and FDG PET/CT imaging are required for diagnosis (). On the basis of follow-up of patients, the differential diagnosis of persistent lymphoma from healing bone may not be reliably done by MRI but PET/CT imaging has superiority in assessing remission status (). Shin DS et al. reported that there was low FDG uptake within cortical bone or adjacent soft tissue around the fracture in benign fracture, rarely in the marrow. The patternof intramedullary FDG uptake between malignant and benign fractures were significantly different. The sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT were 89.5%, 86.7% and 88.2%, respectively, with a cut-off SUVmax set at 4.7. The time interval between fracture and PET/CT did not significantly influence FDG uptake at the fracture site (). It has been reported that FDG PET/CT is a superior imaging modality to demonstrate early lymphoma involvement of bones (). However, FDG PET/CT has some limitations especially in evaluation of minimally residual disease and therapy response in patients with diffuse bone marrow uptake because of growth stimulating factor (GSF) usage ().\nWe report an unusual case of extranodal lymphoma of bone and kidneys shown by FDG PET/CT scan. The simultaneous tibia and bilateral renal involvement is rarely seen in lymphoma. This case illustrates the imaging findings of the extranodal DLBCL of kidney and bones and benefits of FDG PET/CT imaging in evaluating the extent of disease and assessing the treatment response in lymphoma.\nConflicts of Interest\nThere are no conflicts of interest.
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.