CASE REPORT Bilateral Primary Renal Lymphoma Presented as Homogenous Renal Enlargement And Acute Interstitial Nephritis Lei Wei, Hanmin Wang, Di Wang, Feng Ma, Li Li, Shiren Sun* Department of Nephrology, Xijing Hospital, Xi'an, Shaanxi 7100032,China. *Correspondence: Department of Nephrology, Xijng Hospital, No.127, Changle Road, Xi'an, Shaanxi7100032, P. R. China. E-mail: sunshiren@medmail.com.cn. Received May 2018 & Accepted December 2018 Primary renal lymphoma(PRL) is an extremely rare form of extranodal lymphoma andexhibitsas single (10-20%), multifocal nodules (60%), renal invasion from contiguous retroperitoneal disease (25-30%), diffuse infiltration (20%) or perirenal involvement (10%)[1] .Here we report a case of bilateral primary renal lymphoma in a 13 year- old boy who presented with homogenous nephromegaly and acute interstitial nephritis(AIN).The renal biopsy revealed primary renal T lymphoblastic lymphoma. Hyper-CVAD regimen was initiated and the renal function had been recovered after the first round of chemotherapy. To our knowledge, there have only been three reports of primary renal T lymphoblastic lymphoma including ours so far. All the three patients were young and showed as AIN and bilateral renal enlargement. We also reviewed 16 cases of PRL presenting with AIN and enlarged kid- neys that have been reported since 1997. Although PRL is quite rare, it must be taken into account when making a differential diagnosis of AIN. Renal biopsy is the gold standard and intensive chemotherapy can preserve the renal function. Keywords: lymphoma; renal mass; interstitial nephritis INTRODUCTION Primary renal lymphoma (PRL) is an extremely rare form of extranodal lymphoma and exhibits as single (10-20%), multifocal nodules (60%), renal invasion from contiguous retroperitoneal disease (25-30%), diffuse infiltration (20%) or perirenal involvement (10%)(1). Here we report a case of bilateral primary renal lymphoma in a 13 year-old boy who presented with homogenous nephromegaly and acute interstitial nephritis(AIN).The renal biopsy revealed primary renal T lymphoblastic lymphoma. Hyper-CVAD regimen was initiated and the renal function had been recovered after the first round of chemotherapy. To our knowledge, there have only been three reports of primary renal T lymphoblastic lymphoma including ours so far. All the three patients were young and showed as AIN and bilateral renal enlargement. We also reviewed 16 cases of PRL presenting with AIN and en- Urology Journal/Vol 17 No. 3/ May-June 2020/ pp. 317-320. [DOI: 10.22037/uj.v0i0.4596] Figure 1. Histopathological examination of core biopsy specimen showing diffuse infiltration of interstitium by monomorphous atypical lymphocytes(H&E, x200 magnification) Figure 2. Immunohistological stainings showed that the neoplastic cells were positive for CD3+, CD1a+ and Ki-67 and negative for Tdt. (x200 magnification). larged kidneys that have been reported since 1997. Al- though PRL is quite rare, it must be taken into account when making a differential diagnosis of AIN. Renal biopsy is the gold standard and intensive chemotherapy can preserve the renal function. CASE REPORT A 13-year old boy without any medical history was ad- mitted to our department for fatigue, anorexia, arthral- gia and weight loss. Careful physical examination re- vealed an low-grade fever (38.2° C) and boggy swelling of his joints. There was no peripheral lymphadenopathy or hepatosplenomegaly. The routine blood tests showed elevated serum creatinine of 3.31mg/dL, uric acid of 42.62mg/dL and lactate dehydrogenase of 367U/L. He had hemoglobin of 103g/L, platelet count 185×109/L, white blood cell count 10.01×109/L with a differential of 70.4% neutrophils. Twenty-four hour urinary protein was 385mg/dL. Urine analysis revealed the trace protein and no red blood corpuscle. The peripheral blood smear showed no abnormal findings. Abdominal ultrasonog- raphy revealed bilateral renal symmetrical enlargement with lengths of 14cm and medulla spongy appearance. The renal biopsy was performed and showed a diffuse interstitial infiltration with lymphomatous cells com- pressing tubules and surrounding preserved glomeruli. Additional staining confirmed T-lymphoblastic lym- phoma with CD3+ and CD1a+. Ki-67 stained more than 90% of the cells indicating a high-growth fraction (Fig- ure 1). FDG PET-CT showed a diffusely intense FDG uptake in both kidneys with a standard uptake value of 4.84 and intense patchy uptake in the bone marrow of multiple bones in axial and appendicular skeleton Case Report 413 Figure 3. PET demonstrated enlarged kidneys with abnormal in- tense cortical FDG accumulation and intense patchy uptake in the bone marrow of multiple bones in axial and appendicular skeleton. Age/sex Clinical manifestations Scr (mg/dL) UA (mg/dL) Pro (mg/d) LDH (U/L) RenalSize(cm) Histology Treatment Renal function Follow-up Ref. 57/M dyspnoea, anemia - - - - - DLBCL R-CHOP ↑ - 9 27/F nausea, vomiting, fever 5.18 9.23 - 644 - DLBCL R-CHOP - - 10 14/M headache, flank pain, 5.4 17.2 - 622 28/26 DLBCL CCG-5942 ↑ alive at 11 emesis, weight loss 2 weeks 68/F flank pain , dysuria 2.4 - 472 1820 14/14.5 DLBCL - ↓ died at 12 10 days 5/M hypertension 2.0 10.3 - 6354 16.6/17.4 T-LBL CCG-1961 - died at 7 2 months 21/F fever, weight loss, 14.60 - - 1124 13.6/13.7 DLBCL VACOP-B - - 13 abdominal pain 47/M fever, weakness 1.79 - 390 16.7/14.6 DLBCL CHOP ↑ alive at 14 1 year 28/M asymptomatic 9.11 - - 408 - DLBCL R-CHOP ↑ alive at 15 3 months 70/M confusion 9.42 - - - - B-LBL - - - 16 23/M chest pain, weight loss - - 230 - 15/15 T-LBL VDCLP ↑ alive at 8 2 year 62/M lumbar pain, oliguria, 8.0 - 1220 919 - DLBCL - - - 17 renal failure 17/M weight loss, joint pain, 5.3 9.2 - 696 20.7/19.8 NHL of COP+ ↑ - 18 flank pain, fever B cells COPADM 52/M ankleswelling , 4.11 - 400 - 15/15 T cell VAPEC-B ↑ - 19 weight gain , lymphoma 22/M fever, weight loss 3.8 - - 528 15/15 B-LBL COPADEM ↑ died at 1 20 year 11/F anorexia, vomitting, 5.79 10.1 - - 17/17 Birkitt’s COP+ ↑ died 21 weight loss, flank pain lymphoma COPADM 6/F abdominal pain, fever 2.8 - - - - Peripheral T - - - 22 cell lymphoma Abbreviations: -, not provided; N, normal;↑, improved; ↑, worsened; Scr, serum creatinine; UA, uric acid; Pro, proteinuria; LDH, lactate dehydrogenase; DLBCL, diffuse large B cell lymphoma; B-LBL, B lymphoblastic lymphoma; T-LBL, T lymphoblastic lymphoma; NHL, Non-Hodgkin's Lymphoma; R-CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab;VDCLP, vincristin,predni- solone,daunorubicin, cyclophosphamide, L-Asparaginase, prednisolone; COP, cyclophosphamide, vincristine, prednisolone; COPADM, cyclophosphamide, vincristine, prednisolone, adriamycin, methotrexate; Ref., reference. Table 1. Literature review of the 16 cases of bilateral primary renal lymphoma presenting with acute interstitial nephritis since 1997. Primary renal lymphoma-Wei L et al. Case Report 318 Vol 17 No 03 May-June 2020 319 (Figure 2). Bone marrow biopsy evaluation identified 16% lymphoblasts. Flow cytometry of the bone marrow identified a large population of cells expressing CD1a and Tdt. Cerebrospinal fluid specimen analysis was in- terpreted as unremarkable. Combining the clinical and pathological findings, the patient was diagnosed with primary renal T cell lymphoblastic lymphoma. Inten- sive systemic chemotherapy with hyperfractionated cyclophosphamide, vincristine, therarubicin and dexa- methasone (hyper-CVAD) and intrathecal chemother- apy were determined as appropriate treatment. Three weeks after the chemotherapy, a repeated ultrasonog- raphy showed the lengths of both kidney decreased to 11cm. His serum creatinine was 1.23mg/dL and uric acid was 6.65mg/dL. The patient’s renal function and uric acid kept normal until the last visit. Unfortunately, he died of pulmonary infection after allogeneic bone marrow transplantation at 17 months after diagnosis. DISCUSSION Acute interstitial nephritis has a large variety of etiolo- gies including drugs, infections, autoimmune disorders and hematological diseases. Although extremely rare, acute interstitial nephritis can be a primary clinical manifestation of renal lymphoma. Drug-induced or al- lergic interstitial nephritis and other systemic diseases (IgG4 related disease, Sjogren syndrome etc.) should be considered in the differential diagnosis with PRL presenting with massive lymphomatous infiltration. Criteria to diagnose PRL can be concluded by the fol- lowing four features: renal enlargement, lymphomatous infiltration, no nodal or extra-nodal involvement, and improved renal function after chemotherapy(2,3). PLR is quite rare as no more than 70 cases have been reported so far(4). Due to a relatively aggressive behavior and de- layed diagnosis, most of the patients had a poor progno- sis(5). Therefore, the early diagnosis and rapid intensive treatment are essential to preserve the renal function. Majority of patients with T-LBL present with stage IV disease (80%), B symptoms (50%) and elevated serum lactate dehydrogenase (LDH) levels(6)`. There have been only two cases of primary renal T lymphoblastic lymphoma(7,8), both with young age and enlarged kid- neys, which were similar with ours. Our patient had se- vere hyperuricemia without hyperkalemia, hyperphos- phatemia or hypocalcemia, are probably due to the high metabolite state of tumor cells, other than the tumor lysis syndrome. FDG PET-CT is unspecific tool for the diagnosis of lymphoma due to that physiologic FDG excretion in the kidneys makes the interpretation of the tracer uptake in this organ difficult. However, it shows superiority on the diagnosis of primary renal lymphoma by excluding the nodal or extra-nodal lymphoma and staging of the disease. The present study reviewed 16 cases of bilateral pri- mary renal lymphoma presenting with acute interstitial nephritis since 1997(7-22)(Table 1). There were more male patients than female patients, with a gender ratio of 11:5. These patients aged from 5 to 70 years old, of which 10 were young patients (age < 28 years). Weight loss (7/16), fever (7/16) and flank or abdominal pain (5/16) are most common symptoms. The average renal size was 15.6cm. Most of the patients had increased LDH level. Three patients had co-infection with HCV, HBV or HIV infections. Preponderance of the cases (11/16) are B-cell lineage, and diffuse large B cell lym- phoma are the most common histological type (8/16). After chemotherapy, most patients had improved renal functions. However, their prognoses were not clear with limited information. It was postulated that the pre-existing inflammation recruits lymphoid cells into the renal parenchyma(23). However, the exact mechanisms underlying the differ- ent patterns of malignant cells infiltrating the kidney (diffuse or focal, bilateral or unilateral) remain un- known. Bilateral primary renal lymphoma presented as acute interstitial nephritis and symmetrical nephro- megaly is believed to be a unique entity with specific manifestations of acute kidney injury and elevated LDH and uric acid level. In this setting renal biopsy and FDG PET-CT are useful modalities greatly contributing to the early diagnosis of PRL. REFERENCES 1. Sheth S, Ali S, Fishman E. Imaging of renal lymphoma: Patterns of disease with Pathologic correlation. Radiographics.2006;26:1151-68. 2. Malbrain ML, Lambrecht GL, Daelemans R, Lins RL, Hermans P, Zachée P.Acute renal failure due to bilateral lymphomatous infiltrates. 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