Grand Rounds

A Case of Primary Renal LymphomaSpencer Hart, Chandy Ellimoottil, Danielle Shafer, Vikas Mehta, and Thomas M. Turk

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THE CASE

An 82-year-old woman presented to the emer-gency room after a fall while on anticoagulation.She denied dizziness, palpitations, or loss of con-

sciousness before the event. Her past medical history wasremarkable for coronary artery disease and deep veinthrombosis managed by inferior vena cava (IVC) filterand warfarin therapy. Physical examination findings wereunremarkable, with no noted adenopathy or hepatomeg-aly. A laboratory workup revealed a white blood cellcount of 6000 cells/mm3 (normal 4000-10 000 cells/mm3). Blood urea nitrogen and serum creatinine were 36mg/dL (normal 7-22 mg/dL) and 2.34 mg/dL (normal0.6-1.4 mg/dL), respectively. The patient’s serum creati-nine was elevated from her baseline of 0.90 mg/dL. Inaddition, her serum calcium was elevated to 15.7 mg/dL(normal 8.5-10.5 mg/dL): all other blood chemistries,including liver function tests, were within normal limits.Renal ultrasound revealed a 14-cm heterogeneous rightrenal mass. Subsequent noncontrast computed tomogra-phy (CT) of her chest, abdomen, and pelvis revealedseveral bilateral pulmonary nodules that were too smallto characterize, thyroid nodules and the renal mass,which was shown to be causing a mass effect on the IVC,liver, and duodenum, with no definite extension into theright renal vein or IVC (Figs. 1 and 2). She did have aprominent precarinal lymph node and some noticeableretroperitoneal and mesenteric lymph nodes, but nonewere enlarged by CT criteria. Fine needle aspiration ofthe thyroid nodules were negative for malignancy, andconsistent with benign follicular nodule.

DIFFERENTIAL DIAGNOSISThe kidney may give rise to benign and malignant diseaseprocesses that present as an incidental solid renal masswith no metastatic findings. Although the benign lesions,such as oncocytoma, adenoma, and angiomyolipoma, areon the differential, the size of this mass is concerning for

Financial Disclosure: The authors declare that they have no relevant financialinterests.

From the Department of Urology, Loyola University Medical Center, Maywood, IL;Department of Hematology/Oncology, Loyola University Medical Center, Maywood,IL; Department of Pathology, Loyola University Medical Center, Maywood, IL

Reprint requests: Chandy Ellimoottil, M.D., Department of Urology, Loyola Uni-versity Medical Center, 2160 S. First Avenue, Fahey Center, Room 261, Maywood,

pIL 60153. E-mail: cellimoottil@lumc.edu

Submitted: April 2, 2012, accepted (with revisions): May 14, 2012

Published by Elsevier Inc.

malignancy. Given that renal cell carcinoma (RCC) isthe most common cause of a malignant solid renal massin an elderly patient, it was on the top of our differential.Due to the propensity of RCC to invade the renal veinand metastasize, rapid and aggressive therapy to removethe tumor is crucial in these cases. Primary urothelial cellcarcinoma (UCC) was also considered. UCC should bestrongly considered for patients with risk factors, such asmale gender, history of smoking, and advanced age. Onimaging, this mass was found not to arise from the col-lecting system, so we thought that a primary UCC wasless likely. Metastasis to the kidney from a distant pri-mary tumor is an uncommon occurrence. However, it isimportant to note that metastasis to the kidney maymimic renal cell carcinoma. Identification of these tu-mors early in management is essential to avoid unneces-sary surgery. Sarcoma of the kidney is rare in adults, andthe optimal treatment is not clear. Lymphoma of thekidney was considered; however, most cases of renallymphoma are secondary lesions, and this patient did nothave any discernible lymphadenopathy.

MANAGEMENT AND PATHOLOGY

Presented by Vikas Metha, M.D. (Pathologist)After options were discussed with the patient, includingradical nephrectomy and CT-guided biopsy of the mass,the team elected to perform a biopsy of the mass.

Core biopsy of the right kidney showed diffuse infil-tration by neoplastic lymphoid infiltrate, composed ofmedium-to-large lymphoid cells. Focally, areas of necrosiswere noted (Fig. 3). Immunohistochemical stains showedthe following:

● Positive: CD20, CD5 (weakly in some neoplasticcells), CD10 (subset of neoplastic cells)

● Negative: CD3, Mum1, Bcl-2, Tdt, Bcl-1● Ki-67 stain showed high proliferation fraction of 95%● FISH study results were positive for t (14,18) and

negative for t (11,14) Although there was no evidenceof t (8,14), a translocation involving MYC (partnerunknown) was detected.

ased on these data, the favored diagnosis was B-cellymphoma. A bone marrow biopsy was performed andhowed no morphologic involvement of lymphoma. Theatient was initially treated with one cycle of cyclophos-

hamide, vincristine, and prednisone, while hospitalized

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with Neupogen support. Subsequently, she was placed oncyclophosphamide, doxorubicin, vincristine, and predni-sone with rituximab (R-CHOP).

COMMENT

Presented by Danielle Shafer, M.D. (Oncologist)Although approximately 50% of patients with non-Hodgkin’s lymphoma (NHL) have renal involvement atdeath, primary renal lymphoma (PRL) is extremelyrare.1,2 Primary renal lymphoma describes NHL involv-ng the kidney in the absence of any other organ or nodalisease. Age of presentation is typically above 40; how-ver, cases have been reported in individuals as youngs (21)3,4 PRL also seems to show a sex predispositionor males.4 Presentation of the disease is characterized

by flank pain, weakness, weight loss, hematuria, mal-aise, body aches, abdominal mass, thrombocytopenia,and renal failure.5 Most cases are unilateral, althoughthere have been reported instances of bilateral in-volvement.2,6 Becaues of the aggressive nature of the tu-

or, it often involves local tissues and can invade the renalein and IVC, mimicking renal cell carcinoma.7,8 It is

suspected that PRL may be more common than reported, asthese tumors are aggressive and may therefore show evi-dence of extrarenal lymphomatous disease at the time of

Figure 1. Noncontrast CT scan demonstrating a large renalass.

Figure 2. Noncontrast CT scan showing renal lesion creat-ing a mass effect on the liver, inferior vena cava (IVC), aortaand duodenum.

diagnosis.1,2 r

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The etiology of PRL is still inconclusive, as the kidneydoes not have lymphoid tissue. Repeated injury to renallymphatics because of chronic inflammation, has beensuggested as the cause of lymphoid transformation andsubsequent neoplasia of the lymphoid tissue. This processis similar to that of other extranodal mucosa-associatedlymphoid tissue (MALT) lymphomas, affecting skin,breast, and other nonlymphoid tissues.9,10

The diagnosis of PRL can be made using the followingcriteria: (i) the presence of a renal mass without extrare-nal lymphomatous involvement, (ii) the absence of aleukemic blood picture, and (iii) the absence of lymph-adenopathy or hepatosplenomegaly.11 Diagnosis is chal-enging, given the fact that common tumors such as renalell carcinoma may mimic the presentation of PRL. It isssential, however, to distinguish between the two, asanagement is different. Diagnosis can be confirmedith CT-guided biopsy of the mass.5 A positron emission

omography (PET) scan has been demonstrated to be aotential method of detection of extranodal lymphoma;owever, its efficacy is still under investigation.12 In mosteports, diagnosis was made after nephrectomy for sus-ected renal cell carcinoma.Treatment of PRL is dependent on the grade of the

umor. Low-grade MALT lymphomas can be treated ef-ectively with single-agent rituximab, surgical interven-ion, or radiation.7 Patients who present with intermedi-

ate- or high-grade lymphoma should not undergo surgicalintervention and should be treated with systemic ther-apy. High-grade tumors tend to have extensive involve-ment in the regional tissue, organs, and vasculature.8 Inhese cases, surgical intervention would prove to be det-imental, with increased risk of morbidity and mortality.8

Intermediate and high-grade PRL has, however, beenshown to be responsive to chemotherapy, and should bequickly and aggressively treated to halt a further decreasein renal function and invasion of nearby tissues.12,14 Theiterature demonstrates that an increase in renal functionay be detected in as little as 2 weeks and full recovery

n as little as 4 weeks.12,15 The current treatment stan-dard is 6-8 cycles of R-CHOP. The addition of rituximab,a monoclonal antibody targeting CD20, to the CHOP che-motherapy regimen has been documented to increase re-sponse rates and 5-year patient survival rates; this has beenattributed primarily to the control of systemic disease.12

Proper treatment and early intervention have beendocumented to correlate with improved outcomes. Pa-tients with MALT-like lymphomas were reported to havea better prognosis compared with patients with higher-grade lymphomas.7 Because most patients presentingwith a renal mass undergo nephrectomy, diagnosis of PRLtends to be delayed.5 In addition, many patients presentwith locally advanced disease.3,13 The literature hashown that after 6 cycles of CHOP therapy with ritux-mab, patients can be disease free for 7 months to 6.5ears after treatment.5,14 In their recent report, Villa et al

eported that patients who received rituximab for diffuse

UROLOGY 80 (4), 2012

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large B-cell lymphoma involving the kidney had 5-yearoverall survival rates of 43%.

PRL is a rare diagnosis in patients presenting with arenal mass. Early diagnosis and early intervention areessential for a favorable outcome because of the aggres-sive behavior of the tumor. Diagnosis may be establishedwith biopsy of the mass. Albeit aggressive, PRL respondsto chemotherapy, and improvement in renal functionoccurs rapidly after the onset of therapy. At present, theR-CHOP regimen is the standard treatment of interme-diate- or high-grade PRL. Proper treatment and earlyintervention have been documented to correlate withimproved outcomes.

References1. Kandel LB, McCullough DL, Harrison LH, et al. Primary renal

lymphoma. Does it exist? Cancer. 1987;60:386-391.2. Okuno SH, Hoyer JD, Ristow K, et al. Primary renal non-Hodg-

kin’s lymphoma. An unusual extranodal site. Cancer. 1995;75:2258-2261.

3. Olusanya AA, Huff G, Adeleye O, et al. Primary renal non-Hodgkins lymphoma presenting with acute renal failure. J Natl MedAssoc. 2003;95:220-224.

4. Tuzel E, Ugur Mungan MU, Kutsal Yorukoglu, et al. Primary renallymphoma of mucosa-associated lymphoid tissue. Urology. 2003;61:463.

5. Kose F, Sakalli H, Mertsoylu H, et al. Primary renal lymphoma:

Figure 3. (A) H&E (�10) Core renal biopsy revealed diffomprising large atypical lymphoid cells. (C) Ki-67 immunoColor version available online.)

report of four cases. Onkologie. 2009;32:200-202.

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6. Omer H, Hussein M. Primary renal lymphoma. Nephrology. 2007;12:317-315.

7. Wagner JR, Honig SC, Siroky MB. Non-Hodgkin’s lymphoma canmimic renal adenocarcinoma with inferior vena caval involvement.Urology. 1993;42:720-723.

8. Samlowski EE, Dechet C, Weissman A, et al. 2011. Large cellnon-Hodgkin’s lymphoma masquerading as renal carcinoma withinferior vena cava thrombosis: a case report. J Med Case Reports2011;5:245.

9. Freeman C, Berg JW, Cutler SJ. Occurrence and prognosis ofextranodal lymphomas. Cancer. 1972;29:252-260.

0. Salem Y, Pagliarulo LC, Manyak MJ. Primary small non-cleavedcell lymphoma of kidney. Urology. 1993;42:31-35.

1. Qui L, Unger PD, Dillon RW, et al. Low-grade mucosa associ-ated lymphoid tissue lymphoma involving the kidney: report of3 cases and review of the literature. Arch Pathol Lab Med.2006;130:86-89.

2. Al-Salam, Shaaban A, Alketbi M, et al. S, Shaaban A, Alketbi M,et al: acute kidney injury secondary to renal large B-cell lymphoma:role of early renal biopsy. Int Urol Nephrol. 2011;43:237-240.

3. Niitsu N, Okamura D, Takahashi N, et al. Renal intravascular largeB-cell lymphoma with early diagnosis by renal biopsy: a case reportand review of the literature. Leuk Res. 2009;33:728-730.

4. Villa D, Connors JM, Sehn LH, et al. Diffuse large B-cell lym-phoma with involvement of the kidney: outcome and risk of centralnervous system relapse. Haematologica. 2011;96:1002-1007.

5. Vázquez Alonso F, Sánchez Ramos C, Vicente Prados FJ, et al.Primary renal lymphoma: report of three new cases and literature

sheets of neoplastic lymphoid infiltrate. (B) H&E (�40)(�10), the tumor cells had a very high proliferative index.

usestain

review. Arch Esp Urol. 2009;62:461-465.

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