| | Quiz Page June 2008: Renal Failure, Hematuria, and FeverClinical Presentation  A 74-year-old African American woman was admitted with fever. She had blood pressure of 139/75 mm Hg, temperature of 100.8°F (38.2°C), and no localizing physical findings. She had a white blood cell count of 13.5 × 103/μL (13.5 × 109/L), hemoglobin level of 9.6 g/dL (96 g/L), platelet count of 277 × 103/μL (277 × 109/L), and serum creatinine level of 1.8 mg/dL (159 μmol/L). Urinalysis showed specific gravity of 1.025, 2+ protein, and normal sediment. Her temperature spikes continued reaching 103°F (39.4°C). Results were negative for blood cultures, purified protein derivative, malarial smear, antinuclear antibody, human immunodeficiency virus, Epstein-Barr virus, hepatitis B and C viruses, and Leptospira, Rickettsia, and Brucella species. She showed no vegetation on echocardiograms and no hilar or retroperitoneal lymphadenopathy on computed tomographic scans. No granulomas or tumors were identifiable on bone marrow biopsy. Repeated urinalysis showed red blood cell casts. A 24-hour urine for protein measured 2.32 g, and serum creatinine had increased to 2.1 mg/dL (186 μmol/L). A computed tomography–guided kidney biopsy was performed. ■ What do you see by light microscopy in Figure 1, Figure 2? ■ What is your diagnosis? Discussion What Do You See by Light Microscopy in Figure 1, Figure 2? The glomerulus is enlarged and hypercellular, with large hyperchromatic pleomorphic lymphoid cells showing focal mitotic activity (Fig 1). There also is tubular atrophy and focal widening of the interstitium (Fig 2). What is Your Diagnosis? On cell-specific marker staining, large atypical lymphoid cells in the glomerulus (Fig 3A) and interstitium (Fig 3B) were reactive for the B-cell marker CD20. Smaller interspersed lymphoid cells were positive for the T-cell marker CD3, primarily in the interstitium (Fig 4A) and surrounding malignant lymphoid cells (Fig 4B), characteristic of an intravascular large B-cell lymphoma. Intravascular lymphoma is a rare neoplasm characterized by a peculiar proliferation of malignant lymphoid cells in small blood vessels, usually not identified on peripheral-blood smear or bone marrow biopsy. Intravascular lymphoma often affects the kidneys, causing a variety of manifestations; the most common are fever, proteinuria, and decreased kidney function. The kidney involvement usually does not result in abnormal imaging study results.1 Patients with nephrotic-range proteinuria have been found to have effaced foot processes of glomerular epithelial cells on electron microscopy and negative immunofluorescence microscopy study results, suggestive of minimal change disease.2 Near-normal restoration of original glomerular architecture was reported on repeated biopsy on completion of treatment.6, 7 The absence of immune complexes on immunofluorescence microscopy studies and the clinical setting of fever suggest that the pathogenetic processes more likely are caused in part by a cellular immune reaction to malignant B cells or reactive T cells surrounding malignant B cells. We have also compiled a table (Table 1) highlighting age, sex, clinical presentation, biopsy findings, treatment and outcomes of all cases of intravascular lymphoma reported in English literature from 1985 to 2007. | | |  | Author | Year | Age/Sex | Presentation | Biopsy Findings | Treatment | Outcome | |
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| Iskander et al3 | 1985 | 57/M | Multiple neurological symptoms | IVL, MCD | None | Died | | | D'Agati et al4 | 1989 | 62/F | Nausea, vomiting, cramps, fever | IVL, MCD, focal interstitial infiltration | Steroids | Died | | | Axelsen et al5 | 1991 | 60/F | Fever, pallor, night sweats | IVL, focal interstitial infiltration | Chemotherapy | Few mo | | | Nishikawa et al6 | 1991 | 52/F | Malaise, fever | IVL, MCD | Chemotherapy | 16 wk + | | | Agar et al7 | 1994 | 60/M | Neck pain, fever | IVL, MCD, focal interstitial infiltration | Chemotherapy | 16 wk + | | | Wood et al8 | 1996 | 61/M | Malaise, anorexia, weight loss, fever | IVL, focal interstitial infiltration | Chemotherapy | 20 d | | | Cheng et al9 | 1997 | 35/F | Slurring of speech, blurring of vision, fever | IVL | NA | NA | | | Wang et al10 | 2001 | 77/F | Weakness, lethargy, weight loss | IVL, RCC | Chemotherapy | 6 mo | | | Shaknovich et al2 | 2002 | 85/F | Depression with psychosis, weight loss | IVL, MCD | None | 3 mo + | | | Kakumitsu et al11 | 2003 | 58/M | Fever, edema of lower extremities | IVL, MCD, focal interstitial infiltration | Chemotherapy | 6 wk + | | | Fozza et al12 | 2003 | 53/F | Fever, fatigue, arthralgias | IVL | Chemotherapy | 6 mo | | | Törnroth et al1 | 2003 | 63/M | Skin lesions | IVL, MCD | Chemotherapy | 21 mo | | | | 2003 | 69/M | Fatigue, fever | IVL, MCD | None | 1 mo | | | Ozolek et al13 | 2003 | 72/M | Fatigue, weight loss, polyuria | IVL, MCD | Chemotherapy | NA | | | Cossu et al14 | 2004 | 52/F | Fever, weakness, edema | IVL, MCD, interstitial infiltration | Chemotherapy | 6 mo | | | | |
Final Diagnosis Large B-cell lymphoma, intravascular type, with diffuse glomerular and focal interstitial infiltration. References 1. 1Törnroth T, Heiro M, Marcussen N, Franssila K. Lymphomas diagnosed by percutaneous kidney biopsy. Am J Kidney Dis. 2003;42:960–971. Abstract | Full Text |
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2. 2Shaknovich R, Francois DJ, Cattoreti G, D'Agati VD, Markowitz GS. A rare case of nephrotic syndrome. Am J Kidney Dis. 2002;39:892–895. Full Text |
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3. 3Iskandar SS, Jennette C, Weis LS. Primary cerebral lymphoma with glomerular renal involvement. Arch Pathol Lab Med. 1985;109:524–528. MEDLINE 4. 4D'Agati V, Sablay LB, Knowles DM, Walter L. Angiotropic large cell lymphoma (intravascular malignant lymphomatosis) of the kidney: presentation as minimal change disease. Hum Pathol. 1989;20:263–268. MEDLINE |
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5. 5Axelsen RA, Laird PP, Horn M. Intravascular large cell lymphoma: Diagnosis on renal biopsy. Pathology. 1991;23:241–243. 6. 6Nishikawa K, Sekiyama S, Suzuki T, et al. A case of angiotropic large cell lymphoma manifesting nephrotic syndrome and treated successfully with combination chemotherapy. Nephron. 1991;58:479–482. 7. 7Agar JWM, Gates PC, Vaughan SL, Machet D. Renal biopsy in angiotropic large cell lymphoma. Am J Kidney Dis. 1994;24:92–96. Abstract 8. 8Wood SM, Boyd SM, Taylor JE, Savill J. A case of non-Hodgkin lymphoma presenting primarily with renal failure. Nephrol Dial Transplant. 1996;11:535–536. MEDLINE 9. 9Cheng FY, Tsui WMS, Yeung WTC, Ip LS, Ng CS. Intravascular lymphomatosis: A case presenting with encephalomyelitis and reactive hemophagocytic syndrome diagnosed by renal biopsy. Histopathology. 1997;31:552–554. MEDLINE 10. 10Wang BY, Strauchen JA, Rabinowitz D, Tillem SM, Unger PD. Renal cell carcinoma with intravascular lymphomatosis (A case report of unusual collision tumors with review of literature). Arch Pathol Lab Med. 2001;125:1239–1241. MEDLINE 11. 11Kakumitsu H, Higuchi M, Tanaka K, Shibuya T. Nephrotic syndrome in a patient with intravascular lymphomatosis. Intern Med. 2003;42:98–101. MEDLINE |
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12. 12Fozza C, Bonfigli S, Conti M, Dore F, Longinotti M. Long-lasting fever of unknown origin preceding the diagnosis of intravascular lymphomatosis: A further case stimulates some remarks. Am J Hematol. 2003;74:211–213. MEDLINE |
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13. 13Ozolek J, Nodit L, Bastacky S, Criag F, Nalesnik M. Pathologic Quiz Case: A 72-year-old man with fatigue and proteinuria (Angiotropic (intravascular) large B-cell lymphoma). Arch Pathol Lab Med. 2003;127:1380–1382. 14. 14Cossu A, Deiana A, Lissia A, et al. Nephrotic syndrome and angiotropic lymphoma report of a case. Tumori. 2004;90:510–513. MEDLINE Case provided and authored byJinil Yoo, MD, Sarat Kuppachi, MB, BS, and Praveen Chander, MD, Department of Nephrology, Our Lady of Mercy Medical Center, New York Medical College; and Department of Pathology, Westchester Medical Center, New York Medical College, New York, NY. Financial Disclosure: None. PII: S0272-6386(08)00058-9 doi:10.1053/j.ajkd.2007.11.036 © 2008 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | |
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