SLE: The great imitator strikes again

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<ul><li><p>KIDNEY BIOPSY TEACHING CASE</p><p>itatoes So</p><p>IND l cell c</p><p>Smubeuridetomisofpetioledest</p><p>Aphynes</p><p>repeye</p><p>Tofpretiveand</p><p>Pmm</p><p>minwa</p><p>lymsho</p><p>LbodDNanthypposshorate</p><p>Aputfied</p><p>KiThe biopsy specimen consisted of 5 pieces of tissue</p><p>obtained by needle biopsy varying from 0.2 to 0.5 cm inlencopsco</p><p>sistin</p><p>netwe</p><p>witam</p><p>proThFuh</p><p>ClT</p><p>init 4kidsur</p><p>NglogloImmglogensco</p><p>me</p><p>denT</p><p>pairatoantup,ren</p><p>shnaclucomenamaof</p><p>FR</p><p>24, 2004.Address reprint requests to Jane M. Bell, MD, Nephropathol-</p><p>Amgth that were submitted for examination by light micros-y, immunofluorescence, and electron microscopy. Micro-pic examination showed that all submitted tissue con-ed of a proliferation of enlarged cells with clear cytoplasman alveolar to focally tubular arrangement, showing a</p><p>ogy Associates, 10802 Executive Center Dr, Ste 111, BentonBldg, Little Rock, AR 72211. E-mail:</p><p> 2004 by the National Kidney Foundation, Inc.0272-6386/04/4501-0027$30.00/0doi:10.1053/j.ajkd.2004.05.049</p><p>erican Journal of Kidney Diseases, Vol 45, No 1 (January), 2005: pp 219222 219SLE: The Great ImJane M. Bell, MD, Ramesh Nair, MD, Agn</p><p>EX WORDS: Systemic lupus erythematosus (SLE), rena</p><p>YSTEMIC LUPUS erythematosus (SLE) isan autoimmune disease that may involve</p><p>ltiple organ systems. Renal involvement mayindicated by isolated proteinuria or protein-a and hematuria, possibly with an associatedcrease in renal function. In patients with symp-</p><p>s of renal involvement, renal biopsy typicallyperformed to obtain histological classificationthe type of renal disease. This provides thera-utic guidance and helpful prognostic informa-n. We present a case in which the renal biopsyto an unexpected diagnosis and a very inter-</p><p>ing clinical course.</p><p>CASE REPORT68-year-old African-American woman presented to her</p><p>sician with polyarthralgias, pleuritic chest pain, short-s of breath, and decreased exercise tolerance. She alsoorted blurring of vision, a foreign-body sensation in her, dry mouth, and lower-extremity and periorbital edema.he patients medical history was remarkable for diabetesgreater than 20 years duration, hypertension, and avious cerebrovascular accident. Family history was posi-</p><p>for heart disease, hypertension, diabetes, sarcoidosis,polymyositis.hysical examination showed blood pressure of 162/80Hg; pulse rate, 80 beats/min; respirations, 20 breaths/</p><p>; and weight, 259 lbs. Periorbital edema was noted. Shes afebrile and had no evidence of alopecia, skin rash,phadenopathy, or organomegaly. Chest examinationwed no friction rub.aboratory studies showed a positive antinuclear anti-y titer at 1:1,280, with positive anti-double strandedA (47 IU/mL; normal, 25 IU/mL) and antihistoneibody titers (4.6 IU/mL). Complete blood count showedochromic microcytic anemia. Urinalysis results wereitive for blood and protein. A 24-hour urine collectionwed protein of 6.76 g/24 h. Erythrocyte sedimentationwas 112 mm/h. Complement levels were normal.percutaneous renal biopsy was performed under com-</p><p>ed tomographic guidance. No mass lesions were identi-at the time of biopsy.</p><p>dney Biopsyr Strikes Againlon, MD, and Patrick D. Walker, MD</p><p>arcinoma, renal biopsy, paraneoplastic syndrome.</p><p>work of delicate thin-walled vascular channels. Nucleire intermediate in size and round to slightly irregular,h some showing prominent nucleoli. Ultrastructural ex-ination showed the cells to contain clear cytoplasm withminent lipid vacuoles and scattered glycogen granules.e diagnosis of renal cell carcinoma, clear cell type,rman grade 2 was made (Figs 1 and 2).</p><p>inical Follow-Uphe patient underwent a left nephrectomy 2 weeks after the</p><p>ial biopsy. The nephrectomy specimen showed a 5.0 4.0.0 cm clear cell carcinoma involving the lower pole of the</p><p>ney. No capsular or vascular invasion was identified, andgical margins were negative for tumor.</p><p>on-neoplastic renal tissue showed diffuse and nodularmerulosclerosis consistent with diabetic nephropathy, focalbal sclerosis, and severe arteriosclerosis (Figs 3 and 4).</p><p>unofluorescence stains for immunoglobulin G, immuno-bulin M, immunoglobulin A, C3, C4, C1q, albumin, fibrino-, and and light chains were negative. Electron micro-pic examination showed thickened capillary loops andsangial matrix expansion with nodule formation. No electron-se deposits were identified.he patient reported improvement of her pleuritic chest</p><p>n and arthralgias after surgical recovery. Follow-up labo-ry studies showed the disappearance of antinuclear and</p><p>i-double stranded DNA antibodies. At 1 year of follow-the patient had no evidence of recurrent or metastatic</p><p>al cell carcinoma and no evidence of SLE.</p><p>DISCUSSIONThe existence and nature of a possible relation-ip between rheumatic disorders and malig-ncy have been proposed.1-7 Possibilities in-de rheumatic syndromes as premalignant</p><p>nditions with increased risk for the develop-nt of malignancy, the development of malig-</p><p>ncy secondary to cytotoxic therapy for rheu-tic disorders, and a paraneoplastic associationa rheumatic disorder with a malignancy.</p><p>rom Nephropathology Associates, Little Rock, AR.eceived April 23, 2004; accepted in revised form May</p></li><li><p>batis11enanhafrithetura rrencotioat</p><p>anDNcaplaclidroaptre</p><p>pe 8caSLrenofresbo</p><p>relininiexpomaphsitfrealldrocarlivmaonoc</p><p>Fchaci</p><p>Fpronifi</p><p>BELL ET AL220The diagnosis of SLE was made in this patientsed on fulfillment of the American Rheuma-m Association criteria (presence of at least 4 ofdefined criteria): arthritis, renal disorder, pres-ce of antinuclear antibody, and presence ofti-double stranded DNA antibody. She alsod a history of pleuritic chest pain, although noction rub was heard on examination. Based on</p><p>significant proteinuria and presence of hema-ia, lupus nephritis was strongly suspected, andenal biopsy was performed. The diagnosis ofal cell carcinoma on the renal biopsy was</p><p>mpletely unexpected given the clinical situa-n and because no mass lesion was appreciatedthe time of the biopsy procedure.The improvement in symptoms and disappear-ce of the antinuclear and anti-double strandedA antibodies after resection of the renal cell</p><p>rcinoma suggests the possibility of a paraneo-stic syndrome. Classification of any set ofnical abnormalities as a paraneoplastic syn-me is based on 2 criteria: the syndrome must</p><p>pear after the onset of the malignancy, andatment of the malignancy must result in disap-</p><p>ig 1. Clear cell carcinoma showing trabecular ar-itecture and prominent vascular channels (periodicdSchiff; original magnification200).arance of paraneoplastic symptoms. In thisse, the development of signs and symptoms ofE in close association with the discovery of aal cell carcinoma, followed by the resolutionsymptoms and absence of autoantibodies afterection of the tumor, indicate fulfillment ofth requirements.Symptoms of a paraneoplastic syndrome notated to tumor mass or tumor invasion are seen10% of patients with cancer at the time oftial diagnosis, and up to 50% of patientsperience a paraneoplastic syndrome at someint during their course.7 Paraneoplastic rheu-tic syndromes are not uncommon. Hypertro-ic osteoarthropathy, dermatomyositis/polymyo-is, and paraneoplastic vasculitis are seen mostquently. Subacute cutaneous lupus occasion-y has been described as a paraneoplastic syn-me associated with solid tumors, includingcinoma of the lung,9-11 stomach,12 breast,13er,14 and uterus,15 as well as with hematologiclignancies.5 To the best of our knowledge,ly 7 reports of SLE or lupus like syndromescurring as paraneoplastic syndromes can be</p><p>ig 2. Nuclei are intermediate in size with scatteredminent nucleoli (periodic acidSchiff; original mag-cation400).</p></li><li><p>fouincnonopalunwilikforthamalikphrepwitheSL</p><p>thetiohekidphres</p><p>pronehadiabeAnthebepa</p><p>renanceunpafacrheandissylatnaatiof</p><p>FingSc</p><p>FbraSc</p><p>SLE: THE GREAT IMITATOR STRIKES AGAIN 221nd in the literature. The associated neoplasmslude ovarian adenocarcinoma,16 ovarian semi-ma,17 bronchioalveolar carcinoma,18 carci-ma of the breast (2 patients),19 alveolar softrt sarcoma,20 epidermoid carcinoma of theg,21 and Castlemans disease.22 The 2 patients</p><p>th carcinoma of the breast developed lupuse syndromes after receiving radiation therapyadvanced local disease, raising the possibilityt tissue irradiation may have initiated an abnor-l immunologic response that led to the lupuse syndrome. Although myopathy23 and anti-ospholipid antibody syndrome24,25 have beenorted as paraneoplastic syndromes associated</p><p>th renal cell carcinoma, this case representsfirst report of a paraneoplastic association of</p><p>E with renal cell carcinoma.The absence of evidence of lupus nephritis in</p><p>nephrectomy specimen requires reexamina-n of the cause of the patients proteinuria andmaturia. In areas away from the neoplasm, theney showed classic features of diabetic ne-</p><p>ropathy. Can this explain the laboratory testult alterations seen in this patient? Certainly,</p><p>ig 3. Glomeruli from nephrectomy specimen show-well-formed mesangial nodules (periodic acid</p><p>hiff; original magnification200).teinuria is common in patients with diabeticphropathy. However, hematuria, although per-ps less commonly considered a feature ofbetic nephropathy, also is associated with dia-</p><p>tic nephropathy in up to 30% of patients.26other possible explanation of the hematuria ispresence of the renal cell carcinoma itself</p><p>cause hematuria is found in 50% to 60% oftients with such a neoplasm.The occurrence of a neoplasm and the occur-ce of SLE are both relatively common events,</p><p>d coincidental occurrence of the 2 in a patientrtainly is possible. Although a search for anderlying malignancy is not indicated in everytient with SLE, it is worthwhile to examinetors that might indicate that SLE or a similarumatic/autoimmune process is associated withunderlying malignancy. This issue has beencussed in reviews of paraneoplastic rheumatic</p><p>ndromes.1,7 Clinical findings found to corre-e with the presence of an underlying malig-ncy include such epidemiologic consider-ons as history of malignancy or family historymalignancy, exposure to carcinogens, late age</p><p>ig 4. Glomerulus with thickened basement mem-nes and mesangial expansion (periodic acid</p><p>hiff; original magnification400).</p></li><li><p>at onset of rheumatic syndrome (50 years),prominent constitutional symptoms (fever, mal-aise, and weight loss), and a poor response toconventional medical treatment. Only 1 of thesefindings, age of onset older than 50 years, waspre</p><p>sentiosersytatmabioshpegra</p><p>Tsuppre</p><p>1syn29:</p><p>2tati</p><p>3Cu</p><p>4rhe198</p><p>5fes721</p><p>6ma</p><p>30:7</p><p>lier8</p><p>De9</p><p>subass</p><p>1741</p><p>acu</p><p>nom</p><p>De</p><p>11. Blanc D, Kienzler JL: Lupus erythematosus gyratusrepens. Report of a case associated with a lung carcinoma.Clin Exp Rheumatol 7:129-134, 1982</p><p>12. Kuhn A, Kaufman I: Subakuter kutaner lupus erythe-matodes als paraneoplastisches syndrom. Z Hautkr 61:581-583, 1986</p><p>1lupcas</p><p>1491</p><p>lupnom</p><p>1cuthypade</p><p>1nuc</p><p>syn1</p><p>clinova</p><p>8341</p><p>mu</p><p>veo</p><p>1car</p><p>2synCaOn</p><p>2syslun211</p><p>2plawittolo</p><p>2parMe</p><p>2lismcar</p><p>2antaut200</p><p>2red74:</p><p>BELL ET AL222sent in our patient.To the best of our knowledge, this case repre-ts the first report of a paraneoplastic associa-</p><p>n of SLE with renal cell carcinoma. It alsoves as a reminder that rheumatic/autoimmune</p><p>ndromes, particularly when atypical in presen-ion, may herald the presence of an underlyinglignancy. Moreover, it is a warning that apsy performed for medical renal disease may</p><p>ow an unexpected malignancy, even thoughrformed under ultrasound or computed tomo-phic guidance.</p><p>ACKNOWLEDGMENThe authors thank Dr Stephen Bonsib for assistance andport and Denise Norwood for help with manuscriptparation.</p><p>REFERENCES. Naschitz J, Rosner I, Rozenbaum M, et al: Rheumaticdromes: Clues to occult neoplasia. Semin Arthritis Rheum43-55, 1999. Caldwell DS, McCallum RM: Rheumatologic manifes-ons of cancer. Med Clin North Am 70:385-417, 1986. Brooks PM: Rheumatic manifestations of neoplasia.</p><p>rr Opin Rheumatol 4:90-93, 1992. Butler RC, Thompson JM, Keat ACS: Paraneoplasticumatic disorders: A review. J R Soc Med 80:168-172,7. Castro M, Conn DL, Su WPD, et al: Rheumatic mani-</p><p>tations in myelodysplastic syndromes. J Rheumatol 18:-727, 1991. Leandro MJ, Isenberg DA: Rheumatic diseases and</p><p>lignancyIs there an association. Scand J Rheumatol185-188, 2001. Fam A: Paraneoplastic rheumatic syndromes. Bail-es Best Pract Res Clin Rheumatol 14:515-533, 2000. McLean DI: Cutaneous paraneoplastic syndromes. Arch</p><p>rmatol 122:765-767, 1986. Brenner S, Golan H, Gat A, et al: Paraneoplasticacute cutaneous lupus erythematosus: Report of a caseociated with cancer of the lung. Dermatology 194:172-, 19970. Dawn G, Wainwright NJ: Association between sub-te cutaneous lupus erythematosus and epidermoid carci-a of the lung: A paraneoplastic phenomenon. Clin Exp</p><p>rmatol 27:717-718, 20023. Neumann R, Schmidt JB, Niebauer G: Subacuteus erythematosus-like gyratum erythema: Report of ae associated with a breast cancer. Dermatologica 173:146-, 19864. Ho C, Shumack SP, Morris D: Subacute cutaneousus erythematosus associated with hepatocellular carci-a. Australas J Dermatol 42:110-113, 2001</p><p>5. McKenna KE, Hayes D, McMillen JC: Subacuteaneous lupus erythematosus-like gyrate erythema andertrichosis lanuginosa acquisita associated with uterinenocarcinoma. Br J Dermatol 127:443-444, 19926. Freundlich B, Makover D, Maul GG: A novel anti-lear antibody associated with a lupus-like paraneoplasticdrome. Ann Intern Med 109:295-297, 19887. Kahn MF, Solnica J, Bourgeois P: Disappearance ofical and biological evidence of SLE after removal of anrian seminoma: 21 Years follow-up. J Rheumatol 13:833-, 19868. Kraus A, Garza-Elizondo MA, Diaz-Jouanen E: Alti-systemic disease (lupus-like) preceding bronchioloal-lar carcinoma. Clin Rheumatol 4:192-195, 19859. Wallach H: Lupus-like syndrome associated with</p><p>cinoma of the breast. Arch Intern Med 137:532-535, 19770. Rossi G, Lucioni M, Sammarchi L, et al: Uncommondromes and treatment manifestations of malignancy:</p><p>se 1. Unusual association of lupus and sarcoma. J Clincol 21:166-167, 20031. Loche F, Schwarze HP, Durieu C, et al: A case oftemic lupus erythematosus associated with cancer of theg: A paraneoplastic association? Br J Dermatol 143:210-, 20002. Mascaro JM Jr, Ferrando J, Sole MT, et al: Paraneo-</p><p>stic pemphigus: A case of long-term survival associatedh systemic lupus erythematosus and polymyositis. Derma-gy 199:63-66, 19993. Solon AA, Gilbert CS, Meyer C: Myopathy as aaneoplastic manifestation of renal cell carcinoma. Am Jd 97:491-492, 19944. Papagiannis A, Cooper A, Banks J: Pulmonary embo-</p><p>and lupus anticoagulant in a woman with renal cellcinoma. J Urol 152:941-942, 19945. Ather MH, Mithani S, Bhutto S, et al: Lupus type</p><p>icoagulant in a patient with renal cell carcinoma: Anoimmune paraneoplastic syndrome. J Urol 167:2129,26. ONeill WM, Wallin JD, Walker PD: Hematuria andblood casts in typical diabetic nephropathy. Am J Med</p><p>389-395, 1983</p><p>SLE: The Great Imitator Strikes AgainCASE REPORTKidney BiopsyClinical Follow-Up</p><p>DISCUSSIONACKNOWLEDGMENTREFERENCES</p></li></ul>