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Journal of Clinical Oncology, Vol 21, Issue 13 (July), 2003: 2624-2625
© 2003 American Society for Clinical Oncology


DIAGNOSIS IN ONCOLOGY

Some Unusual Paraneoplastic Syndromes

CASE 4. PARANEOPLASTIC NEPHROTIC SYNDROME IN A PATIENT WITH LUNG CANCER

Benjamin Ebert, Kitt Shaffer, Helmut Rennke

Dana-Farber Cancer Institute, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA

A 69-year-old man with a 100 pack/year history of cigarette smoking was noted to have a lung mass on screening chest x-ray. A chest computed tomography (CT) revealed a 4 x 3–cm right lower-lobe (RLL) lung mass and a 1-cm precarinal node. Non–small-cell lung cancer was diagnosed by CT-guided biopsy of the pulmonary mass. A head CT and bone scan were negative for metastases. He was asymptomatic, and he chose to defer treatment of his lung cancer for 3 months until after his daughter’s marriage. Four months after diagnosis and before any therapy, he developed hemoptysis, worsening dyspnea, and bilateral lower-extremity edema. He noted that his urine had become extremely frothy. On physical examination, he had decreased breath sounds in the right lung base, abdominal distension, and 3+ lower-extremity edema. A chest CT showed progression of his malignancy with RLL collapse, mediastinal adenopathy up to 3 cm in size, and a left upper-lobe nodule. Laboratory studies were significant for a serum albumin of 2.3 mg/dL and a creatinine unchanged at 1.4 mg/dL. Urinalysis showed 3+ protein, and a 24-hour urine collection contained 10.2 grams of protein. His serum cholesterol level was elevated at 308 mg/dL. A serum protein electrophoresis, antinuclear antibody (ANA), and renal ultrasound were unremarkable. He was treated with concomitant chemotherapy and radiation therapy consisting of 3,750 Gy of radiation to the RLL in 15 fractions, as well as weekly carboplatin at an area under the curve of 2 and taxol 50 mg/m2 for 5 weeks. Hemoptysis and dyspnea resolved in the first month of treatment. Lower-extremity edema and abdominal distension improved gradually over 3 months. According to CT scans, his RLL mass decreased in size, and his RLL collapse resolved and remained stable over the subsequent 9 months (Fig 1Go). His blood pressure was controlled with lisinopril (Zestril; AstraZeneca, London, United Kingdom) and hydrochlorothiazide. His albumin increased to 3.7 gm/dL, his proteinuria decreased to 540 mg/24 hours, and his creatinine remained stable (Fig 2Go).



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Fig 1. Computed tomography scan showing decreased right lower lobe mass.

 


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Fig 2. Graphs showing (A) 24-hour urine total protein, (B) serum albumin, and (C) serum creatinine.

 
Lung cancer is among the malignancies most commonly associated with a paraneoplastic nephrotic syndrome.1–3 Membranous nephropathy is most commonly associated with solid malignancies, whereas minimal change disease is seen most often in patients with Hodgkin’s disease.1,2,4 Presentation with nephrotic syndrome occurs before the diagnosis of cancer in approximately 40% of patients, at the time of diagnosis in 40% of patients, and after diagnosis in 20% of patients.2 Treatment of the neoplasm is associated with improvements in proteinuria.3,5 The pathogenesis of this paraneoplastic syndrome has been attributed to the production of cancer-related antigens, with subsequent damage to the glomerular basement membrane by antigen-antibody complexes.6 An alternative hypothesis is that an autoantibody, produced in response to the malignancy, may cross-react with and damage the glomerular basement membrane.

Hypoalbuminemia is common in patients with lung cancer. A small subset of these patients will have nephrotic syndrome because of a paraneoplastic process.

REFERENCES

1. Lee JC, Yamauchi H, Hopper J: The association of cancer and the nephrotic syndrome. Ann Intern Med 64:41–51, 1965

2. Burstein DM, Korbet SM, Schwartz MM: Membranous glomerulonephritis and malignancy. Am J Kidney Dis 22:5–10, 1993[Medline]

3. Shikata Y, Hayashi Y, Yamazaki H, et al: Effectiveness of radiation therapy in nephrotic syndrome associated with advanced lung cancer. Nephron 83:160–164, 1999[Medline]

4. Davison AM: Renal diseases associated with malignancies. Nephrol Dial Transplant 16:13–14, 2001 (suppl 6)[Free Full Text]

5. Boon ES, Vrij AA, Nieuwhof C, et al: Small cell lung cancer with paraneoplastic nephrotic syndrome. Eur Respir J 7:1192–1193, 1994[Abstract]

6. Costanza ME, Pinn V, Schwartz RS, et al: Carcinoembryonic antigen-antibody complexes in a patient with colonic carcinoma and nephrotic syndrome. N Engl J Med 289:520–522, 1973[Medline]


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