Quiz page answers September 2004

Article Outline

• What is your clinical differential diagnosis?
• What is your final interpretation of the above findings?
• Final diagnosis: anti-GBM antibody-mediated glomerulonephritis with superimposed ANCA-associated vasculitis

A 70-year-old white man with a history of intermittent microscopic hematuria presented with generalized fatigue, low-grade fever, cough with a small amount of discolored sputum, and vague abdominal pain. He was taking lisinopril for hypertension and had borderline diabetes. Computed tomography of the abdomen and pelvis was negative. A chest radiograph showed increased markings, suggestive of fibrosis. Laboratory results were as follows: normal amylase and liver enzyme levels, hematocrit from 38%, and 3.8 g/24 h proteinuria without casts or active sediment. Creatinine levels increased from 1.2 to 2.8 mg/dL (106 to 248 μmol/L). He was treated with gatifloxacin for a urinary tract infection and scheduled for follow-up. He developed acute ischemic bowel requiring resection, with nonspecific pathologic findings. The hospital course was complicated by hypotension and cardiac/multisystem failure. Creatinine levels increased to 7.2 mg/dL (636 μmol/L) and hemodialysis was initiated. Proteinuria was now 5 g/24 h with numerous red blood cells in the urine. Antinuclear antibody, anti-deoxyribonucleic acid, hepatitis B surface antigen, hepatitis C, cryoglobulin, complements, cytoplasmic antineutrophil cytoplasmic antibodies (ANCAs), and serum protein electrophoresis test results were normal. Perinuclear ANCA was positive at 1:160. Renal biopsy was performed.

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What is your clinical differential diagnosis? 

The clinical differential diagnoses included microscopic polyangiitis and acute tubular necrosis superimposed on a glomerulonephritis.

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• Figures 31A and 31B. 

  What do you see by light microscopy?

• There are necrotizing crescentic lesions with early fibrous organization involving all glomeruli. Noninvolved segments of glomeruli do not show overt proliferation (Jones’ silver stain; original magnification [A] ×200, [B] ×400).

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• Figure 31C. 

  What additional light microscopic lesion do you see?

• There is fibrinoid necrosis of the arterial wall with a mild transmural leukocytic infiltrate (Jones’ silver stain; original magnification ×200).

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• Figure 31D. 

  What do you see by immunofluorescence microscopy (anti-immunoglobulin G antibody immunofluorescence)?

• Immunofluorescence shows intense linear staining of the glomerular basement membrane (GBM) (anti-immunoglobulin G antibody; original magnification ×200). Electron microscopy showed no deposits.

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What is your final interpretation of the above findings? 

The light microscopy shows a pauciimmune necrotizing crescentic glomerulonephritis with associated extraglomerular arterial lesions. The differential from this examination would include Wegener’s granulomatosis and microscopic polyangiitis. However, the immunofluorescence findings are diagnostic of anti-GBM antibody-mediated glomerulonephritis, but this diagnosis cannot account for the extraglomerular vasculitic lesions, as the anti-GBM antibody is directed to a GBM collagen, alpha 3 type IV. Thus, the final diagnosis is anti-GBM antibody-mediated glomerulonephritis, with superimposed ANCA-related vasculitis, also supported by the patient’s positive perinuclear ANCA. Subsequently, anti-GBM antibodies were detected in his serum.

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Final diagnosis: anti-GBM antibody-mediated glomerulonephritis with superimposed ANCA-associated vasculitis 

Case provided by Yihan Wang, MD, and Agnes B. Fogo, MD, Department of Pathology, Vanderbilt University Medical Center, Nashville, TN.

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