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We present a case of renal and systemic vasculitis that was temporally associated with the clinical presentation of renal cell carcinoma. Although such associations are rare, vasculitis affecting the kidney does appear to confer an increased risk of renal cancer, particularly in the presence of Wegener's granulomatosis.
A man of 53 was admitted with a four-week history of rash, arthralgia and malaise. He had also noticed peri-oral numbness and intermittent numbness affecting his right thigh. There was no history of oral ulceration. He had previously been well apart from a history of hypertension, controlled by nifedipine. He was a non-smoker.
On examination he was overweight (115 kg). He had numerous splinter haemorrhages, mild episcleritis and vasculitic skin lesions over the feet. There was diminished pin-prick sensation in the peri-oral region and over the toes on the right. Red cells and granular casts were seen on urine microscopy. Haemoglobin was 13.1 g/dL, white cell count 15.3 × 109/L with pronounced eosinophilia (neutrophils 8.2, lymphocytes 1.1, eosinophils 5.6), and platelets 370 × 109/L. Erythrocyte sedimentation rate was 76 mm/h, C-reactive protein 86 mg/L. Liver function tests were normal. Serum creatinine was 85 μmol/L, creatinine clearance 134 mL/min, and 24-hour urinary protein excretion 1.23 g. Antinuclear antibody, ANCA, rheumatoid factor, and tests for cryoglobulins and glomerular basement membrane antibodies were negative. Complement levels were normal. Blood cultures were sterile and an echocardiogram was normal. A chest X-ray was difficult to interpret because of the patient's size, and a CT of the chest was arranged. Renal ultrasound was reported as demonstrating two normal-sized kidneys with increased parenchymal echogenicity, consistent with intrinsic renal disease.
Systemic vasculitis was suspected and the patient was started on oral prednisolone 60 mg daily. Diagnostic renal biopsy was performed four days later. The specimen contained 35 glomeruli, 5 of which showed segmental areas of fibrinoid necrosis with inflammatory exudates and a crescentic epithelial reaction. One other glomerulus showed an old segmental lesion with chronic scarring. Immunofluorescence staining was negative for all conjugates. There was mild tubular and interstitial atrophy but minimal lymphocytic infiltration and no evidence of tubulitis.
Oral cyclophosphamide was started, with improvement of symptoms and rapid resolution of the eosinophilia. A CT of the chest four weeks after the biopsy showed normal lung fields but a lesion arising from the left kidney (Figure 1). Repeat scanning after six weeks showed a similar appearance. At exploratory laparotomy a tumour was found arising from the left kidney with no evidence of intra-abdominal spread. Nephrectomy was performed, and histological examination of the specimen showed a multicystic renal cell carcinoma of classical clear cell type. The tumour appeared low grade, with some areas corresponding to Fuhrman nuclear grade 3. There was no evidence of tumour or vasculitis in the uninvolved parenchyma of the upper pole, although some of the glomerular tufts showed capsular adhesion.
Cyclophosphamide was stopped and steroids were reduced to 5 mg daily over the subsequent six months. Twelve months after nephrectomy there is no evidence of recurrence of tumour or vasculitis, although ANCA tests have become weakly positive with a titre of 1:320, PR3 (ELISA) positive.
Malignancy is found in around 5% of patients with vasculitis. The strongest association is with hairy cell leukaemia, while colon, lung and renal cell carcinomas seem to be the commonest solid-tumour associations1. The reason for this association is unclear, although postulated mechanisms include immune complex formation with tumour antigens, shared tumour and vessel wall antigens, and impaired clearance of normally produced immune complexes2.
Within the vasculitides, renal cell carcinoma seems particularly strongly associated with Wegener's granulomatosis. Several case reports have described the association, and epidemiological work appears to confirm it3. The finding of proteinase 3 within a human renal cell cancer line led to the analysis of 477 patients with Wegener's granulomatosis4. The odds ratio for malignant neoplasm in this group was 1.8, but the odds ratio for renal cell carcinoma was 8.7 when the comparison group was patients with rheumatoid arthritis. The diseases occurred simultaneously in five out of seven patients with Wegener's granulomatosis. 91% of the cases with Wegener's and malignancy were PR3 c-ANCA positive, although PR3 was not found in the malignant tissues of eight of the Wegener's patients who were tested.
Our patient did not meet the full criteria for Wegener's granulomatosis and must therefore be classified as having non-specific vasculitis. However, the PR3 c-ANCA positivity and presentation early in the illness suggest that a more typical picture might have evolved over time. Aside from the increased risk conferred by the renal vaculitis, it should be noted that obesity and hypertension are further risk factors for the development of renal cell carcinoma5.
In this case of vasculitis, a potentially curable renal carcinoma was detected as an incidental finding. Renal cell carcinoma is easily detected by ultrasound and/or CT scanning, investigations which are often performed at the initial presentation of renal dysfunction. This case report illustrates that these investigations may also detect occult malignancy, and that there should be a heightened awareness of this possibility in patients presenting with Wegener's granulomatosis and c-ANCA positive vaculitis.