Wegener's granulomatosis associated with renal cell carcinoma

Objective. To determine the frequencies and types of malignant neoplasms occurring before or simultaneously with the diagnosis of Wegener's granulomatosis (WG), and to test for the presence of 'Wegener's autoantigen,' proteinase 3 (PR3), in malignant tissues from WG patients to ascertain whether an association exists between malignancy and WG. Methods. A retrospective statistical analysis was performed on the medical records of 477 patients with WG as compared with a control group of 479 patients with rheumatoid arthritis (RA). A murine monoclonal antibody was used to test malignant tissues for the presence of PR3. Results. A malignant neoplasm was found in 23 patients in the WG group and in 18 patients in the control group. The odds ratio for malignant neoplasm in the WG group was 1.79 (P = 0.0876, 95% confidence interval [95% CI] 0.92-3.48). Seven patients with renal cell carcinoma were found in the WG group compared with 1 patient in the control group, for an odds ratio of 8.73 (P = 0.0464, 95% CI 1.04-73.69). Simultaneous occurrence of cancer and WG was observed in 14 patients with WG compared with 1 control patient, for an odds ratio of 18.00 (P = 0.0059, 95% CI 2.30-140.67). Furthermore, the diseases occurred simultaneously in 5 of the 7 patients with both WG and renal cell carcinoma, but not in the single patient in the control group with RA and renal cell carcinoma. PR3 could not be detected in any of the 8 malignant tissue samples (4 renal cell carcinomas) investigated in the patients from the WG group. Conclusion. The close temporal association between renal cell carcinoma and WG suggests that malignancy is, in some cases, a trigger for the development of WG. However, since PR3 was not found in malignant tissues from the WG patients, the immunopathologic mechanisms leading to autoimmunity and vasculitis remain unclear.