Lymphomatoid granulomatosis. Clinicopathologic study of four cases and literature review

Lymphomatoid granulomatosis (LYG) is a poorly understood inflammatory angiitis of uncertain pathogenesis with histological similarities to Wegener's granulomatosis (WG) and atypical lymphoma. Pulmonary, constitutional, cutaneous, and central nervous system manifestations predominate, but clinical signs are extraordinarily diverse. Clinical, roentgenographic, and laboratory abnormalities are nonspecific and the diagnosis is frequently missed or delayed. We describe four cases of LYG and review the previous literature with emphasis on clinical and histological features, course, and therapy. The histological characteristics of LYG are described, and compared and contrasted with WG and atypical lymphoma. In addition to reviewing typical clinical features, we report rare findings noted in two of our cases, e.g., retroperitoneal fibrosis and lytic and blastic bone lesions which expand the spectrum of the disorder and emphasize its protean nature. Our four cases reconfirm the frequency of diagnostic delay, high mortality, and poor responsiveness to therapy. In the review of our cases and previously published data, no therapeutic regimen consistently altered the course of the disease. The efficacy of corticosteroids, immunosuppressive and cytotoxic agents remains uncertain due to variable drug and dosage schedules, lack of comparable patient populations, and retrospective nature of previous reports. However, it appears that corticosteroids may transiently alter manifestations of LYG, but do not prevent ultimate progression. Cyclophosphamide may have contributed to arrest of the disease in our Cases 3 and 4, as well as in sporadic cases from the literature, but its overall efficacy appears to be limited. Multiple-agent chemotherapy has been associated wih occasional responses, but generally has been unsuccessful. Surgery and radiation therapy may be helpful in selected patients with localized disease. The role of corticosteroids, cytotoxic agents, and radiation therapy, alone or in combination, needs to be clarified by prospective cooperative trials.