Treatment and Natural History Study of Lymphomatoid Granulomatosis

BACKGROUND: * Lymphomatoid granulomatosis (LYG) is an angiocentric destructive proliferation of lymphoid cells predominantly involving the lungs, skin, kidneys, and central nervous system. * It is divided into three grades, depending on the degree of necrosis and cellular atypia. The grades of disease are histologically based and do not necessarily correlate with clinical outcome. However, like other Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPD's), LYG can transform into an aggressive large B-cell lymphoma, which would be included within the grade 3 category. It is important to note that not all grade 3 lesions are a large B-cell lymphoma. * Current evidence shows that LYG is a disease of B cells. OBJECTIVES: * To determine the response and long-term efficacy of alpha-Interferon in patients with lymphomatoid granulomatosis (LYG). * To determine the response and long-term efficacy of dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin rituximab (EPOCH-R) chemotherapy in patients with grade 3 LYG or in patients who have failed interferon. ELIGIBILITY: * Patients must have a tissue diagnosis of grade 1, 2 and/or 3 LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). * Patients with any stage of disease will be eligible. * Previously untreated and treated patients are eligible. * Patients aged 12 or older will be eligible. DESIGN: * Interferon is used as initial treatment in patients with grades 1 and 2 LYG. Patients will receive interferon for one year past complete remission (CR). * Patients who progress after or during interferon, and patients with grade 3 LYG will receive aggressive combination chemotherapy with DA-EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone). * Patients who fail one treatment approach may be crossed over to the other. * A total of 105 patients will be enrolled at this single institution.