CNS Involvement in Primary Mediastinal Large B-Cell Lymphoma By Philippe C. Bishop, Wyndham H. Wilson, Debra Pearson, John Janik, Elaine S. Jaffe, and Patrick C. Elwood Purpose: The risk of CNS involvement by non- Hodgkin’s Lymphoma (NHL) has been associated with bone marrow and/or testicular involvement; however, it was recently reported that the number of extranodal sites is a more reliable predictor of CNS disease. Be- cause primary mediastinal thymic large B-cell lym- phoma (PMLCL) has a high propensity for involving extranodal sites, we investigated the frequency and pattern of CNS involvement in PMLCL. Patients and Methods: The medical records of 219 patients with aggressive NHL, consecutively entered onto protocols at the National Cancer Institute between 1987 and 1998, were retrospectively reviewed. Results: Twenty-three patients (11%) had clinical and pathologic features of PMLCL. These patients were young (median age, 29 years), female (61%), and presented with massive mediastinal adenopathy (70%). Extra- nodal disease occurred at presentation in 70% and at relapse in 93% of patients and involved contiguous intrathoracic structures and/or distant sites, including the lungs, kidneys, liver, adrenals, ovaries, pancreas, and bone. Six patients (26%) developed CNS involve- ment, two (9%) at presentation and four (27%) at relapse. All had extranodal disease, but only one had bone marrow involvement. Parenchymal and leptomen- ingeal CNS disease occurred in four and three patients, respectively. Conclusion: CNS involvement in PMLCL is associated with extranodal involvement other than bone marrow and may reflect the unique biology of this disease. The propensity to involve the CNS parenchyma raises the concern that intrathecal prophylaxis may not be effec- tive and suggests that CNS imaging should be consid- ered in patients with extranodal disease. J Clin Oncol 17:2479-2485. r 1999 by American Society of Clinical Oncology. C NS INVOLVEMENT BY lymphoma is a poor prognos- tic event, particularly when it occurs at relapse. 1-4 In hematopoietic malignancies with a high incidence of CNS involvement, such as acute lymphoid leukemia, prophylaxis and early diagnosis of CNS disease has led to major increases in survival. Similar benefits may be seen in patients at high risk of developing CNS involvement by lymphoma. 5,6 Indeed, these benefits may be even greater in the future as more effective treatment is developed for systemic disease. Unlike other aggressive lymphoid malig- nancies, however, most patients with large-cell lymphomas are not uniformly at risk of developing CNS disease, so it is necessary to identify the subset of patients who will benefit from CNS prophylaxis. Earlier studies have shown that patients with involvement of bone marrow, testicles, and/or paranasal sinuses are at high risk of developing CNS disease, and intrathecal chemotherapy prophylaxis is usually considered in such patients. 7 Unfortunately, the conclusions from many of these studies are unsatisfying because they include multiple different histologies and/or therapies. 1-4 Recently, van Besien et al 6 performed a multivariate analysis of risk factors for CNS recurrence in patients with large-cell lymphoma and identified involvement of more than one extranodal site and increased lactate dehydrogenase (LDH) as independent predictors. On the basis of this report, we were interested in examining the incidence of CNS involvement in primary mediastinal (thymic) large B-cell lymphoma (PMLCL) because of its propensity to affect extranodal tissues. 8 A striking clinical feature of PMLCL is its proclivity to involve multiple extranodal tissues such as the lungs, kidneys, adrenals, liver, and/or ovaries. 9,14-17 In contrast to other large B-cell lymphomas, PMLCL tends to affect young women and often presents as an anterior mediastinal mass arising from the thymus with invasion of adjacent tissue. 9-15 Al- though 50% to 80% of patients with limited-stage disease achieve long-term survival with cyclophosphamide, hydroxy- daunorubicin, vincristine, prednisone, and bleomycin (CHOP)–based therapy, high-risk patients with bulky medi- astinal masses and/or extranodal disease tend to relapse and salvage therapy, including high-dose therapy with stem-cell transplantation, is often unsuccessful. 9,13,14,16-21 To investigate the frequency and pattern of CNS involve- ment in PMLCL, we reviewed the cases of adult patients with aggressive non-Hodgkin’s lymphoma (NHL) treated in the Medicine Branch of the National Cancer Institute (NCI) over an 11-year period and identified 23 cases with clinical and pathologic features diagnostic of PMLCL. Herein, we present our findings of CNS involvement in PMLCL and discuss clinical recommendations. From the Division of Clinical Science, Medicine Branch, National Cancer Institute, Bethesda, MD. Submitted January 4, 1999; accepted March 22, 1999. Address reprint requests to Patrick C. Elwood, MD, National Cancer Institute, 9000 Rockville Pike, Bldg 10/12N226, Bethesda, MD 20892. r 1999 by American Society of Clinical Oncology. 0732-183X/99/1708-2479 Journal of Clinical Oncology, Vol 17, No 8 (August), 1999: pp 2479-2485 2479 Information downloaded from jco.ascopubs.org and provided by at NIH LIBRARY on March 27, 2015 from 128.231.237.6 Copyright © 1999 American Society of Clinical Oncology. All rights reserved.