The Pathologic and Clinical Heterogeneity of Lymphocyte-Depleted Hodgkin's Disease By Jeffrey A. Kant,* Susan M. Hubbard, Dan L. Longo, Richard M. Simon, Vincent T. DeVita, Jr, Patients with Hodgkin's disease of the lymphocyte- depleted subtype (LDHD) have been said to have a poor prognosis. However, reports of this subtype are complicated by the fact that the histologic diagnosis of LDHD is often not straightforward, and its distinc- tion from aggressive non-Hodgkin's lymphomas (NHL) can be difficult. We have reviewed our patients with LDHD at the National Cancer Institute (NCI) in light of an additional decade of experience with neo- plastic and non-neoplastic conditions mimicking Hodgkin's disease. Of 198 patients who received MOPP (mechloretha- mine, vincristine, procarbazine, prednisone) treat- ment at the NCI for Hodgkin's disease between 1964 and 1976, 43 (22%) were originally classified as LDHD. The initial diagnostic biopsies from 39 of these patients were reviewed and revealed ten with NHL, nine with LDHD, and 13 with nodular sclerosing Hodgkin's disease of the lymphocyte-depleted sub- type (NSLD). The other seven patients had Hodgkin's disease without a lymphocyte-depleted component. The NHL patients were further subclassified as dif- fuse, large-cell (two cases) and large-cell, immuno- blastic (eight cases). The pathologic review was done T HE modern histopathologic classification of Hodgkin's disease was introduced in 1966 by Lukes, Butler, and Hicks.1,2 Early clinico- pathologic studies indicated that the lymphocyte- depleted subtype (LDHD) had the most aggres- sive natural history and poorest prognosis. 3 " However, recent reports including long-term fol- From the Laboratory of Pathology and the Medicine Branch, National Cancer Institute, National Institutes of Health, Bethes- da, Md. Submitted May 6, 1985; accepted Oct 23, 1985. Presented in part at the Annual Meetings of the American Society of Hematology, December 1983, and the International Academy of Pathology, March 1984. *Present address:Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104. Address reprint requests to Elaine S. Jaffe, MD, Bldg 10, Room 2NI10, NIH, Bethesda, MD 20205. This is a US government work. There are no restrictions on its use. 0732-183X/86/0403-0005$0.00/0 and Elaine S. Jaffe without knowledge of clinical features which were examined after review in the three major subgroups. Of ten patients with NHL, only three had a complete remission (CR), and median survival was 7 months. Nine of the NHL patients presented with features that are unusual for patients with Hodgkin's disease, such as bulky abdominal disease, epitrochlear lymphade- nopathy, or hypercalcemia. CRs were attained by 67% and 85% of patients in the LDHD and NSLD groups, respectively: median survival had not been reached in either group with a median of 14 years of follow-up. Lymphocyte-depleted Hodgkin's disease, ade- quately treated, is in our limited group of patients no worse than other histopathologic subtypes of Hodg- kin's disease. The erroneous inclusion of patients with high-grade NHLs into this subtype of Hodgkin's dis- ease may be one reason for earlier literature reports of its more aggressive nature. The diagnosis of LDHD should be made cautiously, particularly in patients with clinical features that are unusual for Hodgkin's disease at presentation. J Clin Oncol 4:284-294 (1986). This is a US govern- ment work. There are no restrictions on its use. low-up of patients treated with systemic chemo- therapy suggest that LDHD can be treated just as successfully as other histologic subtypes of Hodgkin's disease. 12-15 The diagnosis and classification of lympho- mas is widely appreciated to be a difficult area in pathology. A particularly difficult problem, even for experienced hematopathologists, is the dis- tinction of Hodgkin's disease of the lymphocyte- depleted or mixed cellularity (MCHD) types from non-Hodgkin's lymphomas (NHL), other tumors, and even reactive processes that feature Reed-Sternberg-like cells.' 16 Two thirds of pa- tients mistakenly diagnosed as Hodgkin's dis- ease in a Southwest Oncology Group (SWOG) study were initially believed to be LDHD and MCHD.17 Many of these patients, who presented clinically with extranodal sites of involvement unusual for Hodgkin's disease, in fact had NHL. Many of the lymphomas or other processes that mimic Hodgkin's disease are now more Journal of Clinical Oncology, Vol 4, No 3 (March), 1986: pp 284-294 284 16, 2011 from 200.131.50.10 Information downloaded from jco.ascopubs.org and provided by at Centro Federal de Educação Tecnológica de Ouro Preto on July Copyright © 1986 American Society of Clinical Oncology. All rights reserved.