Prerealwho Series

Most publications prior to the combined morphologic and immunophenotypic classification included patients with both NLPHL and CHL. Both LPHL and CHL patients were eligible for the same clinical trials. Only a small minority had LPHL and many of them were undoubtedly misdiagnosed and actually had LRCHL. Even retrospective studies as recent as 1995, which purported to analyze the specific subset of patients with LPHL, still relied on now outdated and imprecise diagnostic criteria and, therefore, must have included a significant number of LRCHL patients.

Nevertheless, many large historical series of patients with LPHL (which predated the REAL/WHO criteria and clearly included patients with CHL and, in particular, LRCHL) recognized their distinct presentation and course.4-612-16 The patients were predominantly male, generally young, and frequently had asymptomatic, nonbulky, stage I or limited stage II disease involving peripheral lymph nodes. Although some series observed a pattern of frequent and sometimes late relapses, virtually all series recognized the excellent overall survival. Many of these studies observed a disturbing pattern of deaths due to other, often treatment-related, malignancies and cardiovascular disease. Some of these series appreciated differences in long-term outcome between this subtype compared to other subtypes of HL.

The development of non-Hodgkin's lymphoma (NHL) in patients with CHL or LPHL has been well documented.1217-24 A review from the International Data Base on Hodgkin's Disease appreciated a higher risk of NHL in patients with LPHL compared to those with CHL.25 The NHL, primarily diffuse large B-cell lymphoma (DLBCL) and frequently the T-cell/histio-cyte rich variant of DLBCL (TC/HR DLBCL), may occur simultaneously with, or sometimes years after, the diagnosis of LPHL even without any treatment.23 24 In many of these cases, a clonal progression from HL to NHL has been documented.24 26 27 Given the difficulty in sometimes distinguishing NLPHL and TC/HR DLBCL, some patients who actually had TC/HR DLBCL may have been initially misdiagnosed with NLPHL.11'24'27 28 Consequently, the risk of developing NHL may actually be overestimated. While the risk of NHL after HL may be higher in NLPHL compared to CHL patients, the absolute risk is still very low— probably less than 5%.

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