NLPHL has a characteristic morphology, immunopheno-type, presentation, and natural history. The clinician must recognize both its pathological and clinical characteristics and question the diagnosis if the two are discordant. Most of these patients have an excellent prognosis although long-term follow-up (i.e., greater than 10 years) in morphologically and immunophenotypically defined patients is limited. Based on the excellent 10-year survival and the relatively high risk of death from causes other than HL, therapy must not only adequately control, if not cure, the HL and ideally prevent the evolution to NHL, but also minimize both short- and long-term toxicities. This goal is perhaps even more important with NLPHL than with CHL. Future treatment strategies may incorporate anti-CD20 monoclonal antibodies, (e.g., rituximab). When relapse is suspected, a biopsy is mandatory to distinguish recurrent NLPHL from DLBCL and progressively transformed germinal centers (a benign lymphadenopathy that may occur before, after, or concurrently with NLPHL and is not necessarily indicative of disease relapse). Finally, these patients require indefinite follow-up since late relapses are possible.

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