Andrés JM Ferreri

BACKGROUND AND OBJECTIVES: This study explored variations in the clinical manifestations of intravascular lymphoma (IVL) on the bases of the association with hemophagocytosis and the country where the diagnosis was made. DESIGN AND METHODS: The clinical features of 50 Western patients with IVL were compared with those of 123 patients with IVL diagnosed in Eastern countries (87 diagnosed in Japan and 36 in other Asian countries), previously reported in English literature, and collected by an electronic bibliographic search. RESULTS: Hemophagocytosis was absent in Western patients, but reported in 38 (44%) Japanese patients (p=0.00001) and in seven (19%) patients from other Asian countries (p=0.002). No clinical differences were evident between patients with hemophagocytosis-negative IVL diagnosed in Western countries, Japan and other Asian Countries. Conversely, Japanese and non-Japanese patients with hemophagocytosis-related IVL more frequently had stage IV disease, fever, hepato-splenic involvement, marrow infiltration, dyspnea, anemia, and thrombocytopenia, and rarely exhibited cutaneous or central nervous system involvement. Lymph node and peripheral blood involvement was uncommon in all subgroups. In Western patients, anthracycline-based chemotherapy was associated with a 52% remission rate, and a 2-year overall survival of 46%. INTERPRETATION AND CONCLUSIONS: The clinical features of IVL vary according to the association with hemophagocytosis, regardless of the country in which the diagnosis is made. Western, Japanese and other Asian patients with hemophagocytosis-negative IVL display similar clinical characteristics and should be considered as having classical IVL. Patients with hemophagocytosis-related IVL show significantly different clinical features. Both forms have a poor prognosis. Extensive molecular studies are needed to explore whether these clinical differences might reflect discordant biological entities within IVL.

Intravascular large B-cell lymphoma (IVL), or ‘angiotropic lymphoma’, was earlier regarded, since the original description in 1959 by L. Pfleger and J. Tappeiner, as an endothelial neoplasia with vascular dissemination. Tissue biopsy is usually mandatory for the diagnosis of IVL; this is due to the lack of a pathognomonic diagnostic immunophenotypic marker for this lymphoma. Most importantly, blood vessel lumen, other than being merely a vehicle, is also a site of active replication for IVL cells; indeed, mitotic features are often easily recognizable within the lymphomatous population. Neuroimaging discloses central nervous system involvement only in half of patients with neurological symptoms. Patients with cutaneous variant of IVL survive significantly longer than others, independently of the International Prognostic Index and all the other prognostic variables investigated. Radiotherapy may be considered the exclusive treatment for IVL in elderly patients with single cutaneous lesions; outside this context, the role of radiotherapy remains to be determined.