血管内リンパ腫update―不明熱の原因疾患としての重要性

Intravascular Large B-cell Lymphoma: An Important Cause of Fever of Unknown Origin

Ⅰ．血管内リンパ腫とは―その多様性も含めて

　血管内リンパ腫（intravascular large B-cell lymphoma：IVLBCL）は，主に節外臓器の微小血管内を閉塞性に進展する悪性リンパ腫であり，病理組織学的にはび漫性大細胞型B細胞リンパ腫（diffuse large B-cell lymphoma：DLBCL）の亜型である。2001年のWHO Blue Bookの第3版^1）にはDLBCLの亜型として，2008年の第4版^2）では独立した疾患単位として記載されている。第4版では，大動脈や大静脈を除いた血管腔特に毛細血管への選択的増殖をきたす節外性大細胞B細胞型リンパ腫の稀な型であるとされている。

　血管内リンパ腫は，1959年にPflegerとTappeiner^3）によって報告されて以来，全身の微小血管の腫瘍性閉塞によるさまざまな徴候が報告されている。本邦のMuraseら^4，5）によって血球貪食症候群を伴った亜型Asian variantが報告されその病態が明らかにされつつある。

Abstract

　Intravascular large B-cell lymphoma (IVLBCL) is an important cause of fever of unknown origin (FUO) and multiple organ failure (MOF).　Earlier, most IVLBCL cases were diagnosed only postmortem; however, now, it is possible to diagnose and treat these cases antemortem.　Although hematogeneous dissemination of malignant tumor cells except lymphoma is beyond the scope of present treatment regimens, IVLBCL (hematogeneous dissemination of lymphoma) can be treated by chemotherapy so correct diagnosis is important.

　The onset and clinical course of IVLBCL is heterogeneous.　Many IVLBCL cases show rapid deterioration, but some have a relatively indolent early period that transforms to rapid progression later.　Leukemic appearance is not uncommon.　It is difficult to distinguish between IVLBCL and lymphomas originating from extra-nodular organs with systemic dissemination into extra-nodular organs.

　Minimally invasive and highly sensitive procedures are required for its accurate diagnosis: bone marrow aspiration and biopsy, and random skin biopsy are recommended.　If IVLBCL is suspected, to achieve the correct diagnosis, we should avoid glucocorticoid therapy before a biopsy is obtained, even in serious cases.

　IVLBCL shows remarkable response to treatment with rituximab-containing chemotherapy (R-CHOP).　Delayed administration of rituximab and reduced dose of chemotherapy on the first course may be initially indicated in elderly,poor performance status or cases with high tumor burden.　High-dose chemotherapy with autologous hematopoietic stem cell rescue should be considered,if possible.　Aggressive combination therapy with high dose methotrexate is a recent idea because of central nervous system involvement,or relapse is common and there is poor prognosis.