Diffuse large B-cell lymphoma with haemophagocytic syndrome (BCL-HS) has been reported mainly in Asia and is regarded as a distinct variant of intravascular lymphoma (IVL). However, it is unclear whether all cases of BCL-HS fall within the framework of IVL and available clinical information is limited. We analysed 25 cases with BCL-HS, including 11 autopsied cases (median, 66 years; male-female ratio, 1.1:1). The patients presented with fever, anaemia, thrombocytopenia, hepatosplenomegaly, haemophagocytosis, bone marrow invasion, respiratory disturbance and disseminated intravascular coagulopathy, but usually lacked lymphadenopathy, mass formation, neurological abnormalities and skin lesions. The clinical course was aggressive with a median survival of 7 months. The morphological findings were uniform: large lymphoid cells infiltrated vessels and/or sinusoids of the liver, marrow, lung, kidney and other organs. They were positive for CD19, CD20, CD79a and HLA-DR, but negative for CD10, CD23 and CD30. CD5 was positive in five out of 17 cases. Our critical review indicates that BCL-HS is the equivalent of the Asian variant of IVL.

Granulopoiesis is tightly regulated to meet host demands during both “steady-state” and “emergency” situations, such as infections. The transcription factor CCAAT/enhancer binding protein β (C/EBPβ) plays critical roles in emergency granulopoiesis, but the precise developmental stages in which C/EBPβ is required are unknown. In this study, a novel flow cytometric method was developed that successfully dissected mouse bone marrow cells undergoing granulopoiesis into five distinct subpopulations (#1–5) according to their levels of c-Kit and Ly-6G expression. After the induction of candidemia, rapid mobilization of mature granulocytes and an increase in early granulocyte precursors accompanied by cell cycle acceleration was followed by a gradual increase in granulocytes originating from the immature populations. Upon infection, C/EBPβ was upregulated at the protein level in all the granulopoietic subpopulations. The rapid increase in immature subpopulations #1 and #2 observed in C/EBPβ knockout mice at 1 d postinfection was attenuated. Candidemia-induced cell cycle acceleration and proliferation of hematopoietic stem/progenitors were also impaired. Taken together, these data suggest that C/EBPβ is involved in the efficient amplification of early granulocyte precursors during candidemia-induced emergency granulopoiesis.

Summary. Perforin gene (PRF1) mutations appear to occur in about 30% of patients with haemophagocytic lymphohistiocytosis (HLH). We tested perforin expression and gene mutations in 14 HLH patients and six patients with EpsteinBarr virus-associated HLH (EBV-HLH) in Japan. Five of the 14 HLH patients had perforin abnormalities. The presence of PRF1 genetic abnormality correlated well with the lack of perforin expression as determined by flow cytometry. Sequencing showed that four patients had a compound heterozygous mutation while the fifth patient had a homozygous mutation. Three of the mutations we detected were novel. In contrast, none of the six EBV-HLH patients showed perforin abnormalities. Our data, combined with the PRF1 mutations in three previously reported Japanese patients, suggest that the 1090-1091delCT and 207delC mutations of the perforin gene are frequently present in Japanese HLH patients (62AE5% and 37AE5% respectively). Examination of the geographical origins of the ancestors in the perforin-mutant HLH patients revealed that they mostly came from the Western part of Japan, suggesting that the present-day cases may largely derive from a common ancestor.

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