An Asian variant of intravascular lymphomatosis: an updated review of malignant histiocytosis-like B-cell lymphoma.

Malignant histiocytosis-like B-cell lymphoma (MH-like BCL) is characterized clinically by hemophagocytic syndrome (HPS), bone marrow involvement at presentation, and an aggressive clinical course. Yet, it remains an ill-defined disease entity. We recently described five cases of MH-like BCL and suggested that these may be regarded as a peculiar variant of intravascular lymphomatosis (IVL), based on clinical and pathological observation. Interestingly, this type of lymphoma has been reported exclusively among Asians, with few reports from Western countries, and therefore we propose that this variant be noted as an Asian variant of IVL(AIVL). To evaluate the incidence of this variant, we performed a literature search for English or Japanese studies dealing with MH-like BCL or B-cell IVL associated with HPS (IVL with HPS). We found 18 reports of MH-like BCL and 16 reports of IVL with HPS and re-evaluated the clinicopathologic aspects of each study with respect to AIVL. Although several differences were noted, such as gender, presence of respiratory changes, bone marrow invasion and disseminated intravascular coagulopathy, there were also overlapping profiles and they appeared to be consistent with the AIVL single disease entity. Of particular note was the absence of peripheral lymphadenopathy and tumor formation which posed diagnostic problems in the initial phase of the presentations. Thus, based on analysis of the clinical findings of these 34 cases, the diagnostic criteria for AIVL consists primarily of cytopenia (anemia and/or thrombocytopenia), hepatosplenomegaly, absence of peripheral lymphadenopathy and tumor formation, and erythrocyte-hemophagocytosis along with intravascular proliferation of the neoplastic B cells. The pathologic findings of the 19 autopsied cases which fulfilled the criteria are also summarized, and they reveal morphologic, immunologic, and genotypic features of typical IVL.

A study of the possible etiologic association of Epstein-Barr virus with reactive hemophagocytic syndrome in Hong Kong Chinese.

The herpes group of viruses, particularly Epstein-Barr virus (EBV), has frequently been implicated in the causation of reactive hemophagocytic syndrome (RHS) in the Western populations. EBV has also been implicated in the rare fulminant form of RHS occurring in Oriental children. However, our previous adult-predominant study indicated little clinical and serological evidence of EBV infection in patients with RHS in Hong Kong. In the present study, we further examined this issue using a more sensitive and specific technique for the demonstration of EBV, ie, in situ hybridization for EBV encoded RNA (EBER). The 43 Chinese patients studied were mostly adults with a mean age of 44 years, and a male to female ratio of 1.5:1. About two-thirds (28) of patients had associated malignant lymphoma at the time of diagnosis. Five patients had documented infection (typhoid fever 2; systemic candidiasis 1; adenovirus pneumonia 1; viral encephalitis 1), and two had systemic lupus erythematosus. EBER signals were detected in only 11 cases (25.6%). All positive cases were associated with malignant lymphoma, and the positive signals were exclusively localized to the lymphoma cells but not in the histiocytes. On comparing the results (11 of 28 cases positive; 39.3%) with our previous data on EBER-expression in malignant lymphomas in Hong Kong, no significant difference is observed in the frequency of EBV-positivity between the two groups of lymphomas. Thus, a definite pathogenetic link between EBV and lymphoma-associated RHS cannot be established. However, the overrepresentation of T and T/NK lineage lymphoma in this sample of lymphoma-associated with RHS (61%) versus nonselected cases of lymphomas (31%) suggests that it is the T and T/NK cell origin of the lymphoma rather than the EBV positivity that predisposes to RHS. Notwithstanding the previous findings, EBER in situ hybridization may still serve as a useful adjunct in the investigation of patients with RHS, because the presence of EBER-positive cells should raise a strong suspicion of an underlying malignant lymphoma.