Flow Cytometric Findings in Hemophagocytic Lymphohistiocytosis.
Chad M McCall, Shirley Fuller, Shiyama Mudali, Robert J Arceci, Christopher D Gocke, Milena Vuica-Ross, Kathleen H Burns, Michael J Borowitz, Amy S Duffield. Johns Hopkins, Baltimore, MD
Background: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome that is often fatal. HLH may be inherited, but more commonly arises secondary to Epstein-Barr virus (EBV) infection, hematologic malignancies, or rheumatologic diseases.
Design: Seventeen patients were identified who were diagnosed with HLH between 2001-2010 and had flow cytometric analysis of peripheral blood (PB) (4) or bone marrow (13) performed at the time of diagnosis.
Results: Two patients had primary HLH, and the others had HLH secondary to EBV (7), EBV and a concurrent hematologic malignancy (2), hematologic malignancy (1), rheumatologic conditions (4), and tuberculosis (1). The average age was 21 (range: 6 months-75 years), with 10 males and 7 females. Quantitative abnormalities were noted in the marrow regardless of etiology. On average there was a relative decrease in myeloid cells (36.3%; range 4-72%). Lymphoid cells were relatively increased (42.2%; range 11-75%), with abundant T-cells in most cases and increased NK cells in one case. All but one case had prominent HLA-DR+ T-cells. Of the nine patients with EBV-associated HLH, five had expansions of CD8 T-cell populations with variable levels of expression of CD5, CD7 and/or CD3, but this was not consistent from case to case. The cases of HLH that were not EBV-associated included one case that had T-cells with a range of CD5 expression, but did not demonstrate any populations of T-cells similar to those in the EBV+ cases. The myeloid series showed left-shifted myelopoiesis often with near complete absence of normal mature CD10+ granulocytes. Three cases of PB showed heterogeneous or moderate HLA-DR on the granulocytes, possibly reflecting release of immature granulocytes. Two cases had granulocytes with abnormal side scatter, two had unusually dim CD13 and one had dim CD33.
Conclusions: HLH can show a range of findings on flow cytometric analysis of the bone marrow or PB. The marrow often showed a relative decrease in myeloid elements and increase in lymphocytes. Prominent and unusual but phenotypically variable CD8+ T-cells may be present, particularly in EBV-associated HLH. Most cases showed left-shifted myelopoiesis with occasional altered expression of myeloid antigens. While not specific, flow cytometric findings in HLH are different from those seen in normal marrows and care should be taken not to overinterpret phenotypic findings in these patients as indicative of primary marrow disorders or lymphoma.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 236, Tuesday Morning