[1573] Hemophagocytic Lymphohistiocytosis (HLH): Review of Bone Marrow Morphology and Correlation with Laboratory Findings

T Mounajjed, H Al-Ghawi, JQ Mo. Cincinnati Children Hospital Medical Center, Cincinnati, OH

Background: HLH is a life-threatening disease, primarily affecting children, characterized by uncontrolled proliferation of activated lymphocytes and histiocytes driven by a cytokine storm. Hemophagocytosis is the hallmark of HLH. Histologic examination of bone marrow (BM), one of the most frequently involved organs, is critical for diagnosis. However, BM morphologic findings of HLH are not fully characterized. The aim of this study is to evaluate the BM morphologic features of HLH and correlate them with laboratory findings.
Design: We retrospectively reviewed BM smears and biopsies of 40 patients (pts) with HLH (diagnosed based on 2004 guidelines) and a control group (CG) of 21 cases of HLH clinical and morphologic mimics. We designed a grading system of hemophagocytic activity (HA) based on the frequency of hemophagocytosis in the BM smear and compared morphology between the two groups.

Grading of HA

Grade	# of Hemophagocytic figures
0	Absent
1	Rare (<5/smear)
2	Occasional (>10/smear)
3	Easily seen on 10X
4	Easily seen on 4X

Clinical and laboratory data were collected and correlated with morphologic findings.
Results: HLH pts and CG aged 0.2 to 27 yrs (average=6.9 yrs). Average BM cellularity was 76% in HLH pts compared to 68% in CG (no significant difference). HA was present in 88% of HLH pts. A significant increase in histiocytes and atypical lymphocytes was seen in a significantly higher proportion of HLH pts compared to CG (p<0.05). HLH pts showed a significantly higher grade of HA compared to CG (p<0.05). The engulfed hematopoietic cells were intact in HLH. In contrast, they were degenerated and accompanied by cellular debris and hemosiderin pigment in HLH mimics. The grade of HA in HLH BMs did not correlate with cytopenias, Ferritin or Triglyceride levels, natural killer or cytotoxic T cell function, Perforin expression, CD4/CD8 ratio, or soluble IL-2 receptor levels.
Conclusions: BM examination is critical for HLH diagnosis and has a sensitivity of 88%. Unlike previous reports of BM hypocellularity in HLH, our study showed an average BM cellularity of 76%. An HA grade-2, increased histiocytes and atypical lymphocytes, and presence of intact engulfed hematopoietic cells are key morphologic features of HLH. In contrast, HLH mimics often show absent or rare HA, no significant increase of histiocytes and atypical lymphocytes, and degenerated engulfed cells accompanied by cellular debris and hemosiderin pigment. The grade of HA in HLH does not correlate with laboratory findings.
Category: Pediatrics

Monday, March 9, 2009 11:15 AM

Platform Session: Section H2, Monday Morning