Sensitivity and Specificity of Bone Marrow Hemophagocytosis in Hemophagocytic Lymphohistiocytosis

  1. Hamayun Imran2
  1. 1Department of Pathology of the University of South Alabama Medical Center
  2. 2Department of Pediatrics of the University of South Alabama Medical Center
  1. Address correspondence to Dr. Jacek M. Polski, M.D.,; Department of Pathology, University of South Alabama Medical Center; 2451 Fillingim Street, Mobile, AL 36617; phone: 215 471 7790; fax: 251 471 7884; e mail: jpolski{at}usouthal.edu

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal disease characterized by abnormal activation of T-lymphocytes and macrophages. The diagnosis of HLH can be established if there is a family history of HLH, or evidence of genetic defects, or if 5 of 8 clinicopathologic criteria are fulfilled. This case-control study aimed to examine the extent of hemophagocytosis on the bone marrow examination of patients fulfilling diagnostic criteria for HLH. Hemophagocytosis in 6 bone marrow aspirates from 3 HLH patients was compared with 20 random control bone marrows. Macrophages with hemophagocytosis were counted using a Miller ocular disc in fields corresponding to 9,000 nucleated cells. Mean hemophagocytosis count in the HLH cases was estimated at 0.082% (range 0–0.31%), whereas in the controls it was 0.009% (range 0–0.04%). The sensitivity of hemophagocytosis was 83% with a specificity of only 60%. This demonstrates that rare hemophagocytosis can be seen in bone marrow aspirates from patients without a clinical diagnosis of HLH. It also shows that hemophagocytosis has too low a specificity to be a screening test for HLH. While the hemophagocytosis counts are significantly higher in HLH cases than in controls, overlap of the counts precludes using hemophagocytosis as a reliable indicator of HLH. A rise in the hemophagocytosis count threshold of 0.05–0.13% would increase the specificity to 100%. We suggest that the diagnostic scheme for HLH needs revision, and can be improved by addressing minimum hemophagocytosis count threshold.

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