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Researchers Recommend New Processes for Bone Marrow Screening for HLH

December 30, 2021

For patients suspected of having hemophagocytic lymphohistiocytosis (HLH), bone marrow biopsy is often used to identify the presence of hemophagocytosis and assess for underlying malignancy. However, while bone marrow biopsy is an easily accessible test, there currently are no evidence-based guidelines on the reporting of hemophagocytosis on bone marrow biopsy, noted Caroline Wilson, MBBS, from Canberra Hospital in Australia. There also are no reports of a correlation between hemophagocytosis with the clinical diagnostic criteria for HLH (HLH-2004).

In this study, Dr. Wilson and colleagues aimed to determine if the amount of hemophagocytosis identified in the bone marrow biopsy correlated with HLH-2004 diagnostic criteria and to determine the extent of interobserver variability in reporting hemophagocytosis.

Two hematopathologists independently reviewed bone marrow biopsies from adults who were under investigation for HLH. Hematopathologists were blinded to the original biopsy report. Specimens were categorized according to the average number of actively hemophagocytic cells in each slide (0, 1, 2-4, or ≥5). If there was discordance pertaining to the degree of hemophagocytosis in a given sample, the sample was reviewed by both assessors to reach a consensus.

A total of 62 specimens from 59 patients were available for assessment. An underlying hematologic condition was identified in 34 cases (58%). The most common condition was lymphoma, found in 15 cases (25%).

Dr. Wilson and colleagues found a significant association between the amount of hemophagocytosis identified on the aspirate samples and the number of HLH-2004 criteria met (p<0.05). Hemophagocytosis was present on 31 samples, and there was a significant correlation between the amount of hemophagocytosis and ferritin levels (p<0.05).

Notably, interobserver variability was present in a substantial portion of cases (63%).

Based on these observations, the authors formulated recommendations for reporting of hemophagocytosis in bone marrow specimens, including:

  • Count only macrophages ingesting intact hemopoietic cells.
  • Quantify the average number of active histiocytes per aspirate slide.
  • Count histiocytes away from particles where the cellular outline is clear.
  • Avoid counting conglomerates of histiocytes where the cellular margins are indistinct.
  • On the aspirate specimen, assess for hemophagocytosis on both the trail and squash preparations.
  • Delineating hemophagocytosis on trephine samples is difficult without the use of a CD68 immunohistochemical stain.

These recommendations, Dr. Wilson and authors noted, could help to reduce interobserver variability on the reporting of hemophagocytosis.

Study authors report no relevant conflicts of interest.


Wilson C, Lee W, Cook M, et al. Correlation of hemophagocytosis with clinical criteria of hemophagocytic lymphohistiocytosis and recommendations for screening bone marrow samples in adult patients. Abstract #2645. Presented at the 2020 American Society of Hematology Annual Meeting, December 7, 2020.


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