What is hemophagocytosis on bone marrow?

What is Hemophagocytosis on Bone Marrow?

Hemophagocytosis on bone marrow is a histopathologic finding where activated macrophages (histiocytes) engulf and phagocytose hematopoietic cells—including red blood cells, white blood cells, platelets, or their precursors—visible on bone marrow aspirate or biopsy specimens. 1

Morphologic Characteristics

• Hemophagocytosis appears as enlarged macrophages containing ingested blood cells or cellular debris within their cytoplasm. 1
• CD68 immunohistochemical staining can highlight histiocytes and hemophagocytic cells to improve detection. 2
• The finding is quantifiable: in patients with hemophagocytic lymphohistiocytosis (HLH), hemophagocytosis averages 0.082% of nucleated cells (range 0-0.31%), compared to 0.009% (range 0-0.04%) in controls. 3

Clinical Significance and Diagnostic Context

Hemophagocytosis is neither sensitive nor specific for HLH and can occur in multiple clinical contexts. 1

When Hemophagocytosis Suggests HLH:

• The amount of hemophagocytosis correlates significantly with the number of HLH-2004 diagnostic criteria met (p<0.0001). 4
• In patients with hemophagocytosis present, the degree correlates with ferritin levels (p=0.041). 4
• Hemophagocytosis has 83% sensitivity but only 60% specificity for HLH at standard thresholds. 3
• A threshold of 0.05-0.13% hemophagocytosis increases specificity to 100% for HLH diagnosis. 3

When Hemophagocytosis Does NOT Indicate HLH:

Hemophagocytosis can be a nonspecific finding in multiple conditions without pathologic immune activation, including: 5

• Transfusion-dependent anemia with brisk hemophagocytosis of mature red blood cells 5
• Septicemia and severe infections 1
• Hematologic malignancies (9% of acute myeloid leukemia patients after intensive induction therapy) 1
• Post-chemotherapy states 1

Diagnostic Algorithm for Interpretation

When hemophagocytosis is identified on bone marrow, clinicians must integrate this finding with HLH-2004 criteria rather than relying on morphology alone: 1

1. Assess whether 5 of 8 HLH-2004 criteria are met: fever, splenomegaly, cytopenias (≥2 lineages), hypertriglyceridemia/hypofibrinogenemia, hemophagocytosis, low NK cell activity, ferritin ≥500 μg/L, soluble CD25 ≥2400 U/mL 1

2. Evaluate the clinical context: judge whether the combination, extent, and progression of abnormalities are unusual, unexpected, and otherwise unexplained by the underlying condition alone 1

3. If hemophagocytosis is not initially present but HLH is suspected, serial bone marrow aspirates over time may reveal the finding, as it can develop later in the disease course 1

4. Consider the HScore (which assigns 35 points for hemophagocytosis on bone marrow aspirate) to calculate probability of HLH, with scores >169 suggesting high likelihood 1, 2

Critical Pitfalls to Avoid

• Do not diagnose HLH based solely on hemophagocytosis—this finding requires integration with clinical and laboratory parameters to distinguish pathologic immune activation from other causes. 5
• Marked inter-observer variability exists in quantifying hemophagocytosis; standardized reporting methods improve diagnostic accuracy. 4
• In transfusion-dependent patients, distinguish transfusion-associated hemophagocytosis and hyperferritinemia from true HLH through assessment of biomarkers of pathologic immune activation. 5
• Hemophagocytosis may be absent early in disease; if bone marrow is not conclusive, obtain material from other organs (spleen, lymph nodes, liver) or repeat marrow examination. 1