Marrow Assessment for Hemophagocytic Lymphohistiocytosis Demonstrates Poor Correlation with Disease Probability
Caleb Ho, Xiaopan Yao, Ligeng Tian, Fang-Yong Li, Nikolai Podoltsev, Mina L Xu. Yale University School of Medicine, New Haven, CT; Yale University, New Haven, CT
Background: Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of marked immune activation that can be rapidly fatal. Based on current guidelines, 5 of the following 8 criteria must be met for the diagnosis of non-familial HLH: fever, splenomegaly, cytopenias, hypertriglyceridemia and/or hypofibrinogenemia, elevated ferritin, elevated sCD25, low NK-cell activity and hemophagocytosis. Although a bone marrow biopsy is often performed to check for evidence of hemophagocytosis, there is not only no accepted standard for interpretation but also no evidence that histologic findings aid in the diagnosis of HLH.
Design: We performed a retrospective study of 64 bone marrow biopsies from patients with signs and symptoms suspicious for secondary HLH. Blinded evaluation of marrow biopsies were scored individually by 2 pathologists, including aspirate count for hemophagocytic histiocytes and CD68 immunostaining for histiocytes on core biopsies. Separately, two clinicians reviewed electronic medical records to assign each patient to high or low HLH probability after case discussion. The association between HLH and the histological findings were examined using exact test.
Results: After validation by the clinical team, there were 18 subjects with probable HLH and 46 without. Neither the quantification of hemophagocytic histiocytes on aspirate nor the quantification of CD68 staining on core biopsy correlated with disease status (p=0.11, p=0.25, respectively). Of the clinical/laboratory criteria assessed, the most significant correlations with HLH were ferritin (p<0.0001), cytopenias (p=0.002) and fever (p=0.002). 17 of 18 patients with probable HLH met at least 3 non-histologic criteria compared to 7 out of 46 patients without HLH (p<0.0001).
Conclusions: While bone marrow biopsy evaluation is one of 8 criteria used for the diagnosis of HLH, this study is the first to assess the utility of pathological evaluation across a spectrum of patients suspected to have secondary HLH. Our findings indicate that marrow histologic findings do not correlate with disease status. Although a bone marrow biopsy is recommended to rule out malignancy and/or infection in patients with signs and symptoms of HLH, histologic findings appear to be of little value as an adjunct in the diagnosis of HLH.
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 212, Monday Morning