Peripheral Blood Flow Cytometric Analysis Is Sensitive and Specific for the Early Diagnosis of Hematolymphoid Malignancy in Patients With Hemophagocytic Lymphohistiocytosis

Abstract Objectives Hemophagocytic lymphohistiocytosis (HLH) is an infrequent but potentially life-threatening disease characterized by cytokine dysfunction and activation of macrophages and T cells, resulting in systemic symptoms and organ damage. Most adult HLH cases are secondary to hematolymphoid malignancy (HM) and/or infections. A timely diagnosis followed by targeted treatment is essential to improve clinical outcomes but often is challenging due to variable clinical presentations that overlap with other diseases. Methods Search of an institutional database from 2009 to 2017 in adults from the HLH Task Force study identified 34 cases of HLH. Of the 34 cases, 18 had malignancy (53%) and 11 had infection (35%). A comprehensive review of flow cytometry, morphology, and clinical and laboratory examination was assessed and compared. Results Of 18 cases of malignancy, 17 cases (94%) were HM, including T/NK- or B-cell lymphomas. In nine patients with HM who had peripheral blood flow cytometric (PBFC) tests, seven cases were positive for atypical/neoplastic populations concordant with the final diagnosis either in bone marrow or tissue, whereas none of five non-HM cases were positive. The sensitivity and specificity of PBFC to predict HM were 78% and 100%, respectively. The percentage of the neoplastic population ranged from 0.55% to 92% and was higher in one case of acute myeloid leukemia. The immunophenotypic profile, including large cell size, was sufficiently aberrant to distinguish from indolent clonal lymphocytosis. Conclusion Our study demonstrated the predictive power of PBFC for diagnosing hematolymphoid malignancy in HLH patients with a high sensitivity and specificity. We recommend PBFC (with a STAT result available in hours) to be used as an initial screening test in cases where there is high clinical suspicion for HLH and HM followed by confirmatory tissue diagnosis. This process may aid in a timely diagnosis and treatment to improve the clinical outcomes.