Binucleated lymphocytes on peripheral blood smear associated with poor prognosis in chronic lymphocytic leukemia

Abstract

Abstract Background: Chronic lymphocytic leukemia (CLL) is a common lymphoproliferative disease involving B cells, and small lymphocytic lymphoma (SLL) is regarded as the solid tumor counterpart of CLL. Both of them share the same morphology, which appear as small, mature-appearing lymphocytes with a scanty amount of cytoplasm and a clumped nuclear chromatin. While some cases have reported the presence of binucleated lymphocytes on peripheral blood smears of a small part of CLL patients. However, the prognostic value of this atypical morphologyin CLL patients has not been well acknowledged. Method: We retrospectively reviewed 325 newly diagnosed CLL/SLL patients. Blood smears were performed by Wright-Giemsa stain and used for morphometric assessment. Cytogenetic aberrations were assessed by chromosome banding analysis. Genetic characterization was analyzed by direct Sanger sequencingor FISH. Result: Binucleated lymphocytes observed on peripheral blood smear presented with two similar size and relatively symmetrical nuclei, but varied in size and forms. 308 patients (94.8%) were defined as binucleated lymphocytes negative (BLN) and 17 patients (5.2%) as binucleated lymphocytes positive (BLP). In particular, multinucleated lymphocytes were found in 2 cases. Binucleated lymphocytes were highly correlated with prolymphocytes and dividing lymphocytes. BLP had a higher proportion of complex karyotypes, unmutated IGHV, TP53 mutation or depletion, and a lower proportion of 13q deletion. In addition, there was a significant association between the presence of binucleated lymphocytes and overall survival. In cases withmutated IGHV or without TP53 mutation or deletion, overall survival of BLP was significantly shorter. Conclusion: The observation of binucleated lymphocytes should be considered as a negative prognostic parameter for CLL, especially in lower genetic-risk CLL population. The morphological examination of blood smear in CLL is still worthy, for its advantages of saving of time, laboratory technique, and simplicity and convenience.