Abnormal Eosinophils With Large, Distinctly Basophilic Granules (Harlequin Cells) on Peripheral Blood Smear: A Clue...

Chronic myeloid leukemia (CML) often presents with hematologic findings that overlap with reactive leukocytosis and other myeloproliferative neoplasms (MPNs), creating diagnostic uncertainty that may delay targeted therapy or prompt unnecessary molecular testing. Harlequin cells-abnormal eosinophils containing basophilic granules-are well described in acute myeloid leukemia (AML) with CBFB::MYH11 fusion, but their diagnostic relevance in CML has not been systematically assessed.

We retrospectively reviewed 177 peripheral blood smears: 53 CML; 30 non-CML MPN and related disorders; 59 AML (including three with CBFB::MYH11 fusion); 11 eosinophilia; and 24 reactive cytosis cases. Harlequin cells were stringently defined as abnormal eosinophils containing both typical eosinophilic granules and large, distinctly basophilic (not purplish-orange) cytoplasmic granules to exclude reactive mimics.

Harlequin cells were identified in 72% (38 out of 53) of CML cases, a frequency significantly higher than in non-CML MPN (10%, P < 0.01), AML without CBFB::MYH11 fusion (3.6%, P < 0.01), eosinophilia (0%), and reactive cytosis (0%) groups. They were also observed in 67% (2/3) of AML with CBFB::MYH11 fusion and in 20% (3/15) of primary myelofibrosis, but were absent in polycythemia vera, essential thrombocythemia, and chronic myelomonocytic leukemia. Strictly defined Harlequin cells were not found in any reactive condition.

In the appropriate clinical context, strictly defined Harlequin cells on routine peripheral blood smears may serve as a sensitive and highly specific morphologic clue for CML. Recognition of this readily accessible feature may facilitate prompt BCR::ABL1 confirmatory testing, reduce diagnostic ambiguity, and help avoid unnecessary ancillary studies.