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The rapid collection of exact diagnostic and prognostic data is essential to guide therapy in patients diagnosed with acute leukemia. Basic diagnostic steps confirm the hematopoietic nature of the illness and allow distinction between Acute Lymphoid And Myeloid Leukemia (ALL and AML) throughout morphology, immunophenotype and cytogenetic/molecular analysis. However, because the complete results from the latter assays are not readily available, only morphology and Flow Cytometry (FC) permit to define quickly the cell lineage of the disease, thus orientating treatment. A small group of cases is referred to as Acute Undifferentiated Leukemia (AUL), because unclassifiable by current diagnostic markers [1]. AUL makes up 2-7% of Myeloperoxidase (MPO)-negative leukemias and poses a difficult treatment challenge [1,2]. The importance of a correct diagnostic input is further emphasized by the different results obtained with AML or ALL regimens in mixed lineage acute leukemia, another rare subset with debated diagnosis to treatment relationships [3]. Moreover, although rare in the modern era of improved diagnostic methodology, a pure leukemic presentation of an unrecognized metastatic carcinoma may need to be differentiated from AUL, AML or ALL, an issue which may be aggravated if FC results are inconclusive but treatment cannot be deferred until the availability of the other time-consuming diagnostic procedures.

Acute undifferentiated/unclassifiable leukemia or disseminated non-hematologic neoplasm? When treatment is the compelling decision