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Acute leukemia (AL) cytomorphology- basis for multidisciplinary diagnostic approach

The WHO classification of AL is based on finding of minimally 20% bone marrow (BM) blasts and on the correlation of clinical, morphologic, immunophenotypic and genetic features. AL are classified as myeloid (AML), lymphoid (ALL) and AL with ambiguous lineage (AL-ambl), including undifferentiated AL (AUL) and mixed phenotypic AL (MPAL). Precursor myeloid neoplasms (MN) include: AML with recurrent genetic abnormalities, AML with myelodisplasia, MN-therapy related, AML-not otherwise specified (NOS), myeloid sarcoma, MN related to Down syndrome and blastic plasmocytoid dendritic cell neoplasms (CD56+CD123+). ALL and lymphoblastic lymphomas are classified as precursor lymphoid neoplasms in: B and T lymphoblastic leukemia/lymphoma and B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities. FAB AL classification based on blast cytomorphology and cytochemistry defined 7 AML (M1, M2, M3, M4, M5, M6, M7) and three ALL (L1, L2, L3) subtypes. FAB AL subtypes can be associated with various WHO AL subgroups. Thus, AML- M2 can be WHO categorized as NOS-AML with maturation, AML with t(8 ; 21) or with other cytogenetic abnormalities, as therapy related AML or AML with myelodisplasia. M3 (AML with recurrent cytogenetic abnormalities) with typical hypergranular cytomorphology and microgranular (hypogranular) variant is characterized with t(15 ; 17). In M3 blasts with t(15 ; 17) normal speckled PML (large dots in nucleus) is changed in many small nuclear dots-microgranular immunopositivity pattern. AML associated with t(11 ; 17) or t(5 ; 17) and M3 resembling cytomorphology should be diagnosed as AML with variant RARA translocation. AML with nucleophosmin (NPM1) mutation is usually associated with myelomonocytic and monocytic cytomorphology and with normal karyotype. Blasts with cuplike nucleus are associated with NPM1+ AML and may also have aberrant NPM immunocytochemical cytoplasmic positivity. MPAL usually presented with undifferentiated blasts and lymphoblasts or dimorphic blast populations (myeloblasts or monoblasts and lymphoblasts), but all other FAB subtypes could be also found. In CD56+ T+ NK lymphoblastic leukemia/lymphoma (AL-ambl subtype) blasts expressed L2 morphology. NK/myeloid AL, usually associated with M3 microgranular resembling cytomorpholgy, is considered as AML. The L1 and L2 cytomorpholgy is hallmark of lymphoblastic leukemia/lymphoma. In some B lymphoblastic leukemia/lymphoma "hand mirror" blasts with pseudopod or with coarse azurophilic granules could be seen and cases with t(v ; 11q23) presented with lymphoblasts and monoblasts should be considered as MPAL. In T lymphoblastic leukemia/lymphoma blasts occasionally may resemble more mature lymphoid cells. FAB L3 blasts are associated with WHO- leukemia variant of Burkitt lymphoma. In conclusion: 1) 20% BM blasts is basic criterion for AL diagnosis. But, if cytogenetic abnormality such as t(8 ; 21) is found, number of blasts could be somewhat lower ; 2) cytomorphologic FAB types are associated with different WHO categories ; 3) 5% BM blasts or less is criterion for morphologic remission of disease. However, less than 5% BM blasts with L3 or M3 morphology may point to minimal residual disease ; 4) cytomorphology and cytochemistry of BM and peripheral blood (PB) should be done at diagnosis, if remission is not achieved and at relapse of disease (possibility of blasts lineage switch) and 5) if there is no blasts in PB immunocytochemistry should be done for differentiation blasts from other undifferentiated malignant cells.

acute leukemia cytomorphology; acute leukemia cytochemistry and immunocytochemistry

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