We use a combination of clinical data, hematologic and bone marrow findings, and results of more specific diagnostic testing (immunophenotyping, cytochemical staining) to differentiate between an acute leukemia (myeloid or lymphoid in origin and arising in the marrow) and a lymphoma with a leukemia phase, i.e. neoplastic cells in blood and/or bone marrow. In some cases, particularly with T cell neoplasms, this distinction is difficult and the ultimate decision is based on the main site of diagnosis (solid tissue = lymphoma, blood or bone marrow = leukemia). A similar classification difficulty arises with chronic lymphoid leukemia versus small cell lymphoma, which are considered variants of the same disease, with a mainly tissue phase (lymphoma) or blood/marrow phase (leukemia) resulting in different clinical and hematologic manifestations (Santos and O’Brien 2012, Campo et al 2011). See also an algorithm and spectrums of disease images under leukemia types. Also note, that cytologic and histologic assessment of tissue aspirates (e.g. lymph node) usually cannot be used to differentiate between types of acute leukemia or an acute leukemia and precursor or large cell lymphoma. Morphologic findings in lymph node aspirates can be used to suspect and, in select cases, confirm a diagnosis of acute myeloid leukemia (Kaur et al 2024), however these aspirates should be backed up by flow cytometric immunophenotyping of involved tissues, blood or bone marrow.
| Criteria | Acute myeloid leukemia | Acute lymphoblastic leukemia | Leukemic phase of lymphoma (Stage V) |
| Physical examination | Mild or no enlargement of lymphoid organs (can be moderate to rarely severe). Rarely presents as a mass. | Mild or no enlargement of lymphoid organs (can be moderate to rarely severe). | Moderate to severe enlargement of lymphoid organs. |
| Hemogram | Large number of blasts; multiple cytopenias (non-regenerative anemia, neutropenia, thrombocytopenia) is typical but not always seen. | Large number of blasts (or small to intermediate cells); multiple cytopenias (non-regenerative anemia, neutropenia, thrombocytopenia) is typical but not always seen. | Variable number of lymphoma cells (usually resemble counterpart in tissues); typically no or mild cytopenias (mild non-regenerative anemia most common, moderate thrombocytopenia can be seen with variants of T cell lymphoma). |
| Bone marrow | Large number of blasts which comprise >20% of marrow cells (per WHO definition1), with reduced to minimal numbers of normal hematopoietic precursors. Tumor comprises >70% of marrow cells, with rare cases having a lower percentage of tumor cells (can be mistaken for stage V lymphoma). | Large number of blasts (these can be small, intermediate or large) with >25% of marrow cells (per WHO definition1) found diffusely in the marrow (usually >50%), with reduced numbers of normal hematopoietic precursors. | Variable numbers of lymphoma cells (resemble counterpart in tissues); may still have some normal blood cell precursors. Lymphoma cells usually in foci or patches and usually <25% of all marrow cells (per WHO definition1). |
| Phenotyping tests: Flow cytometry, cytochemistry and immunocytochemistry or immunohistochemistry (note, the best phenotyping test is flow cytometry) | Positive for monocyte, granulocyte, or megakaryocytic markers (erythroid markers are lacking in animals). Aberrant expression of lymphoid markers is possible and some AML can be clonal (Stokol et al 2017). | Positive for B or T lymphoid markers. Rarely show aberrant expression of myeloid markers. | Positive for B or T lymphoid markers.
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1 Swerdlow SH, Campo E, Harris NL, Jaffe ES, Stein H, Thiele J, et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Bosman FT, Jaffe ES, Lakhani SR, Ohgaki H, editors. Lyon, France: International Agency for Research on Cancer (2008).
