Diagnosis of acute leukemia is based on the assessment of morphological features of bone marrow cells and peripheral blood. The diagnosis is established only when so-called blast cells in the bone marrow or peripheral blood are characterized by a delicate net structure of nuclear chromatin. The number of blast cells in this case should be 20% or more.

If it is less in the bone marrow, but its content in the blood is 20% or more, then the diagnosis of acute leukemia is also established. Determining the belonging of tumor cells to the myeloid or lymphoid hematopoietic lines when using the usual Romanovsky – Giemsa staining is possible only in 70% of cases. For a more precise definition, other diagnostic approaches are needed: immunophenotyping, cytochemical, cytogenetic, molecular biological and cultural studies.

A new WHO classification can be called a list of diseases characterized by a specific set of features, since it lacks a single classification feature that existed, for example, in developing the FAB classification (morphology and cytochemistry of blast cells). As a result, some forms of OL can simultaneously be assigned to different categories.

Thus, acute leukemias with Hq23 translocations are assigned to the first classification category, but the 11q23 segment anomaly is often detected in patients with secondary acute leukemia. At the same time, secondary acute myeloblastic leukemias are separated into a separate category, so it is not clear how to classify AML, which arose after previous chemotherapy of a tumor and is characterized by anomalies of the 11q23 segment, as a disease of the first category or the third.

There is also a question regarding other consistently detectable chromosomal aberrations: for example, why in the first classification category such anomalies as t (6; 9) and anomalies of chromosome 3 that have clear morphological and clinical characteristics are not considered.

In those situations when it is not possible to analyze the karyotype of blast cells, the only principle by which acute leukemia, morphological, will be classified. Again, it is unclear to which classification category AML is classified, which, for example, according to the FAB classification, is characterized as myelomonoblastic, but arose after prior chemotherapy and in which signs of myelodysplasia are determined in the bone marrow.

The presence of myelodysplasia is the basis for the selection of the second classification category. As noted earlier, morphological signs of dysplasia are detected in patients with different types of AML (myeloblastic, myelomonous and monoblastic, erythroblastic, rarely promyelocytic, etc.), with AML developed from MDS, secondary AML. This pattern was previously noted by other international experts, so it is not quite clear why a special category was selected.

Previously, it was believed that the presence of signs of myelodysplasia determines an unfavorable prognosis, and therefore, it seems that leukemias with these symptoms were considered as a separate category. However, it has now been established that the symptoms of myelodysplasia in the debut of the disease are observed quite often and do not affect the results of therapy.

In the new WHO classification, acute lymphoblastic leukemia is considered in the section of tumors arising from the precursor cells of T and B lymphocytes. In the section of lymphatic tumors from the early progenitor cells are presented:
1) lymphoblastic leukemia / lymphoma from B-lymphocyte progenitor cells (synonym: acute lymphoblastic leukemia from B-cell precursors);
2) lymphoblastic leukemia / lymphoma from T-lymphocyte progenitor cells (synonym: acute lymphoblastic leukemia from T-lymphocyte progenitor cells).

Perhaps the equivalent use of the presented definitions, the authors of the classification only believe that when the content of blast cells in the bone marrow is 25% and it is more expedient to speak of acute leukemia, less than 25% of lymphoblastic lymphoma. However, most often these terminological difficulties are speculative, since the therapy is the same in either case.

In accordance with the FAB classification, the described forms of acute lymphoblastic leukemia were defined as variants L1 and L2, however, at present, these names are practically not used. According to the FAB classification, the third form of ALL, in the modern classification, is assigned to a large section of tumors from mature (determined by immunophenotype) B-cells as Berkitt-like leukemia / lymphoma. Unfortunately, the new classification does not give clear immunophenotypic characteristics of specific sub-variants of B-and T-cell lymphoblastic leukemias, which often causes difficulties in interpreting the results of flow fluorocytometry.

Differential diagnosis of acute lymphoblastic leukemia

The differential diagnosis of acute lymphoblastic leukemia and non-Hodgkin’s lymphomas (NHL) in the blast-type leukemization stage necessitates a detailed immunological study. Those hemoblastosis in which the blasts have the phenotype of early progenitors are designated as ALL / NHL, and the rest – as NHL from peripheral cells. So, when expressing antigens of early B-precursors (CD19, CD20, CD22), TdT enzyme and in the absence of membrane immunoglobulin, B-ALL / NHL is diagnosed, and in the presence of T-precursor phenotype – T-ALL / NHL.

Similar difficulties are encountered in the differential diagnosis of acute non-lymphoblastic leukemia (ONL) and myeloid sarcomas. Currently, myeloid sarcomas in the WHO classification are considered in the section of acute leukemia and can be presented as the first manifestation of the disease with rapid leukemization by the type of acute non-lymphoblastic leukemia (ONLL).

The cellular composition of myelosarcoma can be represented by blasts of various types or by maturing elements of the granulocyte series. Morphocytochemical and immunophenotypic characteristics of blasts, cytogenetic abnormalities are identical to those observed in acute non-lymphoblastic leukemia (ONLL).

In patients with multiple myeloma, plasma cell leukemia may occur. It usually manifests itself as a terminal phase of myeloma, although there are descriptions of cases when it is regarded as an independent disease. The leukemic population in the blood and bone marrow is represented by plasmablasts, as well as protoplasmocytes and plasma cells. All elements of the plasma line are morphocytochemically and immunophenotypically characterized as B cells with clonal expression of immunoglobulins.

Diagnosis of hemoblastosis

Diagnosis of hemoblastosis can be difficult with scanty punctate bone marrow. This can be observed in aplastic conditions, myelofibrosis, MDS with fibrosis or tumor metastases. In cases where a proliferative pathological clone has been identified (myeloblasts, megakaryoblasts), acute leukemia with myelofibrosis is diagnosed, otherwise acute or chronic idiopathic myelofibrosis is diagnosed. In acute panmielosis, in contrast to chronic idiopathic myelofibrosis, young forms of myelopoiesis, including mononuclear megakaryocytes, predominate in the bone marrow.

Acute leukemias also have to be differentiated from blast crises in the inventories and, in particular, CML. Special difficulties are presented when the CML manifests with a blast crisis. The presence of the Ph-chromosome in most cases helps to establish the diagnosis of CML. It should be noted that the Philadelphia chromosome is also detected in rare cases of myeloblastic and in 25% lymphoblastic leukemia, which makes diagnosis difficult. Imperious crises of CML can be myeloid and lymphoid, and differential diagnosis is carried out with the appropriate variant of acute leukemia. The picture of the bone marrow in the myeloid blast crisis of CML is much more variegated than in ONLL: eosinophils, basophils may be present in the granulocyte sprout, pathological microforms of megakaryocytes are found.

Cells in the blast population are more diverse in their morphoimmunological features compared with acute leukemia, myeloblasts, erythroblasts, megakaryoblasts can be detected at the same time, and lymphoblasts in some cases. The picture of lymphoid blast crisis is more monomorphic and similar to that in ALL. Ph-positive clone in CML and ALL is different in its functional features, which is associated with the structural features of BCR / ABL oncogenes in these two hemoblastosis. In ALL, the BCR / ABL gene encodes the abnormal p190 protein, and in CML, the p210 protein is produced. With the help of molecular research methods (PCR reaction) establish an accurate diagnosis.

Certain diagnostic difficulties may also occur in the differential diagnosis of ONLL and metastases of alveolar rhabdomyosarcoma and neuroblastoma in children.

Acute non-lymphoblastic leukemia differentiate

M5a acute nonlymphoblastic leukemia is differentiated from leukemias of the M0, Ml and M7 variants, as well as from acute lymphocytic leukemia. In these cases, the leading criteria are cytochemical and immunophenotypic parameters. A specific feature of monoblasts M5a and M5b is α-naphthyl acetate esterase, which is inhibited by sodium fluoride. Acute monoblastic leukemia with maturity is also differentiated from atypical promyelocytic leukemia without grain. Characteristic cytochemical markers (non-specific esterase and peroxidase) make it easy to distinguish them.

In the differential diagnosis of M6 and other variants of acute non-lymphoblastic leukemia, it is necessary to take into account the possibility of two subvariants of the disease: with the presence of an extended pathological red sprout (erythromyelosis) and with total bone marrow metaplasia with leukemic erythroblasts (erythroid leukemia).

In the first case, differentiated from RAIB MDS. If the number of erythroid progenitors is more than 50%, then the number of blasts should be recalculated to the non-erythroid fraction. In the event that the number of blasts exceeds 20%, M6 is diagnosed with acute non-lymphoblastic leukemia, in the opposite – RIBS MDS. If dysplasia is expressed in more than 50% of myelopoiesis cells, then, at the suggestion of the WHO classification, a variant of acute non-lymphoblastic leukemia with multilinear dysplasia is diagnosed.

In erythroleukemia, differential diagnosis is carried out with megakaryoblastic and lymphoblastic leukemias. The presence of erythroid erythroblasts (NAE3, NAE9, glycophorin A) and the absence of megakaryocytic and lymphoid antigens are taken into account.

Megakaryoblastic leukemia is distinguished from M0 and M6 in acute non-lymphoblastic leukemia based on the expression of specific antigens (CD41 and CD61). It should be noted that leukemic megakaryoblasts sometimes differ in some morphocytochemical features, which indirectly can suggest the need for advanced immunophenotypic studies. Thus, the irregular shape of the cells, the presence of outgrowths of the cytoplasm, its pronounced basophilia, the presence of megakaryocytes in the blood and their nuclei suggest a megakaryoblastic variant of acute non-lymphoblastic leukemia.

In addition, megacaryoblastic leukemia is differentiated from acute panmielosis with myelofibrosis. The presence of more than 50% of blasts expressing specific antigens, and the absence of trilinear myeloid cell dysplasia, make it possible to diagnose acute megakaryoblastic leukemia, even with fibrosis.