Acute lymphoblastic leukemia (ALL) – diagnosis
Acute lymphoblastic leukemia (ALL) includes leukemias, the tumor substrate of which is represented by progenitor cells of the lymphoid series. There are two variants of leukemia, depending on the direction of differentiation of blast cells: acute B-lymphoblastic leukemia / lymphoma from progenitor cells and acute T-lymphoblastic leukemia / lymphoma from progenitor cells.
Most of the observations are regarded as acute leukemia, however, cases with a pronounced extramedullary lesion and a number of blasts in the bone marrow of less than 25%, according to the WHO classification, belong to lymphomas.
The presence of individual cytogenetic abnormalities in acute lymphoblastic leukemia (ALL) has significant prognostic significance, therefore, in B-acute lymphoblastic leukemia (ALL), a number of variants are distinguished depending on the characteristics of the karyotype.
1. B-lymphoblastic leukemia / precursor lymphoma: t (9; 22) (q34; qll); BCR / ABL; t (v; llq23); MLL restructuring; t (l; 19) (q23; pl3) PBX / E2A; t (12; 21) (pl2; q22) TEL / AMN; ALL hypodiploid; ALL hyperdiploid (> 50).
2. T-lymphoblastic leukemia / precursor lymphoma.
The allocation of morphological types of lymphoblasts according to the FAB classification depending on their size [prevalence of microform L1 or mesoform P2] did not play a significant role in determining treatment tactics or in the prognosis of the disease. The type of blasts with basophilia and vacuolation of LZ cytoplasm is more characteristic of Burkitt’s lymphoma and is not specific for progenitor cells. The morphocytochemical signs of B- and T-lymphoblasts have some differences: • B-lymphoblasts are characterized by significant morphological diversity. Cells can be regular or elongated, sometimes they resemble the shape of a hand mirror. The size of the blasts varies from micro to mesoform. The nuclei are round, oval or folded, with dense chromatin and rare nucleoli. The cytoplasm is scanty, slightly basophilic, sometimes contains a slight granularity. The nuclear cytoplasmic ratio is high or moderate.
• B-lymphoblasts do not contain peroxidases, lipids and ASD-chloroacetate esterase. In half of the cases, small granules of PAS-positive substance and acid phosphatase in a fine granular form are found in them.
• T-lymphoblasts are usually monomorphic, medium-sized, rounded, with irregularly folded nuclei. The cytoplasm is scanty, moderately basophilic. The nuclear cytoplasmic ratio is high.
• T-lymphoblasts do not contain peroxidase, ASD-chloroacetate esterase and lipids. PAS-positive substance is rarely found in the form of a single granule. A characteristic feature is the presence of large granules of enzymes: acid phosphatase, nonspecific esterase, and acid nonspecific esterase.
Depending on the stage of lymphoblasts differentiation, subvariants of B-and T-linear acute lymphoblastic leukemia (ALL) are distinguished. The diagnosis is based on cell immunophenotyping data. The frequency of detection of these subvariants is different. Different chromosomal abnormalities are characteristic of different subvariants.
Leukemia from B-linear progenitor cells occurs in approximately 75% of adult patients with acute lymphoblastic leukemia (ALL). In all cases, blast cells express CD19 and / or CD79a and / or cytoplasmic CD22 molecules. As differentiation to these antigens are added, new, specific to the subsequent stages of maturation. Among B-linear leukemias, the following immunosupportants are distinguished: pro-B, pre-pre-B, pre-B, and B-ALL. The presence of t (9; 22), t (4; ll) and t (l; 19), observed in pro-B and pre-pre-B variants, is an independent indicator of an unfavorable prognosis.
Translocation (9; 22) occurs in adult patients with acute lymphoblastic leukemia (ALL) quite often (about 25%). Ph-positive and Ph-negative lymphoblasts do not have morphocytochemical and immunophenotypic differences, therefore the data of cytogenetic studies are necessary when choosing the tactics of treatment in patients with acute lymphoblastic leukemia (ALL). The prognostic value for subvariants of B-linear acute lymphoblastic leukemia (ALL) also has a change in the number of chromosomes in the blasts: hyperploidy is favorable, and hypoploidy is an unfavorable sign.
T-linear variants occur in approximately 25% of cases of acute lymphoblastic leukemia (ALL). Two immunosuppressants are distinguished: early pre-T and mature T-ALL. Both of them are characterized by the expression of the CD7 antigen. Pre-T-acute lymphoblastic leukemia (ALL), in turn, is subdivided according to the presence of the “common” antigen into CD10-positive and CD10-negative subvariants. T-linear leukemias are characterized by rearrangements of T-cell receptor genes located on the 14th and 7th chromosomes, in particular t (10; 14), t (ll; 14), t (l; 14) and inv14.