Diagnosis and subclassification of acute lymphoblastic leukemia

Sabina Chiaretti, Gina Zini, Renato Bassan, Sabina Chiaretti, Gina Zini, Renato Bassan

Abstract

Acute lymphoblastic leukemia (ALL) is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly between ALL subsets, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT) and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review summarizes how best to identify ALL and the most relevant ALL subsets.

Figures

Figure 1
Figure 1
Common morphological variants of ALL. A) FAB L1 subtype: the lymphoblasts are small and the nuclear and cytoplasmic characteristics appear uniform with scant blue cytoplasm, regular nuclear shape, partially condensed chromatin with barely visible nucleoli and high nucleocytoplasmic ratio; B) FAB L2 subtype: the lymphoblasts are variable in size with irregular nuclear outlines, heterogeneous lacy chromatin, moderately plentiful weakly basophilic cytoplasm and variable nucleocytoplasmic ratio; C) FAB L3 subtype (Burkitt): the lymphoblasts are very large and quite homogeneous with finely granular stippled nuclear chromatin with prominent nucleoli. The cytoplasm is midnight blue and is vacuolated; the majority of such cases are now recognised as representing non-Hodgkin lymphoma rather than ALL. B) in this picture are displayed many lymphoblasts with ALL-L2 morphology and one lymphoblast (right side) with coarse azurophilic cytoplasmic granules.
Figure 2
Figure 2
Rare morphological variants of ALL and MPO negativity. A) ALL with hand-mirror cells: the shape of the elongated lymphoblasts resembles a hand mirror or a tennis racquet with a very high nucleocytoplasmic ratio. Almost all the blasts have a small polar cytoplasmic projection corresponding to a uropod; B) Eosinophil-associated ALL; C) Negative MPO reaction in ALL: a yellow-brown precipitate is visible only in a neutrophil metamyelocyte just to the center of the picture. All the other blast cells are completely peroxidase-negative.
Figure 3
Figure 3
Examples of ALL immunophenotype. A) Pro-B ALL: lymphoblasts are CD19, CD34, CD22, TdT and Cy CD79a positive and CD10 negative; B) Pre-B ALL: lymphoblasts are CD22, CD34, CD19, TdT, cytoplasmic (Cy)CD79a, CD10 and Cy mμ positive; C) Cortical/thymic TALL: Lymphoblasts are cyCD3, CD7, TdT, CD5, and CD1a positive.
Figure 4
Figure 4
Diagnosis and subclassification of adult ALL. To confirm diagnosis and obtain clinically useful information, it is necessary to 1) differentiate rapidly Ph-positive ALL from Ph-negative ALL in order to allow an early introduction of tyrosine kinase inhibitors in the former subset, 2) distinguish between different clinico-prognostic Ph- ALL subsets, and 3) clarify diagnostic issues related to the application of targeted therapy and risk-/minimal residual disease (MRD)-oriented therapy. The early diagnostic phase must be completed within 24–48 hours. Additional test for cytogenetics/genetics, genomics and MRD rely on collection, storage and analysis of large amounts of diagnostic material, and are usually available at later time-points during therapy, however before taking a decision for allogeneic stem cell transplantation (SCT). All this requires a dedicated laboratory, and is best performed within a prospective, well coordinated clinical trial.

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Source: PubMed

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