An immature, precursor lymphoid tumor of either precursor B (pre-B) or T (pre-T) lymphocytes known as lymphoblasts makes up the group of neoplasms known as acute lymphoblastic leukemia/lymphoma (ALL).
It is challenging to discern between malignant pre-B and pre-T lymphoblasts morphologically. Immunophenotyping is necessary for ALL subclassification.
Lymphoma against leukemia:
• Leukemia: Lymphoblastic leukemia is defined as the proliferation of lymphoblasts in the bone marrow and peripheral blood.
• Lymphoma: Lymphoblastic lymphoma is the term used to describe lymphoblasts' primary involvement of lymph nodes or extranodal locations.
Precursor B cell malignancies, which are mostly found in children, account for about 85% of ALL cases and manifest as acute leukemias. The remaining 15% of ALLs originate from precursor T cells and manifest as lymphomas in male adolescents, frequently involving the mediastinum (thymus).
Pathogenesis Molecular
Like all cancers, leukemia develops through a series of steps, and ALL cannot be caused by a single mutation. Roughly 90% of ALLs have chromosomal abnormalities, either structural or numerical.
• Numerical abnormality: Found exclusively in B-ALL, hyperploidy (>50 chromosomes) and hypoploidy are the most prevalent.
• Structural abnormality: The Philadelphia chromosome and other balanced chromosomal translocations are also observed. The majority of chromosomal defects dysregulate transcription factors important in the proper development of B and T lymphocytes in terms of both expression and function.
T-ALLs: Gain-of-function mutations in NOTCH1, a gene essential for T cell development, are present in the majority of T-ALLs.
B-ALLs, as seen in Table 20.7: The majority of B-ALLs are caused by loss-of-function mutations in the B cell development-related genes PAX5, E2A, and EBF, or by a balanced translocation t(12;21) involving the RUNX1 (AML1) and ETV6 (TEL) genes (needed in very early hematopoietic precursors).
These mutations cause lymphoid precursors to proliferate without maturing.
The majority of chromosomal abnormalities in ALL change how transcription factors work. A constitutively active BCR-ABL1 tyrosine kinase is encoded by the fusion gene t(9;22) in B-ALL (see Chapter 25). The gene product is a 190 kDa protein. Compared to the BCR-ABL1product protein, which is 210 kDa in size and seen in chronic myelogenous leukemia, this has more tyrosine kinase activity.
Acute Lymphoblastic Leukemia Classification
Clinical Characteristics
Age and Sex: The most prevalent hematological cancer in children is ALL. The most prevalent age range is 1 to 5 years old, and the second peak occurs in adults between the ages of 30 and 40. There's a small male majority.
Start: Sudden.
Symptoms: As a result of blast infiltration, they are associated with decreased marrow function. This covers symptoms brought on by thrombocytopenia, neutropenia, and anemia. Acute leukemia's main characteristics (see pages 154–156) are not the only symptoms that ALL may exhibit.
• Lymphadenopathy: 75 percent of patients have it.
• Hepatosplenomegaly: Compared to hepatatomegaly, splenomegaly is more prevalent.
• Mediastinal mass: Airways and blood arteries in the mediastinum may be compressed by a mediastinal thymic mass.
• Involvement of the central nervous system: more common in ALL (pre-B) patients, it may expand into the meninges.
• Enlarged testicles.
Results of the Lab
• Total WBC count: There is a noticeable increase in the total white cell count, which ranges from 20 × 109 /L to 200 × 109 /L. In rare instances, the count can be lower or even normal.
Subleukemic leukemia is identified by a peripheral blood blast count of less than 4 × 109 /L and a total white cell count below 4 × 109 /L.
- Aleukemic leukemia: When there are no blasts in the peripheral blood and a low total white cell count (< 4 × 109 /L), the condition is referred to as aleukemic leukemia.
In such circumstances, a bone marrow examination that shows 20% or more blast cells is necessary for the diagnosis.
Hemoglobin: It can drop to as low as 3 g/dL and does so gradually.
- RBCs: They exhibit anemia of the normocytic normochromic type.
- WBCs: The overall count typically rises noticeably. Few people with pancytopenia may show up.
Normal myeloid series may be replaced by blasts, which can result in neutropenia. ◆ Lymphoblasts: 20% of them must be present to meet WHO diagnostic criteria.
blasts or higher. Markers specific to lymphocytes are needed to distinguish between B and T cells morphologically.
◆ Lymphoblast morphology (in B- and T-ALL):
◊ Dimensions: Greater than little lymphocyte Elevated ratio of nucleus to cytoplasm
◊ Nucleus: Condensed chromatin is visible. There are either no nucleoli or very few, and they are frequently surrounded by a rim of condensed chromatin. The Nuclear membrane is extensively split, giving the appearance of being twisted.
◊ Cytoplasm: Scant to moderate basophils with granular structure.
It is important to distinguish between myeloblasts and lymphoblasts.
• Platelets: Skin and mucosal bleeding is frequently caused by thrombocytopenia.
Lymphoblast cytochemistry
Block positivity, as seen by cytoplasmic clumps of PAS-positive material, is demonstrated by the Periodic Acid-Schiff (PAS) stain.
• Lack of myeloperoxidase.
• Sudan black B negative.
Bone Marrow
• Cellularity: The multiplication of blasts, which replace healthy hematopoietic cells, has caused the bone marrow to become noticeably hypercellular.
• Reduced myelopoiesis and erythropoiesis.
• Megakaryocytes progressively decrease throughout megakaryopoiesis.
Blasts: These cells make up 20–100% of the marrow. The French-American-British (FAB) classification system describes lymphoblasts morphologically as L1, L2, and L3.
Phenotyping of immune responses
Pre-B and pre-T lymphoblasts express a specific DNA polymerase known as deoxynucleotidyl-transferase (TdT), which is positive in more than 95% of ALL cases.
Lineage-specific markers are necessary to distinguish between ALLs originating from T cells and precursor B cells.
- B-ALLs are stopped at different points in the pre-B cell developmental process. The pan B cell marker CD19, the transcription factor PAX5, and CD10 (CALLA—common ALL antigen) are expressed by immature B cells, also known as lymphoblasts. B-ALLs that are very immature are CD10 negative. more developed "late pre-B." CD10, CD19, CD20, and the cytoplasmic IgM heavy chain (μ chain) are expressed by ALLs.
- T-ALLs are stopped in their pre-T cell development at different phases. All T cells with precursor characteristics express CD1, CD2, CD3, CD5, and CD7.
