**6. 2016 WHO classification of B lymphoid neoplasms**

The current WHO classification uses morphologic, immunophenotypic, genotypic, and clinical features to classify the lymphoid neoplasms into five broad categories as precursor B-cell neoplasms, peripheral B-cell neoplasms, precursor T-cell neoplasms, peripheral T-cell neoplasms and Hodgkin lymphoma. Hodgkin lymphoma though originates from B-cell has distinctive pathologic features and is treated as a separate entity (**Table 1**).

The WHO classification distinguishes two major categories within B-cell lymphomas:

a.Precursor B-cell neoplasms

b.Mature B-cell neoplasms

#### **6.1 Precursor B-cell neoplasms**

Acute lymphoblastic leukemia/lymphoma (ALLs) are neoplasms composed of immature B (pre-B) which are referred to as lymphoblasts. About 85% are B-ALLs, which typically manifest as childhood acute "leukemia." Many of the chromosomal aberrations seen in ALL dysregulate the expression and function of transcription factors required for normal B development. B-ALLs have loss-of-function mutations

**51**

*B-Cell Lymphomas*

*DOI: http://dx.doi.org/10.5772/intechopen.87370*

*6.1.1 Morphology and immunophenotype*

("BCR-ABL1—like ALL").

**WHO classification of B lymphoid neoplasms**

*B-lymphoblastic leukemia/lymphoma* B-lymphoblastic leukemia/lymphoma, NOS

*Mature B-cell neoplasms*

*6.1.3 Treatment and prognosis*

*6.1.2 New provisional entities in recent WHO classification*

B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2);BCR-ABL1 B-lymphoblastic leukemia/lymphoma with t(v;11q23.3);KMT2A rearranged

B-lymphoblastic leukemia/lymphoma with t(5;14)(q31.1;q32.3) IL3-IGH B-lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3);TCF3-PBX1 Provisional entity: B-lymphoblastic leukemia/lymphoma, BCR-ABL1–like Provisional entity: B-lymphoblastic leukemia/lymphoma with iAMP21

lymphoma with hyperdiploidy B-lymphoblastic leukemia/lymphoma with hypodiploidy

in genes that are required for B-cell development, such as Paired Box 5 (PAX5), E2-alpha (E2A), and early B-cell factor (EBF), or a balanced t(12;21) involving the genes translocation-Ets-leukemia virus (ETV6) and Runt Related Transcription Factor 1 (RUNX1), two genes that are needed in very early hematopoietic precursors. All of these varied mutations disturb the differentiation of lymphoid precursors and promote maturation arrest, and in doing they induce increased self-renewal, a stem cell-like phenotype. Approximately 90% of ALLs have numerical or structural chromosomal changes. Most common is hyperploidy (>50 chromosomes), but hypoploidy and a variety of balanced chromosomal translocations are also seen [1, 25, 38]. Patients present with fatigue due to anemia; fever due to infections secondary to neutropenia; and bleeding due to thrombocytopenia. They can so present with mass effects caused by neoplastic infiltration, including bone pain, generalized lymphadenopathy, splenomegaly, hepatomegaly; testicular enlargement; headache, vomiting, and nerve palsies due to central nervous system involvement [1, 25].

In leukemic presentations, the marrow is hypercellular and packed with lymphoblasts, which replace the normal marrow elements, lymphoblasts have more condensed chromatin, less conspicuous nucleoli, and smaller amounts of cytoplasm that usually lacks granules. Histochemical stains show periodic acid-Schiff–positive cytoplasmic material. Immunostaining for terminal deoxynucleotidyl transferase (TdT), is positive in more than 95% of cases in addition to B-cell markers. B-ALLs are arrested at various stages of development. The lymphoblasts usually express the pan B-cell marker CD19/CD22/CD79a and the transcription factor PAX5. CD10 is expressed in common ALL and pre-B ALLs express in addition cytoplasmic IgM heavy chain (μ chain) and surface immunoglobulins in mature forms (**Figure 1**).

• B-ALL with intrachromosomal amplification of chromosome 21 [24, 39, 40].

• B-ALL with translocations involving tyrosine kinases or cytokine receptors

Treatment includes chemotherapy, steroids, radiation therapy and marrow transplantation. About 95% of children obtain a complete remission, and 75–85% are cured

B-lymphoblastic leukemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1 B-lymphoblastic leukemia/

#### *B-Cell Lymphomas DOI: http://dx.doi.org/10.5772/intechopen.87370*

*Normal and Malignant B-Cell*

**5. Investigations**

creatinine, calcium, and albumin.

kin-2 receptor, tumor necrosis factor).

treated as a separate entity (**Table 1**).

a.Precursor B-cell neoplasms

b.Mature B-cell neoplasms

**6.1 Precursor B-cell neoplasms**

abdominal symptoms.

sive therapy.

lymphoid tumors are frequently caused by proteins secreted from the tumor cells or from immune cells that are responding to the tumor. Specific examples include the plasma cell tumors, in which much of the pathophysiology is related to the secretion of whole antibodies or Ig fragments; Significant cytopenias are rare, unless marrow involvement is extensive, or there are associated immune-mediated cytopenias, hypersplenism, or, rarely, hemophagocytosis. Hepatosplenomegaly is a common feature of advanced low-grade B-cell lymphoma. Bleeding manifestations are common in lymphoblastic lymphomas/leukemia with marrow involvement [1, 2].

Complete history and physical examination; inquiry about B symptoms, human immunodeficiency virus risk, infections, autoimmune diseases, immunosuppres-

Complete blood cell count and peripheral smear examination including hemo-

Biochemistry profile—lactate dehydrogenase; alkaline phosphatase, uric acid,

Imaging—computed tomography of chest, abdomen, pelvis, and neck, Selected

radiologic procedures as clinically appropriate (e.g., gallium, positron emission tomography scan, magnetic resonance imaging, ultrasound, bone scan).

Bone marrow aspiration and biopsy—morphology, immunophenotyping,

Gastrointestinal endoscopy for patients with Waldeyer ring involvement or

The current WHO classification uses morphologic, immunophenotypic, genotypic, and clinical features to classify the lymphoid neoplasms into five broad categories as precursor B-cell neoplasms, peripheral B-cell neoplasms, precursor T-cell neoplasms, peripheral T-cell neoplasms and Hodgkin lymphoma. Hodgkin lymphoma though originates from B-cell has distinctive pathologic features and is

Cytologic assessment of third space fluids (pleura, peritoneum) in case of effusions. Other blood evaluations: levels of ß 2-microglobulin and cytokines (interleu-

The WHO classification distinguishes two major categories within B-cell lymphomas:

Acute lymphoblastic leukemia/lymphoma (ALLs) are neoplasms composed of immature B (pre-B) which are referred to as lymphoblasts. About 85% are B-ALLs, which typically manifest as childhood acute "leukemia." Many of the chromosomal aberrations seen in ALL dysregulate the expression and function of transcription factors required for normal B development. B-ALLs have loss-of-function mutations

Lumbar puncture with cytology in patients with CNS involvement.

globin, total leukocyte count with differential and platelet count.

cytogenetics, molecular tests, and gene rearrangement studies.

**6. 2016 WHO classification of B lymphoid neoplasms**

**50**

in genes that are required for B-cell development, such as Paired Box 5 (PAX5), E2-alpha (E2A), and early B-cell factor (EBF), or a balanced t(12;21) involving the genes translocation-Ets-leukemia virus (ETV6) and Runt Related Transcription Factor 1 (RUNX1), two genes that are needed in very early hematopoietic precursors. All of these varied mutations disturb the differentiation of lymphoid precursors and promote maturation arrest, and in doing they induce increased self-renewal, a stem cell-like phenotype. Approximately 90% of ALLs have numerical or structural chromosomal changes. Most common is hyperploidy (>50 chromosomes), but hypoploidy and a variety of balanced chromosomal translocations are also seen [1, 25, 38].

Patients present with fatigue due to anemia; fever due to infections secondary to neutropenia; and bleeding due to thrombocytopenia. They can so present with mass effects caused by neoplastic infiltration, including bone pain, generalized lymphadenopathy, splenomegaly, hepatomegaly; testicular enlargement; headache, vomiting, and nerve palsies due to central nervous system involvement [1, 25].
