*6.2.2 Highlights in recent WHO classification*

Cytopenias or disease-related symptoms are now insufficient to make a diagnosis of CLL with <5 × 109 /L PB CLL cells.

#### **Figure 2.**

*Small lymphocytic lymphoma showing diffuse effacement by small lymphoid cells.*

Large/confluent and/or highly proliferative proliferation centres are adverse prognostic indicators [24, 41–44].

Mutations of potential clinical relevance, such as TP53 (tumor protein 53), NOTCH1 (*Notch* homolog *1*), SF3B1 (Splicing Factor 3b Subunit 1), ATM (Ataxia telangiectasia mutated), and BIRC3 (Baculoviral IAP repeat-containing protein 3), have been recognized

#### *6.2.3 Treatment and prognosis*

The treatment, course and prognosis depend primarily on the clinical stage. Median survival is 4–6 years but can be more than 10 years in those with minimal tumor burdens. Factors associated with worse outcome include (1) deletions of 11q and 17p, (2) lack of somatic hypermutation, (3) expression of ZAP-70(z-chainassociated protein kinase), and (4) presence of NOTCH1 mutations. CLL also have the risk of transformation into diffuse large B -cell lymphoma [1, 25]. Symptomatic patients are generally treated with "gentle" chemotherapy and immunotherapy with antibodies against proteins found on the surface of CLL/SLL cells, particularly CD20. Hematopoietic stem cell transplantation is being offered to the relatively young. The most promising new therapy is Bruton's tyrosine kinase (BTK) inhibitors [1, 25].

#### **6.3 Follicular lymphoma**

Follicular lymphoma (FL) is the most common form of indolent NHL. It usually presents in middle age and afflicts males and females equally. Follicular lymphoma likely arises from germinal center B cells and is strongly associated with chromosomal translocations involving BCL2 (B-cell lymphoma 2). Its hallmark is a (14; 18) translocation that juxtaposes the IGH locus on chromosome 14 and the BCL2 locus on chromosome 18. The t (14; 18) is seen in up to 90% of follicular lymphomas and leads to overexpression of BCL2. Follicular lymphoma tends to present with painless, generalized lymphadenopathy. Involvement of extranodal sites, such as the gastrointestinal tract, central nervous system, or testis, is relatively uncommon [1, 25, 45, 46].

**55**

**Figure 3.**

*showing BCL2 positivity.*

*B-Cell Lymphomas*

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

*6.3.1 Morphology and immunophenotype*

*6.3.2 Highlights in recent WHO classification*

peutic approach may be sufficient.

determined [24, 47–51].

In situ follicular neoplasia.

lymphoma.

*6.3.3 Pediatric-type FL*

Follicular lymphoma usually shows effacement of nodal architecture by follicular nodules that occupy both cortex and the medulla with two cell types in varying proportions: (1) Centrocytes which are small cells with irregular or cleaved nucleus and scant cytoplasm (2) Centroblasts which are larger cells with open nuclear chromatin, several prominent nucleoli, and modest amounts of cytoplasm. Based on the number of these centroblasts FL is classified into Grade 1, 2, and 3a,b. Grade 1 follicular lymphomas have 0–5 centroblasts per HPF; 6–15 centroblasts per HPF as grade 2, and greater than 15 per HPF as grade 3 follicular lymphomas. Low-grade (grades 1 and 2) follicular lymphomas are composed of a relatively homogeneous population of small cleaved lymphocytes. Grade 3 follicular lymphomas, which by definition have an increased number of large noncleaved cells and have been provisionally subcategorized into 3a and 3b, with the former having a mix of cleaved and large noncleaved cells, and the latter having sheets or large clusters of large noncleaved cells Peripheral blood involvement is seen in about 10% of cases. Bone marrow involvement occurs in 85% of cases and characteristically takes the form of paratrabecular lymphoid aggregates. The neoplastic cells express CD19, CD20, CD10, surface Ig, and BCL6 (B-cell lymphoma 6). BCL2 is expressed in more than

90% of cases. CD5 and cyclin D1 are negative. Ki67 is low [25] (**Figure 3**).

• Mutational landscape better understood but the clinical impact remains to be

• New name for in situ follicular lymphoma reflects low risk of progression to

• A localized clonal proliferation with excellent prognosis; a conservative thera-

• Occurs in children and young adults, rarely in older individuals.

*Follicular lymphoma showing nodular pattern with neoplastic follicles occupying cortex and medulla and* 

*Normal and Malignant B-Cell*

**Figure 2.**

prognostic indicators [24, 41–44].

have been recognized

*6.2.3 Treatment and prognosis*

**6.3 Follicular lymphoma**

*Small lymphocytic lymphoma showing diffuse effacement by small lymphoid cells.*

Large/confluent and/or highly proliferative proliferation centres are adverse

Mutations of potential clinical relevance, such as TP53 (tumor protein 53), NOTCH1 (*Notch* homolog *1*), SF3B1 (Splicing Factor 3b Subunit 1), ATM (Ataxia telangiectasia mutated), and BIRC3 (Baculoviral IAP repeat-containing protein 3),

The treatment, course and prognosis depend primarily on the clinical stage. Median survival is 4–6 years but can be more than 10 years in those with minimal tumor burdens. Factors associated with worse outcome include (1) deletions of 11q and 17p, (2) lack of somatic hypermutation, (3) expression of ZAP-70(z-chainassociated protein kinase), and (4) presence of NOTCH1 mutations. CLL also have the risk of transformation into diffuse large B -cell lymphoma [1, 25]. Symptomatic patients are generally treated with "gentle" chemotherapy and immunotherapy with antibodies against proteins found on the surface of CLL/SLL cells, particularly CD20. Hematopoietic stem cell transplantation is being offered to the relatively young. The most promising new therapy is Bruton's tyrosine kinase (BTK) inhibitors [1, 25].

Follicular lymphoma (FL) is the most common form of indolent NHL. It usually presents in middle age and afflicts males and females equally. Follicular lymphoma likely arises from germinal center B cells and is strongly associated with chromosomal translocations involving BCL2 (B-cell lymphoma 2). Its hallmark is a (14; 18) translocation that juxtaposes the IGH locus on chromosome 14 and the BCL2 locus on chromosome 18. The t (14; 18) is seen in up to 90% of follicular lymphomas and leads to overexpression of BCL2. Follicular lymphoma tends to present with painless, generalized lymphadenopathy. Involvement of extranodal sites, such as the gastrointestinal tract, central nervous system, or testis, is relatively uncommon [1,

**54**

25, 45, 46].
