**6.5 Marginal zone lymphomas**

Marginal zone lymphoma (MZL) is a group of B-cell tumors that arise from lymph nodes, spleen, or extranodal tissues. In most cases, there is evidence of somatic hypermutation of memory B-cell origin. The disease begins as a polyclonal immune reaction. With time, however, tumors may acquire additional mutations that render their growth and survival antigen-independent, such as the (11; 18), (14; 18), or (1; 14) chromosomal translocations, which are relatively specific for extranodal marginal zone lymphomas [1, 25].

### *6.5.1 Nodal marginal zone B-cell lymphoma*

Nodal marginal zone B-cell lymphomas are uncommon lymphomas in which the tumor cells resemble the cytology of those in splenic and extranodal marginal zone B-cell lymphomas of MALT, but there is no evidence for splenic or extranodal disease. Clinically, these lymphomas appear more extensive at presentation than

MALT lymphomas. They have a tendency to early relapse, and a small minority transform to large cell lymphoma.

#### *6.5.2 Splenic marginal zone B-cell lymphoma*

Splenic marginal zone B-cell lymphoma (SMZL) is a small B-cell lymphoma of the white pulp of the spleen that often involves the splenic hilar lymph nodes, bone marrow, and peripheral blood. Patients with splenic marginal zone B-cell lymphoma characteristically present with splenomegaly and many have B-symptoms (fever, weight loss, and night sweats). Peripheral blood shows circulating neoplastic lymphocytes that have a villous appearance. These cases were previously termed 'splenic lymphoma with villous lymphocytes'.

### *6.5.3 Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue*

Extranodal marginal zone B-cell lymphomas arises in normal sites for mucosal immunity (MALT), such as intestinal Peyer patches, or in sites of inflammation triggered by autoimmune disorders, such as Hashimoto thyroiditis or Sjögren syndrome, or by infection (*Helicobacter pylori*-associated chronic gastritis. They may regress if the inciting agent (e.g., *Helicobacter pylori*) is eradicated suggesting that extranodal marginal zone lymphomas arise in chronically inflamed tissues that lie on a continuum between reactive lymphoid hyperplasia and full-blown lymphoma. Transformation to large cell lymphoma may occur. The t(11; 18) chromosomal abnormality is more specific and involves fusion of the API2 gene (an apoptosis inhibitor) on chromosome 11q21 and the MLT1 gene (a caspase-like protease) on chromosome 18q21. It is found in 40% of patients with MALT lymphomas. Two, less common, translocations are t(1; 14) (p22; q32) and t(14; 18) (q32; 21). These three translocations are not found in marginal zone B-cell lymphomas of spleen and lymph node.

#### *6.5.4 Morphology and immunophenotype*

These lymphomas are composed of small- to medium-sized lymphocytes that exhibit variable cytological features. In some cases, lymphocytes with irregular nuclear contours resembling follicular small cleaved cells or centrocytes may predominate. Other cases may be composed primarily of cells with abundant pale cytoplasm resembling monocytoid B cells. Cases with an abundance of small lymphocytes or plasma cells also may be seen. Regardless of the neoplastic cells' appearance, they produce a diffuse infiltrate that invades epithelial structures, producing lymphoepithelial lesions (**Figure 5**).

The lymphoid component expresses B-cell markers such as CD20, CD19 and CD43 and monotypic surface Ig (usually IgM without IgD). Negative for CD5, CD10, CYCLIN D1, and CD23.

#### *6.5.5 Treatment and prognosis*

Management of gastric MALToma with antibiotic therapy for *H. pylori* resulted in regression of lymphoma. Cases with the t(11;18)(q21;q21) appear to be resistant to *H. pylori* eradication therapy, Radiation therapy or single-agent chemotherapy is also effective in low-grade MALToma. MALT lymphomas have an indolent natural course and are slow to disseminate. Recurrences that can occur after many years. Median survival has been variable. SMZL tends to respond favorably to splenectomy alone in contrast to its poor response to chemotherapy [1, 25].

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*B-Cell Lymphomas*

**Figure 5.**

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

**6.6 Lymphoplasmacytic lymphoma**

*Extranodal marginal zone lymphoma of stomach showing lymphoepithelial lesions.*

*6.6.1 Morphology and immunophenotype*

usually IgM but can also be IgG or IgA (**Figure 6**).

criteria even though finding is not specific for LPL [24, 55, 56].

closely related to LPL and other B-cell lymphomas than to myeloma.

*6.6.2 Highlights in recent WHO classification*

*6.6.3 Treatment and prognosis*

Lymphoplasmacytic lymphoma is a B-cell neoplasm of older adults that usually presents in the sixth or seventh decade of life and is characterized by tumor cells that undergo terminal differentiation to plasma cells. Most commonly, the plasma cell component secretes monoclonal IgM, often in amounts sufficient to cause a hyperviscosity syndrome known as Waldenström macroglobulinemia. Unlike multiple myeloma, complications stemming from the secretion of free light chains (e.g., renal failure and amyloidosis) are relatively rare and bone destruction does not occur. About 90% of Lymphoplasmacytic lymphoma are associated with acquired mutations in Myeloid differentiation factor 88 (MYD88) [55, 56]. The dominant presenting complaints are nonspecific and include weakness, fatigue, and weight loss. Approximately half the patients have lymphadenopathy, hepatomegaly, and splenomegaly. Anemia caused by marrow infiltration is common. About 10% of patients have autoimmune hemolysis caused by cold agglutinins. Cryoglobulinemia resulting from the precipitation of macroglobulins at low temperatures, which produces symptoms such as Raynaud phenomenon and cold urticaria [1, 25].

The neoplasm is composed of infiltration of lymphocytes, plasma cells, and plasmacytoid lymphocytes in varying proportions, often accompanied by mast cell hyperplasia. The lymphoid cells expresses CD20 and surface Ig, the plasma cells secretes the same Ig that is expressed on the surface of the lymphoid cells. This is

MYD88 L265P mutation in the vast majority of cases impacting diagnostic

LPL is an incurable progressive disease, however the tumor growth can be controlled with low doses of chemotherapy and immunotherapy with anti-CD20 antibody. Symptoms caused by the high IgM levels like hyperviscosity and hemolysis can be alleviated by plasmapheresis. The clinical course is typically indolent,

IgM monoclonal gammopathy of undetermined significance (MGUS) is more

*Normal and Malignant B-Cell*

*tissue*

transform to large cell lymphoma.

*6.5.2 Splenic marginal zone B-cell lymphoma*

'splenic lymphoma with villous lymphocytes'.

*6.5.4 Morphology and immunophenotype*

lymphoepithelial lesions (**Figure 5**).

CD10, CYCLIN D1, and CD23.

*6.5.5 Treatment and prognosis*

MALT lymphomas. They have a tendency to early relapse, and a small minority

*6.5.3 Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid* 

Extranodal marginal zone B-cell lymphomas arises in normal sites for mucosal immunity (MALT), such as intestinal Peyer patches, or in sites of inflammation triggered by autoimmune disorders, such as Hashimoto thyroiditis or Sjögren syndrome, or by infection (*Helicobacter pylori*-associated chronic gastritis. They may regress if the inciting agent (e.g., *Helicobacter pylori*) is eradicated suggesting that extranodal marginal zone lymphomas arise in chronically inflamed tissues that lie on a continuum between reactive lymphoid hyperplasia and full-blown lymphoma. Transformation to large cell lymphoma may occur. The t(11; 18) chromosomal abnormality is more specific and involves fusion of the API2 gene (an apoptosis inhibitor) on chromosome 11q21 and the MLT1 gene (a caspase-like protease) on chromosome 18q21. It is found in 40% of patients with MALT lymphomas. Two, less common, translocations are t(1; 14) (p22; q32) and t(14; 18) (q32; 21). These three translocations are not found in marginal zone B-cell lymphomas of spleen and lymph node.

These lymphomas are composed of small- to medium-sized lymphocytes that exhibit variable cytological features. In some cases, lymphocytes with irregular nuclear contours resembling follicular small cleaved cells or centrocytes may predominate. Other cases may be composed primarily of cells with abundant pale cytoplasm resembling monocytoid B cells. Cases with an abundance of small lymphocytes or plasma cells also may be seen. Regardless of the neoplastic cells' appearance, they produce a diffuse infiltrate that invades epithelial structures, producing

The lymphoid component expresses B-cell markers such as CD20, CD19 and CD43 and monotypic surface Ig (usually IgM without IgD). Negative for CD5,

Management of gastric MALToma with antibiotic therapy for *H. pylori* resulted in regression of lymphoma. Cases with the t(11;18)(q21;q21) appear to be resistant to *H. pylori* eradication therapy, Radiation therapy or single-agent chemotherapy is also effective in low-grade MALToma. MALT lymphomas have an indolent natural course and are slow to disseminate. Recurrences that can occur after many years. Median survival has been variable. SMZL tends to respond favorably to splenec-

tomy alone in contrast to its poor response to chemotherapy [1, 25].

Splenic marginal zone B-cell lymphoma (SMZL) is a small B-cell lymphoma of the white pulp of the spleen that often involves the splenic hilar lymph nodes, bone marrow, and peripheral blood. Patients with splenic marginal zone B-cell lymphoma characteristically present with splenomegaly and many have B-symptoms (fever, weight loss, and night sweats). Peripheral blood shows circulating neoplastic lymphocytes that have a villous appearance. These cases were previously termed

**58**

**Figure 5.** *Extranodal marginal zone lymphoma of stomach showing lymphoepithelial lesions.*
