Chapter12- PERIPHERAL B-CELL NEOPLASMS: Marginal Zone Lymphomas

Question 1

What are Marginal Zone Lymphomas?

Answer 1

The category of marginal zone lymphoma encompasses a heterogeneous group of B-cell tumors that arise within lymph nodes, spleen, or extranodal tissues.

The extranodal tumors were
initially recognized at mucosal sites and are often referred to as mucosa-associated lymphoid
tumors (or “maltomas”).

In most cases, the tumor cells show evidence of somatic hypermutation and are considered to be of memory B-cell origin.

Question 2

Although all marginal zone lymphomas share certain features, those occurring at extranodal
sites deserve special attention because of their unusual pathogenesis and three exceptional
characteristics.

Answer 2

• They often arise within tissues involved by chronic inflammatory disorders of autoimmune or infectious etiology; examples include the salivary gland in Sjögren disease, the thyroid gland in Hashimoto thyroiditis, and the stomach in Helicobacter gastritis.
• • They remain localized for prolonged periods, spreading systemically only late in their course.
• • They may regress if the inciting agent (e.g., Helicobacter pylori) is eradicated .

Question 3

The characteristics suggest that extranodal marginal zone lymphomas arising in chronically
inflamed tissues lie on what?

Answer 3

a continuum between reactive lymphoid hyperplasia and full-blown lymphoma.

Question 4

What is the pahogenesis of tMarginal Zone lymphoma ?

Answer 4

The disease begins as a polyclonal immune reaction.

With the acquisition of stillunknown
initiating mutations, a B-cell clone emerges that still depends on antigen-stimulated

T helper cells for signals that drive growth and survival. At this stage, withdrawal of the
responsible antigen causes tumor involution.

A clinically relevant example is found in gastric
“maltoma,” in which antibiotic therapy directed against H. pylori often leads to tumor regression
( Chapter 17 ).

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.

All of these translocations up-regulate the expression and function of BCL10 or MALT1, protein components of a signaling complex that activates NF-κB and promotes the growth and survival of B cells. [5]

With further clonal evolution, spread to distant sites and transformation to diffuse
large B-cell lymphoma may occur.

This theme of polyclonal to monoclonal transition during lymphomagenesis is also applicable to the pathogenesis of EBV-induced lymphoma and is
discussed more fully in Chapter 7.