Splenic marginal zone lymphoma (SMZL) is a type of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...

(specifically a

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...

) made up of

B-cells B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

that replace the normal architecture of the

white pulp White pulp is a histological designation for regions of the spleen (named because it appears whiter than the surrounding red pulp on gross section), that encompasses approximately 25% of splenic tissue. White pulp consists entirely of lymphoid ...

of the

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

. The neoplastic cells are both small lymphocytes and larger, transformed

lymphoblast __NOTOC__ A lymphoblast is a modified naive lymphocyte with altered cell morphology. It occurs when the lymphocyte is activated by an antigen (from antigen-presenting cells) and increased in volume by nucleus and cytoplasm growth as well as new mRN ...

s, and they invade the mantle zone of splenic follicles and erode the

marginal zone The marginal zone is the region at the interface between the non-lymphoid red pulp and the lymphoid white-pulp of the spleen. (Some sources consider it to be the part of red pulp which borders on the white pulp, while other sources consider it t ...

, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar

lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that incl ...

are involved along with the peripheral

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...

. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.

Cause

The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation. SMZL is a form of

known to be associated with

Hepatitis C virus The hepatitis C virus (HCV) is a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus of the family '' Flaviviridae''. The hepatitis C virus is the cause of hepatitis C and some cancers such as liver cancer (hepatoc ...

infection.

Molecular biology

Immunophenotype

The relevant markers that define the immunophenotype for SMZL are shown in the adjacent table. The lack of CD5 expression is helpful in the discrimination between SMZL and

chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, n ...

small lymphocytic lymphoma Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). Early on, there are typically no symptoms. Later, non-painful lymph node swelling, feeling tired, fever, nig ...

, and the lack of CD10 expression argues against follicular lymphoma.

Mantle cell lymphoma Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma (NHL), comprising about 6% of NHL cases. There are only about 15,000 patients presently in the United States with mantle cell lymphoma. It is named for the mantle zone of the lymph ...

is excluded due to the lack of CD5 and cyclin-D1 expression.

Genetics

Clonal rearrangements of the

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

genes (heavy and light chains) are frequently seen. The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported.

Diagnosis

Enlargement of the spleen is a requirement for the diagnosis of SMZL and is seen in nearly all people affected by SMZL (often without lymphadenopathy). Aside from the uniform involvement of the

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, the

bone marrow Bone marrow is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoieti ...

is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare. Circulating

cells are sometimes present in peripheral

, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation. Autoimmune thrombocytopenia and

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...

sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral

samples. A

monoclonal Monoclonality refers to the state of a line of cells that have been derived from a single clonal origin. Thus "monoclonal cells" can be said to form a single clone. The term ''monoclonal'' comes from the Ancient Greek ''monos'', meaning "alone" o ...

paraprotein A myeloma protein is an abnormal antibody (immunoglobulin) or (more often) a fragment thereof, such as an immunoglobulin light chain, that is produced in excess by an abnormal monoclonal proliferation of plasma cells, typically in multiple myelo ...

is detected in a third of patients without hypergammaglobulinemia or hyperviscosity. Reactive germinal centers in splenic

are replaced by small neoplastic lymphocytes that efface the mantle zone and ultimately blend in with the

with occasional larger neoplastic cells that resemble blasts. The red pulp is always involved, with both nodules of larger neoplastic cells and sheets of the small neoplastic lymphocytes. Other features that may be seen include sinus invasion,

epithelial histocytes Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellular ...

, and plasmacytic differentiation of neoplastic cells. Involved hilar

adjacent to the spleen show an effaced architecture without preservation of the marginal zone seen in the spleen. SMZL in

displays a nodular pattern with morphology similar to what is observed in the splenic hilar

Prognosis

Three-quarters of patients survive five or more years; more than half of patients with SMZL survive more than a decade after diagnosis. Patients who have a hemoglobin level of less than 12 g/dL, a

lactate dehydrogenase Lactate dehydrogenase (LDH or LD) is an enzyme found in nearly all living cells. LDH catalyzes the conversion of lactate to pyruvate and back, as it converts NAD+ to NADH and back. A dehydrogenase is an enzyme that transfers a hydride from one ...

level higher than normal, and/or a blood serum

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...

levels of less than 3.5 g/dL are likely to have more an aggressive disease course and a shorter survival. However, even high-risk patients have even odds of living for five years after diagnosis. Some genetic mutations, such as mutations in ''NOTCH2'', are also correlated with shorter survival.

Epidemiology

Less than 1% of all lymphomas are splenic marginal zone lymphomas and it is postulated that SMZL may represent a large fraction of unclassifiable CD5- chronic lymphocytic leukemias. The typical patient is over the age of 50, and gender preference has been described.

Synonyms

Under older classification systems, the following names were used:

References

External links

{{DEFAULTSORT:Splenic Marginal Zone Lymphoma Lymphoma Hepatitis C virus-associated diseases