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 b ...

(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 enlar ...

) made up of B-cells 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 ti ...

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 A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...

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 The mantle zone (or just mantle) of a lymphatic nodule (or lymphatic follicle) is an outer ring of small lymphocytes surrounding a germinal center. It is also known as the "corona". It contains transient lymphocytes. It is the location of th ...

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 to ...

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

hilar Hilum may refer to: * Hilum (anatomy), a part of an organ where structures such as blood vessels and nerves enter the body * Hilum (botany), a scar on a seed or spore created by detachment See also * Fovea (disambiguation), another term associat ...

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 includ ...

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 the c ...

. The neoplastic cells circulating in the peripheral blood are termed

villous lymphocytes Villus ( la, "shaggy hair", plural villi) may refer to: * Intestinal villus, refers to any one of the small, finger-shaped outgrowths of the epithelial lining of the wall of the intestine. Clusters of projections are referred as intestinal villi. ...

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 ( hepato ...

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, nigh ...

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 ...

, and the lack of

CD10 Neprilysin (), also known as membrane metallo-endopeptidase (MME), neutral endopeptidase (NEP), cluster of differentiation 10 (CD10), and common acute lymphoblastic leukemia antigen (CALLA) is an enzyme that in humans is encoded by the ''MME'' ge ...

expression argues against

follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. The cancer originates from the uncontrolled division of specific types of B-cells known as centrocytes and centroblasts. These cells normal ...

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 n ...

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 hematopoietic ce ...

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 Immune thrombocytopenic purpura (ITP), also known as idiopathic thrombocytopenic purpura or immune thrombocytopenia, is a type of thrombocytopenic purpura defined as an isolated low platelet count with a normal bone marrow in the absence of othe ...

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, th ...

sometimes seen in patients with SMZL. Circulating

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 myelom ...

is detected in a third of patients without

hypergammaglobulinemia Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin. It is a type of immunoproliferative disorder. Types Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunogl ...

hyperviscosity Hyperviscosity syndrome is a group of symptoms triggered by an increase in the viscosity of the blood. Symptoms of high blood viscosity include spontaneous bleeding from mucous membranes, visual disturbances due to retinopathy, and neurologic sympt ...

Reactive germinal centers Reactive may refer to: *Generally, capable of having a reaction (disambiguation) *An adjective abbreviation denoting a bowling ball coverstock made of reactive resin *Reactivity (chemistry) *Reactive mind *Reactive programming See also *Reactanc ...

in splenic

are replaced by small neoplastic

that efface the

and ultimately blend in with the

with occasional larger neoplastic cells that resemble

blasts In cell biology, a precursor cell, also called a blast cell or simply blast, is a partially differentiated cell, usually referred to as a unipotent cell that has lost most of its stem cell properties. A precursor cell is also known as a pro ...

. The

red pulp The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorgani ...

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 Sinus may refer to: Anatomy * Sinus (anatomy), a sac or cavity in any organ or tissue ** Paranasal sinuses, air cavities in the cranial bones, especially those near the nose, including: *** Maxillary sinus, is the largest of the paranasal sinuses, ...

invasion, epithelial histocytes, 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

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 on ...

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