Splenic marginal zone lymphoma
Encyclopedia
Splenic marginal zone lymphoma (SMZL) is a lymphoma
made up of B-cells that replace the normal architecture of the white pulp of the spleen
. The neoplastic cells are both small lymphocytes and larger, transformed blasts, and they invade the mantle zone
of splenic follicles and erode the marginal zone
, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar
lymph nodes are involved along with the peripheral blood
. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.
is seen in almost all patients, commonly without lymphadenopathy. Aside from the uniform involvement of the spleen
, the bone marrow
is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.
Circulating lymphoma
cells are sometimes present in peripheral blood
, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.
Autoimmune thrombocytopenia and anemia
sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral blood
samples. A monoclonal
paraprotein
is detected in a third of patients without hypergammaglobulinemia
or hyperviscosity.
Reactive germinal centers in splenic white pulp are replaced by small neoplastic lymphocytes that efface the mantle zone
and ultimately blend in with the marginal zone
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, and plasmacytic differentiation of neoplastic cells.
Involved hilar lymph nodes adjacent to the spleen
show an effaced architecture without preservation of the marginal zone
seen in the spleen.
SMZL in bone marrow
displays a nodular pattern with morphology similar to what is observed in the splenic hilar
lymph nodes.
The relevant markers that define the immunophenotype for SMZL are shown in the table to the right.
The lack of CD5
expression is helpful in the discrimination between SMZL and chronic lymphocytic leukemia
/small lymphocytic lymphoma, and the lack of CD10 expression argues against follicular lymphoma
. Mantle cell lymphoma
is excluded due to the lack of CD5
and cyclin-D1 expression.
The deletion 7q21-32 is seen in 40% of SMZL patients, and translocations of the CDK6 gene located at 7q21 have also been reported.
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
made up of B-cells that replace the normal architecture of the white pulp of the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
. The neoplastic cells are both small lymphocytes and larger, transformed blasts, and they invade the mantle zone
Mantle zone
The mantle zone of a lymphatic nodule is an outer ring of small lymphocytes surrounding a germinal center.It is also known as the "corona".It contains transient lymphocytes....
of splenic follicles and erode the marginal zone
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. A marginal zone also exists in lymph nodes.-Composition and markers:It is composed of cells derived...
, ultimately invading the red pulp of the spleen. Frequently, the bone marrow and splenic hilar
Hilum (anatomy)
In human anatomy, the hilum is a depression or fissure where structures such as blood vessels and nerves enter an organ.-Examples of hila:* Hilum of kidney, admits the renal artery, vein, ureter, and nerves...
lymph nodes are involved along with the peripheral blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. The neoplastic cells circulating in the peripheral blood are termed villous lymphocytes due to their characteristic appearance.
Synonyms
Under older classification systems, the following names were used:| Classification system | Name |
|---|---|
| Rappaport | well-differentiated lymphocytic lymphoma |
| Lukes-Collins | small lymphocytic lymphoma |
| Working Formulation | small lymphocytic lymphoma |
| FAB | splenic lymphoma with circulating villous lymphocytes |
Cause
The cell of origin is postulated to be a post-germinal center B-cell with an unknown degree of differentiation.Diagnosis
With splenic involvement a requirement for a diagnosis of SMZL, splenomegalySplenomegaly
Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant of the human abdomen. It is one of the four cardinal signs of hypersplenism, some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any...
is seen in almost all patients, commonly without lymphadenopathy. Aside from the uniform involvement of the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
is frequently positive in patients with SMZL. Nodal and extranodal involvement are rare.
Circulating lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
cells are sometimes present in peripheral blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, and they occasionally show short villi at the poles of cells and plasmacytoid differentiation.
Autoimmune thrombocytopenia and anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
sometimes seen in patients with SMZL. Circulating villous lymphocytes are sometimes observed in peripheral blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
samples. A monoclonal
Monoclonal
Monoclonal cells are defined as a group of cells produced from a single ancestral cell by repeated cellular replication. Thus they can be said to form a single "clone". The process of replication can occur in vivo, or may be stimulated in vitro for laboratory manipulations...
paraprotein
Paraprotein
A paraprotein is an immunoglobulin or immunoglobulin light-chain that is produced in excess by the clonal proliferation of plasma cells. Detection of paraproteins in the urine or blood is most often associated with benign MGUS , where they remain "silent", and multiple myeloma. An excess in the...
is detected in a third of patients without hypergammaglobulinemia
Hypergammaglobulinemia
Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin.It is a type of immunoproliferative disorder.- Types :...
or hyperviscosity.
Reactive germinal centers in splenic white pulp are replaced by small neoplastic lymphocytes that efface the mantle zone
Mantle zone
The mantle zone of a lymphatic nodule is an outer ring of small lymphocytes surrounding a germinal center.It is also known as the "corona".It contains transient lymphocytes....
and ultimately blend in with the marginal zone
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. A marginal zone also exists in lymph nodes.-Composition and markers:It is composed of cells derived...
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
Sinus (anatomy)
Sinus is Latin for "bay", "pocket", "curve", or "bosom". In anatomy, the term is used in various contexts.A sinus is a sack or cavity in any organ or tissue, or an abnormal cavity or passage caused by the destruction of tissue...
invasion, epithelial histocytes, and plasmacytic differentiation of neoplastic cells.
Involved hilar lymph nodes adjacent to the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
show an effaced architecture without preservation of the marginal zone
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. A marginal zone also exists in lymph nodes.-Composition and markers:It is composed of cells derived...
seen in the spleen.
SMZL in bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
displays a nodular pattern with morphology similar to what is observed in the splenic hilar
Hilum (anatomy)
In human anatomy, the hilum is a depression or fissure where structures such as blood vessels and nerves enter an organ.-Examples of hila:* Hilum of kidney, admits the renal artery, vein, ureter, and nerves...
lymph nodes.
Immunophenotype
| Antigen | Status |
|---|---|
| CD20 CD20 B-lymphocyte antigen CD20 or CD20 is an activated-glycosylated phosphoprotein expressed on the surface of all B-cells beginning at the pro-B phase and progressively increasing in concentration until maturity.... |
Positive |
| CD79a CD79A CD79a molecule, immunoglobulin-associated alpha, also known as mb-1, is a human gene.The mb-1 gene codes for a phosphoprotein, designated CD79a CD79a molecule, immunoglobulin-associated alpha, also known as mb-1, is a human gene.The mb-1 gene codes for a phosphoprotein, designated CD79a CD79a... |
Positive |
| CD5 CD5 (protein) CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive... |
Negative |
| CD10 | Negative |
| CD23 CD23 CD23, also known as Fc epsilon RII, or FcεRII, is the "low-affinity" receptor for IgE, an antibody isotype involved in allergy and resistance to parasites, and is important in regulation of IgE levels. Unlike many of the antibody receptors, CD23 is a C-type lectin... |
Negative |
| CD43 CD43 Leukosialin also known as sialophorin or CD43 is a transmembrane cell surface protein that in humans is encoded by the SPN gene.- Function :... |
Negative |
| cyclin D1 Cyclin D1 G1/S-specific cyclin-D1 is a protein that in humans is encoded by the CCND1 gene.Immunohistochemical staining of cyclin D1 antibodies is used to diagnose mantle cell lymphoma.-Interactions:... |
Negative |
The relevant markers that define the immunophenotype for SMZL are shown in the table to the right.
The lack of CD5
CD5 (protein)
CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive...
expression is helpful in the discrimination between SMZL and chronic lymphocytic leukemia
Chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
/small lymphocytic lymphoma, and the lack of CD10 expression argues against follicular lymphoma
Follicular lymphoma
Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second most common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells , which has at least a partially follicular pattern...
. Mantle cell lymphoma
Mantle cell lymphoma
Mantle cell lymphoma is one of the rarest of the non-Hodgkin's lymphomas , comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. While it is difficult to treat and seldom considered cured, investigations into better treatments are actively pursued worldwide...
is excluded due to the lack of CD5
CD5 (protein)
CD5 is a cluster of differentiation found on a subset of IgM-secreting B cells called B-1 cells, and also on T cells. B-1 cells have limited diversity of their B-cell receptor due to their lack of the enzyme terminal deoxynucleotidyl transferase and are potentially self-reactive...
and cyclin-D1 expression.
Genetics
Clonal rearrangements of the immunoglobulin 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.