Hepatosplenic T-cell lymphoma
Encyclopedia
Hepatosplenic T-cell lymphoma is a rare and generally incurable form of lymphoma
.
, spleen
, and bone marrow
.
is rare, comprising less than 5% of all cases, and is most common in young adults and adolescents. A distinct male gender preference has been described.
Cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with the immunosuppressant azathioprine
. The majority occurred in patients with Inflammatory Bowel Disease
. Adolescents and young adult males were the major cohort of cases. They presented with a very aggressive disease course and, with one exception, died of the lymphoma. The FDA has required changes to the labeling to inform users and clinicians of the issue.
.
, anemia
, and leukocytosis
is common in patients with hepatosplenic T-cell lymphoma. The discovery of neoplastic cells in peripheral blood is often a finding late in the clinical course.
and liver
are always involved, with bone marrow
involvement frequently present. Nodal involvement is exceedingly rare.
and inconspicuous nucleoli.
is commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. Immunohistochemistry
can aid in the detection of this lymphoma
.
.
7q has been observed in all cases described so far, sometimes in conjunction with other chromosomal abnormalities such as trisomy
8.
. Allogeneic bone marrow transplant has been proven to attain remission for over five years and possibly cure hepatosplenic 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...
.
Definition
Hepatosplenic T-cell lymphoma is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show a significant sinusoidal infiltration in the liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, 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...
, and 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...
.
Epidemiology
This lymphomaLymphoma
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...
is rare, comprising less than 5% of all cases, and is most common in young adults and adolescents. A distinct male gender preference has been described.
Etiology
The cell of origin for this disease is an immature cytotoxic T-cell clonally expressing the γδ T-cell receptor. This disease is seen more often in immunosuppressed solid organ transplant recipients, an association that has led to the hypothesis that long-term immune stimulation in the setting of immunosuppression is the causative agent.Cases of hepatosplenic T-cell lymphoma (HSTCL) have been reported in patients treated with the immunosuppressant azathioprine
Azathioprine
Azathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
. The majority occurred in patients with Inflammatory Bowel Disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
. Adolescents and young adult males were the major cohort of cases. They presented with a very aggressive disease course and, with one exception, died of the lymphoma. The FDA has required changes to the labeling to inform users and clinicians of the issue.
Clinical Presentation
The typical clinical finding in a patient with hepatosplenic T-cell lymphoma is hepatosplenomegalyHepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
.
Laboratory Findings
The constellation of thrombocytopeniaThrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, 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...
, and leukocytosis
Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections...
is common in patients with hepatosplenic T-cell lymphoma. The discovery of neoplastic cells in peripheral blood is often a finding late in the clinical course.
Sites of Involvement
The spleenSpleen
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...
and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
are always involved, with 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...
involvement frequently present. Nodal involvement is exceedingly rare.
Morphology
The neoplastic cells in this disorder show a monotonous appearance, with a small amount of cytoplasmCytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
and inconspicuous nucleoli.
Spleen and liver
This disease shows a distinct sinusoidal pattern of infiltration which spares the splenic white pulp and hepatic portal triads.Bone marrow
While the bone marrowBone 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 commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. Immunohistochemistry
Immunohistochemistry
Immunohistochemistry or IHC refers to the process of detecting antigens in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. IHC takes its name from the roots "immuno," in reference to antibodies used in the procedure, and...
can aid in the detection of this 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...
.
Peripheral blood
Cells of a similar morphology observed in solid organs are observed in peripheral bloodBlood
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....
.
Immunophenotype
The immunophenotype for hepatosplenic T-cell lymphoma is a post-thymic, immature T-cell.| Status | Antigens |
| Positive | CD3 CD3 CD3 or CD-3 may be:* CD3 , an antigen, cluster of differentiation protein , part of the T cell receptor complex on a mature T lymphocyte* Ford CD3 platform* MediaMax CD-3, copy protection scheme* MiniCD, a 3-inch CD... , TCRδ1, TIA-1 |
| Negative | CD4 CD4 CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984... , CD5 CD5 CD5 or CD-5 may be:* Child development-5, for five-year old children, a more developmentally appropriate acronym for kindergarten* cluster of differentiation 5 molecule, type I transmembrane protein* compact disc, 5-inch CD, usually music CD... , CD8 CD8 CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene... |
Genetic findings
Clonal rearrangement of the γ gene of the T-cell receptor is the hallmark of this disease. A few cases have shown rearrangement of the T-cell receptor β gene. IsochromosomeIsochromosome
An isochromosome is a chromosome that has lost one of its arms and replaced it with an exact copy of the other arm. This is sometimes seen in some females with Turner syndrome or in tumor cells. This may also cause an isochromosome to have two centromeres The chromosome arm is already copied during...
7q has been observed in all cases described so far, sometimes in conjunction with other chromosomal abnormalities such as trisomy
Trisomy
A trisomy is a type of polysomy in which there are three copies, instead of the normal two, of a particular chromosome. A trisomy is a type of aneuploidy .-Description and causes:...
8.
Treatment
CHOP-R frequently induces remission initially, but most patients relapse and die within 2 years. Autologus bone marrow transplantion is currently being investigated in the treatment of hepatosplenic lymphomaLymphoma
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...
. Allogeneic bone marrow transplant has been proven to attain remission for over five years and possibly cure hepatosplenic lymphoma.