Enteropathy-Associated T-cell Lymphoma
Encyclopedia
Enteropathy-Associated T-cell Lymphoma (EATL), also enteropathy-type T-cell lymphoma (ETTL), is a type of T-cell lymphoma
that affects the small intestine
. It is the most common primary gastrointestinal T-cell lymphoma, arising from the T cells that are found between the cells that line the small intestinal (brush border cells
or small intestinal epithelial cells). These cancerous T-cells are a consequence of prolonged, untreated coeliac disease
in genetically susceptible individuals.
It can be further classified in type I and II EATL.
(e.g. wheat gluten). In gluten-sensitive
individuals with EATL, 68% are homozygotes of the DQB1 subtype at the HLA-DQB1
locus . (See Coeliac Disease
, HLA-DQ
, HLA DR3-DQ2
) A DQ isoform that appears to be responsible for EATL in the overwhelming number of cases is highly effective at presenting a proteolytically protected region of α2-gliadin to T-cells, constant over-stimulation of T-cell eventually results in neoplastic growth. EATL typically appears after the 4th decade of life, within 3 years of coeliac disease diagnosis or in undiagnosed coeliacs. In treated coeliacs, EATL may be preceded by refractory coeliac disease 1(RCD1) or, prominently, refractory celiac disease 2 (RCD2), in which EATL is a frequent outcome Refractory coeliac disease is no longer favorably responsive to wheat-gluten abstinence. Beyond the RCD1 stage, many drugs are not effective, and undetected coeliac disease leading to de novo EATL generally has a poor outcome.
The genetic association with celiac disease and HLA loci defines type I EATL. Type II doesn´t show these associations and frequently presents with bulky disease.
Early recognition of coeliac disease, particularly with a focus on DQ2 homozygotes and in affected family members, is the only effective prevention, though bone marrow transplant was suggested as a treatment during early RCD2.
Among the most influential prognostic factors is bulky disease, defined by a tumor mass >5cm.
T-cell lymphoma
The T-cell lymphomas are the four types of lymphoma that affect T cells. These account for perhaps one in ten cases of non-Hodgkin lymphoma.They can be associated with Epstein Barr virus and Human T-cell leukemia virus-1.-Types:The four classes are:...
that affects the small intestine
Small intestine
The small intestine is the part of the gastrointestinal tract following the stomach and followed by the large intestine, and is where much of the digestion and absorption of food takes place. In invertebrates such as worms, the terms "gastrointestinal tract" and "large intestine" are often used to...
. It is the most common primary gastrointestinal T-cell lymphoma, arising from the T cells that are found between the cells that line the small intestinal (brush border cells
Brush border
A brush border is the name for the microvilli-covered surface of simple cuboidal epithelium and simple columnar epithelium cells found in certain locations of the body. Microvilli are approximately 100 nanometers in diameter and their length varies from approximately 100 to 2,000 nanometers in...
or small intestinal epithelial cells). These cancerous T-cells are a consequence of prolonged, untreated coeliac disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
in genetically susceptible individuals.
Epidemiology
EATL is most frequent in Europe, where it represents 9.4% of all Peripheral T cell lymphomas. Association with celiac disease is consistently demonstrated in only 30% of patients. The global incidence of this lymphoma is rare, being about 0.5 to 1 per million.Classification
EATL can be classified as an extranodal Peripheral T Cell lymphoma, category it shares with Hepatosplenic T cell lymphoma, and Panniculitic T Cell lymphoma.It can be further classified in type I and II EATL.
Genetics
Enteropathy associated T-cell lymphoma (EATL) is environmentally induced as a result of the consumption of Triticeae glutensTriticeae glutens
Triticeae glutens are seed storage proteins found in mature seeds of grass tribe Triticeae. Seed glutens of non-Triticeae plants have varieties of similar properties, but none singly can perform on a par with those of the Triticeae taxa, particularly the triticum species...
(e.g. wheat gluten). In gluten-sensitive
Gluten sensitivity
Gluten sensitivity belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy .Gluten...
individuals with EATL, 68% are homozygotes of the DQB1 subtype at the HLA-DQB1
HLA-DQB1
Major histocompatibility complex, class II, DQ beta 1, also known as HLA-DQB1, is a human gene and also denotes the genetic locus that contains this gene...
locus . (See Coeliac Disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
, HLA-DQ
HLA-DQ
HLA-DQ is a cell surface receptor type protein found on antigen presenting cells. DQ is an αβ heterodimer of the MHC Class II type. The α and β chains are encoded by HLA-DQA1 and HLA-DQB1, respectively. These two loci are adjacent to each other on chromosome 6p21.3. Both the α-chain and β-chain...
, HLA DR3-DQ2
HLA DR3-DQ2
HLA DR3-DQ2 is double serotype that specifically recognizes cells from individuals who carry a multigene HLA DR, DQ haplotype.Certain HLA DR and DQ genes have known involvementin autoimmune diseases. DR3-DQ2, a multigene...
) A DQ isoform that appears to be responsible for EATL in the overwhelming number of cases is highly effective at presenting a proteolytically protected region of α2-gliadin to T-cells, constant over-stimulation of T-cell eventually results in neoplastic growth. EATL typically appears after the 4th decade of life, within 3 years of coeliac disease diagnosis or in undiagnosed coeliacs. In treated coeliacs, EATL may be preceded by refractory coeliac disease 1(RCD1) or, prominently, refractory celiac disease 2 (RCD2), in which EATL is a frequent outcome Refractory coeliac disease is no longer favorably responsive to wheat-gluten abstinence. Beyond the RCD1 stage, many drugs are not effective, and undetected coeliac disease leading to de novo EATL generally has a poor outcome.
The genetic association with celiac disease and HLA loci defines type I EATL. Type II doesn´t show these associations and frequently presents with bulky disease.
Early recognition of coeliac disease, particularly with a focus on DQ2 homozygotes and in affected family members, is the only effective prevention, though bone marrow transplant was suggested as a treatment during early RCD2.
Treatment
EATL has mainly been treated with CHOP and CHOP-like regimens, the exposure to anthracycline drugs being a favorable prognostic factors.Prognosis
According to the Peripheral T cell lymphoma project, median overall survival is 10 months, while median failure free survival is only 6 months. The international prognostic index is not useful in defining prognosis in this entity, but Peripheral Index for T cell lymphoma is.Among the most influential prognostic factors is bulky disease, defined by a tumor mass >5cm.