Enteropathy-associated T-cell lymphoma

Enteropathy-Associated T-cell Lymphoma (EATL) is a T-cell lymphoma of 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). [Isaacson, PG. Intestinal Lymphoma (1994) 25(10):1020-9] These cancerous T-cells are a consequence of prolonged, untreated coeliac disease in genetically susceptible individuals.

Genetics

Enteropathy associated T-cell lymphoma (EATL) is environmentally induced as a result of the consumption of Triticeae glutens (e.g wheat gluten). In gluten-sensitive individuals with EATL, 68% are homozygotes of the DQB1HQBA|02 subtype at the HLA-DQB1 locus .cite journal |author=Al-Toma A, Verbeek WH, Hadithi M, von Blomberg BM, Mulder CJ |title=Survival in Refractory Coeliac Disease and Enteropathy associated T cell Lymphoma: Retrospective evaluation of single centre experience |journal= Gut|volume= 56|issue= | pages = 1373|year=2007 |pmid=17470479 |doi=10.1136/gut.2006.114512] (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-glaidin to T-cells, constant over-stimulation of T-cell eventually results in neoplastic growth.cite journal | author = Jores RD, Frau F, Cucca F, "et al" | title = HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease | journal = Scand. J. Gastroenterol. | volume = 42 | issue = 1 | pages = 48–53 | year = 2007 | pmid = 17190762 | doi = 10.1080/00365520600789859] EATL typically appears after the 4th decade of life, within 3 years of coeliac disease diagnosis or in undiagnosed coeliacs.cite journal | author = Al-Toma A, Goerres MS, Meijer JW, "et al" | title = Cladribine therapy in refractory celiac disease with aberrant T cells | journal = Clin. Gastroenterol. Hepatol. | volume = 4 | issue = 11 | pages = 1322–7; quiz 1300 | year = 2006 | pmid = 16979946 | doi = 10.1016/j.cgh.2006.07.007] cite journal | author = Al-Toma A, Goerres MS, Meijer JW, Peña AS, Crusius JB, Mulder CJ | title = Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma | journal = Clin. Gastroenterol. Hepatol. | volume = 4 | issue = 3 | pages = 315–9 | year = 2006 | pmid = 16527694 | doi = 10.1016/j.cgh.2005.12.011] In treated coeliacs, EATL may be preceded by refractory coeliac disease 1(RCD1) or, prominantly, refractory celiac disease 2 (RCD2), in which EATL is a frequent outcomecite journal | author = Al-Toma A, Verbeek WH, Mulder CJ | title = Update on the management of refractory coeliac disease | journal = Journal of gastrointestinal and liver diseases : JGLD | volume = 16 | issue = 1 | pages = 57–63 | year = 2007 | pmid = 17410290 | doi = ] 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.

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 treatement during early RCD2.cite journal |author=Meijer JW, Mulder CJ, Goerres MG, Boot H, Schweizer JJ |title=Coeliac disease and (extra)intestinal T-cell lymphomas: definition, diagnosis and treatment |journal=Scand. J. Gastroenterol. Suppl. |volume= |issue=241 |pages=78–84 |year=2004 |pmid=15696854 |doi= |url=]

See Also

* Coeliac Disease
* Lymphoma
* MALT

References