Enteropathy-associated T-cell lymphoma

Enteropathy-associated T-cell lymphoma (formerly termed enteropathy-associated T-cell lymphoma, type 1)
Other names	Enteropathy-associated T-cell lymphoma, type I
Micrograph of enteropathy-associated T cell lymphoma (upper right of image). H&E stain.
Specialty	Oncology, hematology, gastroenterology
Complications	Bowel obstructions, bowel perforations
Causes	Complication of celiac disease
Risk factors	Genetic predisposition
Prevention	Gluten-free diet
Prognosis	guarded

Enteropathy-associated T-cell lymphoma (EATL), previously termed enteropathy-associated T-cell lymphoma, type I and at one time termed enteropathy-type T-cell lymphoma (ETTL), is a complication of coeliac disease in which a malignant T-cell lymphoma develops in areas of the small intestine affected by the disease's intense inflammation.^[1] While a relatively rare disease, it is the most common type of primary gastrointestinal T-cell lymphoma.^[2]

EATL had been defined as a single type of small intestine lymphoma, but in 2008, the World Health Organization (WHO) divided the disease into two subtypes: 1) EATL type I, which occurs in individuals with coeliac disease, a chronic immune disorder causing inflammatory responses to dietary gluten primarily in the upper reaches (i.e. jejunum and duodenum) of the small intestine; and 2) EATL type II, a disorder similar to EATL type I that occurs without coeliac disease. While type I and II EATL share many similar features, post-2008 studies found some significant differences between the two types. In 2016, the WHO redefined the two diseases as separate entities, keeping the term enteropathy-associated T-cell lymphoma for the coeliac disease-associated lymphoma and terming type 2 disease as monomorphic epitheliotropic intestinal T cell lymphoma (MEITL).^[3] EATL is five to ten times more common than is MEITL.^[4] The WHO also defined a third type of intestinal T-cell lymphoma that cannot not be classified as EATL or MEITL as peripheral T-cell lymphoma not otherwise specified (ITCL-NOS).^[5]

EATL arises from the malignant transformation of small-intestinal intraepithelial lymphocytes (IEL). IEL are a heterogeneous group of principally T-cell lymphocytes residing in epithelial tissues that interface the environment, such as the mucosa of the bronchi, reproductive tract and gastrointestinal tract.^[6] At these sites, IEL are exposed and regulate immune responses to non-dietary and dietary antigens, pathogenic and non-pathogenic organisms and injured self tissues.^[7] Gastrointestinal tract IEL appear in the epithelium of the small intestine, colon, stomach and esophagus, residing between the epithelial cells that line these organs' lumens.^[7] These IEL often exhibit natural killer and cytotoxic T-cell cell activation markers,^[6] contain various toxic agents (e.g. perforin, granzyme) and therefore are capable, if activated, of causing severe tissue injuries.^[4] With coeliac disease, the IEL react to the glutelins in dietary gluten by increasing their numbers, becoming pathologically active, producing chronic inflammation that injures intestinal cells, interfering with nutrient absorption and creating an environment conducive to their malignant transformation into EATL.^[1]

Optimal treatment of EATL has used regimens consisting of intensive chemotherapy, hematopoietic stem cell transplantation and, in cases with bulky, obstructive and/or perforated bowel disease, surgical intervention.^[3] The disease has a five-year overall survival rate of only ~20%.^[8] However, recent studies focusing on the malignant IEL in EATL have increased understanding of the disease and suggested newer chemotherapy-based strategies and novel molecular targets that might be attacked therapeutically to improve the disease's prognosis.^[7]