Enteropathy-Associated T-Cell Lymphoma (EATL) is a rare and aggressive non-Hodgkin lymphoma. This cancer primarily originates from T-cell lymphocytes located in the lining of the small intestine. The term “enteropathy” refers to a disease of the intestines, indicating the primary site of this malignancy. EATL can spread to other areas of the body, including lymph nodes, bone marrow, liver, lung, and skin.
The Celiac Disease Connection
EATL has a strong association with celiac disease, an autoimmune condition where consuming gluten triggers an immune response that damages the small intestine. The persistent inflammation and chronic immune stimulation within the small intestine in individuals with celiac disease are thought to contribute to the risk of EATL development. EATL is a serious complication that can arise in individuals with long-standing or refractory celiac disease, even if they adhere to a strict gluten-free diet.
Historically, EATL was broadly categorized into two types: Type I (classic EATL) and Type II (monomorphic EATL). Classic EATL is strongly associated with celiac disease, particularly in patients with latent or refractory forms. The World Health Organization (WHO) reclassified these in 2016, retaining the term EATL for the celiac disease-associated lymphoma (Type I) and re-designating Type II as Monomorphic Epitheliotropic Intestinal T-cell Lymphoma (MEITL).
MEITL, unlike classic EATL, has a weaker or no clear association with celiac disease and presents with distinct morphological and immunophenotypic features. Classic EATL, which is five to ten times more common than MEITL, is particularly prevalent in Western countries, while MEITL is more common in Asian populations. Genetic factors, such as the HLA-DQ2 homozygosity, which increases susceptibility to celiac disease, also represent a risk factor for developing EATL.
Identifying the Symptoms
The symptoms of EATL can often overlap with those of celiac disease, which can make early diagnosis challenging. Common presentations include severe abdominal pain, persistent diarrhea, and significant unintentional weight loss. Patients may also experience fatigue, fever, and night sweats.
More severe complications can indicate the presence of EATL. These include gastrointestinal bleeding, which might manifest as blood in the stool, or symptoms of bowel obstruction, such as severe cramping, vomiting, and an inability to pass gas or stool. Intestinal perforation, a tear in the bowel wall, is another serious complication that can lead to acute abdominal pain and peritonitis, and can occur as an initial symptom in nearly half of patients. Worsening malabsorption despite strict adherence to a gluten-free diet in individuals with a history of celiac disease should raise suspicion for EATL.
How EATL is Diagnosed and Treated
Diagnosing EATL requires obtaining tissue samples from the small intestine. Endoscopy with multiple biopsies is a primary method. In some cases, capsule endoscopy or balloon-assisted enteroscopy may be used to reach less accessible small bowel areas.
Once tissue samples are obtained, pathological review is necessary. This includes immunohistochemistry, which uses antibodies to identify specific markers on the cancer cells, and molecular tests, such as T-cell receptor gene rearrangement studies, to confirm the diagnosis and differentiate EATL from other lymphomas or severe celiac disease. Imaging studies, including CT scans and PET scans, are also used to determine the extent of the disease and for staging.
Treatment for EATL is aggressive and often involves intensive systemic chemotherapy regimens. Anthracycline-based chemotherapy is a standard induction therapy, often administered after surgical debulking to remove the main tumor mass, particularly if complications like obstruction or perforation are present. For eligible patients, autologous stem cell transplantation (ASCT) may be considered after chemotherapy. In an ASCT, the patient’s own stem cells are collected before high-dose chemotherapy, which allows for more aggressive treatment to kill cancer cells, and then reinfused to restore bone marrow function. Surgical intervention is also a consideration for managing complications like bowel obstruction or perforation, or for obtaining diagnostic biopsies. The complexity of EATL treatment often necessitates a multidisciplinary team approach.
Understanding the Outlook
EATL has historically been associated with a poor prognosis, largely due to its aggressive nature and the tendency for late diagnosis. The median overall survival has been reported as low as 7 to 10 months, with a 5-year survival rate varying significantly, ranging from 8% to 60% depending on additional therapies.
Despite these historical challenges, advancements in diagnostic techniques and treatment protocols are improving outcomes. Newer chemotherapy regimens, along with the potential for targeted therapies, are being explored. Factors influencing the prognosis include the stage of the disease at diagnosis, the patient’s overall health status, and their response to initial treatment. Continued research and clinical trials are ongoing to identify more effective treatments and improve the outlook for individuals with EATL.