What are the presentation and diagnostic criteria for Enteropathy-Associated T-Cell Lymphoma (EATL)?

Presentation and Diagnosis of Enteropathy-Associated T-Cell Lymphoma (EATL)

Clinical Presentation

EATL typically presents in patients around age 60 years with symptoms of severe malabsorption, weight loss, diarrhea, and abdominal pain, often in the context of known or undiagnosed celiac disease. 1

Key Presenting Features:

• Gastrointestinal symptoms: Persistent diarrhea, weight loss, and malabsorption despite adherence to gluten-free diet in celiac disease patients 1
• Acute complications: Gastrointestinal bleeding, fever, night sweats, bowel obstruction, or perforation requiring emergency surgery 1
• Nutritional deficiencies: Severe malnutrition with deficiencies in fat-soluble vitamins (A, D, E, K), folate, vitamin B12, iron, copper, and zinc 1
• Physical findings: Low body mass index, loss of muscle mass/strength, ascites/edema, and hypoalbuminemia (an independent predictor of mortality) 1

Clinical Context:

• Association with celiac disease: EATL Type I is strongly associated with celiac disease (80-90% of cases), while the entity previously called EATL Type II (now reclassified as MEITL) is not associated with celiac disease 1
• Progression pathway: EATL often develops through refractory celiac disease type 2 (RCD2), characterized by aberrant clonal T-cell expansion 1
• Epidemiology: EATL accounts for less than 1% of all non-Hodgkin lymphomas and comprises 5% of all peripheral T-cell lymphomas 1

Diagnostic Approach

Initial Diagnostic Workup:

When EATL is suspected in a patient with refractory celiac disease or concerning symptoms, perform small bowel imaging with capsule endoscopy combined with CT or MR enterography to identify complications. 1

Imaging Studies:

• Capsule endoscopy: Quantifies extent and severity of villous atrophy and identifies strictures, inflammation, erosions, ulcers, or mass lesions 1
• CT or MR enterography: Demonstrates bowel wall thickening, mesenteric adenopathy, small bowel masses, or ulcerative jejunoileitis 1
• PET/CT scan: Preferred imaging modality as T-cell lymphomas often have extranodal disease inadequately imaged by CT alone 1

Histopathologic Diagnosis:

The gold standard for EATL diagnosis is histological examination obtained through small bowel enteroscopy or surgical resection. 2

• Tissue acquisition: When imaging shows suspicious lesions, proceed with small bowel enteroscopy to secure pathologic diagnosis 1
• Immunophenotyping: Use flow cytometry, immunohistochemistry, and T-cell receptor rearrangement studies to distinguish EATL from RCD2 1
• Key immunophenotypic features: Loss of normal surface markers CD3 and CD8 with preserved expression of intracytoplasmic CD3, and detection of monoclonal T-cell receptor rearrangement 1

Distinguishing EATL from Refractory Celiac Disease Type 2:

Critical distinction: RCD2 shows aberrant clonal intraepithelial lymphocytes but without frank lymphoma, while EATL represents malignant transformation 1

• RCD2 features: Persistent villous atrophy despite 12 months of strict gluten-free diet, with aberrant T-cell population (loss of CD3/CD8 surface markers) 1
• Progression risk: RCD2 carries high risk of transformation to EATL, with 5-year survival of less than 20% due to nutritional complications and lymphoma development 1

Important Diagnostic Caveats:

• TCR clonality alone is insufficient: Clonal T-cell receptor rearrangements can be detected in newly diagnosed celiac disease and RCD1, so TCR results must be assessed with immunophenotypic, histologic, and clinical findings 1
• Ulcerative jejunoileitis: Finding of inflammatory ulceration of the small bowel in RCD should raise strong suspicion for lymphoma 1
• Repeat imaging: Obtain repeat imaging in RCD2 patients who are clinically worsening due to increased lymphoma risk 1

Staging and Baseline Assessment:

Once EATL is diagnosed, complete staging with:

• PET/CT scan (preferred over CT alone) for accurate assessment of extranodal disease 1
• Comprehensive nutritional assessment including albumin, micronutrient levels, and body mass index 1
• Assessment of performance status and surgical candidacy, as poor nutritional status compromises ability to deliver chemotherapy 3

Prognosis at Diagnosis:

EATL carries an extremely poor prognosis with median overall survival of 10 months and failure-free survival of 6 months. 1 Poor prognostic factors include extent of disease at diagnosis, multifocal small bowel involvement, poor general health, and complications such as perforation that preclude chemotherapy 1.