EATL & Celiac Disease
Enteropathy-associated T-cell lymphoma (EATL) and Celiac disease are closely linked. Refractory celiac disease (RCD) may be diagnosed prior to EATL (more frequently) or concomitant with EATL (less frequently). In some patients with EATL, celiac disease is clinically silent and only diagnosed at autopsy. Type I Refractory Celiac Disease: It accounts for 70-80% of all refractory celiac disease cases. The intestinal morphology is similar to uncomplicated celiac disease. The symptoms are milder than type II RCD. The intraepithelial lymphocytes have normal morphology and express CD8, surface CD3, and TCR. No specific genetic or molecular changes have been identified. The risk of developing EATL is low and the 5-yr survival rate is 80-96%. Type II Refractory Celiac Disease: The symptoms are severe and the patients are profoundly malnourished due to protein-losing enteropathy. Endoscopy frequently shows large ulcers or strictures. Extraintestinal manifestations are present in 45-60% of cases. There is total or subtotal villous atrophy. Intraepithelial lymphocytes are present throughout the gastrointestinal tract. They have abnormal immunophenotype (absence of CD8, surface CD3, and TCR expression). Recurrent gains of chromosome 1q22-44 are found in both type II RCD and EATL. Loss of tumor suppressor gene p16 at 9p21 is seen in 40% of cases of RCD, type II, especially in those with ulcerative jejunitis. T-cell receptor beta or gamma are clonally rearranged in almost all cases. There is high risk of developing EATL (30-50% of cases in 4-6 years). The 5-yr survival rate is 45-60%. This image shows changes of Celiac disease in the mucosa adjacent to EATL. There is villous atrophy and blunting, crypt hyperplasia, intraepithelial lymphocytes, and chronic inflammation.