Enteropathy-associated T-cell Lymphoma



Enteropathy-associated T-cell Lymphoma


Sa A. Wang, MD





Key Facts


Terminology



  • T-cell lymphoma of intestine



    • Arises from intraepithelial T cells


Etiology/Pathogenesis



  • Classical cases of EATL arise in patients with evidence of celiac disease



    • Serologic tests (+); evidence of celiac disease (+)


    • Associated clinical findings: Gluten intolerance, dermatitis herpetiformis, and hyposplenism


    • Refractory celiac disease is precursor lesion


  • In monomorphic variant of EATL, association with celiac disease is not proven


Clinical Issues



  • Most commonly involves jejunum or ileum


  • EATL is often initially diagnosed by intestinal resection at time of acute abdomen


  • Prognosis is very poor due to late diagnosis


Ancillary Tests



  • Array CGH



    • Chromosomal gain of 9q31.33-qter or deletions within 16q12.1 (23% of cases)


Top Differential Diagnoses



  • Peripheral T-cell lymphoma, not otherwise specified


  • ALK(-) anaplastic large cell lymphoma


  • Extranodal NK-/T-cell lymphoma, nasal type


Diagnostic Checklist



  • Available data suggest that EATL can be divided into 2 types: 1 (classical) and 2 (monomorphous)







Enteropathy-associated T-cell lymphoma destroying mucosa and infiltrating into muscle wall of jejunum. Nonneoplastic epithelium is also present image.






Enteropathy-associated T-cell lymphoma, type 1, involving jejunum. Lymphoma cells are large and pleomorphic. Numerous eosinophils and some neutrophils are present in the background.


TERMINOLOGY


Abbreviations



  • Enteropathy-associated T-cell lymphoma (EATL)


Synonyms



  • Intestinal T-cell lymphoma


Definitions



  • T-cell lymphoma of intestine arising from intraepithelial T cells


ETIOLOGY/PATHOGENESIS


Classical Variant EATL (EATL Type 1)



  • Type 1 comprises 80-90% of cases of EATL


  • These tumors are associated with celiac disease



    • Serological tests (+); association with HLA DQ2 or HLA DQ8


    • Pathologic evidence of celiac disease in uninvolved intestinal mucosa


    • Associated clinical findings: Gluten intolerance, dermatitis herpetiformis, and hyposplenism


  • Refractory celiac disease (RCD) is precursor lesion



    • Definition



      • Persistent enteropathy-associated histologic changes on biopsy despite strict gluten-free diet for > 12 months or


      • Severe persistent symptoms necessitating clinical intervention independent of duration of gluten-free diet


    • In some cases of RCD, intraepithelial lymphocytes show



      • Immunophenotypic aberrancy


      • Monoclonal T-cell receptor gene rearrangement


      • Gain of chromosome 1q


      • These cases may be considered as EATL in situ


Monomorphic Variant (EATL Type 2)



  • Association with celiac disease or other risk factors is not proven


  • 10-20% of cases


CLINICAL ISSUES


Epidemiology



  • Incidence



    • Annual rate of 0.5-1 per 1,000,000 people in Western countries



      • Greatest frequency in areas with high prevalence of celiac disease, particularly Northern Europe


      • Accounts for ˜ 35% of all small intestinal lymphomas


      • < 5% of all gastrointestinal tract lymphomas


  • Age



    • Median: 60 years


  • Gender



    • Affects males and females equally


Site



  • EATL most commonly arises in jejunum or ileum



    • Often involves mesenteric lymph nodes


  • Presentation in duodenum, stomach, colon may occur rarely



    • Lymphomas arising in these sites show genetic alterations similar to classic EATL in jejunum or ileum


    • RCD can involve duodenum, stomach, or colon


  • Patients usually do not have peripheral lymphadenopathy


  • EATL can disseminate to liver, bone marrow, spleen, skin, and other organs


Presentation



  • Clinical history of celiac disease



    • Small proportion of patients have childhood-onset celiac disease



    • Most patients have adult-onset celiac disease


    • Typical symptoms of celiac disease



      • Diarrhea with bulky, foul-smelling, floating stools


      • Malabsorption: Anemia, weight loss, vitamin deficiency


      • Dermatitis herpetiformis


    • In some patients, celiac disease and EATL are diagnosed at same time


    • Most patients with monomorphic variant of EATL do not have clinical history of celiac disease


  • Clinical findings at time EATL is initially diagnosed



    • Most patients have weight loss, abdominal pain, and diarrhea



      • Nonspecific; overlaps with celiac disease


    • Some patients can have B symptoms


    • Substantial subset of patients present with small bowel obstruction or perforation



      • In many of these patients, diagnosis of lymphoma is made by laparotomy


    • In patients with known celiac disease, lymphoma occurs ˜ 5-10 years after celiac disease diagnosis



      • Often heralded by clinical relapse after a period of good response to gluten withdrawal


      • In some patients, lymphoma develops in course of progressive deterioration of RCD


    • Presentation of patients with monomorphic EATL is similar, except there is no history of celiac disease


Endoscopic Findings



  • Lymphoma



    • Multiple ulcerating raised mucosal masses or


    • 1 or more larger ulcers or


    • Large exophytic mass


  • Mucosal changes related to RCD



    • Scalloping, fissuring, loss of folds, or mosaic pattern


Laboratory Tests



  • Celiac disease



    • Serology



      • IgA anti-tissue transglutaminase and IgA endomysial antibody are most sensitive and specific tests


      • Anti-gliadin antibody tests have low sensitivity and specificity, no longer used routinely


    • HLA typing



      • For DQ2 and DQ8 may be useful in individuals with equivocal findings


Treatment

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Enteropathy-associated T-cell Lymphoma

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