Enteropathy-associated T-cell lymphoma C86.2

Aggressive non-Hodgkin's lymphoma of the gastrointestinal tract, often associated with a gluten-sensitive enteropathy (celiac disease). The tumor arises from intestinal intraepithelial cytotoxic T cells. The small intestine and the mesentery are most frequently affected; other localizations in the gastrointestinal tract are less frequent.

In older classifications, according to:

• EATL type 1: associated with gluten sensitive enteropathy in 80-90%, CD56 negative (EATZL often develops from EATL type 2, but can also occur "de novo" in individuals with celiac disease (Chander U et al. 2018).
• EATL type 2: in 10-20% no association with gluten-sensitive enteropathy, CD56-positive (new nomenclature: monomorphic epitheliotropic intestinal T-cell lymphoma).

Classified.

According to the current WHO classification of 2017, the name "EATL" is used only for the previous type 1.

Rare disease; <5% of all gastrointestinal lymphomas and <1% of all non-Hodgkin lymphomas are enteropathy-associated T-cell lymphomas

Occurrence mostly in the 6th to 7th decade of life

Abdominal pain (most common symptom); furthermore, symptoms of gluten-sensitive enteropathy are detectable such as steatorrhea, flatulence, weight loss, malabsorption, gastrointestinal hemorrhage, anemia, B symptoms, intestinal obstruction, or intestinal perforation (Chander U et al. 2018).

A large proportion of patients present with advanced stage disease. Many patients are not diagnosed with gluten-sensitive enteropathy until enteropathy-associated T-cell lymphoma is also diagnosed.

Cutaneous manifestations are possible in the setting of systemic lymphoma. Although the clinical picture raises a suspicion of cutaneous lymphoma, it can otherwise only be verified by the histological and molecular biological pattern (Bisig B et al. 2022) .

Evidence of T-cell clonality, tumor cells of variable size and, depending on the type, expression of various receptors such as CD56 or CD8. Genetically, ETL often show chromosomal gains from 9q33-q34. The detection of recurrent activating mutations in members of the JAK/STAT pathway, may suggest that deregulation of cytokine signaling is an early event in lymphomagenesis.

Consistent gluten-free diet, steroids in patients with EATL type 1 and refractory symptoms of gluten-sensitive enteropathy.

Chemotherapy not yet standardized, participation in trials recommended; usually CHOP regimen, if necessary with an additional application administration of etoposide (in patients < 60 years).

Autologous stem cell transplantation is also a therapeutic option.

The tumor behaves aggressively. Frequent metastasis to the liver, spleen, skin and other organs. Typical complication is intestinal perforation. The median survival rate from diagnosis is 10 months.

Consistent gluten-free diet can prevent the development of the disease.

Gastrointestinal lymphomas are almost exclusively non-Hodgkin lymphomas (NHL). They arise somewhat more frequently in the stomach than in the intestine and mostly originate from B cells. Aggressive NHL, especially diffuse large B-cell lymphoma or enteropathy-associated T-cell lymphoma, are more frequently found in the gastrointestinal tract than indolent lymphomas (De Leval L et al. 2015).

1. Bisig B et al (2022) Cutaneous presentation of enteropathy-associated T-cell lymphoma masquerading as a DUSP22-rearranged CD30+ lymphoproliferation. Virchows Arch 481:653-657
2. Chander U et al (2018) Pathogenesis of enteropathy-associated T cell lymphoma. Curr Hematol Malig Rep13:308-317.
3. De Leval L et al (2015) Recent advances in intestinal lymphomas. Histopathology 66: 112-135.
4. Ganapathi KA et al. (2014) Early lymphoid lesions: conceptual, diagnostic and clinical challenges. Haematologica 99: 1421-1432.
5. Luchtel RA et al (2018) Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas with DUSP22 rearrangements. Blood 132:1386-1398
6. Malamut G et al.(2014) Small intestinal CD4+ T-cell lymphoma is a heterogeneous entity with common pathology features. Clin Gastroenterol Hepatol 12: 599-608.
7. Margolskee E et al (2013) Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinic features. PLoS One 8: e68343.
8. Perry AM et al (2013) Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood 122: 3599-3606
9. Takeuchi K et al.(2010) Lymphomatoid gastropathy: A distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood 116: 5631-5637.