Table 3.

Comparative features of NK/T-cell lymphomas and lymphoproliferative disorders (LPDs) involving the gastrointestinal (GI) tract

	Refractory celiac disease type II	Enteropathy-associated T-cell lymphoma	Monomorphic epitheliotropic intestinal T-cell lymphoma	Intestinal T-cell lymphoma, NOS	Indolent clonal T-cell LPD of the GI tract	Indolent NK-cell LPD of the GI tract	Intestinal extranodal NK/T-cell lymphoma, nasal type
Clinical presenting features	Persistance or recurrence of diarrhea and villous atrophy in < 1% of patients with celiac disease under gluten-free diet	Abdominal symptoms, diarrhea, obstruction, or perforation in patients with celiac disease or refractory celiac disease	Intestinal obstruction or perforation	Very rare, no predisposing factors known	Abdominal symptoms	Incidental discovery or abdominal symptoms	Bleeding or perforation
Localization	Small intestine	Small intestine > colon, stomach, often multifocal	Small intestine > colon	Colon > small intestine, stomach, extraintestinal spread	Small intestine and colon more commonly than upper GI tract	Stomach ("lymphomatoid gastropathy") more commonly than small intestine and colon	Small intestine or colon
Macroscopy/ endoscopy	Mucosal atrophy and/or ulcerative lesions (ulcerative jejunitis)	Ulcerations + / − strictures, infiltrative tumor; necrosis common	Infiltrative tumor; necrosis uncommon	Tumor	Mucosal ulcers or polyps, or normal-appearing mucosa	Erosions, ulcerations or normal-appearing mucosa	Infiltrative tumor; necrosis common
Histology	Villous atrophy, increased IEL, ulceration	Pleomorphic medium- to large-sized cells, angiocentrism and angioinvasion common	Monomorphic, small to medium-sized cells, epitheliotropism,	Pleomorphic medium to large cells	Non-destructive infiltrate, small lymphocytes without significant atypia	Usually non-destructive infiltrate, medium to large, atypical cells, no necrosis or IEL	Usually pleomorphic morphology, frequent angiocentrism, angioinvasion and necrosis
Immuno phenotype	sCD3 − CD3 + CD4 − CD5 − CD7 + CD8 − CD103 +	CD3 + CD4 − CD5 − CD7 + CD8 − CD103 +	CD3 + CD4 − CD5 − CD7 + CD8 + CD103 +	CD3 + CD4 CD8	CD3 + CD4 CD5 CD7 + / − CD8	CD3 + CD4 − CD5 − CD7 + CD8 −	cCD3 + CD4 − CD5 − CD7 + CD8 −
	CD30 −	CD30 +	CD30 −	CD30	CD30 −	CD30 −	CD30
	CD56 −	CD56 −	CD56 +	CD56	CD56 −	CD56 +	CD56 +
TCR expression	Negative	Negative > αβ > γδ	γδ > αβ or negative > double positive	Negative or αβ or γδ	αβ	Negative	Negative > αβ or γδ
Cytotoxic markers	Positive	Positive	Positive	Variable	Variable	Positive	Positive
EBV	Negative	Negative	Negative	Variable	Negative	Negative	Positive
Genes altered	JAK1, STAT3, TNFAIP3, KMT2D, TET2	JAK1 STAT3, TNFAIP3, KMT2D, TET2	SETD2, STAT5B, JAK3, GNAI2, TP53, MYC	JAK1, JAK3, SETD2, STAT5B, TET2	STAT::JAK2 fusion, JAK/STAT pathway genes	JAK3, other miscellaneous genes	BCOR, DDX3X, TP53, STAT3