Table 2.

Main clinicopathologic characteristics of non-cutaneous extranodal T and NK-cell lymphomas, and their differential diagnoses

2022 ICC entity	Clinicopathologic features	Phenotypic features	Differential diagnoses
Extranodal NK/T-cell lymphoma, nasal type	Ulcerated tumor in the nasal area, less commonly in skin, gastrointestinal tract or elsewhere; more common in Asia and Latin America Variable cytomorphology, angiocentricity, and necrosis	Positive: EBV (EBER +), CD2, CD3, CD56, TIA1, GzB and/or perforin Negative: CD4 Variable: CD30, p53, CD5, CD8 TCR: negative (most cases, NK cells) > TCRδ + > TCRβF1 +	Reactive inflammatory infiltrates with necrosis (non-specific, Wegener granulomatosis) Lymphomatoid granulomatosis EBV + mucosal CD30 + T-cell lymphoproliferative disorder Aggressive NK-cell leukemia Chronic active EBV disease Primary nodal EBV + T/NK-cell lymphoma
Enteropathy-associated T-cell lymphoma	Small intestinal tumor or ulcer in patients with preceding celiac disease or unknown celiac disease Pleomorphic tumor cells and polymorphic infiltrate	Positive: CD3, CD7, CD30, CD103, TIA1, GzB and/or perforin Negative: EBV, CD56, CD8 TCR: silent > TCRβF1 + > TCRδ +	Refractory celiac disease Monomorphic epitheliotropic intestinal T-cell lymphoma Anaplastic large cell lymphoma Intestinal T-cell lymphoma, NOS
Monomorphic epitheliotropic intestinal T-cell lymphoma	Small intestinal tumor Typically monomorphic medium-sized	Positive: CD8, CD56, CD2, CD3, CD7, CD103, TIA1 + GzB + / − perforin Negative: EBV, CD4, CD5, CD30, H3K36me3 Variable: CD20 and B-cell markers, MYC, p53 TCR: TCRδ + > TCRβF1 + > TCRβF1 − /TCRδ − or TCRβF1 + /TCRδ +	Enteropathy-associated T-cell lymphoma Indolent NK-cell or indolent clonal T-cell lymphoproliferative disorder of the gastrointestinal tract Extranodal NK/T-cell lymphoma, nasal type Extranodal marginal zone lymphoma of MALT type
Intestinal T-cell lymphoma, NOS	Presentation most commonly in the colon Morphology variable, usually pleomorphic	Positive: CD3 Negative: none Variable: EBV, CD30, CD56, TIA1 + GzB + / − perforin TCR: TCRβF1 + > TCRδ +	Enteropathy-associated T-cell lymphoma Monomorphic epitheliotropic intestinal T-cell lymphoma Peripheral T-cell lymphoma, NOS Anaplastic large cell lymphoma
Hepatosplenic T-cell lymphoma	Splenomegaly, cytopenias, hepatomegaly, frequent context of dysimmunity Medium sized cells, sinusoidal pattern	Positive: CD2, CD3, CD7, TIA1 Negative: EBV, CD4, CD57 Variable: CD8, CD56 TCR: TCRδ + > TCRβF1 +	T-cell large granular lymphocytic leukemia (T-LGLL) Aggressive NK-cell leukemia Intravascular lymphomas (bone marrow) Reactive expansions of γδ T cells
Breast implant-associated ALCL	Seroma + / − tumor lesion associated with breast implant Large anaplastic cells	Positive: CD30 (strong), CD4, CD45, EMA, Negative: ALK, EBV, CD5, CD7, B-cell markers Variable: CD3, CD8, TIA1, GzB, perforin, PD-L1 TCR: often silent	Periprosthetic reactive inflammatory effusions ALCL, ALK-negative Hodgkin lymphoma EBV + fibrin-associated large B-cell lymphoma