Extranodal T- and NK-cell lymphomas

Abstract

Non-cutaneous extranodal NK/T cell lymphoproliferations constitute a heterogenous group of rare neoplasms, occurring primarily in the gastro-intestinal tract, nasal area, spleen, and liver. Their nomenclature refers to their usual clinical presentation and predilection for specific anatomic sites—i.e. extranodal NK/T-cell lymphoma, nasal-type, hepatosplenic T-cell lymphoma, primary intestinal T-cell lymphomas, indolent lymphoproliferative disorders of the gastrointestinal tract, and breast implant-associated anaplastic large cell lymphoma. Extranodal tissues may also be involved by T-cell leukemias, or other entities usually presenting as nodal diseases. Primary extranodal entities range from indolent to highly aggressive diseases. Here, we will review the clinicopathologic features of the pertinent entities including the recent advances in their molecular and genetic characterization, with an emphasis on the changes introduced in the 2022 International Consensus Classification of lymphoid neoplasms, and highlight the diagnostic criteria helpful to sort out the distinction with potential mimickers.

A comparison of the International Consensus and 5th WHO classifications of T‐cell lymphomas and histiocytic/dendritic cell tumours

“…It has a poor outcome, more common large cytotoxic T-cell rather than NK-cell derivation, 32,33 common TET2 gene mutation, distinct molecular signature, 34 and immune pathway upregulation as well as lower genomic instability. 35 Extranodal NK/T cell lymphoma, 36 qualified as 'nasal type' in the WHO-HAEM4 and ICC is renamed extranodal NK/T cell lymphoma (ENKTL) in WHO-HAEM5 due to frequent localization in other extranodal sites at presentation. Intravascular NK/T-cell lymphoma considered a form of ENKTL in WHO-HAEM4, is now placed under aggressive NK-cell leukaemia in the WHO-HAEM5 as a provisional entity.…”

“…36 Infiltration by small Tlymphocytes in RCD-II is not restricted to the intestinal epithelium but may extend to the lamina propria. 36 Abnormal intraepithelial lesions (IELs) in RCD-II are CD3+ (cytoplasmic), CD2+, CD5−, CD7+, CD8−/+, CD30−, CD56−, CD103+, and positive for cytotoxic molecules (TIA1+/− granzyme or perforin) and rarely for the NK receptor NKp46. 37 The abnormal IELs in RCD-II exhibit clonal TRG or TRB gene rearrangements.…”

“…37 RCD-II has a high risk of progression to EATL that should be suspected when large lymphoid atypical cells expressing CD30 are present. 36 The distinction between EATL and MEITL has been further refined by means of genomic studies 39 (Table 3). In particular, the T-cell receptor (TCR) is silent in most EATL patients whilst it is expressed in the majority of MEITL cases that derive more frequently from gamma-delta T-cells than from alpha-beta T-cells.…”

“…Extranodal NK/T cell lymphoma, 36 qualified as ‘nasal type’ in the WHO‐HAEM4 and ICC is renamed extranodal NK/T cell lymphoma (ENKTL) in WHO‐HAEM5 due to frequent localization in other extranodal sites at presentation. Intravascular NK/T‐cell lymphoma considered a form of ENKTL in WHO‐HAEM4, is now placed under aggressive NK‐cell leukaemia in the WHO‐HAEM5 as a provisional entity.…”

“…RCD‐II occurs in about 1% of patients with coeliac disease and is defined by the presence of persistent gastrointestinal symptoms, usually chronic diarrhoea and hypoalbuminemia that may lead to malnutrition, and villous atrophy, despite a strict gluten‐free diet for at least 6–12 months, once other conditions have been excluded 36 . Infiltration by small T‐lymphocytes in RCD‐II is not restricted to the intestinal epithelium but may extend to the lamina propria 36 .…”