Lymphoma & related disorders

General

WHO 2022 & ICC-T / NK cell



Last author update: 19 July 2023
Last staff update: 19 July 2023

Copyright: 2022-2024, PathologyOutlines.com, Inc.

PubMed Search: WHO hematolymphoid T / NK cell

Tom Deng, M.D.
Patricia Tsang, M.D., M.B.A.
Page views in 2023: 1,026
Page views in 2024 to date: 265
Cite this page: Deng T, Tsang P. WHO 2022 & ICC-T / NK cell. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lymphomaWHOHAEM5ICCTcell.html. Accessed February 26th, 2024.
Definition / general
  • 2 new classification systems for T / NK cell lymphoid neoplasms emerged in 2022 and evolved from the previous WHO revised 4th edition of 2016 (WHO HAEM4R)
  • Putative new entities with limited data are designated as provisional in the WHO HAEM4R and ICC while no provisional designation exists in WHO HAEM5 (see table 1)
  • Updates include newly defined entities, more encompassing umbrella terms, deletion of old entities and modified nomenclature
Major updates
  • Certain newly incorporated entities are unique to one or the other of the updated classifications (see table 1)
    • Tumor-like lesions with T cell predominance (Kikuchi-Fujimoto disease, indolent T lymphoblastic proliferation and autoimmune lymphoproliferative syndrome) are included only in WHO HAEM5
    • Primary cutaneous peripheral T cell lymphoma, NOS is a newly introduced term in WHO HAEM5 to describe rare cases of cutaneous T cell lymphoma that do not fit into existing entities
    • Type II refractory celiac disease is recognized as an entity in ICC as a precursor of enteropathy associated T cell lymphoma (EATL)
  • New entities have been added concurrently to WHO HAEM5 and ICC
    • Indolent NK cell lymphoproliferative disorder (LPD) of the gastrointestinal (GI) tract, previously thought to be reactive, is newly recognized as neoplastic by WHO HAEM5 and ICC
    • Previously included as a variant of peripheral T cell lymphoma, not otherwise specified (PTCL, NOS), EBV positive nodal T and NK cell lymphoma is a distinct entity in WHO HAEM5, that is equivalent to primary nodal EBV positive T / NK cell lymphoma in ICC (provisional entity)
  • Breast implant associated anaplastic large cell lymphoma (ALCL): upgraded from provisional status (WHO HAEM4R) to a definite entity (J Clin Oncol 2020;38:1102)
  • Certain T / NK cell neoplastic entities have new nomenclature
    • Indolent T cell LPD of the GI tract has been renamed as indolent T cell lymphoma of the GI tract (WHO HAEM5) or indolent clonal T cell LPD of the GI tract (ICC) due to its potential for disease dissemination, associated morbidity and monoclonal nature
    • Category of nodal lymphomas of T follicular helper (TFH) origin is now unified into a single entity comprising 3 subtypes with new nomenclature
      • Angioimmunoblastic T cell lymphoma (WHO HAEM4R) is now nodal TFH cell lymphoma, angioimmunoblastic type (WHO HAEM5) or follicular helper T cell lymphoma, angioimmunoblastic type (ICC)
      • Follicular T cell lymphoma (provisional, WHO HAEM4R) is now nodal TFH cell lymphoma, follicular type (WHO HAEM5) or follicular helper T cell lymphoma, follicular type (ICC)
      • Nodal peripheral T cell lymphoma with TFH phenotype (provisional, WHO HAEM4R) has been renamed nodal TFH cell lymphoma, NOS (WHO HAEM5) or follicular helper T cell lymphoma, NOS (ICC)
    • Chronic LPD of NK cells, a provisional entity in WHO HAEM4R, has been upgraded to NK large granular lymphocytic leukemia (WHO HAEM5) to reflect the clonal nature of the NK cells
      • Shares certain similarities with T large granular lymphocytic leukemia (e.g., cytologic features and recurrent STAT3 mutations) (Cancers (Basel) 2022;14:5236)
      • Nomenclature and provisional status remain the same under ICC
    • Primary cutaneous acral CD8 positive T cell lymphoma has been downgraded to an LPD in WHO HAEM5 and ICC due to its indolent nature
    • Extranodal NK / T cell lymphoma, nasal type is known simply as extranodal NK / T cell lymphoma under the WHO HAEM5
    • Hydroa vacciniforme-like LPD, an indolent EBV related lesion seen mostly in children, has been renamed hydroa vacciniforme LPD under both classifications
    • Chronic active EBV infection of T and NK cell type, systemic form has been upgraded to systemic chronic active EBV disease (WHO HAEM5) or chronic active EBV disease (ICC)
      • Premalignant, potentially life threatening condition with clonal proliferation of EBV infected T or NK cells that can cause systemic inflammation and organ failure (Immunol Med 2018;41:162)
  • While NK lymphoblastic leukemia / lymphoma, a provisional entity in WHO HAEM4R, remains provisional under ICC, it has been eliminated from WHO HAEM5 (Virchows Arch 2023;482:11)
    • Biologically heterogeneous; overlaps other CD56+ neoplastic entities (e.g., blastic plasmacytoid dendritic cell neoplasm, T lymphoblastic leukemia / lymphoma, acute myeloid leukemia and acute undifferentiated leukemia)
Diagrams / tables

Table 1: T / NK cell entities - comparison of WHO (2016), WHO (2022) and ICC (2022)
WHO HAEM4R WHO HAEM5 ICC
Precursor T cell neoplasms
T lymphoblastic leukemia / lymphoma T lymphoblastic leukemia / lymphoma, NOS T lymphoblastic leukemia / lymphoma

Early T cell precursor lymphoblastic leukemia / lymphoma

Early T cell precursor lymphoblastic leukemia
Early T cell precursor acute lymphoblastic leukemia, NOS
Early T cell precursor acute lymphoblastic leukemia, BCL11B activated
NK lymphoblastic leukemia / lymphoma* [Entity removed] NK cell acute lymphoblastic leukemia*
Tumor-like lesions with T cell predominance
[Not included] Kikuchi-Fujimoto disease [Not included]
[Not included] Indolent T lymphoblastic proliferation [Not included]
[Not included] Autoimmune lymphoproliferative syndrome [Not included]
Mature T / NK cell leukemias
T prolymphocytic leukemia T prolymphocytic leukemia T cell prolymphocytic leukemia
T cell large granular lymphocytic leukemia T large granular lymphocytic leukemia T cell large granular lymphocytic leukemia
Chronic lymphoproliferative disorder of NK cells* NK large granular lymphocytic leukemia Chronic lymphoproliferative disorder of NK cells*
Adult T cell leukemia / lymphoma Adult T cell leukemia / lymphoma Adult T cell leukemia / lymphoma
Sézary syndrome Sézary syndrome Sézary syndrome
Aggressive NK cell leukemia Aggressive NK cell leukemia Aggressive NK cell leukemia
Primary cutaneous T cell lymphomas
Primary cutaneous CD4 positive small or medium T cell LPD* Primary cutaneous CD4 positive small or medium T cell LPD Primary cutaneous small or medium CD4 positive T cell LPD
Primary cutaneous acral CD8 positive T cell lymphoma* Primary cutaneous acral CD8 positive lymphoproliferative disorder Primary cutaneous acral CD8 positive lymphoproliferative disorder
Mycosis fungoides Mycosis fungoides Mycosis fungoides
Primary cutaneous CD30 positive T cell LPD: lymphomatoid papulosis Primary cutaneous CD30 positive T cell LPD: lymphomatoid papulosis Primary cutaneous CD30 positive T cell LPD: lymphomatoid papulosis
Primary cutaneous CD30 positive T cell LPD: primary cutaneous anaplastic large cell lymphoma Primary cutaneous CD30 positive T cell LPD: primary cutaneous anaplastic large cell lymphoma Primary cutaneous CD30 positive T cell LPD: primary cutaneous anaplastic large cell lymphoma
Subcutaneous panniculitis-like T cell lymphoma Subcutaneous panniculitis-like T cell lymphoma Subcutaneous panniculitis-like T cell lymphoma
Primary cutaneous gamma / delta T cell lymphoma Primary cutaneous gamma / delta T cell lymphoma Primary cutaneous gamma / delta T cell lymphoma
Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T cell lymphoma* Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T cell lymphoma Primary cutaneous CD8 positive aggressive epidermotropic cytotoxic T cell lymphoma
[Not included] Primary cutaneous peripheral T cell lymphoma, NOS [Not included]
Intestinal T cell and NK cell lymphoid proliferations and lymphomas
Indolent T cell lymphoproliferative disorder of the gastrointestinal tract* Indolent T cell lymphoma of the gastrointestinal tract Indolent clonal T cell LPD of the gastrointestinal tract
[Not included] Indolent NK cell LPD of the gastrointestinal tract Indolent NK cell LPD of the gastrointestinal tract
Enteropathy associated T cell lymphoma Enteropathy associated T cell lymphoma Enteropathy associated T cell lymphoma
Type II refractory celiac disease
Monomorphic epitheliotropic intestinal T cell lymphoma Monomorphic epitheliotropic intestinal T cell lymphoma Monomorphic epitheliotropic intestinal T cell lymphoma
Intestinal T cell lymphoma, NOS Intestinal T cell lymphoma, NOS Intestinal T cell lymphoma, NOS
Hepatosplenic T cell lymphoma
Hepatosplenic T cell lymphoma Hepatosplenic T cell lymphoma Hepatosplenic T cell lymphoma
Anaplastic large cell lymphoma
Anaplastic large cell lymphoma, ALK positive ALK positive anaplastic large cell lymphoma Anaplastic large cell lymphoma, ALK positive
Anaplastic large cell lymphoma, ALK negative ALK negative anaplastic large cell lymphoma Anaplastic large cell lymphoma, ALK negative
Breast implant associated anaplastic large cell lymphoma* Breast implant associated anaplastic large cell lymphoma Breast implant associated anaplastic large cell lymphoma
Nodal T follicular helper (TFH) cell lymphoma
Angioimmunoblastic T cell lymphoma Nodal TFH cell lymphoma, angioimmunoblastic type Follicular helper T cell lymphoma, angioimmunoblastic type
Follicular T cell lymphoma* Nodal TFH cell lymphoma, follicular type Follicular helper T cell lymphoma, follicular type
Nodal peripheral T cell lymphoma (PTCL) with TFH phenotype* Nodal TFH cell lymphoma, NOS Follicular helper T cell lymphoma, NOS
Other peripheral T cell lymphomas
Peripheral T cell lymphoma, NOS Peripheral T cell lymphoma, NOS Peripheral T cell lymphoma, NOS
EBV positive NK / T cell lymphomas
[Not included] [variant of PTCL, NOS] EBV positive nodal T and NK cell lymphoma Primary nodal Epstein-Barr virus positive T / NK cell lymphoma*
Extranodal NK / T cell lymphoma, nasal type Extranodal NK / T cell lymphoma Extranodal NK / T cell lymphoma, nasal type
EBV positive T and NK cell lymphoid proliferations and lymphomas of childhood
Severe mosquito bite allergy Severe mosquito bite allergy Severe mosquito bite allergy
Hydroa vacciniforme-like lymphoproliferative disorder Hydroa vacciniforme lymphoproliferative disorder, classic or systemic Hydroa vacciniforme lymphoproliferative disorder, classic or systemic
Chronic active EBV infection of T and NK cell type, systemic form Systemic chronic active EBV disease Chronic active EBV disease (T and NK cell phenotype)
Systemic EBV positive T cell lymphoma of childhood Systemic EBV positive T cell lymphoma of childhood Systemic EBV positive T cell lymphoma of childhood
Note: asterisk (*) denotes a provisional entity
Microscopic (histologic) images

Contributed by Tom Deng, M.D.
Angiocentric destruction

Angiocentric destruction

Coagulative necrosis

Coagulative necrosis

CD3 positive large cells

CD3

CD56

CD56

EBV positivity by ISH

EBER

Board review style question #1

Which of the following conditions is categorized by the WHO 5th edition (2022) as a tumor-like condition with T cell predominance?

  1. Castleman disease
  2. Cold agglutinin disease
  3. Erdheim-Chester disease
  4. Kikuchi-Fujimoto disease
Board review style answer #1
D. Kikuchi-Fujimoto disease is considered as a tumor-like condition with T cell predominance, which is a newly defined category in the WHO 5th edition (2022). Answers C and B are incorrect because Erdheim-Chester disease is a histiocytic lesion while cold agglutinin disease is predominated by plasma cells. Answer A is incorrect because Castleman disease is a proliferation of mostly B cells or plasma cells.

Comment Here

Reference: WHO 2022 & ICC-T / NK cell
Board review style question #2
Which of the following conditions is newly recognized by the WHO 5th edition (2022) and International Consensus Classification as neoplastic?

  1. Indolent NK cell lymphoproliferative disorder of the gastrointestinal tract
  2. Indolent T lymphoblastic proliferation
  3. NK lymphoblastic leukemia / lymphoma
  4. Primary cutaneous acral CD8 positive lymphoproliferative disorder
Board review style answer #2
A. Indolent NK cell lymphoproliferative disorder of the gastrointestinal tract, previously thought to be reactive, is newly recognized as neoplastic. Answer B is incorrect because indolent T lymphoblastic proliferation is not considered neoplastic under WHO 5th edition (2022) but a tumor-like lesion with T cell predominance. Answer C is incorrect because NK lymphoblastic leukemia / lymphoma, a provisional entity under the WHO 4th revised edition, is no longer considered a distinct entity. Answer D is incorrect because primary cutaneous acral CD8 positive lymphoproliferative disorder has been downgraded from lymphoma due to its indolent clinical course.

Comment Here

Reference: WHO 2022 & ICC-T / NK cell
Back to top
Image 01 Image 02