Anaplastisch T-cel lymfoom

WHO 2022: Anaplastic large cell lymphoma


WHO-HAEM5 recognizes 3 entities within the family of anaplastic large cell lymphomas (ALCL), which are mature T-cell lymphomas characterized by pleomorphic tumour cells with uniform strong expression of CD30 and often defective expression of T-lineage markers.

  • ALK-positive anaplastic large cell lymphoma

  • ALK-negative anaplastic large cell lymphoma

  • Breast implant-associated anaplastic large cell lymphoma


NB. Primary cutaneous ALCL is grouped under primary cutaneous T-cell lymphoid proliferations and lymphomas acknowledging its clinico-pathological relation to these disorders and highly favorable outcome in contrast to systemic ALK- ALCL.

ALK positive anaplastic large cell lymphoma (ALK+ ALCL)

ALK-positive ALCL was acknowledged as a heterogeneous entity. Recent genomic analyses have led to recognition of several genetic contexts with prognostic implications, although there are currently insufficient data to determine if these are best regarded as prognostic markers or molecular subtypes.


ALK negative anaplastic large cell lymphoma (ALK- ALCL)

ALK-negative ALCL bearing TP63 rearrangements, loss of TP53 and/or overexpression of IL-2Rα are associated with poor outcomes. Although initial reports suggested DUSP22 rearrangement to be associated with a favorable 5-year overall survival comparable to ALK+ ALCL, more recent studies have not confirmed this association. Some specific molecular alterations in ALK- ALCL have been shown to correlate with

morphologic features. ALCLs with DUSP22 rearrangement are characterized by neoplastic cells with a “doughnut cell” appearance and sheet-like growth pattern with less pleomorphic cells; LEF1 expression may serve as a surrogate marker for this

molecular alteration. A subset of cases with Hodgkin-like morphology shows aberrant ERBB4 protein expression, while more anaplastic cells are seen in cases with JAK2 rearrangement.


Breast implant-associated ALCL (BIA-ALCL)

BIA-ALCL is an entity distinct from other ALK- ALCL; notably it is a usually non-invasive neoplasm arising in association with textured-surface breast implants and is associated with an excellent outcome. Invasion of adjacent structures, however, worsens the prognosis. Recent studies highlight the importance of TH2 allergic inflammatory response, a role for immune-evasion via amplification of 9p24.1 and overexpression of PD-L1 in over 50% of the cases and constitutive JAK-STAT activation by somatic mutations of STAT3, STAT5B, JAK1 and JAK2 and loss-of function mutations of SOCS1 and SOCS3.