ALCL by any other name: the many facets of anaplastic large cell lymphoma.

Anaplastic large cell lymphomas (ALCLs) encompass a group of CD30(+) non-Hodgkin T-cell lymphomas. While the different subtypes of ALCLs may share overlapping clinical patient demographics as well as histological and immunohistochemical phenotypes, these tumours can drastically differ in clinical behaviour and genetic profiles. Currently, four distinct ALCL entities are recognised in the 2016 WHO classification: anaplastic lymphoma kinase (ALK)(+), ALK(-), primary cutaneous and breast implant-associated. ALK(+) ALCL demonstrates a spectrum of cell cytology ranging from small to large lymphoma cells and characteristic 'hallmark' cells. ALK(+) ALCL consistently demonstrates ALK gene rearrangements and carries a favourable prognosis. ALK(-) ALCL morphologically and immunohistochemically mimics ALK(+) ALCL but lacks the ALK gene rearrangement. ALK(-) ALCLs are associated with variable prognoses depending on specific gene rearrangements; while DUSP22-rearranged cases have favourable outcomes similar to ALK(+) ALCLs, cases with p63 rearrangements carry a dismal prognosis and 'triple-negative' cases (those lacking ALK, DUSP22 and TP63 rearrangements) have an intermediate prognosis. Primary cutaneous ALCL presents as a skin lesion, lacks the ALK gene translocation and carries a favourable prognosis, similar or superior to ALK(+) ALCL. Breast implant-associated ALCL presents as a seroma with a median of 8-10 years after implant placement, lacks the ALK gene translocation and has an overall favourable but variable prognosis, depending on extent of disease at diagnosis and treatment. In this review, we present the clinical, pathological and genetic features of the ALCLs with emphasis on practical points and differential diagnoses for practising pathologists.