Département de Pathologie, CHU de Toulouse, Institut Universitaire du Cancer de Toulouse, Toulouse, France
Inserm, U.1037, centre de recherche en cancérologie de Toulouse-Purpan, laboratoire d’excellence Toucan, Toulouse, F-31100 France
Unité hémopathies lymphoïdes, groupe hospitalier Henri Mondor, Créteil, France
Inserm U955 et université Paris-Est, Créteil, France
Département de pathologie, groupe hospitalier Henri Mondor, Créteil, France
Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a new entity recognised in the 2017 updated WHO classification of haematological neoplasms. Described for the first time in 1997, the prevalence of BI-ALCL is estimated at between 0.1 and 5 in every 100,000 women with breast implants. The diagnosis of BI-ALCL is based on the pathological examination of the capsule or periprosthetic effusion showing a proliferation of large cytotoxic T lymphocytes expressing CD30 and epithelial membrane antigen (EMA). In 2016, the first French series of BI-ALCL patients described for the first time two BI-ALCL histological subtypes that correlated with the two main clinical presentations: in situ BI-ALCL found in patients with seroma, characterised by lymphoma cells along the border and/or suspended in a serous/fibrinoid material, which is associated with excellent prognosis; and ii) infiltrative BI-ALCL, mostly found in patients with a tumour mass, characterised by invasion of the capsule, with the worst prognosis. The therapeutic management and prognosis of BI-ALCL depend on the extension of the tumour, staged according to the MD Anderson TNM classification. BI-ALCL has an excellent prognosis with overall survival at three and five years of 93% and 89%, respectively. While in situ BI-ALCL (80%) is effectively treated by a capsulectomy alone, infiltrative BI-ALCL (20% of BI-ALCL) is more aggressive and requires a more intensive therapeutic approach. The pathogenesis of BI-ALCL may be explained by multiple intrinsic and extrinsic factors, such as chronic antigenic stimulation due to implant immunogenicity or the microbiome, host genetic susceptibility and acquired genetic alterations. Several distinct steps are likely to result in the transformation of reactive cytotoxic T cells to polyclonal T-cell proliferation, and subsequently BI-ALCL clonal lymphoma. In 2020, the genomic characterisation of a large series of BI-ALCL cases using whole-exome sequencing confirmed the key role of the JAK/STAT pathway, but also highlighted the importance of epigenetic dysregulation in BI-ALCL pathogenesis. Although BI-ALCL is a rare disease, its incidence has doubled in the past seven years in France, leading to the National Agency for the Safety of Medicines (l’Agence Nationale de Sécurité du Médicament [ANSM]) recalling macro-textured and polyurethane implants from the French market. Since 2018, in France, a BI-ALCL registry sponsored by the LYSA/LYSARC collects all clinical and biological data of BIALCL patients via a national multidisciplinary tumour board meeting and Lymphopath network funded by French National Cancer Institute (INCa) that will provide new therapeutic guidelines for improving therapeutic management of BI-ALCL patients and delineate the genetic and environmental risk factors of this disease.