title: Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.
abstract: BACKGROUND
  ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants.
  
  
  METHODS
  Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed.
  
  
  RESULTS
  The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively.
  
  
  CONCLUSIONS
  In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal.
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse INSERM, U.1037, Centre de recherche en cancérologie de Toulouse-Purpan, Toulouse laurent.c@chu-toulouse.fr.
authors.forename: C
authors.initials: C
authors.lastname: Laurent
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse.
authors.forename: A
authors.initials: A
authors.lastname: Delas
authors.affiliation: Department of Pathology, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil INSERM U955, Université Paris-Est, Créteil.
authors.forename: P
authors.initials: P
authors.lastname: Gaulard
authors.affiliation: INSERM U955, Université Paris-Est, Créteil Lymphoid Malignancies Unit, AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Créteil.
authors.forename: C
authors.initials: C
authors.lastname: Haioun
authors.affiliation: Department of Pathology, Centre Hospitalier Hôtel Dieu, Nantes.
authors.forename: A
authors.initials: A
authors.lastname: Moreau
authors.affiliation: Department of Pathology, Institut Paoli-Calmettes, Marseille.
authors.forename: L
authors.initials: L
authors.lastname: Xerri
authors.affiliation: Department of Pathology, Centre Hospitalier Lyon-Sud, Lyon.
authors.forename: A
authors.initials: A
authors.lastname: Traverse-Glehen
authors.affiliation: Department of Pathology, Hôpital Gui de Chauliac-Saint Eloi, Montpellier.
authors.forename: T
authors.initials: T
authors.lastname: Rousset
authors.affiliation: Department of Pathology, Centre Hospitalier de Brest, Brest, France.
authors.forename: I
authors.initials: I
authors.lastname: Quintin-Roue
authors.affiliation: Département de Pathologie, Montréal, Canada.
authors.forename: T
authors.initials: T
authors.lastname: Petrella
authors.affiliation: Department of Pathology, Hôpital Ambroise Paré, Boulogne.
authors.forename: J F
authors.initials: JF
authors.lastname: Emile
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse.
authors.forename: N
authors.initials: N
authors.lastname: Amara
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse.
authors.forename: P
authors.initials: P
authors.lastname: Rochaix
authors.affiliation: Department of Pathology, Hôpital Hautepierre, Strasbourg.
authors.forename: M P
authors.initials: MP
authors.lastname: Chenard-Neu
authors.affiliation: Department of Pathology, Centre Hospitalier Henri Duffaut, Avignon.
authors.forename: A M
authors.initials: AM
authors.lastname: Tasei
authors.affiliation: Department of Pathology, Hôpital René Huguenin, Saint Cloud.
authors.forename: E
authors.initials: E
authors.lastname: Menet
authors.affiliation: Histo-Pathology Institut, Nantes.
authors.forename: H
authors.initials: H
authors.lastname: Chomarat
authors.affiliation: Department of Pathology, Hôpital Gui de Chauliac-Saint Eloi, Montpellier.
authors.forename: V
authors.initials: V
authors.lastname: Costes
authors.affiliation: Department of Pathology, Hôpital Nord, Marseille.
authors.forename: L
authors.initials: L
authors.lastname: Andrac-Meyer
authors.affiliation: Department of Pathology, Centre Hospitalier Pasteur L'Archet, Nice.
authors.forename: J F
authors.initials: JF
authors.lastname: Michiels
authors.affiliation: Department of Pathology, Centre Léon Bérard, Lyon, France.
authors.forename: C
authors.initials: C
authors.lastname: Chassagne-Clement
authors.affiliation: Pathology institut of Lausanne, Centre Hospitalier Universitaire Vaudois, Suisse, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: de Leval
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse INSERM, U.1037, Centre de recherche en cancérologie de Toulouse-Purpan, Toulouse.
authors.forename: P
authors.initials: P
authors.lastname: Brousset
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse INSERM, U.1037, Centre de recherche en cancérologie de Toulouse-Purpan, Toulouse.
authors.forename: G
authors.initials: G
authors.lastname: Delsol
authors.affiliation: Department of Pathology, Institut Universitaire du Cancer-Oncopole, Toulouse INSERM, U.1037, Centre de recherche en cancérologie de Toulouse-Purpan, Toulouse.
authors.forename: L
authors.initials: L
authors.lastname: Lamant
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D018427:Breast Implants / Q000009:adverse effects*; D005260:Female; D006689:Hodgkin Disease / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D017730:Ki-1 Antigen / Q000378:metabolism; D017728:Lymphoma, Large-Cell, Anaplastic / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D016411:Lymphoma, T-Cell, Peripheral / Q000139:chemically induced / Q000401:mortality / Q000473:pathology*; D008875:Middle Aged; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012828:Silicones / Q000009:adverse effects*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D017730:Ki-1 Antigen; D011948:Receptors, Antigen, T-Cell; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D012828:Silicones; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: anaplastic/Hodgkin-like subtypes; cytotoxic T-cell; implant-ALCL; mass; seroma