title: Intravascular large B-cell lymphoma associated with silicone breast implant, HLA-DRB1*11:01, and HLA-DQB1*03:01 manifesting as macrophage activation syndrome and with severe neurological symptoms: a case report.
abstract: BACKGROUND
  Silicone implants have been successfully used for breast augmentation and reconstruction in millions of women worldwide. The reaction to the silicone implant is highly variable; it can lead to local inflammatory symptoms, and sometimes to systemic symptoms and disease. Over 80 cases of anaplastic lymphoma kinase-negative anaplastic large cell lymphoma have been reported in patients with silicone breast implants and have been accepted as a new clinical entity. To the best of our knowledge, an intravascular large B-cell lymphoma associated with a silicone breast implant has not been reported previously.
  
  
  METHODS
  A 48-year-old Caucasian woman who presented with high fever was found to have splenomegaly on physical examination. A laboratory diagnosis revealed pancytopenia, hypertriglyceridemia, and hyperferritinemia. She developed signs of altered sensorium, hemiparesis, aphasia, and cauda equina syndrome. On further evaluation, she fulfilled the necessary five out of eight criteria for diagnosis of macrophage activation syndrome/hemophagocytic lymphohistiocytosis. Dexamethasone administration was followed by prompt improvement; however, 3 days later she again manifested high fever, which persisted despite administration of immunoglobulin and cyclosporine A. Her silicone breast implant was considered a possible contributor to her macrophage activation syndrome and was therefore removed. A histological examination of the capsule tissue showed an extensive lymphohistiocytic/giant cell foreign body reaction suggestive of autoimmune/inflammatory syndrome induced by adjuvants. However, the histological examination unexpectedly also revealed an intravascular large B-cell lymphoma.
  
  
  CONCLUSIONS
  The genetic background of our patient with silicone breast implants might have predisposed her to three rare and difficult to diagnose syndromes/diseases: macrophage activation syndrome/hemophagocytic lymphohistiocytosis, autoimmune/inflammatory syndrome induced by adjuvants, and intravascular large B-cell lymphoma. The simultaneous manifestation of all three syndromes suggests causal interrelationships. Human leukocyte antigen testing in all women who undergo silicon breast implantation could in the future enable us to better evaluate the risk of potential side effects.
authors.affiliation: Division of Infectious Diseases, Ospedale Generale, 39100, Bolzano, Italy. molosw@hotmail.com.
authors.forename: Oswald
authors.initials: O
authors.lastname: Moling
authors.affiliation: Department of Hematology, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piccin
authors.affiliation: Department of Pathology, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Tauber
authors.affiliation: Department of General Surgery, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Peter
authors.initials: P
authors.lastname: Marinello
authors.affiliation: Rheumatology Unit, Department of Medicine, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Canova
authors.affiliation: Department of Hematology, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Casini
authors.affiliation: Department of Pathology, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Negri
authors.affiliation: Rheumatology Unit, Department of Medicine, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Bernd
authors.initials: B
authors.lastname: Raffeiner
authors.affiliation: Division of Infectious Diseases, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Binazzi
authors.affiliation: Division of Infectious Diseases, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Latha
authors.initials: L
authors.lastname: Gandini
authors.affiliation: Laboratory of Immunogenetics, Transfusion Medicine Service, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Vecchiato
authors.affiliation: Division of Infectious Diseases, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Rimenti
authors.affiliation: Department of Hematology, Ospedale Generale, 39100, Bolzano, Italy.
authors.forename: Atto
authors.initials: A
authors.lastname: Billio
mesh_terms: D058846:Antibodies, Monoclonal, Murine-Derived; D000971:Antineoplastic Combined Chemotherapy Protocols; D019928:Breast Implantation / Q000009:adverse effects*; D018427:Breast Implants / Q000009:adverse effects*; D003221:Confusion; D003520:Cyclophosphamide; D020878:Device Removal / Q000379:methods; D003937:Diagnosis, Differential; D004317:Doxorubicin; D005260:Female; D005334:Fever; D005549:Foreign-Body Reaction / Q000209:etiology / Q000235:genetics / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology*; D006801:Humans; D051359:Lymphohistiocytosis, Hemophagocytic / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000601:surgery; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D055501:Macrophage Activation Syndrome / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D010198:Pancytopenia; D011241:Prednisone; D012086:Reoperation; D000069283:Rituximab; D020034:Silicone Gels / Q000009:adverse effects*; D016896:Treatment Outcome; D014750:Vincristine
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C571759:R-CHOP protocol; D020034:Silicone Gels; D000069283:Rituximab; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone
keywords: Autoimmune inflammatory syndrome induced by adjuvants (ASIA); Hemophagocytic lymphohistiocytosis (HLH); Intravascular large B-cell lymphoma (IVLBCL); Macrophage activation syndrome (MAS); Silicone breast implant; Siliconosis