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Breast Implant-Associated Anaplastic Large Cell Lymphoma

  • T-Cell and Other Lymphoproliferative Malignancies (J Zain, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognised malignancy of T lymphocytes exclusively associated with textured breast implants. This review aims to evaluate existing theories regarding the epidemiology, pathogenesis, clinical evaluation and management of the disease.

Recent Findings

The true incidence of BIA-ALCL is difficult to define. Prevailing pathogenic theories recognise the interplay between textured implants, Gram-negative bacteria, host genetics (e.g. JAK/STAT, p53) and time. Patients typically present with a delayed seroma and less commonly with a capsular mass or systemic disease at an average of 8–10 years after implantation. BIA-ALCL staging has evolved from a “liquid tumour” model to a “solid tumour” classification. For localised disease, surgery involving complete capsulectomy and implant removal is the cornerstone of treatment. For more advanced disease, treatment includes surgery followed by chemotherapy (combination anthracycline-based), radiotherapy and the antibody drug conjugate (brentuximab vedotin).

Summary

The interplay between the Gram-negative biofilm, implant texturing, genetic mutations and time has been implicated in pathogenesis of BIA-ALCL. The identification of a putative infectious cause is not unique to lymphomagenesis. Future research, investigating BIA-ALCL genetic mutations and immunological modulation with Gram-negative biofilm in BIA-ALCL models is warranted.

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References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Barnsley GP, Sigurdson LJ, Barnsley SE. Textured surface breast implants in the prevention of capsular contracture among breast augmentation patients: a meta-analysis of randomized controlled trials. Plast Reconstr Surg. 2006;117(7):2182–2190.

  2. Wong CH, Samuel M, Tan BK, Song C. Capsular contracture in subglandular breast augmentation with textured versus smooth breast implants: a systematic review. Plast Reconstr Surg. 2006;118(5):1224–36.

    Article  CAS  PubMed  Google Scholar 

  3. Ajdic D, Zoghbi Y, Gerth D, Panthaki ZJ, Thaller S. The relationship of bacterial biofilms and capsular contracture in breast implants. Aesthet Surg J. Mar 2016;36(3):297–309.

    Article  PubMed  PubMed Central  Google Scholar 

  4. den Braber ET, de Ruijter JE, Smits HT, Ginsel LA, von Recum AF, Jansen JA. Effect of parallel surface microgrooves and surface energy on cell growth. J Biomed Mater Res. 1995;29(4):511–8.

    Article  Google Scholar 

  5. Henderson PW, Nash D, Laskowski M, Grant RT. Objective comparison of commercially available breast implant devices. Aesthet Plast Surg. 2015;39(5):724–32.

    Article  Google Scholar 

  6. Sforza M, Zaccheddu R, Alleruzzo A, et al. Preliminary 3-year evaluation of experience with SilkSurface and VelvetSurface motiva silicone breast implants: a single-center experience with 5813 consecutive breast augmentation cases. Aesthet Surg J. 2018;38(suppl_2):S62–73.

    Article  PubMed  Google Scholar 

  7. •• Hu H, Jacombs A, Vickery K, Merten SL, Pennington DG, Deva AK. Chronic biofilm infection in breast implants is associated with an increased T-cell lymphocytic infiltrate: implications for breast implant-associated lymphoma. Plast Reconstr Surg. 2015;135(2):319–29 This study identified the distinct microbiome in BIA-ALCL, identifying a possible infectious contributing cause.

    Article  CAS  PubMed  Google Scholar 

  8. Hu H, Johani K, Almatroudi A, Vickery K, van Natta B, Kadin ME, et al. Bacterial biofilm infection detected in breast implant-associated anaplastic large-cell lymphoma. Plast Reconstr Surg. 2016;137(6):1659–69.

    Article  CAS  PubMed  Google Scholar 

  9. Shahriari N, Ferenczi K, Heald PW. Breast implant-associated anaplastic large cell lymphoma: a review and assessment of cutaneous manifestations. Int J Womens Dermatol. 2017;3(3):140–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Talwalkar SS, Miranda RN, Valbuena JR, Routbort MJ, Martin AW, Medeiros LJ. Lymphomas involving the breast: a study of 106 cases comparing localized and disseminated neoplasms. Am J Surg Pathol. 2008;32(9):1299–309.

    Article  PubMed  Google Scholar 

  11. Blombery P, Prince HM, Seymour JF. Primary breast lymphoma-population-level insights into an infrequent but increasingly recognized subtype of lymphoma. J Natl Cancer Inst. 2017;109(6).

  12. Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126(1):17–25.

    Article  CAS  PubMed  Google Scholar 

  13. Savage KJ, Harris NL, Vose JM, Ullrich F, Jaffe ES, Connors JM, et al. ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project. Blood. Jun 15 2008;111(12):5496–504.

    Article  CAS  PubMed  Google Scholar 

  14. •• Clemens MW, Medeiros LJ, Butler CE, et al. Complete surgical excision is essential for the management of patients with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol. 2016;34(2):160–8 This study proposed the “solid tumour” staging classifaction of BIA-ALCL and demonstrated the importance of complete surgical excision in the management of disease.

    Article  CAS  PubMed  Google Scholar 

  15. Clemens MW, Brody GS, Mahabir RC, Miranda RN. How to diagnose and treat breast implant-associated anaplastic large cell lymphoma. Plast Reconstr Surg. 2018;141:586e–98e.

    Article  CAS  PubMed  Google Scholar 

  16. Doren EL, Miranda RN, Selber JC, Garvey PB, Liu J, Medeiros LJ, et al. U.S. epidemiology of breast implant-associated anaplastic large cell lymphoma. Plast Reconstr Surg. 2017;139(5):1042–50.

    Article  CAS  PubMed  Google Scholar 

  17. •• Loch-Wilkinson A, Beath KJ, Knight RJW, et al. Breast implant-associated anaplastic large cell lymphoma in Australia and New Zealand: high-surface-area textured implants are associated with increased risk. Plast Reconstr Surg. 2017;140(4):645–54 This study importantly proposed implant-specific risk for BIA-ALCL and reported the strong association between higher-surface-area textured implants and BIA-ALCL.

    Article  CAS  PubMed  Google Scholar 

  18. McGuire P. Reply: risk factor analysis for capsular contracture, malposition, and late seroma in subjects receiving natrelle 410 form-stable silicone breast implants. Plast Reconstr Surg. 2017;140(3):500e.

    Article  CAS  PubMed  Google Scholar 

  19. McGuire P, Reisman NR, Murphy DK. Risk factor analysis for capsular contracture, malposition, and late seroma in subjects receiving natrelle 410 form-stable silicone breast implants. Plast Reconstr Surg. Jan 2017;139(1):1–9.

    Article  CAS  PubMed  Google Scholar 

  20. Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen JS, et al. Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. Plast Reconstr Surg. 2015;135(3):695–705.

    Article  CAS  PubMed  Google Scholar 

  21. Pennock ND, White JT, Cross EW, Cheney EE, Tamburini BA, Kedl RM. T cell responses: naive to memory and everything in between. Adv Physiol Educ. 2013;37(4):273–83.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Turner S. An exploration into the origins and pathogenesis of anaplastic large cell lymphoma, anaplastic lymphoma kinase (ALK)-positive. Cancers 2017;9(141).

  23. Malcolm TI, Hodson DJ, Macintyre EA, Turner SD. Challenging perspectives on the cellular origins of lymphoma. Open Biol 2016;6(9).

  24. Lowe DB, Storkus WJ. Chronic inflammation and immunologic-based constraints in malignant disease. Immunotherapy. 2011;3(10):1265–74.

    Article  PubMed  Google Scholar 

  25. Burg G, Kempf W, Haeffner A, et al. From inflammation to neoplasia: new concepts in the pathogenesis of cutaneous lymphomas. Recent Results Cancer Res. 2002;160:271–80.

    Article  PubMed  Google Scholar 

  26. Han A, Newell EW, Glanville J, et al. Dietary gluten triggers concomitant activation of CD4+ and CD8+ alphabeta T cells and gammadelta T cells in celiac disease. Proc Natl Acad Sci U S A. 2013;110(32):13073–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hardy MY, Tye-Din JA. Coeliac disease: a unique model for investigating broken tolerance in autoimmunity. Clin Transl Immunol. 2016;5(11):e112.

    Article  Google Scholar 

  28. Lechner MG, Megiel C, Church CH, Angell TE, Russell SM, Sevell RB, et al. Survival signals and targets for therapy in breast implant-associated ALK--anaplastic large cell lymphoma. Clin Cancer Res. 2012;18(17):4549–59.

    Article  CAS  PubMed  Google Scholar 

  29. Sansone P, Bromberg J. Targeting the interleukin-6/Jak/stat pathway in human malignancies. J Clin Oncol. 2012;30(9):1005–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Gao SP, Mark KG, Leslie K, Pao W, Motoi N, Gerald WL, et al. Mutations in the EGFR kinase domain mediate STAT3 activation via IL-6 production in human lung adenocarcinomas. J Clin Invest. 2007;117(12):3846–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kadin ME, Deva A, Xu H, Morgan J, Khare P, MacLeod RAF, et al. Biomarkers provide clues to early events in the pathogenesis of breast implant-associated anaplastic large cell lymphoma. Aesthet Surg J. 2016;36(7):773–81.

    Article  PubMed  Google Scholar 

  32. Wolfram D, Rabensteiner E, Grundtman C, Böck G, Mayerl C, Parson W, et al. T regulatory cells and TH17 cells in peri-silicone implant capsular fibrosis. Plast Reconstr Surg. 2012;129(2):327e–37e.

    Article  CAS  PubMed  Google Scholar 

  33. Fleury EF, Rego MM, Ramalho LC, et al. Silicone-induced granuloma of breast implant capsule (SIGBIC): similarities and differences with anaplastic large cell lymphoma (ALCL) and their differential diagnosis. Breast Cancer (Dove Med Press). 2017;9:133–40.

    CAS  Google Scholar 

  34. Mazzocchi M, Dessy LA, Corrias F, Scuderi N. A clinical study of late seroma in breast implantation surgery. Aesthet Plast Surg. 2012;36(1):97–104.

    Article  Google Scholar 

  35. Ravi-Kumar S, Sanaei O, Vasef M, Rabinowitz I, Fekrazad MH. Anaplastic large cell lymphoma associated with breast implants. World J Plast Surg. 2012;1(1):30–5.

    PubMed  PubMed Central  Google Scholar 

  36. Cappellano G, Ploner C, Lobenwein S, Sopper S, Hoertnagl P, Mayerl C, et al. Immunophenotypic characterization of human T cells after in vitro exposure to different silicone breast implant surfaces. PLoS One. 2018;13(2):e0192108.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mladick RA. Significance of Staphylococcus epidermidis causing subclinical infection. Plast Reconstr Surg. 2005;115(5):1426–7 author reply 1427–1428.

    Article  CAS  PubMed  Google Scholar 

  38. Clinton A, Carter T. Chronic wound biofilms: pathogenesis and potential therapies. Lab Med. 2015;46(4):277–84.

    Article  PubMed  Google Scholar 

  39. Myint AA, Lee W, Mun S, Ahn CH, Lee S, Yoon J. Influence of membrane surface properties on the behavior of initial bacterial adhesion and biofilm development onto nanofiltration membranes. Biofouling. 2010;26(3):313–21.

    Article  PubMed  Google Scholar 

  40. Teughels W, Van Assche N, Sliepen I, Quirynen M. Effect of material characteristics and/or surface topography on biofilm development. Clin Oral Implants Res. 2006;17(Suppl 2):68–81.

    Article  PubMed  Google Scholar 

  41. Jacombs A, Tahir S, Hu H, Deva AK, Almatroudi A, Wessels WLF, et al. In vitro and in vivo investigation of the influence of implant surface on the formation of bacterial biofilm in mammary implants. Plast Reconstr Surg. 2014;133(4):471e–80e.

    Article  CAS  PubMed  Google Scholar 

  42. Ryan MP, Adley CC. Ralstonia spp.: emerging global opportunistic pathogens. Eur J Clin Microbiol Infect Dis. 2014;33(3):291–304.

    Article  CAS  PubMed  Google Scholar 

  43. Pajkos A, Deva AK, Vickery K, Cope C, Chang L, Cossart YE. Detection of subclinical infection in significant breast implant capsules. Plast Reconstr Surg. 2003;111(5):1605–11.

    Article  PubMed  Google Scholar 

  44. Rieger UM, Mesina J, Kalbermatten DF, Haug M, Frey HP, Pico R, et al. Bacterial biofilms and capsular contracture in patients with breast implants. Br J Surg. 2013;100(6):768–74.

    Article  CAS  PubMed  Google Scholar 

  45. Schreml S, Heine N, Eisenmann-Klein M, Prantl L. Bacterial colonization is of major relevance for high-grade capsular contracture after augmentation mammaplasty. Ann Plast Surg. 2007;59(2):126–30.

    Article  CAS  PubMed  Google Scholar 

  46. Virden CP, Dobke MK, Stein P, Parsons CL, Frank DH. Subclinical infection of the silicone breast implant surface as a possible cause of capsular contracture. Aesthet Plast Surg. 1992;16(2):173–9.

    Article  CAS  Google Scholar 

  47. Galdiero M, Larocca F, Iovene MR, Francesca M, Pieretti G, D’Oriano V, et al. Microbial evaluation in capsular contracture of breast implants. Plast Reconstr Surg. 2018;141(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  48. Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 2014;345(2):196–202.

    Article  CAS  PubMed  Google Scholar 

  49. Wang MY, Liu XF, Gao XZ. Helicobacter pylori virulence factors in development of gastric carcinoma. Future Microbiol. 2015;10(9):1505–16.

    Article  CAS  PubMed  Google Scholar 

  50. Munford RS. Sensing gram-negative bacterial lipopolysaccharides: a human disease determinant? Infect Immun. 2008;76(2):454–65.

    Article  CAS  PubMed  Google Scholar 

  51. Jappe U. Superantigens and their association with dermatological inflammatory disease: facts and hypotheses. Acta Derm Venereol. 2000;20:321–8.

    Article  Google Scholar 

  52. Irwin MJ, Hudson KR, Ames KT, Fraser JD, Gascoigne NR. T-cell receptor beta-chain binding to enterotoxin superantigens. Immunol Rev. 1993;131:61–78.

    Article  CAS  PubMed  Google Scholar 

  53. Kadin ME, Morgan J, Xu H, Glicksman CA. CD30+ T Cells in late seroma may not be diagnostic of breast implant-associated anaplastic large cell lymphoma. Aesthet Surg J. 2017;37(7):771–5.

    Article  PubMed  Google Scholar 

  54. Morrissey D, O'Sullivan GC, Tangney M. Tumour targeting with systemically administered bacteria. Curr Gene Ther. 2010;10(1):3–14.

    Article  CAS  PubMed  Google Scholar 

  55. Myckatyn TM, Parikh RP. Discussion: breast implant-associated anaplastic large cell lymphoma in Australia and New Zealand: high-surface-area textured implants are associated with increased risk. Plast Reconstr Surg. 2017;140(4):655–8.

    Article  CAS  PubMed  Google Scholar 

  56. Blombery P, Thompson ER, Jones K, Arnau GM, Lade S, Markham JF, et al. Whole exome sequencing reveals activating JAK1 and STAT3 mutations in breast implant-associated anaplastic large cell lymphoma anaplastic large cell lymphoma. Haematologica. 2016;101(9):e387–90.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Crescenzo R, Abate F, Lasorsa E. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 2015;27(4):516–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Di Napoli A, Jain P, Duranti E, et al. Targeted next generation sequencing of breast implant-associated anaplastic large cell lymphoma reveals mutations in JAK/STAT signalling pathway genes, TP53 and DNMT3A. Br J Haematol. 2018;180(5):741–4.

    Article  PubMed  Google Scholar 

  59. Letourneau A, Maerevoet M, Milowich D, et al. Dual JAK1 and STAT3 mutations in a breast implant-associated anaplastic large cell lymphoma. Virchows Arch. 2018. https://doi.org/10.1007/s00428-018-2352-y.

  60. Oishi N, Brody GS, Ketterling RP, Viswanatha DS, He R, Dasari S, et al. Genetic subtyping of breast implant-associated anaplastic large cell lymphoma. Blood. 2018;132:544–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Pastorello RG, D'Almeida Costa F, Osorio C, et al. Breast implant-associated anaplastic large cell lymphoma in a Li-FRAUMENI patient: a case report. Diagn Pathol. 2018;13(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Lee YS, Filie A, Arthur D, Fojo AT, Jaffe ES. Breast implant-associated anaplastic large cell lymphoma in a patient with Li-Fraumeni syndrome. Histopathology. 2015;67(6):925–7.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Clemens MW, Horwitz SM. NCCN consensus guidelines for the diagnosis and management of breast implant-associated anaplastic large cell lymphoma. Aesthet Surg J. 2017;37(3):285–9.

    Article  PubMed  Google Scholar 

  64. Di Napoli A, Pepe G, Giarnieri E, et al. Cytological diagnostic features of late breast implant seromas: from reactive to anaplastic large cell lymphoma. PLoS One. 2017;12(7):e0181097.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Alcala R, Llombart B, Lavernia J, Traves V, Guillen C, Sanmartin O. Skin involvement as the first manifestation of breast implant-associated anaplastic large cell lymphoma. J Cutan Pathol. 2016;43(7):602–8.

    Article  PubMed  Google Scholar 

  66. Kim B, Roth C, Chung KC, Young VL, van Busum K, Schnyer C, et al. Anaplastic large cell lymphoma and breast implants: a systematic review. Plast Reconstr Surg. 2011;127(6):2141–50.

    Article  CAS  PubMed  Google Scholar 

  67. Tardio JC, Granados R. Axillary lymphadenopathy: an outstanding presentation for breast implant-associated ALK-negative anaplastic large cell lymphoma. Int J Surg Pathol. 2015;23(5):424–8.

    Article  CAS  PubMed  Google Scholar 

  68. Cheson BD, Fisher RI, Barrington SF. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–68.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Laurent C, Delas A, Gaulard P, Haioun C, Moreau A, Xerri L, et al. Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes. Ann Oncol. 2016;27(2):306–14.

    Article  CAS  PubMed  Google Scholar 

  70. Campanale A, Boldrini R, Marletta M. 22 cases of breast implant-associated ALCL: awareness and outcome tracking from the Italian Ministry of Health. Plast Reconstr Surg. 2018;141(1):11e–9e.

    Article  CAS  PubMed  Google Scholar 

  71. de Boer M, van Leeuwen FE, Hauptmann M, Overbeek LIH, de Boer JP, Hijmering NJ, et al. Breast implants and the risk of anaplastic large-cell lymphoma in the breast. JAMA Oncol. 2018;4(3):335–41.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Clemens MW, Nava MB, Rocco N, Miranda RN. Understanding rare adverse sequelae of breast implants: anaplastic large-cell lymphoma, late seromas, and double capsules. Gland Surg. 2017;6(2):169–84.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, et al. Five-year results of brentuximab vedotin in patients with relapsed or refractory systemic anaplastic large cell lymphoma. Blood. 2017;130(25):2709–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to H. Miles Prince.

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Conflict of Interest

Prof. Deva is a consultant, research coordinator, educator to Allergan, Mentor (Johnson & Johnson), Sientra, Motiva and Acelity (KCI.) He has previously coordinated industry-sponsored research for these companies relating to both biofilms and breast prostheses. Prof. Prince is a consultant and holds research grants with Allergan, Takeda Oncology and Millenium Pharmaceuticals. Dr. P. Rastogi has no affiliations or financial interests to disclose.

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This article is part of the Topical Collection on T-Cell and Other Lymphoproliferative Malignancies

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Rastogi, P., Deva, A.K. & Prince, H.M. Breast Implant-Associated Anaplastic Large Cell Lymphoma. Curr Hematol Malig Rep 13, 516–524 (2018). https://doi.org/10.1007/s11899-018-0478-2

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