Elsevier

Journal of Autoimmunity

Volume 65, December 2015, Pages 64-73
Journal of Autoimmunity

Review article
Silicone implants and lymphoma: The role of inflammation

https://doi.org/10.1016/j.jaut.2015.08.009Get rights and content

Highlights

  • Chronic infection and inflammation have been implicated as the causative mechanisms in the development of lymphomas.

  • The connection between ALCL and breast implants has been hypothesized for several years. Since the earliest report in 1997, numerous cases were described, with 173 cases of breast-implant associated ALCL being recently reported.

  • An immune reaction to silicone or other substances used in manufacturing process of breast implants, might cause T cell infiltration with later clonal expansion of T lymphocytes. The T-cell response may be as well reaction to biofilms.

  • Skin injuries and Sjögren's syndrome are two conceptual models providing intriguing insight to the connection between silicone implants and ALCL.

Abstract

The risk of hematological malignancies is mainly determined by genetic background, age, sex, race and ethnicity, geographic location, exposure to certain chemicals and radiation; along with the more recently proposed immune factors such as chronic inflammation, immunodeficiencies, autoimmunity, and infections. Paradigmatic examples include the development of lymphoma in Sjögren's syndrome and Hashimoto thyroiditis, gastric MALT lymphoma in Helicobacter pylori infection, or lymphomas associated with infections by Epstein–Barr virus, human herpes virus 8 (HHV 8) and leukemia/lymphoma virus 1 (HTLV-1). A growing number of reports indicates an increased risk of lymphoma, particularly of the anaplastic large cell (ALCL) type. The implants, specifically those used in the past, elicit chronic stimulation of the immune system against the prosthetic material. This is particularly the case in genetically susceptible hosts. We suggest that polyclonal activation may result in monoclonality in those at risk hosts, ultimately leading to lymphoma. We suggest that patients with an inflammatory response against silicone implants be monitored carefully.

Introduction

Materials used as implants were developed with the purpose to be chemically inert, exhibit temperature stability, resistance to oxidation, microorganisms, mechanical strain, and body fluids. Additionally they are to cause no inflammation or hypersensitivity, maintain their shape, be amenable to sterilization, and should not be carcinogenic [1]. Silicone was the first material believed to display such features and was originally used as a human medical implant in 1946 for the repair of large bile ducts [2]. Silicone is currently found in numerous devices used in medical practice: including breast and larynx implants, elastomeric toe and finger joints, hydrocephalus shunts, implantable infusion pumps and ports, tissue expanders, intraocular lenses, pacemaker and defibrillation devices, penile and testicular prostheses [3]. The effects of silicone on chronic inflammation must also take into account the numerous factors proposed to facilitate tolerance breakdown and autoimmunity development in women [4], [5] and the genetic and epigenetic susceptibility [6], [7], [8].

Section snippets

Silicone

Silicones refer to a large family of organic silicone polymer products with a main chain of alternating silicon and oxygen atoms. Typically, each silicon in the chain carries two methyl groups and the material is called polydimethylsiloxane (PDMS), seen in Fig. 1. The physical and chemical properties of the polymer are determined by the chain length, with longer chains more viscous than shorter ones. Further vulcanization of the polymer crosslinks individual chains and, depending on the degree

Breast implants

Breast implants are performed for either esthetic reasons or reconstruction following mastectomy. Since the introduction of silicone gel prosthesis in 1962 by Cronin and Gerow, breast augmentation has become the most commonly performed operation in cosmetic surgery [35]. It has been estimated that this procedure has been performed on over 10 million women worldwide [36]. Breast implants contain a type of medical silicone called polydimethylsiloxane (PDMS) and can be further classified as: (i)

Primary breast lymphomas

Lymphoma is a rare form of primary breast malignancy, accounting for 0.04–5% of all breast tumors and approximately 1.7% of extranodal lymphomas which may be found in the skin (21%), soft tissues (17%), bone (17%), lungs (11%), and liver (8%) [40], [41], [42], [43], [44], [45], [46], [47], [48], [49]. The majority (∼90%) of breast lymphomas are of B-cell origin; T-cell lymphomas however are predominantly peripheral. Anaplastic large cell lymphoma (ALCL) accounts for 3% of newly diagnosed

Clinical features of breast-implant associated ALCL

Implants were developed with intention of being biologically inert, however subsequent observations led to the restriction of their use by the FDA between 1992 and 2006 [73]. It is currently estimated that over 10 million women worldwide have breast implants [36]; based on the progressively increasing number of breast implant associated ALCL, the FDA issued a new alert in 2011 [72]. France observed 18 cases of breast implant associated ALCL since 2011. Subsequently in 2015 the Ministry of

Cardiac pacemakers and defibrillators

Pacemakers are generally made of titanium, silicone elastomer, polyurethane, and other materials. The literature reports three cases of diffuse large B-cell lymphoma (DLBCL), two arising in the pacemaker pocket and one in the implantable cardioverter-defibrillator pocket [87], [88], [89], [90]. Other neoplasms: including B-cell neoplasms, extramedullary plasmacytoma, multiple myeloma, carcinoma of the breast, sarcoma, and inflammatory myofibroblastic tumor can be found in the site of the

Proposed mechanisms for breast-implant associated ALCL

Silicone implants are associated with mild to severe scarring of the surrounding tissue, ultimately leading to development of a capsule [119]. In some cases, inflammation may perpetuate and eventually lead to polyclonal and possibly monoclonal lymphocytic activation. We believe that the immune response to silicone includes a local and a systemic component. The systemic response has been termed siliconosis and includes a constellation of signs and symptoms: the presence of diffuse pain, morning

Final remarks

In predisposed individuals, individual background plays a major role in dictating immune system response to external stimuli, through genetic [149], [150] and epigenetic [151], [152], [153] features. Either transient (e.g. infections) or permanent (i.e. implants) stimulation may cause further chronic immune system activation [154], [155], [156] possibly due also to an adjuvant effect. This effect can alternatively lead to the development of autoimmune diseases or lymphoma, ultimately depending

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