Women with breast implants have a minimal increased risk of developing lymphoma – information for healthcare professionals (18-11-2021)
Information for relevant medical specialties
Since 2014, the Danish Medicines Agency has received a total of 13 reports about women who developed lymphoma known as Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). The relevant medical specialties have been informed about this previously. The Danish Medicines Agency is not aware of any other Danish cases but is closely following the development in and outside Denmark.
What is BIA-ALCL, and how is it treated?
Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) is an extremely rare form of cancer (non-Hodgkin lymphoma) that extends from/is found in the fibrous capsule surrounding the breast implant. The disease causes abnormal growth of T lymphocytes that have a strong gene expression of the Cytokine receptor CD30 protein on the surface and which are negative for anaplastic lymphoma kinase-1 (ALK-1).
About 1,000 cases have been reported worldwide. Contrary to most lymphomas, these T cell lymphomas often have a relatively benign course, especially if malignant cells are only found in the seroma fluid and there is no massive tumour component. In such cases, BIA-ALCL can simply be treated by removing the implant and the entire surrounding fibrous capsule (an “en bloc resection”, the recommendation being to include a small amount of surrounding tissue to ensure a free margin). Chemotherapy and/or immunotherapy have been given in some cases, and a small number of patients also needed radiotherapy. A total of 36 patients have died due to the disease1 2 3.For women with a confirmed BIA-ALCL diagnosis and two implants, it is recommended to remove both implants and the surrounding fibrous capsule.
The above figure is from a report from the FDA.10
Incidence of BIA-ALCL
Only a few studies have calculated the incidence rate of BIA-ALCL since data on the use of different types of implants are not freely available. The TGA, the medicines agency in Australia, has assessed overall that the absolute risk of the disease is currently between one in 3,000 to one in 30,000 women with implants, depending, among other things, on implant type, but with considerable uncertainty due to insufficient registration [11-15]. A European study has recently estimated the prevalence of BIA-ALCL for all European countries. Among the countries accounting for the majority of reported cases, the incidence rate was one out of 9,121 women with implants. The incidence rate in Denmark was estimated at one out of 7,061 women with implants (Pompeo et al.)
What causes it?
The causal mechanism remains unclear, but there are speculations whether the texture of the implant, biofilm formation, chronic inflammation, surgical techniques, etc. may play a part in the development of this lymphoma. However, many of the reported cases do not provide information on all the properties of the implants.
The following appears from the abstract of the latest report from the Scientific Committee on Health, Environmental and Emerging Risks (SCHEER) “FINAL Opinion on the safety of breast implants in relation to anaplastic large cell lymphoma” from 26 March 2021: “The pathogenic mechanisms of the induction of BIA-ALCL are not well understood; current hypotheses include genetic predisposition, bacterial contamination resulting in chronic inflammation, shell shedding of particulates resulting in chronic inflammation, shell surface characteristics leading to friction resulting in inflammation, and implant associated reactive compounds.” The disease latency varies between a few to 20 or even more years. There are several alternatives to breast implants that involve plastic surgery techniques, either using autologous flap tissue or autologous fat transfer. However, patients’ characteristics may limit the application of these techniques. There is a need for further research to better understand the aetiology and pathogenesis of BIA-ALCL. Reporting of new BIA-ALCL cases by the relevant registries is also of major importance to obtain a better estimate of the risk of BIA-ALCL for patients with a breast implant.”
At what point should BIA-ALCL be suspected?
Seroma formation around the implant is a common clinical manifestation, usually occurring six months or later after surgery; any such cases should be evaluated for BIA-ALCL. The swelling will be accompanied by discomfort, tenderness and possibly pain. More rarely, a tumour formation is seen usually in association with the fibrous capsule surrounding the implant, and lymph-node affection can also be seen.
How to evaluate the patient
The diagnosis is usually made by an ultrasound-guided tumour biopsy, if a tumour is present, or an aspirate of seroma fluid for pathological and microbiological testing. The treatment course should be supplemented by mammography and an ultrasound scan, including of the lymph nodes in the armpit and neck. A PET-CT scan is relevant as baseline examination, usually once the diagnosis has been confirmed. If no other explanation for the patient’s persistent seroma is found, surgery should be considered. Both fluid and scar tissue obtained from surgery should be submitted for pathological testing. It is important to instruct the pathologist to make a cytological/histological examination of the samples for the purpose of an evaluation for BIA-ALCL as this requires special staining and immunohistochemical analysis. If BIA-ALCL is suspected, the entire fibrous capsule surrounding the implant should be removed because the disease is capable of infiltrating the capsular tissue.
Should breast implants be removed in healthy women?
Based on the very moderate risk of developing BIA-ALCL, it is not recommended to remove implants in healthy women.
This is partly because of the risks associated with the surgical procedure itself, and partly because it is not known if it will actually reduce the person’s risk of developing the disease.
Remember to report all cases to the Danish Medicines Agency
All suspected and verified cases of BIA-ALCL must be reported as medical device incidents to the Danish Medicines Agency LINK.
France has banned certain types of breast implants
On 4 April 2019, the French authorities banned breast implants with a certain textured surface from six different manufacturers on the French market, the reason being that a possible causal relationship between BIA-ALCL and the implants cannot be ruled out. The ban does not cover export/import/manufacture, so the products may, in principle, still be marketed and used in the EU and the rest of the world. LINK and LINK. The manufacturer Allergan has subsequently chosen to stop the production and sale of its Biocell textured implant.
More information
Lisbet Rosenkrantz Hölmich, Clinical Professor, Consultant, MD , Herlev Hospital, Department of Plastic Surgery, serves as specialist with contact to foreign researchers and is gathering the Danish data. In this connection, she offers to help with reporting and can facilitate contact to haematologists, etc. This obviously requires that patients have consented to the disclosure of their data. In addition, Francesco Annibale d´Amore, Consultant Haematologist and Clinical Professor and Chair, MD, Aarhus University Hospital, Department of Haematology, makes himself available for collegiate advice.
Contact
The Medical Devices department, or Morten Sichlau Bruun, Special Adviser.