The UK Guidelines on the Diagnosis and Treatment of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL)
Click here to download a free full text copy of the “UK Guidelines on the Diagnosis and Treatment of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) on behalf of the Medicines and Healthcare products Regulatory Agency (MHRA) Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group (PRASEAG)”, published in the Journal of Plastic, Reconstructive & Aesthetic Surgery 2021. The licence is open access, which means it can be used for non-commercial educational purposes.
What is BIA-ALCL?
The blood cells in our body comprise red cells that carry oxygen and white cells that are part of our immune system. White blood cells comprise B-cells and T-cells that are circulating in the blood or are in the soft tissues of our body. Lymphomas are a type of cancer of these white blood cells. There are many (over 100) different types of lymphoma. Anaplastic Large Cell Lymphoma (ALCL) is an uncommon type of lymphoma. It is specifically a cancer of the T-cells. It can occur in anyone in their life-time (men and women) regardless of whether they have had surgery for anything. Although it is known to occur in the breasts of women who have never had breast implants, and is extremely rare, with an estimated risk of 3 in 100 million, it has been shown to occur with greater frequency in people in the tissue around some types of breast implant. As it is rare it has taken years of research to understand more about it, as even in 2019 when there have been tens of millions of women who have had breast implants across the world over the last 50-years, the number of cases of this uncommon lymphoma that have ever been reported around the world is under 2000. Individual lifetime risk may be 1 in 1000 or lower depending on which data set you review, and which type of implant you are looking at. Statistics on ALCL are prone to change. If you have breast implants, be reassured that this is an uncommon cancer and if it does occur is usually highly treatable when detected early; so educate yourself about how it can present, so you can always get on the correct diagnostic pathway promptly if you get symptoms. But be aware that the symptoms can be the same as someone with a ruptured implant, who has had trauma to the breast or who has no lymphoma. This means it can require patience to evaluate possible causes if you get a change that needs assessing- this in itself can cause you anxiety. When lymphoma of this type (ALCL) occurs in women with breast implants it is called Breast Implant Associated – Anaplastic Large Cell Lymphoma (BIA-ALCL). In this setting, it is distinct from other lymphomas, in that it begins in the tissue immediately next to the cosmetic breast implant- we call this tissue the ‘capsule’.
Is BIA-ALCL a New Disease?
It is not a new disease, but because it is so uncommon we are learning more about it each year, especially now that an association with implants has been discovered. The first patient reported with ALCL next to an implant was in 1997 associated with a saline breast implant. Most medical people have only begun to hear about it in the last 10-years, and it was only recognized as a new disease entity in March 2016 by the World Health Organisation. Because it is so uncommon, most surgeons will have never dealt with a case personally. To put this into perspective, although we see around 60,000 new cases of breast cancer per year in the UK, we would only see around 10-20 new cases of BIA-ALCL per year.
We do know a lot more about it in 2021 compared to just 4-years ago. It is talked about at our surgical planning consultations for breast surgery whenever an implant is going to be used for either cosmetic breast surgery or reconstructive breast surgery. We understand that talking about rare risks can cause alarm and distress but it is important that you as a patient are informed about anything bad that could happen from having an implant- and this is also part of the informed consent process under my care. So please do not be alarmed by surgeons talking about it and if you have any concerns please bring them up. Very rare disorders can be difficult to study, but this is getting better with modern technology as data can be grouped together from across the World – over the last 10-years people have started to collect good quality data on BIA-ALCL and it is being studied by scientists – we are learning more about it.
How Common Is BIA-ALCL?
A number of years ago the frequency of occurrence of BIA-ALCL was under-estimated at 1 in 300,000 breast implants or an annual incidence of 0.1 to 0.3 per 100,000 women with implants. With better reporting the true incidence is now better understood. It may occur more commonly in some areas of the world than others, or this may be in part due to reporting differences; we are not certain. For example in Australia, there seems to be a higher incidence and a suggestion recently was that in some hospitals the occurrence was 1 in 2500 in women with Biocell macro textured implants. One specific hospital in Australia has had over 5 cases associated with it, and another surgeon in New York, has also had a cluster of 8 cases associated with his own practice with reconstructive surgery given his case series a rate of approximately 1 in 350.
The UK regulator (the MHRA) informed surgeons and hospitals in 2011 that there had been no cases reported in the UK and the evidence was uncertain, but they encouraged any cases to be reported. In 2014 the MHRA gave an update on the first 3 cases that were reported. Since then regular data collected by the MHRA had still only revealed 41 cases ever reported by November 2017, and this figure in August 2020 stands at 78 cases. Assessing the background number of implants that are inserted per year in the UK is beset with difficulty. But this is ultimately important if we are to derive a ‘risk estimate’. Some women do of course have several different implant types over a number of years as they may undergo reconstructive surgery with initial use of a tissue expander before changing to an implant, or they have cosmetic implants and have exchanges for problems, for size changes, or even a style change. Therefore, if a patient is diagnosed with BIA-ALCL, the whole chain of previous implants used needs to be known, but we might not know which was the ‘culprit’ implant, or did they all contribute? Currently the risk estimates in the UK are determined by the regulator, the MHRA. The actual number of implants used is not known, as the manufacturers do not publish this data as it is deemed commercially sensitive. One study in Australia that has provided useful information was based on sales data provided by two of the largest manufacturers of breast implants in the world, Mentor and Allergan. They only released their sales data to the investigative researchers. A third manufacturer, Nagor, did not provide their figures for that study leaving some to question their reasons. The other source of information on the numbers of implants being placed per year in the UK is the national Breast and Cosmetic Implant Registry; however this digital registry was only recently commenced (in October 2016) and it has been evolving since its inception. In their first report (Oct 2016 to June 2018), it has been stated that “305 organisations have registered to enter data, of which 275 have done so. Data was submitted to the registry from 109 NHS and 166 independent sector organisations. Since the registry opened on 10 October 2016, 20,095 patients have been recorded as having at least one operation”.
So the figures on estimated implants used per year are difficult to understand, and my own crude estimates are that it is likely to be somewhere between 20 to 50,000 implants placed per year. The figures are really very uncertain though and further developments and more transparency is required. We would therefore expect to see a low number of cases each per year in the UK. Knowing the true frequency of occurrence will require that formal compulsory registries are established in countries across the world using a similar core data set so that collaboration is possible. In addition it is important that the surface texture of the different implants in use is categorised uniformly so that evaluation, comparison, and then communication is as accurate as possible.
For now we must support our own regulatory agency, who are best placed to have the necessary overview of the data to update surgeons and patients of any changes required. The MHRA figures as of November 2021, are based on all textured implant sales data and they quote the rate of BIA-ALCL to be uncommon at 1 in 15,000 implants sold (taking into account the pooled data of all implants used in the UK).
On a further note, as of November 2021, Mr Turton has never seen BIA-ALCL in any of his own breast augmentation or reconstruction patients in over 16-years of performing this surgery as a specialist. As we are a regional centre in Leeds, patients with possible BIA-ALCL are referred to Mr Turton and the multidisciplinary team to help with diagnosis or treatment. All patients under his care have had successful treatment. It is important to remember that it is an uncommon disorder but an important one to know about.
Latest Information On BIA-ALCL
The European Commission published their report in 2017 which can be downloaded here. Our own regulatory agency for devices is called the MHRA. They provide the guidance to hospitals and Doctors about the safety of implants. Their update on BIA-ALCL can be found here. The MHRA have also provided an statement (see here) on the Allergan textured breast implant brand, one of the most popular used throughout Europe over the last 20-years. Some of the most recent information on BIA-ALCL can also be found on the American web sites. The American Society of Plastic Surgeons provide an update authored by Mark Clemens, Associate Professor, Department of Plastic Surgery, at the MD Anderson Cancer Center, Texas. Dr Clemens has a special research interest in BIA-ALCL and Dr Clemens lectures around the world on this topic. The American Regulatory Agency, the FDA provides intermittent updates throughout the year and you can check their latest information here.
Although the first case of BIA-ALCL was in association with a saline filled breast implant, it has been shown to occur independently of the filler material and has been more commonly associated with textured implants (including micro-polyurethane) with no cases to date reported with the sole use of smooth surfaced silicone implants. However, uncertainty exists as most of the ALCL cases reported in breast implant patients failed to include information about the texture of the shell and some manufacturers only imprinted their manufacturer stamp on the back of their implants in the last 10 years.
One of the previous theories on causation of BIA-ALCL was that it is related to a biofilm. A biofilm is where bacteria are attached to an implant surface and surrounded by a protective layer of glycoprotein. It is theorised that in a tiny fraction of patients with breast implants, for whatever reason, the body’s immune system in the layer of tissue next to the implant causes the tissue based white blood cells (these are specifically the T-cells) to multiply and then become cancerous and that this is in response to bacteria in biofilm. But as yet there is no conclusive evidence this is the case and more recent thoughts are that this is not the main driver. However it seems sensible to minimise the risk of bacteria getting on to the implant when it is inserted. Mr Turton uses a 14-stage multi-step protocol to do this. This includes using the correct type of antibacterial skin preparation in theatre, meticulous sterile surgical technique by the whole team, minimising excessive movement around the operating room by non essential staff, using nipple shields to cover your nipple area during the operation- the nipples have bacteria in the ducts just under the skin surface and can easily contaminate the operative field even after surgery has started. It includes changing the surgical gloves prior to the placement of the implant. This is done just in case there is an microscopic contamination on the gloves form the patient’s skin. The implant is rinsed in a triple antiseptic/antibiotic mix. I use surgical Betadine, an iodine preparation that kills bacteria, in combination with two other antibiotics. The implant is inserted into the breast not by forceful pushing where it rubs against the skin edge, by through a special plastic covered funnel device that reduces force on the implant, reduces tissue stretch, and prevents any contact of the implant with the patient’s skin (skin has bacteria in the pores and in the skin squames). In addition the betadine/two antibiotic solutions are mixed and flushed over the implants after they have been inserted in the breast space. Mr Turton learnt this process directly through a personal visit to one of the World’s most expert cosmetic breast surgeon’s who co-developed the 14-point protocol, in Dallas, USA.
Although ALCL is uncommon, the fact that something bad might happen creates a fear. This fear can be disproportionately high given that this is uncommon but if this is the case and you want to have breast implants, it might be better that you decide not to do so, or to use the smooth shell implants. These are a very good alternative for many patients, and extremely popular it the USA. There are next to no cases reported in the world-wide literature from the 1960s to 2020, of any patient developing BIA-ALCL who has only ever had a smooth shelled breast implant, and where there was certainty that no prior exposure to a textured device occurred. Although it is likely that it will occur occasionally we feel that the risk with smooth impacts is lower than that with textured implants. But smooth implants are best placed in a partial sub-pectoral position otherwise capsular contraction is a higher occurrence than with the textured variety. Where some texturing is required Microtextures are available and these might also be a good alternative to macrotexturing. However, please understand that when dealing with something that is relatively rare, there is less reliable data to differentiate between one product and another as the very vast majority of patients with implants do of course never have the problem. To put this into perspective, please remember that during a woman’s lifetime the UK statistics demonstrate that in a woman without any breast implant has a 1 in 8 chance of getting the usual types of female breast cancer. We know this risk does not go up with implants. The occurrence of lymphoma around a breast implant is therefore over a hundred times less likely than a woman’s lifetime risk of breast cancer. The risk of other cancers during a woman’s lifetime (that are the same irrespective of whether you have a breast implant or not) are as follows: lung cancer- 1 in 17; bowel cancer- 1 in 25; uterine cancer- 1 in 36; melanoma- 1 in 40; cervical cancer- 1in 45; brain or other CNS tumour- 1 in 69; ovarian cancer- 1 in 78
Presenting symptoms and signs
All women should report any changes in their breasts. Most of the time changes are related to normal physiological changes (breast pain is often hormonal for example). If the breast is knocked, or you have a fall and hit the breast it is possible to get a swelling around the implant like the one in the photo above. However, these would go away of their own accord, usually after a few weeks of wearing a sports-bra. If something seems out of the ordinary after breast augmentation and it fails to improve after a week or two, it should be looked at by a specialist in this field.
The most common presenting symptom for BIA- ALCL is an obviously swollen breast- usually occurring for no good reason. It is caused by the formation of a delayed fluid collection (>1 year since implant placement) usually on one breast. The fluid build up is between the implant surface and the capsule. It is occasionally associated with a localised abnormal looking capsule thickening or a mass, that might be felt, or seen on USS, or only seen if the surgeon operates and looks at it directly from the inside. However more commonly the capsule may look entirely normal except for the fluid, which often contains free floating debris that is best appreciated on ultrasound or under a microscope. A number of cases have been reported in the absence of a peri-prosthetic fluid collection in association with a severe capsular contraction, a mass in the breast or under the arm, a persistent rash or intense deep itch or as a cutaneous nodule. BIA-ALCL may also occur on both sides at the same time, although this is even more rare.
The differential diagnosis of late serous fluid collection (which actually occurs with far greater frequency than ALCL being the cause), includes infection, trauma, haematoma (blood), implant rupture, double capsule, synovial metaplasia, other breast surgery being done when implants are present, breast cancer and idiopathic causes. These causes greatly outweigh the occurrence of a BIA-ALCL seroma and need to be considered and differentiated by a specialist. Patients without a clear attributable cause or who have a non-resolving peri-prosthetic fluid collection should be further evaluated-: BIA-ALCL needs to be considered.
You would normally be referred to an NHS diagnostic breast unit in a teaching hospital. You should see a consultant who has expert knowledge on breast implants and understands about ALCL. Investigation will therefore be considered with imaging such as ultrasound. Fluid can be drained off under ultrasound guidance and sent for special lymphoma cell tests if appropriate after analysis of the fluid under a microscope and by a process called flow cytometry (a test looking for characteristic CD30 positive cells). The very first time such fluid is drawn off is the best time for the test, and so ensure the person doing the procedure understands how the fluid is to be sent and too whom to check for ALCL.
A breast MRI for further evaluation might be required, and referral to a breast multidisciplinary team (MDT) with experience of this disease would be recommended. If there is a strong suspicion, or uncertainty, you may need your implant to be removed and the capsule excised for histology.
It is paramount that the cytology and pathology request forms state ‘for the exclusion of BIA-ALCL’ so that specific staining and haematopathology review is performed. If surgical exploration has been carried out, fresh seroma fluid and the capsule should be sent for cytology and histopathology to rule out BIA-ALCL. It should be remembered that the appearance of the capsule is often quite normal to the naked eye with the exception of the copious serum. So a normal appearance alone should not be a discriminator if the diagnosis is suspected.
Diagnostic evaluation of seroma fluid should also include standard culture and cytological evaluation. The pathologist must be made aware of the suspicion of BIA-ALCL so that, where appropriate, Wright Giemsa staining and cell block, with further immunohistochemistry testing for CD30 and Anaplastic Lymphoma Kinase (ALK) markers will be performed if appropriate. BIA-ALCL can only be confirmed if there are morphologically abnormal lymphocytes, and it is found in association with the implant capsule or within the effusion and is confirmed on immuno-histochemistry as being CD30 positive and ALK negative. If seroma fluid tests negative for ALCL, it might be a ‘false negative’, so if there is still a concern further testing might still be pursued.
Any abnormal breast mass associated with an implant should be biopsied and in addition to standard pathological assessment be additionally assessed for BIA-ALCL, which is now a provisional distinct entity in the World Health Organisation classification of lymphoid neoplasms.
Any patient diagnosed with BIA-ALCL should have a PET-CT to exclude regional or systemic spread. If an abnormal lymph node is found in the axilla it is recommended that it be excised whole for histology at the time of surgery, as fine needle aspiration cytology is inaccurate.
Vigilance is required especially where a late peri-prosthetic seroma occurs, as early treatment with complete capsulectomy (my preferred technique here is the total en-bloc capsulectomy) and implant removal is associated with an excellent prognosis based on follow up data we have to date. There is a need to provide patients with adequate information, and a discussion of BIA-ALCL must be included as part of the consent process and documented in the patient’s medical record where an implant is being used as part of reconstruction or cosmetic breast surgery. Implants available in the UK are still regarded as acceptably safe for use in augmentation and reconstruction operations and the MHRA does not suggest a change in practice with the current data available.
Treatment of BIA-ALCL
For most patients the disease is confined to the inner capsule and will be classified as Stage I disease according to the new classification by Clemens et al. Treatment may include complete en-bloc capsulectomy and implant removal alone, and for Stage 1 disease adjuvant treatment is often not required. More extensive disease or recurrence after initial treatment by capsulectomy mandates further intervention that is often more aggressive because this creates a risk of spread and even dying from ALCL. You would often need chemotherapy in this context. Survival with more advanced presentations would not always occur despite aggressive intervention.
Reporting cases of BIA-ALCL
There is a strong need for more robust and prospectively collected data to enable better understanding of the incidence, pathogenesis and outcomes for patients diagnosed with BIA-ALCL . Any new cases of BIA- ALCL should be discussed at a Breast MDT and Haematology MDT. They must be reported to the MHRA as per their ALCL alert in 2011.
In the U.K, the recently launched Breast and Cosmetic Implant Registry (BIR) also affords opportunities for registering cases of BIA-ALCL. The BIR was primarily designed to record the details of any individual who has breast implant surgery for any reason so that they can be traced in the event of a product recall or other safety concern relating to a specific type of implant, and requires explicit patient consent.
Find out more
To keep patients up to date about BIA-ALCL, in 2017 I co-authored a review article on ALCL on the Association of Breast Surgery web site. Click here to read Mark Clemens’ paper in the Journal of Clinical Oncology from January 2016. Knowledge about ALCL will grow in years to come, and it is important that patients always seek the most up to date information. Our medical devices regulatory agency reports updated information each year on ALCL cases in the UK, and issues guidance to Hospitals, Surgeons as well as information to patients, on the MHRA website.
You can also find useful information on the Australian Government’s website here. The French Regulatory Agency, the ANSM (l’Agence nationale de sécurité du medicament), have a series of articles on BIA-ALCL, which can be accessed here, though be warned- they are not all in English.
Steps you can take
- Ensure your surgeon understands about BIA-ALCL. Ask what steps they take to reduce bacterial contamination of your implant (one possible link but no firm evidence yet).
- Consider the implant types- smooth versus textured. Consider the different types of texturing available and what is most appropriate in your case. There is no one right implant for everyone but risks are different.
- If you are worried and you have implants, see a specialist. For example, if you have swelling or hardening or a lump after breast implant surgery seek advice. See a specialist.
- As recommended by the FDA “before getting breast implants, make sure to talk to your health care provider about the benefits and risks of textured-surface vs. smooth-surfaced implants. If you have breast implants, there is no need to change your routine medical care and follow-up”
- If you are worried about ALCL you may arrange an appointment to speak to me
Brody, G. S. et al. Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. PRS 2015, 135 (3), 695-705
Atlan M. et al. Characterization of Breast Implant Surfaces, Shapes, and Biomechanics: A Comparison of High Cohesive Anatomically Shaped Textured Silicone, Breast Implants from Three Different Manufacturers. Aesthetic Plast Surg 2016, 40 (1), 89-97
Loch-Wilkinson et al. Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia and New Zealand: High-Surface-Area Textured Implants Are Associated with Increased Risk. PRS 2017, 140 (4), 645-654
McGuire, Risk Factor Analysis for Capsular Contracture, Malposition, and Late Seroma in Subjects Receiving Natrelle 410 Form-Stable Silicone Breast Implants. PRS 2017, 139 (1), 1-9
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Adams, W. P. et al. Macro textured Breast Implants with Defined Steps to Minimize Bacterial Contamination around the Device: Experience in 42,000 Implants. PRS 2017, 140 (3), 427-431
de Boer, M. et al. Breast Implants and the Risk of Anaplastic Large-Cell Lymphoma in the Breast. JAMA oncology 2018, 4 (3), 335-34
Magnusson, M. et al. SPECIAL UPDATE: The epidemiology of Breast Implant Associated Large Cell Lymphoma in Australia and New Zealand confirms the highest risk for grade 4 surface breast implants. PRS 2019
Calobrace, M. B. Letter in response to “Determining the True Incidence of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): The Need for Accurate Data”. Aesthetic surgery journal 2019.