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 consists of B-cells and T-cells that are circulating in the blood or are in the soft tissues of our body. Anaplastic Large Cell Lymphoma (ALCL) is a rare type of lymphoma. It is a cancer of the T-cells that can affect anyone in their life-time (men and women) regardless of whether they have had surgery for anything. It is known to occur in the breasts of women who have never had breast implants, but is extremely rare, with an estimated risk of 3 in 100 million. It is so rare most people had never heard of it. If you have breast implants, this rare disease is more common. When it occurs in women with breast implants it is called Breast Implant Associated – Anaplastic Large Cell Lymphoma (BIA-ALCL). In this setting, 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 rare we are learning more about it each year, especially now that an association with implants has been discovered. It was in fact first discovered way back in 1997 associated with a saline breast implant. Most medical people have only heard about it in the last 10-years but because it is so rare, most surgeons have never dealt with a case personally. We do know a lot more about it in 2018 compared to just 1-year 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 this 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?

The first case of BIA-ALCL was reported as recently as 1997. A few years ago the most reliable frequency of occurrence of BIA-ALCL was 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 higher. It looks as though it may occur more commonly in some areas of the world than others. For example in Australia, there seems to be a much higher incidence and a suggestion recently was that in some hospitals the occurrence was 1 in 3000 in women with Biocell macro textured implants. One specific hospital in Australia has had 5 cases. 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 and as data has been collected as of November 2017 the total number of reported cases in the UK was 41. This is against a background of an estimated 100,000 implants being placed per year although those figures are uncertain. We would therefore expect to see a few cases per year in the UK. Knowing the frequency of occurrence requires the implant manufacturers to release their national sales data, and due to commercial sensitivity this has not occurred as yet in the UK (as of September 2017), although Mr Turton has even requested they release this through personal communication. As of November 2017, Mr Turton has never seen BIA-ALCL in any of his breast augmentation patients in over 14 years of performing this surgery. He is also not aware of any of his colleagues who perform breast surgery in Leeds having an occurrence in any of their patients either. It is a rare disorder but an important one to know about.

Latest Information On BIA-ALCL

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. Some of the most recent information on BIA-ALCL can 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 ALCL and 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. In addition the European Commission has published their report in 2017 which can be downloaded 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 current theories on causation of BIA-ALCL is 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 called T-cells) to multiply and then become cancerous and that this is in reponse to bacteria in biofilm. But as yet there is no conclusive evidence this is the case. 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 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 in the gloves form the patient’s skin. The implant is rinsed in surgical Betadine, an iodine preparation that kill bacteria. 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 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 the of the World’s most expert cosmetic breast surgeon’s who developed the 14-point protocol, in Dallas, USA.

 

Although ALCL is very rare, where this uncommon risk is too great a fear, it is better to select to use the smooth shell implant. These are a very good alterantive, but they are best placed in a partial sub-pectoral position otherwise capsular contraction is higher than with the textured variety. Microtextures are available and these might also be a good alternative. However, please understand that when dealing with something that is so rare, there is unreliable 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 thousand times less likely than that.

 

This is an example of a patient who developed a sudden swelling around her left breast implant. This was not ALCL, but what occurred was that the implant was 13 yrs old and had ruptured. She had a Eurosilicone implant that had been placed by another provider 13 years previously. It is a good example of how a swelling around an implant can be caused by rupture. However, a swelling can also be the first sign of the very rare lymphoma ALCL, and patients with a swelling should be assessed by a specialist to make sure it is not something more sinister.

 

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 augnation 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 very small number of cases have been reported in the absence of a peri-prosthetic fluid collection in association with a severe capsular contraction, a mass 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 ultrasound. Fluid can be drained off under ultrasound guidance and sent for special lymphoma cell tests after analysis of the fluid under a microscope and by a process called flow cytometry (a test looking for characteristic CD30 positive cells).

A breast MRI for further evaluation and referral to a breast multidisciplinary team (MDT) with experience of this disease would be recommended, if there is a strong suspicion, or uncertainty.

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 immunohistochemistry testing for CD30 and Anaplastic Lymphoma Kinase (ALK) markers will be performed. BIA-ALCL can only be confirmed if 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.

 

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 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 are still regarded as 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 capsule and will be classified as Stage I disease according to the new, as yet un-adopted classification by Clemens et al. Treatment will include complete capsulectomy and implant removal alone, 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 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

  1. Ensure your surgeon understands about BIA-ALCL. Ask what steps they take to reduce bacterial contamination of your implant (one possible link).
  2. Consider the implant types- smooth versus textured. There is no one right implant for everyone but risks are different.
  3. 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.
  4. 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”
  5. If you are worried about ALCL you may arrange an appointment to speak to me