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 has been less certain, as the manufacturers do not routinely 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. At the time, a third manufacturer, Nagor, did not provide their figures for that study. 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 CDecember 2022, Mr Turton has only had one case of BIA-ALCL in one of his own breast augmentation or reconstruction patients in over 17-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 curative treatment. It is important to remember that it is an uncommon disorder but an important one to know about.

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 15; bowel cancer- 1 in 25; uterine cancer- 1 in 36; melanoma- 1 in 47; brain or other CNS tumour- 1 in 69; ovarian cancer- 1 in 78; bladder cancer 1 in 133; cervical cancer- 1in 142.

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 (which was 13 yrs old) 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 than implant rupture.

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.

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.