Breast Implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL)

What is ALCL?

ALCL is Anaplastic Large Cell Lymphoma, also termed BIA-ALCL (Breast Implant Associated Anaplastic Large Cell Lymphoma). It is a relatively new diagnosis and is a type of lymphoma that is linked to breast implants in a very small number of cases worldwide. Although ALCL develops close to the breast, it is not a type of breast cancer. Instead, ALCL is a rare form of non-Hodgkin lymphoma, which is a type of cancer of the lymphocytes (white blood cells) in the body’s blood stream. In health, lymphocytes circulate in the bloodstream and are involved in the immune system and the ability to protect your body from bacteria and diseases. In ALCL, the lymphocytes are abnormal, which is the key component of a lymphoma.

What causes ALCL?

The exact cause of ALCL is not yet fully understood. The current best evidence suggests that the cause (pathogenesis) stems from a chronic inflammatory state. This leads to high levels of white bloods cells (T cells) and expansion of abnormal cells. Why the body goes into a chronic inflammatory state is also debateable. Theories include bacterial colonisation of the breast implant surface, toxin release, viral infection, macrophage digestion, chronic allergic inflammation and genetic susceptibility. This activates the same pathway seen in other cancers, such as lymphoma (JAK-STAT3 pathway). In summary, breast implants can create a pro-inflammatory microenvironment that facilitates malignant transformation.

Reference:

DeCoster RC, Clemens MW, Di Napoli A, Lynch EB, Bonaroti AR, Rinker BD, Butterfield TA, Vasconez HC (2021). Cellular and molecular mechanisms of breast implant-associated anaplastic large cell lymphoma. Plastic and Reconstructive Surgery.147(1):30e-41e.

How common is ALCL from breast implants?

ALCL is a rare type of cancer that has been linked to certain types of breast implants. The UK Government records ALCL incidence data, and stratifies these by the brand of implants. The data suggests the heavy thickening of some brands of breast implants (no longer on the market) may be responsible, though more research and investigations are being conducted to clarify the exact mechanism. As of December 2021, there were 81 confirmed cases in the UK, with an estimated incidence of 1 in 16,500 implants. Given this is an evolving field in terms of data, for women thinking about breast implant surgery, it is important to have an open discussion with your plastic surgeon about the specific risks. For women with breast implants, there are no safety concerns or legislation that mandate implant removal. However, we advise patients to be alert for symptoms such as a sudden swelling in one breast, feeling unwell, weight loss, or lumps in the breast or axilla. If any of these symptoms arise, prompt medical assessment is advised. 

When does ALCL happen?

Most patients are diagnosed 5 to 15 years after the initial breast augmentation. At Breast Implant Solutions, we see patients after breast implant surgery at varying timepoints to address all their breast implant health needs, and will always be alert to this rare but important diagnosis.  

References:
Leberfinger AN, Behar BJ, Williams NC, et al. Breast implant-associated anaplastic large cell lymphoma: A systematic review (2017). JAMA Surgery. 152:1161–1168.
Doren EL, Miranda RN, Selber JC, et al (2017). U.S. epidemiology of breast implant-associated anaplastic large cell lymphoma. Plastic and Reconstructive Surgery. 139:1042–1050.

Are there different types of ALCL?

ALCL is classified into subtypes based on the anatomical location and the abnormal cell characteristics. ‘Systemic ALCL’ is when the lymph nodes, organs, and skin are affected. Other types of ALCL primarily affect one particular body part, such as the skin or breasts.

What is systemic ALCL?

Systemic ALCL is when the ALCL has spread from the initial area, and involved other parts of the body. This can involve an abnormal change (termed a ‘mutation’) in the anaplastic lymphoma kinase (ALK) gene. Genes are the instructions that inform the functions of cells, such as T lymphocytes (a type of immune white blood cell). Systemic ALCL with a mutated ALK gene is called ‘ALK-positive’, while systemic ALCL without an ALK mutation is called ‘ALK-negative’. This is the reason why ALK is part of the testing process in ALCL.

What are the signs and symptoms of ALCL?

These can vary from person to person, but below is a list of possible symptoms that have been described:

  • Unexplained weight loss: Sudden and unexplained weight loss
  • Breast changes. Swelling, pain, or lump in one or both breasts. This can be years after the initial implant surgery. 
  • Armpit (axilla) changes: Swelling, pain, or lump. Enlarged lymph nodes can be an early sign of ALCL, and may be painful or painless. Abnormal T-cells (lymphoma cells) often build up in lymph nodes, and hence a lump in the armpit may represent an early sign. We encourage self-examination and being alert to any changes
  • Skin lesions: Red/purple marks on the skin, anywhere on the body, are a sign of cutaneous ALCL. These may itch, and change over time. 
  • Fever: Unexplained, persistent fever, sometimes with night sweats
  • Fatigue: Persistent tiredness or fatigue

The above list of symptoms are vague and non-specific, and can occur in many other less serious conditions. If you have breast implants and experience any of the above symptoms, the statistical chance of ALCL as a diagnosis is extremely small. However, if the symptoms persist, the team at Breast Implant Solutions urge prompt medical assessment. ALCL is a complex diagnosis to make, and it requires a precise medical history, physical examination, imaging, and biopsies. Early detection and correct treatment significantly improve the outcome, and patients with ALCL should be treated in specialist regional centres. 

How is ALCL diagnosed?

ALCL is diagnosed in specialist regional centres, where comprehensive investigations are performed, and patients are managed by a multidisciplinary team of experts. Diagnosing ALCL involves multiple steps, and patients may have seen many different hospital providers prior to a diagnosis. Steps include:

  • Consultation: A full medical history is performed, honing in on the implant history, specific symptoms related to ALCL, and risk factors. A full examination is performed to examine the breasts, lymph nodes, and look for skin signs.
  • Biopsy: A tissue sample is required to send to the laboratory to make a diagnosis of ALCL. The biopsy might include fluid drained from around the breast implant. Samples may also be sent from the lymph nodes, skin lesions, or the capsule itself. A pathologist analyses this to look for the large, abnormal, mutated lymphocytes (anaplastic cells).
  • Imaging: Imaging includes breast ultrasound, chest X-ray, CT (computed tomography) scans, PET (positron emission tomography) scans, or MRI (magnetic resonance imaging) scans. 
  • Laboratory testing: Samples are analysed extensively to look for protein markers on the cell surface using a technique called immunohistochemistry. CD30 and ALK (anaplastic lymphoma kinase) are two specific markers. ALK-positive ALCL means that the ALK protein is present on the surface. Other testing techniques include fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR), which looks for genetic abnormalities.

Questions to ask yourself before seeing a doctor to help diagnose ALCL?

How have your breasts changed?

When did you first notice a change in your breasts or implants?

Do you have swollen glands in the neck or elsewhere?

How is your appetite? Has your weight changed?

Are you more tired than usual?

Do you have skin bumps or rashes? 

Is ALCL dangerous? How serious is a diagnosis of ALCL?

Anaplastic large cell lymphoma is a serious condition that requires prompt diagnosis and appropriate treatment in a specialist centre. Prognosis and treatment depends on the type of ALCL, how early it has been diagnosed, and your individual healthcare assessment. Oncologists use an international prognostic index (IPI) to predict outcomes after lymphomas. The index looks at variables including patient age, daily functioning of activities, stage, lymph node involvement.

What is the survival rate of ALCL?

Prognostic data on survival after a diagnosis of ALCL varies according to the sub-type of ALCL, spread, and patient overall health and IPI. The two main ALCL sub-types are primary cutaneous ALCL and systemic ALCL, which is subdivided into ALK-positive or negative. Estimates of 5 years survival of the three subtypes are as follows:

  • Systemic ALCL (ALK-positive): 70% to 90%
  • Systemic ALCL (ALK-negative): 50% to 70%
  • Primary Cutaneous ALCL: 95%

The above are estimates based on population data, and a more accurate personalised answer would be provided by the healthcare team managing the individual patient.

What are the stages of ALCL?

The extent of how much a disease has spread is referred to as the ‘Stage’. In ALCL, the Lugano classification is often used to stage ALCL, which varies from 1 to 4, often in roman numerals I-IV:

  • Stage I: ALCL located to one lymph node region or one organ/tissue, termed ‘extra-lymphatic’
  • Stage II: ALCL affecting at least two lymph node regions on the same side of the diaphragm, or one lymph node region and one ‘extralymphatic’ region on the same side of the diaphragm.
  • Stage III: ALCL presence in lymph nodes on both sides of the diaphragm.
  • Stage IV: ALCL spread to multiple organs, such as the bone marrow, liver, lungs, skin, or other distant sites.

The letters A and B are used to indicate the presence (A) of absence (B) of systemic symptoms (for example, unexplained fever, night sweats, or weight loss)

Is ALCL cancer treatable? How do you treat ALCL?

ALCL treatment is undertaken at specialised regional centres, where further investigations and multidisciplinary management can be instigated. It is imperative that national guidelines are followed, as time to diagnosis and the correct management is crucial in order to maximise the outcomes for the patient. 

Prognosis and treatment options for ALCL vary on ,multiple disease and patient factors. Potential treatments include one or more of the following:

  • Surgery: Surgical removal of the breast implant, total capsulectomy, and nodes
  • Chemotherapy: Drugs are used to kill the cancer cells and stop their growth and division. Chemotherapy is typically given via a vein so the drugs are distributed through your bloodstream to target the cancer cells. Combinations of chemotherapy drugs are often used.
  • Radiotherapy: This involves high energy radiation to target and destroy cancer cells in the desired location. This is especially useful in localised cutaneous ALCL
  • Targeted Therapy: Targeted therapy can inhibit the ALK protein activity
  • Immunotherapy: This treatment promotes the natural immune system to identify and attack cancer cells.
  • Steroids
  • Stem cell transplants

References:
Turton P, El-Sharkawi D, Lyburn I, et al. (2021) UK Guidelines on the Diagnosis and Treatment of Breast Implant-Associated Anaplastic Large Cell Lymphoma on behalf of the Medicines and Healthcare products Regulatory Agency Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group. British Journal of Haematology. 192(3):444-458. 

Has the UK government offered any advice on ALCL?

The UK government has produced extensive documentation on this relatively ‘new’ diagnosis. To summarise the document, ALCL is an uncommon type of non-Hodgkin lymphoma associated with breast implants. The World Health Organization (WHO) defined this variant in 2016. The main symptom is fluid collection around the implant, causing an increase in breast size over a few weeks. BIA-ALCL cases are relatively rare, occurring years after surgery, and have been associated with textured surface implants. As of December 2021, there were 81 confirmed cases in the UK, with an estimated incidence of 1 in 16,500 implants sold. Patient safety is a priority, and the Medicines and Healthcare products Regulatory Agency (MHRA) continues to monitor the situation and work with healthcare professionals and organizations to provide updated advice. Reporting incidents through the MHRA’s Yellow Card Scheme is encouraged, and patients are advised to consult their surgeon or GP if they experience symptoms related to BIA-ALCL.

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