Lymphoma associated with breast implants tends to progress by local invasion, not by distant metastates, writes Dr Daniel Fleming
It is now recognised that a specific type of lymphoma is linked to breast implants and Australia has the highest reported incidence in the world.
The first Australian case of breast implant associated anaplastic large cell lymphoma (BIA-ALCL) was recognised in 2007, 10 years after the first case was described in the US.1
The disease typically presents as a sudden swelling of one breast caused by a seroma. Less commonly it presents as a lump in or around the breast.
It is now mandatory to perform an ultrasound guided fine needle aspiration of any symptomatic fluid collection around an implant and to test for cytology. If atypical cells are seen, immunohistochemistry will also be performed looking for specific cell surface markers.
The diagnosis requires the identification of abnormal T cells which are CD30+ and anaplastic lymphoma kinase (ALK) negative. The provisional 2016 WHO classification considers all cases to be malignant lymphoma.2
Patients then have a CT/PET scan and are referred to a haematologist. Disease progression is by local invasion, not distant metastases.
Unusually for lymphoma, the treatment is surgical, removal of both implants and surrounding capsules and excision of any mass disease. This is curative. Only if invasive disease cannot be completely excised does radiotherapy and/or chemotherapy have a role.3
Is BIA-ALCL linked to any specific type of implant?
The disease occurs in both saline and silicone-gel filled implants. No cases have yet been seen in patients who have only ever had smooth-surface implants. Macrotextured implants, with a greater surface area than microtextured implants, have a higher risk. This has led to the theory that bacterial contamination of the greater surface area may be a cause of the BIA-ALCL but this is not yet proven.4
There are other theories, but the common theme is that the rougher surface of textured implants sets up a chronic inflammatory reaction. This, in genetically susceptible individuals and the presence of some other mediator, perhaps bacteria, causes a transformation of T cells into a malignant clone.
How common is it?
This is not known but estimates are changing, upwards and rapidly.
Initially it was thought to be exceedingly rare, less than one in 100,000 patients with implants. With the advent of testing seromas for cytology, it is becoming clear that this was a gross underestimate.
In 2016, the TGA estimated that it could be as high as one in 1000 and it may be even higher than this.5
The reason Australia has the highest reported incidence is probably a combination of the relatively higher prevalence of textured implants compared with the US, the earlier commencement of, and more frequent testing for, the disease and better reporting systems.
New epidemiological analysis and clinical evidence that early disease can spontaneously regress and may spontaneously resolve, suggests that many cases have been missed but have not progressed to an invasive cancer.
Publishing in the Aesthetic Plastic Surgery Journal, 6 researchers from the Australasian College of Cosmetic Surgery, have noted:
• BIA-ALCL has a seven to eight-year median interval from implantation to diagnosis.
• Textured implants have been widely used in Australia since 1991.
• No cases of the lymphoma were identified in the first 16 years of textured implant use when seromas were not tested for serology.
• As cytology testing has been adopted, there has been a commensurate increase in the diagnosis.
• An increasing proportion of the cases diagnosed are seroma-only disease which is now more than 70% and rising.
This begs the question, what happened to the cases that must have occurred prior to the recognition of the disease and the gradual onset of testing for it? There is no reason to suppose they did not exist as seromas in textured implants, have always occurred and the only change has been the cytology testing.
Cancer registry data shows no increase in non-Hodgkins lymphoma in the relevant period7 so they were not misdiagnosed as some other lymphoma. Therefore, they must have remained indolent, regressed or resolved.
The researchers describe two cases of proven seroma-only BIA-ALCLs, one of which showed more than 95% regression during a nine-month period during which she refused treatment.
The second case had no evidence of the disease when she had definitive surgery 10 weeks after a confirmed diagnosis. This is the first clinical evidence that may explain what the epidemiology has strongly suggested – the seroma-only version of the disease is lymphoproliferative and does not necessarily become malignant.
This would not be altogether surprising. The only other disease with the same cell type and markers is primary cutaneous ALCL.8
This disease has a lymphoproliferative presentation called lymphomatopapulosis which can regress and resolve. The malignant and lymphoproliferative versions of the disease are distinguished clinically as they are identical in the laboratory specimens.
What is the prognosis?
Most patients have seroma-only disease and 100% of these have remained disease-free following bilateral implant removal and total capsulectomy.3,4
Bilateral surgery is recommended because bilateral cases have been described. If a mass or invasive disease is present and this is completely excised, patients do well. Patients with incomplete excision who have radiotherapy and or chemotherapy are also mostly cured.
Nineteen deaths have occurred worldwide, some tragically due to the complications of the aggressive systemic treatment that was initially thought to be necessary for all patients.
All patients who did badly had a mass or invasive disease when they were diagnosed. This mortality is in the context of an estimated 40 million patients who have received breast implants.
Much is not yet understood about BIA-ALCL lymphomas. In summary, the clinical and epidemiological evidence is suggesting:
• It is a disease of non-smooth implants whose cause is not yet known.
• It is much less rare than was originally thought.
• Most cases may be lymphoproliferative and not malignant.
• Currently all patients should have a minimum of implant removal and capsulectomies.
• This may be overtreatment and closely monitored trials of mass negative patients will be necessary to establish if this is so.
If you have a patient diagnosed with BIA-ALCL she will likely be told she has cancer and implant removal and capsulectomy is necessary to prevent spread.
Notwithstanding the provisional WHO classification, if after investigation the patient has seroma-only disease, it is more accurate and kinder to tell her she has a condition which may become a cancer and surgery is recommended to be absolutely safe.
Dr Daniel Fleming is a past president of the Australasian College of Cosmetic Surgery and is chairman of of the college’s BIA-ALCL Safety Committee. He is a member of the TGA’s Expert Advisory Panel on the disease. He has practised cosmetic surgery in Brisbane for 23 years.
References:
1. Keech JA Jr, Creech BJ (1997) Anaplastic T-cell lymphoma in proximity to a saline-filled breast implant. Plast Reconstr Surg 100(2):554–555
2. Swerdlow SH, Campo E, Pileri SA et al (2016) The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 127(20):2375–2390
3. Clemens MW, Medeiros LJ, Butler CE et al (2016) Complete surgical excision is essential for the management of patients with breast implant-associated anaplastic large-cell lymphoma. J Clin Oncol 34(2):160–168
4. Loch-Wilkinson A, Beath KJ, Knight RJW et al (2017) Breast implant-associated anaplastic large cell lymphoma in Australia and New Zealand: high-surface-area textured implants are associated with increased risk. Plast Reconstr Surg 140(4):645–654
5. Breast implants and anaplastic large cell lymphoma. Expert advisory panel advice on association with anaplastic large cell lymphoma (2016). https://www.tga.gov.au/alert/breast-implants
6. Fleming D, Stone J, Tansley P (2018) Spontaneous regression and resolution of breast implant-associated anaplastic large cell lymphoma: implications for research, diagnosis and clinical management. Aesth Plast Surg. https://doi.org/10.1007/s00266- 017-1064-z
7. Australian Institute of Health and Welfare 2017. Cancer in Australia 2017. Cancer series no.101.Cat. no. CAN 100. AIHW, Canberra
8. Kadin ME, Xu H, Pavlov I (2012) Breast implant associated ALCL closely resembles primary cutaneous ALCL. Lab Invest 92(Suppl 1):346A
