Commentary

Understanding breast implant-associated anaplastic large cell lymphoma

Cosmetic breast augmentation and implant-based breast reconstruction after mastectomy remain two of the most commonly performed surgeries by plastic and reconstructive surgeons, both in the United States and globally.

With continued monitoring and data collection, the FDA identified an association between breast implants and anaplastic large cell lymphoma in 2011. In March, the FDA’s General and Plastic Surgery Devices Advisory Panel convened to discuss the long-term risks and benefits of breast implants (see related article).

Since the first acknowledgement of an association, we have gained considerable understanding regarding the disease process, how it presents in patients, and how we can treat it.

Incidence

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is thought to be a rare occurrence.

Sameer A. Patel, MD, FACS
Sameer A. Patel

Because of barriers related to global reporting and implant sales data, the exact incidence is unclear, but it is estimated to be anywhere from one in 4,000 patients to one in 30,000 patients with textured breast implants.

To date, the FDA has noted 457 unique medical device reports of BIA-ALCL.

It is almost always seen in patients with a textured surface implant. In cases diagnosed in patients with smooth implants, almost all had a history of both smooth and textured implants. It is thought that some methods of texturing are more likely to lead to BIA-ALCL than others, as different manufacturers employ different techniques for texturing.

BIA-ALCL is not a true cancer of the breast tissue but, rather, a cancer of the cells of the immune system, specifically a T-cell lymphoma. The cancer usually originates from the fibrous tissue that develops around the implant, which is referred to as a capsule. The development of a chronic biofilm infection is also thought to be an integral step in the development of the cancer.

Diagnosis of BIA-ALCL

The average time for patients with textured implants to present with BIA-ALCL is 8 to 10 years after implantation, but it can develop at any time.

The most common presentation is a late peri-implant seroma in a patient who did not have a previous seroma. Less commonly, patients may notice a lump, swelling under the arm (enlarged lymph node), breast pain, breast enlargement, or skin changes such as a rash or ulceration.

Some patients may require an ultrasound, MRI or a PET/CT if BIA-ALCL is suspected. PET/CT may help stage the disease by identifying associated capsular or chest wall masses, lymph node involvement, organ metastases or bone metastases. Sampling of the fluid or a biopsy of any associated lump is required to confirm the diagnosis. Cytology with immunohistochemistry or flow cytometry is a critical diagnostic step. BIA-ALCL tumor cells consistently express CD30 and seldom express ALK.

Recently, the National Comprehensive Cancer Network proposed a TNM classification and staging system like other American Joint Committee on Cancer staging systems. All confirmed cases should be reported to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology, or PROFILE, registry maintained by the Plastic Surgery Foundation.

Treatment

Patients with BIA-ALCL should be treated by a multidisciplinary team that includes plastic surgery, surgical oncology, medical oncology and radiation oncology.

Surgery is the cornerstone of treatment for BIA-ALCL. Removal of the capsule, the implant, and any associated masses in the breast or axilla is recommended. If present, removal of the contralateral breast implant and capsule should be considered as up to 5% of patients will develop contralateral disease.

Resection to negative margins provides the best outcomes among patients with BIA-ALCL. When clear surgical margins are obtained, 5-year OS is approximately 90% and 5-year event free survival is approximately 50%.

Among patients in whom the cancer has spread beyond the capsule and among those whose cancer has spread to lymph nodes or other organs or bone, the survival is worse. External beam radiation therapy is considered for patients with local residual disease, unresectable disease, chest wall invasion or positive margins.

External beam radiation therapy and/or chemotherapy can be considered if the disease has spread outside of the breast or if the cancer cannot be completely removed. Current chemotherapy regimens for systemic BIA-ALCL include those used for first-line treatment of peripheral T-cell lymphomas — combination anthracycline-based chemotherapy — either alone or combined with the use of brentuximab vedotin (Adcetris, Seattle Genetics).

Decisions for treatment should again be made using a multidisciplinary approach.

Counseling patients

Patients considering breast implants, irrespective of the indication, should be counseled on not only the risk for BIA-ALCL, but risks of implants in general.

Informed consent should be obtained documenting a discussion of risks, including BIA-ALCL.

It is important to note that no clear guidelines have been established by the FDA or any other body regarding management of patients with textured implants.

All patients should continue with routine medical follow-up, including mammograms and MRIs when appropriate.

For asymptomatic patients, no specific screening guidelines have been recommended for BIA-ALCL, nor are there recommendations for breast implant removal. Patients should have periodic follow-up with their plastic surgeons and should report any changes in the size, shape or feel of their breasts to their surgeon for further evaluation and workup.

References:

Clemens MW, et al. Aesthet Surg J. 2019;doi:10.1093/asj/sjy331.

U.S. FDA. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Available at: www.fda.gov/medical-devices/breast-implants/breast-implant-associated-anaplastic-large-cell-lymphoma-bia-alcl. Accessed on April 30, 2019.

For more information:

Sameer A. Patel, MD, FACS, is associate professor in the department of surgical oncology at Fox Chase Cancer Center. He can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111.

Disclosure: Patel reports no relevant financial disclosures.

Cosmetic breast augmentation and implant-based breast reconstruction after mastectomy remain two of the most commonly performed surgeries by plastic and reconstructive surgeons, both in the United States and globally.

With continued monitoring and data collection, the FDA identified an association between breast implants and anaplastic large cell lymphoma in 2011. In March, the FDA’s General and Plastic Surgery Devices Advisory Panel convened to discuss the long-term risks and benefits of breast implants (see related article).

Since the first acknowledgement of an association, we have gained considerable understanding regarding the disease process, how it presents in patients, and how we can treat it.

Incidence

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is thought to be a rare occurrence.

Sameer A. Patel, MD, FACS
Sameer A. Patel

Because of barriers related to global reporting and implant sales data, the exact incidence is unclear, but it is estimated to be anywhere from one in 4,000 patients to one in 30,000 patients with textured breast implants.

To date, the FDA has noted 457 unique medical device reports of BIA-ALCL.

It is almost always seen in patients with a textured surface implant. In cases diagnosed in patients with smooth implants, almost all had a history of both smooth and textured implants. It is thought that some methods of texturing are more likely to lead to BIA-ALCL than others, as different manufacturers employ different techniques for texturing.

BIA-ALCL is not a true cancer of the breast tissue but, rather, a cancer of the cells of the immune system, specifically a T-cell lymphoma. The cancer usually originates from the fibrous tissue that develops around the implant, which is referred to as a capsule. The development of a chronic biofilm infection is also thought to be an integral step in the development of the cancer.

Diagnosis of BIA-ALCL

The average time for patients with textured implants to present with BIA-ALCL is 8 to 10 years after implantation, but it can develop at any time.

The most common presentation is a late peri-implant seroma in a patient who did not have a previous seroma. Less commonly, patients may notice a lump, swelling under the arm (enlarged lymph node), breast pain, breast enlargement, or skin changes such as a rash or ulceration.

Some patients may require an ultrasound, MRI or a PET/CT if BIA-ALCL is suspected. PET/CT may help stage the disease by identifying associated capsular or chest wall masses, lymph node involvement, organ metastases or bone metastases. Sampling of the fluid or a biopsy of any associated lump is required to confirm the diagnosis. Cytology with immunohistochemistry or flow cytometry is a critical diagnostic step. BIA-ALCL tumor cells consistently express CD30 and seldom express ALK.

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Recently, the National Comprehensive Cancer Network proposed a TNM classification and staging system like other American Joint Committee on Cancer staging systems. All confirmed cases should be reported to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma Etiology and Epidemiology, or PROFILE, registry maintained by the Plastic Surgery Foundation.

Treatment

Patients with BIA-ALCL should be treated by a multidisciplinary team that includes plastic surgery, surgical oncology, medical oncology and radiation oncology.

Surgery is the cornerstone of treatment for BIA-ALCL. Removal of the capsule, the implant, and any associated masses in the breast or axilla is recommended. If present, removal of the contralateral breast implant and capsule should be considered as up to 5% of patients will develop contralateral disease.

Resection to negative margins provides the best outcomes among patients with BIA-ALCL. When clear surgical margins are obtained, 5-year OS is approximately 90% and 5-year event free survival is approximately 50%.

Among patients in whom the cancer has spread beyond the capsule and among those whose cancer has spread to lymph nodes or other organs or bone, the survival is worse. External beam radiation therapy is considered for patients with local residual disease, unresectable disease, chest wall invasion or positive margins.

External beam radiation therapy and/or chemotherapy can be considered if the disease has spread outside of the breast or if the cancer cannot be completely removed. Current chemotherapy regimens for systemic BIA-ALCL include those used for first-line treatment of peripheral T-cell lymphomas — combination anthracycline-based chemotherapy — either alone or combined with the use of brentuximab vedotin (Adcetris, Seattle Genetics).

Decisions for treatment should again be made using a multidisciplinary approach.

Counseling patients

Patients considering breast implants, irrespective of the indication, should be counseled on not only the risk for BIA-ALCL, but risks of implants in general.

Informed consent should be obtained documenting a discussion of risks, including BIA-ALCL.

It is important to note that no clear guidelines have been established by the FDA or any other body regarding management of patients with textured implants.

All patients should continue with routine medical follow-up, including mammograms and MRIs when appropriate.

For asymptomatic patients, no specific screening guidelines have been recommended for BIA-ALCL, nor are there recommendations for breast implant removal. Patients should have periodic follow-up with their plastic surgeons and should report any changes in the size, shape or feel of their breasts to their surgeon for further evaluation and workup.

References:

Clemens MW, et al. Aesthet Surg J. 2019;doi:10.1093/asj/sjy331.

U.S. FDA. Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Available at: www.fda.gov/medical-devices/breast-implants/breast-implant-associated-anaplastic-large-cell-lymphoma-bia-alcl. Accessed on April 30, 2019.

For more information:

Sameer A. Patel, MD, FACS, is associate professor in the department of surgical oncology at Fox Chase Cancer Center. He can be reached at Fox Chase Cancer Center, 333 Cottman Ave., Philadelphia, PA 19111.

Disclosure: Patel reports no relevant financial disclosures.