Cases of Breast Implant-Associated Lymphoma Continue to Accumulate

MIAMI BEACH — As more cases of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) emerge, clinical experience has shown the disease to be heterogeneous and that multidisciplinary management provides the best results, a breast surgeon said here.

As of late 2022, the American Society of Plastic Surgeons global tracking network had accumulated 1,333 cases of BIA-ALCL worldwide and 35 associated deaths. The total included 402 cases and eight deaths in the U.S. The FDA has received information on 59 deaths, said Kelly K. Hunt, MD, of the University of Texas MD Anderson Cancer Center in Houston, during the Miami Breast Cancer Conference.

“[BIA-ALCL] is associated with textured breast implants; it does not appear to be associated with smooth implants,” she said. “It’s felt to be the texturing process that results in this disease, but the pathogenesis is really not completely understood yet. There are a lot of different theories, but it’s thought that production of inflammatory cytokines is involved.”

A study published last year indicated that the number of cases of BIA-ALCL in the U.S. and elsewhere has been underestimated. However, the study period ended in 2018. At FDA request, Allergan withdrew its textured implants from the market in 2019. Many women still have the implants because the FDA did not advise removal in the absence of concerning signs or symptoms.

The latest development occurred last year when the FDA issued a safety communication stating that the risks associated with textured breast implants extended beyond ALCL. About 20 cases of squamous-cell carcinoma (SCC) and about 30 cases of B-cell lymphoma had been linked to the devices. Arising in the scar tissue (capsule) surrounding the implant, the SCCs can be particularly aggressive, said Hunt.

“They’re very rare but emerging, and we’re starting to see more and more reports,” she added.

The link between breast implants and ALCL came to light about 15 years ago with a report of about six cases of ALCL involving the breast, three of which occurred in women with breast implants. A search of the literature turned up an additional 15 cases of BIA-ALCL. The first known case of BIA-ALCL was reported in 1997.

BIA-ALCL represents a localized subtype of ALCL, said Hunt. Systemic ALCL tends to be an aggressive disease that requires treatment with chemotherapy, immunotherapy, and stem-cell transplantation. Systemic ALCL is associated with ALK rearrangement (ALK+), whereas ALK– disease often has a poor prognosis. Localized ALK-ALCL included primary cutaneous ALCL (typically indolent), BIA-ALCL, and mucosal ALCL.

Symptoms most often associated with BIA-ALCL are late-onset periprosthetic effusion and increased breast volume and tenderness. Implant rupture also causes effusion that might be mistaken for BIA-ALCL, Hunt noted. Some patients have palpable breast masses, which are indicative of more advanced disease, and in other cases, axillary lymphadenopathy might be present. Less commonly, patients with BIA-ALCL have capsular contracture and deformation of the breast profile.

Surgery, including removal of the implant and capsulectomy, is the primary treatment for BIA-ALCL and appears curative without chemotherapy or radiotherapy in some cases. Complete surgery, including capsulectomy, is associated with the best outcomes and the fewest complications.

Pathologic processing emphasizes comprehensive sampling of the capsule, which usually contains lymphoma cells except in cases of very early-stage disease. At the request of the FDA, an expert panel developed a best practices guideline for pathologic diagnosis of BIA-ALCL. Additionally, the National Comprehensive Cancer Network has developed guidelines for diagnosis and treatment of BIA-ALCL.

“BIA-ALCL is a heterogeneous disease that can involve the implant capsule, soft tissue, regional nodes but distant sites as well,” said Hunt. “Complete capsulectomy is really important for local control and survival. Especially for patients who present with effusion, it’s important to interrogate those and make sure the patient gets treated as early as possible because that can be curative.”

“We evaluate nodal involvement at diagnosis, and we target those PET-avid nodes for resection,” she continued. “We also have a multidisciplinary team that discusses the management of these patients. We have a lot of translational science ongoing, trying to understand not only the pathogenesis [but also] improved opportunities for treatment.”

During a discussion that followed her presentation, Hunt said she removes the capsule from both breasts and has both of them processed. Occasionally, pathologists find undetected BIA-ALCL in the opposite capsule.

Also during the discussion, plastic surgeon Babak Mehrara, MD, of Memorial Sloan Kettering Cancer Center in New York City, pointed out that BIA-ALCL is associated with macrotextured implants, which have been withdrawn from the market. Microtextured implants have not been linked to the malignancy and remain in use.

Not every patient with a macrotextured breast implant develops ALCL. Studies have yet to identify factors that seem to be associated with increased risk, Hunt told MedPage Today.