Researchers at the Rand Corp. said that a systematic review of the literature has led them to conclude that anaplastic large cell lymphoma may be associated with breast implants, but that it is a less-aggressive form of the disease.
The literature review, available to members of the American Society of Plastic Surgery, has been accepted for publication in the journal Plastic and Reconstructive Surgery. It is available online and free to the public at the journal’s website.
The Food and Drug Administration raised the potential for a link between anaplastic large cell lymphoma (ALCL) and implants in January. The agency conducted its own review and found 60 cases of ALCL in the estimated 5 million to 10 million women with breast implants worldwide. The FDA said that the background rate of ALCL in the United States is about 1 in 500,000 women.
In the Rand Corp. study, Dr. Benjamin Kim and associates found 36 cases of non-Hodgkin’s lymphoma in women with implants, and 29 (81%) of those lymphomas were ALCL. The first reported cases date to 1995. Despite the fact that lymphomas of the breast and ALCL are extremely rare, there have been multiple cases reported in the literature of ALCL development next to breast implants, according to the authors.
However, the evidence of the association between implants and ALCL development has been inconclusive, said the authors. This is what prompted their systematic review.
They searched various databases, including PubMed, Embase, and Web of Science, starting as far back as 1966 for PubMed and Embase. They limited the search to human topics and articles written in English. Initially, 884 titles were identified, 83 were selected for review, and 14 more were given to Rand by several clinical experts. In all, 34 studies, covering the 36 cases, were included in the analysis.
Patient characteristics were not noted in all the studies. In the 29 ALCL cases, 14 presented with a seroma and 1 without a seroma; no data were reported for the remaining 14 cases. Data were uneven on whether the implants on the affected or contralateral side had ruptured during surgery, or whether the capsule was associated with inflammation. Treatment data were also full of gaps.
The authors noted that there are at least two – and possibly three – distinct forms of ALCL: ALK-positive ALCL, ALK-negative ALCL, and primary cutaneous ALCL (PCALCL). Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that is expressed in 60%-85% of ALCLs, but rarely in PCALCL, said the authors.
All of the women who developed ALCL had ALK-negative disease (that is, in the instances in which the ALK status was reported). Most of the women who had data reported had the disease localized in the implant capsule. For the women who had outcomes reported, none died from their disease.
The authors concluded that the implant-associated ALCL follows a course that is closer to PCALCL than to the systemic ALK-negative disease.
They noted many limitations to their study, including that ALCL may have been underreported and that there were inconsistencies in how individual pathologists may have interpreted slides. Finally, they acknowledged that not all cases of ALCL are likely reported, which has the effect of "skewing estimates of its true incidence downward."
But the evidence from the review suggests that "implant-associated ALCL is more similar to cutaneous ALCL than systemic ALCL and may therefore only require surgical removal of the affected implant and capsule and clinical follow-up, as opposed to aggressive adjuvant chemotherapy and/or radiation therapy," said the authors.
The study was supported by the Plastic Surgery Educational Foundation and the Aesthetic Surgery Education and Research Foundation through unrestricted grants from Allergan, Mentor Worldwide, and Sientra. Neither the sponsors nor the manufacturers had a role in the design or execution of the study.