When what is now called breast implant–associated anaplastic large cell lymphoma was first recognized and initially described, a number of uncertainties prevailed—mainly, was the association with breast implants real, and was this a true lymphoma? Through the significant efforts of those who tracked down, collected, and reviewed these cases, a more clear-cut understanding was achieved. It appears that there is a real association.

Breast implant–associated anaplastic large cell lymphoma was not being reported in people with systemic lymphomas who just happened to have breast implants, and the association was specific to this histology. Moreover, a characteristic clinical presentation emerged with anaplastic large cell lymphoma confined to a seroma and/or the capsule that surrounded the implant. In a few telling cases, clonal rearrangements of T-cell receptors and other clonal cytogenetic abnormalities were found. It is now generally accepted that this is a rare but real phenomenon.

New Questions Arise

We have become more certain of the “what,” and the “why” largely remains a mystery, but the primary uncertainty became “what to do about it?” Although breast implant–associated anaplastic large cell lymphoma was histologically similar to the systemic disease, there was a sense from the early reports that this was not the same entity as aggressive systemic anaplastic large cell lymphoma. Rather, breast implant–associated anaplastic large cell lymphoma seemed to be more of an indolent or even locally reactive process.

It was almost certain that this was underreported, as the degree of pathology review necessary to diagnose anaplastic large cell lymphoma was not routine for implant removal or capsulectomy occurring after cosmetic surgery. Yet, very few patients had locally disseminated or advanced-stage disease, and fewer deaths were noted than one would expect if aggressive lymphomas were not being diagnosed or treated promptly. In addition, some women reported seromas present for years prior to diagnosis without progression.

Despite this sense of indolence, one could not be certain of this conclusion. Many reports were sparse in terms of details, and follow-up on case reports was short or nonexistent. In addition, most of those diagnosed had received chemotherapy, often with radiation, raising the possibility that it was effective therapy as opposed to indolent biology that has led to a favorable prognosis.

Some Clarification

The enlightening study by Miranda and colleagues published in the Journal of Clinical Oncology and reviewed in this issue of The ASCO Post provides significantly more detail and longer follow-up on the reported cases, clarifying some of the clinical uncertainties.¹ The investigators provided an important refinement of the definition of the condition by excluding cases in which the lymphoma “was confined to skin, patients with breast tumors not adjacent to the fibrous capsule around an implant, or patients who had concomitant systemic disease at time of presentation.”

The inclusion of longer follow-up and the addition of 12 patients (20% of all the cases) who were treated with implant and capsule removal only allow us to see how conservatively managed patients fared. Of the 42 patients with localized disease confined to the capsule, none died of lymphoma, 1 died of unrelated causes, and 93% were in complete remission at last follow-up.

Moreover, there was no apparent advantage to chemotherapy, with equally excellent results in those observed post-surgery or receiving radiation alone. These favorable outcomes lend support to what was previously more of a “gut feeling” that breast implant–associated anaplastic large cell lymphoma is clinically more akin to primary cutaneous anaplastic large cell lymphoma, for which local therapy is the standard and a good prognosis prevails for almost all patients, without the need for chemotherapy.

Persistent Uncertainties

Other uncertainties persist. Follow-up remains short at a median of only 2 years. Median progression-free survival and overall survival are excellent at not reached and 12 years, respectively. However the majority of patients are censored at 2 years or less of follow-up, leaving these curves potentially unstable. And a good prognosis is not guaranteed, since relapses have been seen, including in 14% of those with localized disease.

The main prognostic factor seems to be the presence of a mass within or through the capsule, conferring a moderately worse progression-free and overall survival. If any patients need more aggressive therapy, and this remains unclear, it may be those with tumor masses. The authors highlight this distinction and suggest that those without a mass be diagnosed as having a lymphoproliferative disorder associated with a breast implant, while the term “anaplastic large cell lymphoma” could be reserved for patients with a tumor mass or advanced-stage disease.

However, it is not certain how reliably one can make this distinction with masses as small as 5 mm included in this group. It is possible that there are two biologically different processes, but it is also possible that those with a mass or with nodal disease have merely progressed to more-advanced disease of the same process.

Despite some remaining uncertainties around our understanding of breast implant–associated anaplastic large cell lymphoma, the study by Miranda et al provides useful guidance on approaching and managing what is surely to be an increasingly diagnosed condition.

Disclosure: Dr. Horwitz reported no potential conflicts of interest.

Reference

1. Miranda RN, Aladily TN, Prince HM, et al: Breast implant-associated anaplastic large-cell lymphoma: Long-term follow-up of 60 patients. J Clin Oncol 32:114-120, 2014.