Breast Implant–Associated ALCL: A Unique Entity in the Spectrum of CD30+ Lymphoproliferative Disorders

Abstract

Abstract Learning Objectives Describe the spectrum of diseases, represented by CD30+ lymphoproliferative disorders (LPDs), that can give rise to a reactive process. Discuss the favorable prognoses of reactive CD30+ LPDs and how they do not therefore require aggressive therapy. Explain how implant-associated ALCL (iALCL) follows Hanahan and Weinberg's principles and acquires the ability to metastasize with new mutations. CD30+ lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)− anaplastic large cell lymphoma (ALCL). In January 2011, the U.S. Food and Drug Administration (FDA) announced a possible association between breast implants and ALCL, which was likened to systemic ALCL and treated accordingly. We analyzed existing data to see if implant-associated ALCL (iALCL) may represent a distinct entity, different from aggressive ALCL. We conducted a systematic review of publications regarding ALCL and breast implantation for 1990–2012 and contacted corresponding authors to obtain long-term follow-up where available. We identified 44 unique cases of iALCL, the majority of which were associated with seroma, had an ALK− phenotype (97%), and had a good prognosis, different from the expected 40% 5-year survival rate of patients with ALK− nodal ALCL (one case remitted spontaneously following implant removal; only two deaths have been reported to the FDA or in the scientific literature since 1990). The majority of these patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone with or without radiation, but radiation alone also resulted in complete clinical responses. It appears that iALCL demonstrates a strong association with breast implants, a waxing and waning course, and an overall good prognosis, with morphology, cytokine profile, and biological behavior similar to those of primary cutaneous ALCL. Taken together, these data are suggestive that iALCL may start as a reactive process with the potential to progress and acquire an aggressive phenotype typical of its systemic counterpart. A larger analysis and prospective evaluation and follow-up of iALCL patients are necessary to definitively resolve the issue of the natural course of the disease and best therapeutic approaches for these patients.