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

Abstract

CD30ϩ lymphoproliferative disorders represent a spectrum of diseases with distinct clinical phenotypes ranging from reactive conditions to aggressive systemic anaplastic lymphoma kinase (ALK)Ϫ 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 Ϫ phenotype (97%), and had a good prognosis, different from the expected 40% 5-year survival rate of patients with ALK Ϫ 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. The Oncologist 2013;18:301-307Implications for Practice: Breast implant -associated anaplastic large cell lymphoma (iALCL) is a relatively new and rare entity.Since it was first described in the 1990s it has been treated with aggressive therapies, similar to cutaneous lymphomas until they were designated to their own treatment category. This review demonstrates the similarities of iALCL to primary cutaneous ALCL by its good prognosis, biologic behavior, morphology, and relapsing nature. A larger analysis with prospective evaluation and follow-up of iALCL patients is necessary to definitively resolve the issue of the natural course and best therapeutic approaches for these patients. Less aggressive therapeutic options may be used in the future but this cannot be recommended without further investigation and clinical trials. INTRODUCTION Learning ObjectivesDescribe the spectrum of diseases, represented by CD30 ϩ lymphoproliferative disorders (LPDs), that can give rise to a reactive process. Discuss the favorable prognoses of reactive CD30ϩ LPDs and how they do not therefore require...

The aggressive peripheral T‐cell lymphomas: 2015

“…[29][30][31] These lymphomas are CD30 positive and ALK negative. Patients usually present with swelling associated with a seroma and discomfort in a breast containing a silicone-coated implant.…”

Anaplastični velikocelični limfom, povezan z vsadki dojk

“…je imelo ob postavitvi diagnoze 81 % bolnic prisoten serom, 9 % serom v kombinaciji s solidnim tumorjem, 9 % solidni tumor in 2 % razjedo kože, Story in sod. pa je serom ugotovil pri 53 % bolnic, medtem ko je 35 % bolnic imelo solidni tumor (5,9). Problem, ki ga nakazujejo Miranda in sod.…”

“…Čeprav imajo bolniki s primarno sistemsko ALCL, ki imajo ALK-limfom, nizko 5-letno preživetje (40 %) imajo bolnice, pri katerih gre za s silikonskimi vsadki povezani ALCL, veliko boljše 5-letno preživetje (2,5). Preživetje je pri njih verjetno podobno preživetju bolnikov s primarnim kožnim ALCL (5).…”

Peripheral T cell lymphoma in Asia

“…Most cases had an ALK-negative phenotype, with the exception of a few ALK-positive cases [47,48]. It arises in association with the fibrous capsule or effusion around the silicone breast implant [47].…”

“…An extensive mixed lymphocytic infiltrate adjacent to the fibrous implant capsule suggests the potential role of chronic inflammation and genetic instability in the pathogenesis of breast-implantassociated ALK-negative ALCL [49]. These patients have a good prognosis when the tumor presents solely with effusions around the implant [48]; in contrast, patients who present with a distinct mass may have advanced stage or possibly systemic disease and have a poorer prognosis [50].…”