Tumour Review
Breast implant-associated anaplastic large cell lymphoma: A comprehensive review

https://doi.org/10.1016/j.ctrv.2020.101963Get rights and content

Highlights

  • Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin.

  • Despite its low incidence, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge.

  • Multidisciplinary team approach is essential to well define diagnostic workup and treatment.

Abstract

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a recently recognized non-Hodgkin lymphoma of T-cell origin. Despite the low incidence of this new disease, the increasing use of breast implants for cosmetic or post-mastectomy reconstruction purposes places BIA-ALC as an emerging and compelling medical challenge. The real BIA-ALCL pathogenesis has not been fully uncovered so far, while different putative causal factors have been proposed. Breast implants with textured surfaces seem to be associated with nearly all cases of BIA-ALCL, while the real the risk of disease development has not been well estimated so far. Late onset, persistent seroma around breast implant represents the classical clinical presentation. Most of the BIA-ALCL patients presents with localized disease, which confers an excellent prognosis. Unlike other non-Hodgkin lymphomas, surgical excision of the mass has a key role in the treatment. For patients with advanced and disseminated diseases, the treatment did not differ from other types of T-cell lymphoma. For these reasons, BIA-ALCL represents an emerging disease which requires multidisciplinary team approach to well define diagnostic workup and treatment for each patient. This review article aims to summarize available data on BIA-ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.

Introduction

During the last two decades, the number of breast implants used in aesthetic, oncologic and risk reducing surgery has exponentially increased. Since the identification of the first case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) more than twenty years ago [1], several cases on this very rare disease have been reported, demonstrating a clear association with breast implants. As a result, the World Health Organization (WHO) recognized BIA-ALCL as a disease associated with excellent outcomes in the 2017 classification of haemato-lymphoid neoplasms [2]. Although the majority of cases are localized and can be effectively cured by implant removal and full capsulectomy, a small percentage of patients experiences disease relapses and widespread dissemination, requiring systemic therapies. Considering that the majority of cases were diagnosed in patients with textured implants, the evidence linking BIA-ALCL to this type of implant surface has raised concerns about the long-term safety of these devices. In this context, breast implants have been inserted in the list of agents with high priority for evaluation by the International Agency for Research on Cancer (IARC) for the inclusion in the monographs of carcinogenic risks to humans [3].

The aim of our article is to review the current published knowledge about the link between breast implants and ALCL. First, we will outline available data on BIA-ALCL epidemiology, pathogenesis, diagnostic work-up, and treatment. Second, we will point out the potential psychological implications as well as the risk of perception distortion for women with breast implants, especially for those with previous breast cancer. Lastly, we will summarize the current national recommendations regarding textured breast implants and discuss the diagnostic-therapeutic algorithm for BIA-ALCL management.

Section snippets

Epidemiology

The first case of ALCL in a patient with breast implant was reported by Keech and Creech in 1997 [1]. Since that time, a growing body of literature on the potential association between breast implants and ALCL has been published during the last twenty years. In order to estimate the real incidence and risk for developing BIA-ALCL, several limitations have to be considered. First, the prevalence of women with breast implants (and the type of implant) needs to be known. Multiple factors,

Clinical presentation

Up to 80% of women with BIA-ALCL presents with a persistent seroma or periprosthetic effusion or seroma, that may be accompanied by breast swelling, asymmetry, or pain [15], [16]. In women who

present with delayed seromas (>1 year after implantation of a textured breast implants), the risk of BIA-ALCL is up to 10% [15], [16]. However, the occurrence of delayed seromas is rare (0.05–0.1%) and other more common differential diagnoses to consider include external trauma and infections [17], [18],

Pathogenesis

Although several assumptions have been proposed, the mechanisms that underpin BIA-ALCL etiology and pathogenesis are not well understood yet. However, considering the link between BIA-ALCL and textured implants, several studies have been conducted in this way.

Given that this type of implant is able to promote T-cell infiltration and immune response [26], chronic inflammation has been proposed as potential etiological factor. It is widely recognized the prominent role of chronic inflammation in

Diagnostic work-up

Patients that present with possible signs and symptoms of BIA-ACL, as a delayed seroma or a breast swelling, should undergo immediate evaluation. Ultrasound breast imaging is usually the first choice to assess the presence of effusion or mass and can guide image-guided fine needle aspiration of fluid. Breast MRI may also be helpful, especially in patients that present with a breast mass [7], [24], [39]. Aspiration of fluid or biopsy of the mass is mandatory in case of suspected BIA-ALCL. In the

Treatment

Once the diagnosis of BIA-ALCL has been confirmed, prothesis explantation and complete excision of any residual mass are the recommended approaches.

Given that more than 80% of BIA-ALCL presented with localized diseases (stage IA to IIA according to the TNM classification), surgery alone represents the standard of care. In a retrospective study of 87 BIA-ALCL patients, patients who underwent a total capsulectomy with breast implant removal presented with a better overall survival as compared to

Psychological implications in breast cancer patients at risk for BIA-ALCL: Emotional burden and risk perception distortion

Despite the great importance to talk over the risk of BIA-ALCL with patients, more than 75% of surgeons does not explain about it during pre-surgery consultation [48]. This hindrance in patient and doctor communication is probably due to the high uncertainty to provide an accurate risk assessment and standardized treatment procedures [51]. For cancer patients, undergoing a breast reconstruction surgery has a symbolic meaning: it represents the end of the cancer journey and a new shift in

Conclusions

Breast implant-associated anaplastic large cell lymphoma is a rare disease, with an estimated incidence of 1 per 20 000–30 000 women with breast implants [5]. On the other hand, women with textured implants seems to have higher incidence rate compared to those with smooth implants, reaching an estimated incidence of 1 per 3 000 [5]. Considering these emerging evidences, the attention of national and regulatory agencies towards the use of textured implants has been growing in the last years [68]

Authors’ contributions

AM, GV and GC conducted the bibliographic research, were responsible of the initial text design, initial drafting, and final writing. Each author wrote a section of the manuscript. AM, GC, SAP, FDL, and PV provided and prepared the figures. All the authors discussed, reviewed and approved the final version of the manuscript.

Acknowledgments

None.

Disclosure

Prof Giuseppe Curigliano declares speaker bureau from Novartis, Pfizer, Roche and advisory board for Ellipses, Foundation Medicine, Lilly, Novartis, Pfizer, Roche, Samsung and Seattle Genetics. Prof Stefano Pileri declares speaker bureau from Celgene. Other authors declared no conflict of interest. No funding has been received for the current work.

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