Research Article: Spontaneous Regression and Resolution of Breast Implant-Associated Anaplastic Large Cell Lymphoma: Implications for Research, Diagnosis and Clinical Management

Date Published: February 14, 2018

Publisher: Springer US

Author(s): Daniel Fleming, Jason Stone, Patrick Tansley.

http://doi.org/10.1007/s00266-017-1064-z

Abstract

First described in 1997, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) was recognised by the World Health Organisation in 2016 as a specific disease. It typically presents as a late seroma-containing atypical, monoclonal T cells which are CD30+ and anaplastic lymphoma kinase negative. Until recently, it was thought that the disease was very rare. However, it is being diagnosed increasingly frequently with 56 cases confirmed in Australia by September 2017 and the estimated incidence revised from 1 in 300,000 to between 1 in 1000 and 1 in 10,000 patients with bilateral implants. There is debate about the spectrum of BIA-ALCL. According to the current WHO classification, BIA-ALCL is a cancer in all cases. Treatment guidelines require that it is treated urgently with a minimum of bilateral removal of implants and capsulectomies. Whilst acknowledging the disease has been under diagnosed in the past, with some notable exceptions the BIA-ALCL literature has given scant attention to the epidemiological evidence. Now that it is known that the disease may occur in up to 1 in 1000 patients with a median of 7.5 years from implantation to diagnosis, understanding it in its epidemiological context is imperative. The epidemiology of cancer and lymphoma in women with breast implants strongly suggests that most patients do not have a cancer that will inevitably progress without treatment but instead a self-limiting lympho-proliferative disorder. Although the possibility of spontaneous regression has been raised and the observation made that treatment delay did not seem to increase the risk of spread, the main objection to the lympho-proliferative hypothesis has been the lack of documented cases of spontaneous regression or resolution. Because all cases currently are considered malignant and treated urgently, only case report evidence, interpreted in the proper epidemiological context, is likely to be available to challenge this thinking.

New observations and interpretation of the epidemiology of BIA-ALCL are made. These are supported by the presentation of two cases, which to the best of our knowledge comprise the first documented evidence of spontaneous regression and spontaneous resolution of confirmed BIA-ALCL.

The epidemiology of the disease strongly suggests that the vast majority of cases are not a cancer that will inevitably progress without treatment. The findings presented in the manuscript provide supportive clinical evidence. Consequently, an alternative view of BIA-ALCL with implications for research, diagnosis and clinical management needs to be considered.

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266.

Partial Text

First described in 1997, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) was recognised by the World Health Organisation in 2016 as a specific disease [1, 2]. It typically presents as a late seroma-containing atypical, monoclonal T cells which are CD30+ and anaplastic lymphoma kinase (ALK)−. Until recently, it was thought that the disease was very rare [3]. However, it is being diagnosed increasingly frequently with 56 cases confirmed in Australia by September 2017 and the estimated incidence revised from 1 in 300,000 to between 1 in 1000 and 1 in 10,000 patients with bilateral implants [4, 5]. There is debate about the spectrum of BIA-ALCL [6, 7]. According to the current WHO classification, BIA-ALCL is a cancer in all cases. Treatment guidelines require it is treated urgently with a minimum of bilateral removal of implants and capsulectomies [8]. Whilst acknowledging the disease has been under diagnosed in the past [8], with some notable exceptions the BIA-ALCL literature has given scant attention to the epidemiological evidence [9, 10]. Now that it is known that the disease may occur in up to 1 in 1000 patients with a median of 7.5 years from implantation to diagnosis, understanding it in its epidemiological context is imperative [5, 11]. The epidemiology of cancer and lymphoma in women with breast implants strongly suggests that most patients do not have a cancer that will inevitably progress without treatment but instead a self-limiting lympho-proliferative disorder [12–17]. Although the possibility of spontaneous regression has been raised and the observation made that treatment delay did not seem to increase the risk of spread [9], the main objection to the lympho-proliferative hypothesis has been the lack of documented cases of spontaneous regression or resolution. Because all cases currently are considered malignant and treated urgently, only case report evidence, interpreted in the proper epidemiological context, is likely to be available to challenge this thinking.

We reviewed the available epidemiology and present two cases, which to the best of our knowledge comprise the first documented evidence of spontaneous regression and spontaneous resolution of confirmed BIA-ALCL.

The first known case of BIA-ALCL in Australia was diagnosed in 2007, but recently a rapidly rising incidence has been reported [11]. Forty-six cases had been reported by December 2016 in Australia [5], but by September 2017 further 10 cases had been confirmed with 2 more under investigation [4, 21]. The absence of disease in the explanted capsule has not been classified as spontaneous resolution, and seroma-only disease is still classified as a stage 1 malignancy [2]. Relevantly, until recently only capsular tissue and not seroma fluid was submitted for analysis at explantation [22]. Thus, other cases of spontaneous regression or resolution may have been missed. For example, the case of spontaneous resolution presented here would have been missed had the small, asymptomatic residual seroma fluid not been analysed at explantation. The case presented of spontaneous regression is unique because 7 months elapsed from first presentation and confirmation of seroma to the diagnosis being made on aspiration. Also, there was a further 4-month delay before the patient consented to surgical management. Therefore, 11 months elapsed from her presentation with late seroma to surgical explantation. The case has presented us with an opportunity to follow the natural history of BIA-ALCL for almost 1 year. Until and unless treatment guidelines change, it is unlikely to be repeated as patients with confirmed disease are now treated more expediently.

The epidemiology of the disease strongly suggests that the vast majority of cases are not a cancer that will inevitably progress without treatment. The findings presented in the manuscript provide supportive clinical evidence and emphasise the importance of analysing seroma fluid as well as the capsule at explantation. An alternative view of BIA-ALCL with implications for research, diagnosis and clinical management needs to be considered.

 

Source:

http://doi.org/10.1007/s00266-017-1064-z

 

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