Comparative Analysis of Cytokines of Tumor Cell Lines, Malignant and Benign Effusions Around Breast Implants

2019 ◽  
Vol 40 (6) ◽  
pp. 630-637 ◽  
Author(s):  
Marshall E Kadin ◽  
John Morgan ◽  
Nick Kouttab ◽  
Haiying Xu ◽  
William P Adams ◽  
...  
Keyword(s):  
Breast Implant ◽  
Breast Implants ◽  
Interferon Γ ◽  
Textured Surface ◽  
Malignant Cells ◽  
Level Of Evidence ◽  
Scar Contracture ◽  
Ancillary Test ◽  
Soluble Cd30 ◽  
Insight Into

Abstract Background More than 700 women have developed an anaplastic large T cell lymphoma (ALCL) surrounding textured surface breast implants, termed breast implant–associated ALCL (BIA-ALCL). Most patients with BIA-ALCL present with an accumulation of fluid (delayed seroma) around the implant. However, benign seromas without malignant cells complicating scar contracture, implant rupture, trauma, infection, and other causes are more common. For proper patient management and to avoid unnecessary surgery, a simple diagnostic test to identify malignant seromas is desirable. Objectives The aim of this study was to develop an ancillary test for the diagnosis of malignant seromas and to gain insight into the nature of the malignant cells and their microenvironment. Methods We employed an immunologic assay on only 50 µL of aspirated seroma fluid. The assay measures 13 cytokines simultaneously by flow cytometry. To establish a baseline for clinical studies we measured cytokines secreted by BIA-ALCL and cutaneous ALCL lines. Results Our study of cell line culture supernatants, and 8 malignant compared with 9 benign seromas indicates that interleukin 9 (IL-9), IL-10, IL-13, IL-22, and/or interferon γ concentrations >1000 pg/mL distinguish malignant seromas from benign seromas. IL-6, known to be a driver of malignant cells, is also elevated in benign seromas and does not distinguish them from malignant seromas. Conclusions The cytokine assay introduced in this study can be used together with levels of soluble CD30 to identify malignant seromas. Validation of these findings in a larger prospective patient cohort is warranted. The unique pattern of cytokine expression in malignant effusions surrounding breast implants gives further insight into the pathogenesis and cells of origin of BIA-ALCL. Level of Evidence: 5

scholarly journals Granzyme B Is a Biomarker for Suspicion of Malignant Seromas Around Breast Implants

2020 ◽  
Author(s):  
Marshall E Kadin ◽  
John Morgan ◽  
Haiying Xu ◽  
Caroline Glicksman ◽  
David Sieber ◽  
...  
Keyword(s):  
Early Detection ◽  
Tumor Cells ◽  
Breast Implant ◽  
Granzyme B ◽  
Breast Implants ◽  
Large Cell ◽  
Target Cells ◽  
Cytotoxic Lymphocytes ◽  
Tumor Cell Death ◽  
Level Of Evidence

Abstract Background Granzyme B (GrB) is a serine protease secreted, along with pore-forming perforin, by cytotoxic lymphocytes to mediate apoptosis in target cells. GrB has been detected in tumor cells associated with systemic and breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) but its potential use for detection of early BIA-ALCL has not been fully investigated. Objectives Prompted by the increased incidence of BIA-ALCL, the aim of this study was to assess GrB as a new biomarker to detect early disease in malignant seromas and to better understand the nature of the neoplastic cell. Methods A Human XL Cytokine Discovery Magnetic Luminex 45-plex Fixed Panel Performance Assay was used to compare cytokine levels in cell culture supernatants of BIA-ALCL and other T-cell lymphomas, as well as malignant and benign seromas surrounding breast implants. Immunohistochemistry was employed to localize GrB to cells in seromas and capsular infiltrates. Results Differences in GrB concentrations between malignant and benign seromas were significant (P < 0.001). GrB was found in and around apoptotic tumor cells, suggesting that the protease may be involved in tumor cell death. Conclusions GrB is a useful marker for early detection of malignant seromas and to identify tumor cells in seromas and capsular infiltrates. Because there is an overlap between the lowest concentrations of soluble GrB in malignant seromas and the highest concentrations of GrB in benign seromas, it is recommended that GrB be used only as part of a panel of biomarkers for the screening and early detection of BIA-ALCL. Level of Evidence: 5

Breast Implant-Associated Anaplastic Large Cell Lymphoma in Australia: A Longitudinal Study of Implant and Other Related Risk Factors

2019 ◽  
Vol 40 (8) ◽  
pp. 838-846 ◽  
Author(s):  
Anna Loch-Wilkinson ◽  
Kenneth J Beath ◽  
Mark R Magnusson ◽  
Rodney Cooter ◽  
Karen Shaw ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Breast Implant ◽  
Breast Implants ◽  
Large Cell ◽  
Regulatory Action ◽  
Level Of Evidence ◽  
Large Cell Lymphoma

Abstract Background Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging cancer that has been linked to the use of textured devices. The recent increase in number and frequency of cases has led to worldwide regulatory action. Objectives The authors aimed to longitudinally study BIA-ALCL in Australia since the index case was first reported in 2007. Methods Confirmed historical cases were collected and then prospectively analyzed from October 2015 to May 2019. Clinical and implant exposure data were determined and compared with company sales data for 4 devices to generate implant-specific risk. Results A total 104 cases of BIA-ALCL were diagnosed in Australia with exposure to 149 unique breast implants. The mean age of patients was 48.2 years (range, 22.4-78.5 years). They had an average time from implantation to diagnosis of 6.8 years. A total 51.7% of implants utilized in this cohort were Allergan Biocell devices. The indication for implant usage was for primary cosmetic augmentation in 70%, post-breast cancer reconstruction in 23%, and following weight loss/pregnancy in 7%. The majority of women presented with early (stage 1) disease (87.5%). The risk for developing BIA-ALCL ranged from 1 in 1947 sales (95% confidence interval = 1199-3406) for Silimed Polyurethane devices to 1 in 36,730 (95% confidence interval = 12,568-178,107) for Siltex imprinted textured devices. Conclusions Implants with higher surface area/texture seem to be more associated with BIA-ALCL in Australia. Recent regulatory action to suspend, cancel, or recall some of these higher risk devices is supported by these findings. Level of Evidence: 2

scholarly journals The Kinematics of Breasts Implanted With a Reduced Mass Implant: A Pilot Study

2019 ◽  
Vol 40 (5) ◽  
pp. NP253-NP262 ◽  
Author(s):  
Michelle Norris ◽  
Melissa Jones ◽  
Chris Mills ◽  
Tim Blackmore ◽  
Chris Inglefield ◽  
...  
Keyword(s):  
Pilot Study ◽  
Breast Implants ◽  
Breast Size ◽  
Level Of Evidence ◽  
Dynamic Activity ◽  
Electromagnetic Sensors ◽  
Skin Tension ◽  
Natural Counterpart ◽  
Positional Data ◽  
Insight Into

Abstract Background Breast implants may increase breast skin tension and interact with surrounding tissues to alter breast position and motion during dynamic activity. Reducing implant mass and changing implant location (submuscular/subglandular) may also affect breast kinematics and the subsequent loads on breast structures. Objectives The aim of this pilot study was to describe the kinematics of breasts augmented with reduced-mass implants during standing, walking, and running, compared with natural breasts, and to provide insight into how implant location (submuscular/subglandular) alters breast kinematics. Methods Two breast augmentation participants (12–15 months postsurgery: 32AA presurgery, anatomical submuscular 255 cc B-Lite reduced-mass implant; 32A presurgery, anatomical subglandular 285 cc B-Lite reduced-mass implant) and 2 natural-breasted participants of similar breast size and anthropometrics were recruited. Nipple and torso positional data were recorded with electromagnetic sensors during standing, walking, and running. Nipple kinematics relative to the torso were calculated. Results The B-Lite participants both displayed greater nipple projection and elevation during standing and a 50% reduction in nipple acceleration during walking, when compared with their natural counterparts. During running, the B-Lite subglandular participant displayed decreased nipple kinematics compared with her natural counterpart and lower nipple kinematics compared with the B-Lite submuscular participant during walking and running. Conclusions A combination of implant location (subglandular) and reduced mass minimized nipple kinematics during running. Reducing nipple kinematics during dynamic activity may decrease the loading on breast structures, helping to decrease ptosis and increase the longevity of procedure outcomes. Level of Evidence: 4

Breast Implant Related Anaplastic Large Cell Lymphoma ALK- (ALCL ALK-) – Case Report

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5086-5086 ◽  
Author(s):  
Alejandro Arbelaez ◽  
Laurence Catley ◽  
Louis Pool
Keyword(s):  
Conflicts Of Interest ◽  
Case Reports ◽  
Breast Implant ◽  
Treatment Options ◽  
Fluid Collection ◽  
Case Series ◽  
Breast Implants ◽  
Large Cell ◽  
Lymphoid Cells ◽  
Malignant Cells

Abstract Case presentation A 29 underwent bilateral cosmetic breast augmentation 10 years previously (McGhan Textured Round 400 mL implants). Six months before, she developed slowly progressive right breast pain and inflammatory signs associated with fluid collection around the right breast that was drained. A yellow cloudy fluid was examined and showed atypical large lymphoid cells. The cell block prepared in another institution showed numerous lymphoid cells including large atypical cells with lobated nuclei. PET CT scan was negative, same as bone marrow aspirate and trephine for lymphoma infiltration. Following bilateral removal of the breast implants, further histopathology studies showed no infiltration by lymphoma of the breast capsules or scar tissue. However, right breast peri prosthetic fluid microscopy showed a population of single malignant cells with scanty cytoplasm, numerous mitosis, and nuclei showing single and multiple nucleoli. Some cells showing horseshoe nuclei. The malignant cells were positive for CD30 and LCA and negative for CD20, CD68, AE1-3, and ALK 1. FISH for ALK was not possible (Fig 1) Discussion Primary breast lymphomas are very rare conditions; they represent less than 1% of all NHL and less than 0.7% of all breast malignancies. There have been some cases reported in the medical literature of ALCL ALK- associated with breast implants. All the cases have been described in patients with textured implants, such as in this case and the reason is unknown. There are two main types of ALCL of the breast based on published case reports: a mass and an effusion. Primary breast effusion associated ALCL portends a good prognosis despite the fact that they are ALK-. The development of ALCL proximal to breast implants suggests that they are the result of an immune reaction to the silicone. Whether they represent true malignancy or a localised reactive phenomenon is not entirely clear yet. In previous case series, the condition has been described as indolent. However, given the low incidence of this condition and the limited literature available; it is difficult to know what the best treatment approach is. Following confirmation of the diagnosis, treatment options were discussed with the patient and the preferred option was active treatment with local radiation after removal of breast implants. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Biofilm Derived Oxylipin Mediated Autoimmune Response in Breast Implant Subjects

2020 ◽  
Author(s):  
Imran Khan ◽  
Robert E. Minto ◽  
Christine Kelley-Patteson ◽  
Bruce W. Van Natta ◽  
Colby R. Neumann ◽  
...  
Keyword(s):  
Staphylococcus Epidermidis ◽  
Breast Implant ◽  
Breast Implants ◽  
Chronic Fatigue ◽  
Bacterial Biofilm ◽  
Autoimmune Response ◽  
Host Pathogen Interaction ◽  
Number Of Patients ◽  
Biofilm Bacteria ◽  
Insight Into

AbstractOver 10 million women worldwide have breast implants for breast cancer/prophylactic reconstruction or cosmetic augmentation. In recent years, a number of patients have described a constellation of symptoms that are believed to be related to their breast implants. This constellation of symptoms has been named Breast Implant Illness (BII). The symptoms described include chronic fatigue, joint pain, muscle pain and a host of other manifestations often associated with autoimmune illnesses. In this work, we report that bacterial biofilm is associated with BII. We postulate that the pathogenesis of BII is mediated via a host-pathogen interaction whereby the biofilm bacteria Staphylococcus epidermidis interacts with breast lipids to form the oxylipin 10-HOME. The oxylipin 10-HOME was found to activate CD4+ T cells to Th1 subtype. An increased abundance of CD4+Th1 was observed in the breast tissue of BII subjects. The identification of a mechanism of immune activation associated with BII via a biofilm enabled pathway provides insight into the pathogenesis for implant-associated autoimmune symptoms.

scholarly journals Device-Specific Findings of Imprinted-Texture Breast Implants: Characteristics, Risks, and Benefits

2019 ◽  
Author(s):  
Roger N Wixtrom ◽  
Vikram Garadi ◽  
John Leopold ◽  
John W Canady
Keyword(s):  
Risk Reduction ◽  
Breast Implant ◽  
Capsular Contracture ◽  
Breast Implants ◽  
Surface Metrology ◽  
Textured Surface ◽  
Primary Reconstruction ◽  
Implant Surface ◽  
Risks And Benefits ◽  
Core Study

Abstract Background The relative risks and benefits of various textured breast implants are the focus of considerable discussion. Studies have suggested different risk-benefit profiles for different implant surface topographies. Objectives The study aim was to provide device-specific, quantitative information on Mentor’s imprinted Siltex Textured breast implants with respect to textured surface characteristics and ISO 14607 classification, risk of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), and risk-reduction benefits relative to smooth implants. Methods Surface metrology was performed. Data for smooth and Siltex implants from the prospective MemoryGel Core Study were evaluated by Kaplan-Meier analysis for the most frequently occurring postoperative complications in augmentation and reconstruction leading to subsequent reoperation. Results The overall average surface roughness for Siltex MemoryGel and MemoryShape implants was 29.5 and 36.1 µm, respectively. A statistically significantly lower rate of reoperation in patients with Siltex compared with smooth devices over 10 years was observed for both capsular contracture in subglandular primary augmentation patients (2.02% vs 19.84%) and for asymmetry in primary reconstruction patients (3.88% vs 11.1%). Conclusions Surface analysis demonstrated that Siltex implants fall within the ISO 14607 category of “microtexture” breast implants. These devices exhibited a rare risk of BIA-ALCL (0.0012%) based on the most extensive data available. Relative to smooth implants, these Siltex devices provided risk-reduction benefits for the most common reason of reoperation in patients who underwent primary augmentation (capsular contracture) or primary reconstruction (asymmetry) in the Core Study. These findings provide valuable risk-benefit information for surgeons and their patients. Level of Evidence: 2

scholarly journals The Protective Effect of Breast Implants in Penetrating Trauma

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Christopher J Pannucci ◽  
Nicole M Kurnik ◽  
Mark Brzezienski ◽  
K Kye Higdon ◽  
Alanna M Rebecca
Keyword(s):  
Chest Trauma ◽  
Breast Implant ◽  
Traumatic Injury ◽  
Penetrating Trauma ◽  
Breast Implants ◽  
Future Research ◽  
Level Of Evidence ◽  
Substantial Impact ◽  
Penetrating Chest Trauma

Abstract Breast implants are typically placed for cosmetic or reconstructive purposes, and are recognized to have a substantial impact on aesthetics and quality of life. In addition, the presence of a breast implant on the chest wall has a potential benefit of force diffusion or force absorption in traumatic injury. This article reports a series of three patients with preexisting breast implants who suffered penetrating chest trauma. In each case, the presence of a breast implant was potentially lifesaving. We describe the cases in detail, provide a conceptual discussion, and discuss directions for future research. Level of Evidence: 5

Symptomatic delayed seromas vs incidental findings on MR, and likelihood of BIA-ALCL in women with textured implants.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e20028-e20028
Author(s):  
Paola Ghione ◽  
Elizabeth J. Sutton ◽  
Qunying Hu ◽  
Natasha Galasso ◽  
Nivetha Ganesan ◽  
...  
Keyword(s):  
Median Time ◽  
Incidental Findings ◽  
Incidental Finding ◽  
Breast Implant ◽  
Breast Implants ◽  
Silicone Implants ◽  
Textured Surface ◽  
Asymptomatic Patients ◽  
Asymptomatic Women

e20028 Background: Breast Implant Associated Anaplastic Large Cell Lymphoma (BIA-ALCL), a subtype of ALCL, arises as a seroma in the space between the implant and the capsule, or as an adjacent mass. BIA-ALCL appears to be related to textured-surface implants, after 7-10 years of exposure. We conducted two large cohort studies. The 1st, a retrospective series (Sutton, 2019) assessed the incidental findings of masses or seromas in 1070 women with breast implants undergoing MR for FDA recommended screening for silent ruptures of silicone implants. Incidental finding of seromas or breast masses on MRI were found in 18/1070 (1.7%) women, of which 1/15 had BIA-ALCL, and was symptomatic at the time of MRI. The 2nd, a prospective study (Cordeiro, 2020) defined the incidence of BIA-ALCL (1/355) in a cohort of 3546 women with textured implants followed long term. Within this cohort, there were 28 clinically relevant delayed seromas (0.79%), 8 of which were BIA-ALCL (28.5%). We hypothesize that combining these databases will inform whether asymptomatic women with textured implants may benefit from MR to r/o BIA-ALCL. Methods: The two IRB approved databases were merged. Patients with incidental findings of seroma on MRI were identified. A majority of the MRIs in this merged cohort were performed to follow the FDA recommended screening for silent ruptures. We identified all clinically relevant late seromas sent to hematopathology to r/o BIA-ALCL by cross checking pathology reports containing the words “lymphoma” or “anaplastic” or “ALCL”. Results: 572 women were included in both studies: followed long term and received an MRI after a median time of 7.4 years after breast reconstruction. 8 of 572 women had an incidental finding of seroma on random MRI, and 2 had capsular masses. None of these 10 asymptomatic women have developed BIA-ALCL to date (median follow-up 9 years). 11 of 572 women had a symptomatic seroma or mass, 4 of which later developed BIA-ALCL, a fifth patient was found to have BIA-ALCL on a PET/CT + lymph node, despite being asymptomatic. Median time from last MR to lymphoma was 5 years (3-8 years). Conclusions: In this merged cohort of patients with textured breast implants, incidence of BIA-ALCL in patients with symptomatic late seromas is around 30%, while seromas found incidentally on MR of asymptomatic patients were negative for BIA-ALCL.

Differences in Human Leukocyte Antigen Expression Between Breast Implant–Associated Anaplastic Large Cell Lymphoma Patients and the General Population

2019 ◽  
Vol 39 (10) ◽  
pp. 1065-1070 ◽  
Author(s):  
Sarah E Tevis ◽  
Kelly K Hunt ◽  
Roberto N Miranda ◽  
Caitlin Lange ◽  
Charles E Butler ◽  
...  
Keyword(s):  
General Population ◽  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Breast Implant ◽  
Human Leukocyte ◽  
Breast Implants ◽  
Large Cell ◽  
Textured Surface ◽  
Leukocyte Antigen ◽  
Large Cell Lymphoma

Abstract Background Breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma associated with textured-surface breast implants. Human leukocyte antigen (HLA) polymorphisms have been described with other forms of lymphoma, but have not been described for BIA-ALCL. Objectives The aim of this study was to evaluate HLA polymorphisms in BIA-ALCL patients. Methods We prospectively evaluated HLA alleles in patients with BIA-ALCL. HLA was analyzed by probe-based sequence-specific testing and sequence-based typing. The frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles were evaluated. Allele frequencies in the Caucasian European general population were obtained from the National Marrow Donor Program to serve as normative controls. We estimated the relative risk of BIA-ALCL with 95% confidence intervals from a t test. Results Thirteen patients who had undergone BIA-ALCL and HLA testing were identified from 2017 to 2018. Patients carried 10, 11, and 9 HLA-A, HLA-B, and HLA-C alleles, respectively. There were 8 DRB1 alleles and 5 DQB1 alleles in the BIA-ALCL patients. The A*26 allele occurred significantly more frequently in the general population compared with BIA-ALCL patients (0.2992 vs 0.07692, P < 0.001). Conclusions Our results identify a difference between HLA A*26 in patients who develop BIA-ALCL and the general population, and may signify genetic susceptibility factors responsible for germline genetic variation in HLA in patients with BIA-ALCL. Further work is needed to elucidate if these alleles are predictive for BIA-ALCL in women with textured-surface breast implants. Level of Evidence: 4

scholarly journals Finding Consensus After Two Decades of Breast Implant-Associated Anaplastic Large Cell Lymphoma

2019 ◽  
Vol 33 (04) ◽  
pp. 270-278 ◽  
Author(s):  
Mark W. Clemens ◽  
Ryan C. DeCoster ◽  
Berry Fairchild ◽  
Alexander A. Bessonov ◽  
Fabio Santanelli di Pompeo
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Breast Implant ◽  
Breast Implants ◽  
Large Cell ◽  
World Health ◽  
Textured Surface ◽  
Early Stage Disease ◽  
Large Cell Lymphoma

AbstractBreast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging and indolent, but potentially fatal cancer of the immune system that can develop around textured-surface breast implants. The World Health Organization first recognized BIA-ALCL as a unique clinical entity in 2016. To date, over 600 confirmed cases have been reported worldwide. BIA-ALCL most commonly presents with disease confined to the capsule, as a seroma or a mass adjacent to the implant. While BIA-ALCL has a fairly indolent clinical course, with an excellent prognosis in early stage disease, disseminated cancer and death have also been reported. In this review, the authors focus on the early diagnosis and treatment, including reconstructing the breast following BIA-ALCL, and also discuss recently updated National Comprehensive Cancer Network guidelines. They also review the current epidemiology and risk factors associated with BIA-ALCL. Finally, they discuss important medicolegal considerations and the bioethics surrounding the continued use of textured-surface breast implants.

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