Breast Implant-associated Anaplastic Large Cell Research Articles

The association between breast implants and anaplastic large cell lymphoma - a comprehensive review

Introduction and purpose: Recently, the topic of the incidence of breast implant-associated anaplastic large cell lymphoma has become very popular. The aetiology of the disease is not fully understood. Many women worldwide have undergone breast implant surgery, so raising awareness about the possibility of developing BIA-ALCL is crucial for early diagnosis. The aim of this article is to review and compile the currently available knowledge regarding the association of anaplastic large cell lymphoma with breast implants in patients who have undergone implant plastic surgery. Brief description of the state of knowledge: Literature data indicate a multifactorial aetiology of BIA-ALCL. Textured surface breast implants are suspected to be a significant risk factor, as they may lead to the development of chronic inflammation. The most common symptoms of BIA-ALCL include the accumulation of serous fluid around the breast implant, pain, swelling or breast asymmetry. A proper diagnostic and therapeutic process improves the prognosis. Material and methods: A comprehensive literature review was conducted using PubMed and Google Scholar databases. The search strategy was based on the following terms: BIA-ALCL; lymphoma; breast implants; textured implants. Conclusions: Although BIA-ALCL is a rare disease, it is important to know the risk factors and clinical signs that may suggest the disease. A proper diagnostic process allows the disease to be detected at an early stage and treated effectively. Knowledge of the occurrence of potential complications of implant surgery allows patients to take informed consent and increases vigilance on the part of clinicians.

BIA-ALCL and BIA-SCC: Updates on Clinical Features and Genetic Mutations for Latest Recommendations

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) and Breast Implant-Associated Squamous Cell Carcinoma (BIA-SCC) are emerging neoplastic complications related to breast implants. While BIA-ALCL is often linked to macrotextured implants, current evidence does not suggest an implant-type association for BIA-SCC. Chronic inflammation and genetics have been hypothesized as key pathogenetic players, although for both conditions, the exact mechanisms and specific risks related to breast implants are yet to be established. While the genetic alterations in BIA-SCC are still unknown, JAK-STAT pathway activation has been outlined as a dominant signature of BIA-ALCL. Recent genetic investigation has uncovered various molecular players, including MEK-ERK, PI3K/AKT, CDK4-6, and PDL1. The clinical presentation of BIA-ALCL and BIA-SCC overlaps, including most commonly late seroma and breast swelling, warranting ultrasound and cytological examinations, which are the first recommended steps as part of the diagnostic work-up. While the role of mammography is still limited, MRI and CT-PET are recommended according to the clinical presentation and for disease staging. To date, the mainstay of treatment for BIA-ALCL and BIA-SCC is implant removal with en-bloc capsulectomy. Chemotherapy and radiation therapy have also been used for advanced-stage BIA-ALCL and BIA-SCC. In-depth characterization of the tumor genetics is key for the development of novel therapeutic strategies, especially for advanced stage BIA-ALCL and BIA-SCC, which show a more aggressive course and poor prognosis.

The Risk of Breast Implant-Associated Anaplastic Large Cell Lymphoma; A Systematic Review and Meta-Analysis

Abstract Background Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging disorder that has gained global attention throughout the past era. The present meta-analysis was performed to retrieve the risk of BIA-ALCL from population-based epidemiological studies. Factors associated with BIA-ALCL were evaluated to identify patients at higher risk of BIA-ALCL. Methods A systematic literature search was executed throughout 12 databases. All epidemiological studies encompassing patients with breast implants either for aesthetic or reconstructive purposes and reported the risk of BIA-ALCL were included. Studies reported the risk factors of BIA-ALCL were included. Results The present meta-analysis included 17 articles, encompassing 525,475 patients with breast implants. There were 254 patients with BIA-ALCL with a mean duration to the diagnosis of BIA-ALCL of 13.16 years (95% CI 11.7–14.6, P < 0.001). There were 44 patients with textured breast implants and two with smooth implants. Patients with breast implants were 28.86 times more at high risk of BI-ALCL (95% CI 3.123–266.681). The risk ranged from 0 to 1 per 1000 cases with breast implants, with a similar risk among patients seeking aesthetic and reconstructive surgeries. The risk was 0 to 1 case per 1000 cases among patients with textured breast implants. There was a significant association between the history of breast cancer and BIA-ALCL (P = 0.0016). Conclusion This meta-analysis confirmed the association between breast implants and ALCL. There was a similar risk of BIA-ALCL among patients with aesthetic or reconstructive surgeries. Patients with a history of breast cancer were at higher risk of BIA-ALCL. Level of Evidence III 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 www.springer.com/00266.

Abstract PO1-10-02: Breast cancer among transgender and non-binary patients on gender affirming hormone therapy: a single institution experience

Abstract Background: Estrogen exposure is a known risk factor for the development of breast cancer in women. Less clear is the risk posed by gender affirming hormone therapy (GAHT) in both transgender men and transgender women. We aimed to characterize the breast cancers that have arisen in our institution’s transgender patient population including biomarker profile, method of diagnosis, and stage at diagnosis. Methods: For this retrospective cohort study, patients from the Mount Sinai Health System were identified using the electronic medical record from 2016-2023. A cohort of transgender or non-binary patients with breast cancer was established by using ICD-10 codes for carcinoma in situ of breast (D-05) and malignant neoplasm of breast (C-50) and a diagnosis or medical history encompassing gender identity disorders (ICD-10-CM: F64) or a chief complaint related to transgender health. Chart review enabled selection of patients who have a history of GAHT. Patients with incomplete medical records were excluded from analysis. Results: 14 patients met criteria and were included for final analysis. Mean age at diagnosis was 51.7 (31-65) years and 86% (12/14) were at or above 40 years of age at diagnosis and eligible for routine screening mammography. The cohort encompassed six trans men (assigned female at birth), seven trans women (assigned male at birth), and one genderqueer person (assigned female at birth). Family history was not significant for most of the cohort. Two patients had a first-degree relative with a history of breast cancer; both were BRCA negative. Four patients (29%) were diagnosed via screening mammography; six patients (43%) were diagnosed after palpating a breast or axillary mass; and four patients (29%) had not undergone screening but were diagnosed via breast imaging mandated prior to planned chest masculinization surgery. At time of initial presentation, the diagnostic stage was DCIS in five patients (36%); LCIS in one patient (7%); stage 1 cancer in four patients (29%); stage 2 cancer in three patients (21%); and breast implant-associated anaplastic large cell lymphoma in one patient (7%). 50% (7/14) of patients had an active or past prescription for testosterone-based GAHT, and 50% (7/14) patients had an active or past prescription for estrogen-based GAHT. Mean duration of all GAHT prior to diagnosis was 16.6 years (mean duration of estrogen-based GAHT was 27.6 years and mean duration for testosterone-based GAHT was 5.7 years). Biomarker profiles were available for twelve patients; 8/12 (67%) patients were diagnosed with estrogen receptor (ER) positive cancer, four (33%) with ER negative cancers. Of patients on estrogen-based GAHT, three presented with ER+ and four presented with ER- cancers. 10/14 patients had bilateral mastectomies and 4/14 had lumpectomies. Discussion/Conclusion: The mode of cancer detection suggests that screening mammography is under-utilized among transgender and non-binary patients who use GAHT. This represents a health care disparity involving a vulnerable patient population. The biomarker profile among this population demonstrates that both estrogen-responsive and estrogen-nonresponsive cancers can arise in the setting of prior or ongoing gender affirming estrogen or testosterone. Citation Format: Nithya Krishnamurthy, Ethan Ravetch, Christina Weltz. Breast cancer among transgender and non-binary patients on gender affirming hormone therapy: a single institution experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-10-02.

Abstract PO1-20-08: Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy

Abstract Primary squamous cell carcinoma of the breast is a rare entity, and there are a limited number of cases in the literature describing squamous cell carcinoma arising from breast implants. It has been hypothesized that these implant-associated cancers may arise from epithelialization of the implant capsule followed by chronic inflammation. None of the cases in the literature were treated with immunotherapy. We present a case of an aggressive, primary sarcomatoid squamous cell carcinoma of the breast arising from a breast implant that was treated unsuccessfully with simultaneous chemotherapy and immunotherapy following TEMPUS testing. Introduction: Breast augmentation is the most common plastic surgery procedure performed worldwide, with more than 300,000 done in the United States every year. While breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is extensively discussed in recent literature, other breast implant-associated cancers are rarer and less studied. Breast implant-associated squamous cell carcinoma (BIA-SCC) specifically is an extremely rare complication of breast augmentation and no guidelines for treatment exist. The American Society of Plastic Surgeons (ASPS) released a statement on BIA-SCC on 9/2022 following a safety communication from the FDA, and it is recommended health care providers submit case reports of BIA-SCC to a patient registry. Case study: We present the case of a female patient who underwent bilateral breast augmentation in 2006 with Mcghan textured, pre-pectoral, areolar saline implants. In 2022, she presented with swelling and a lump in her breast and underwent bilateral breast implant removal with capsulectomy. Pathology showed triple negative sarcomatoid squamous cell carcinoma of the right breast capsule. TEMPUS testing on the breast biopsy revealed a PIK3CA mutation and PD-L1 negative status. Her case was discussed with a multi-disciplinary team including plastic surgery, multiple oncologists, and radiation oncology and her clinical picture was determined to be most consistent with BIA-SCC. Based on the KEYNOTE-522 study, she was determined to be a candidate for neoadjuvant therapy with pembrolizumab and chemotherapy as she was newly diagnosed, previously untreated, nonmetastatic, and had a triple negative tumor. She received two cycles of carboplatin, paclitaxel, and pembrolizumab but unfortunately rapidly progressed with chest wall extension, multiple new pulmonary nodules, worsening lymphadenopathy, right ventricular tumor thrombus, and new malignant pleural effusion and was transitioned to hospice. Discussion: Seven cases of BIA-SCC, one case of squamous cell carcinoma (SCC) after liquid silicone injection augmentation, one case of squamous metaplasia on the breast implant capsule, and one case of epithelization of the breast implant capsule have been previously described in the literature (Table 1). None of the available cases of BIA-SCC report TEMPUS testing, and none of the patients were treated with immunotherapy. The origin of BIA-SCC is unclear, but several theories have been described including chronic inflammation leading to conversion of epithelial tissue on the capsule to SCC. It is unknown how the breast implant capsule might become epithelialized to begin with – introduction of epithelium intraoperatively during augmentation, rupture of epidermal cysts, existence of epithelium in the area from a childhood injury or from birth, or epithelization from chronic shear forces from the augmentation or leakage of the implant are all possibilities. With the ongoing data gathering through the FDA patient registry, we will continue to learn more about these rare cancers and potentially get further insight into their origins. Table 1 An overview of cases of BIA-SCC in the literature Citation Format: Emily Podany, Katherine Clifton. Primary breast implant-associated squamous cell carcinoma with subsequent TEMPUS testing and failure of immunotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-20-08.

D9. Updated Epidemiology Of Breast Implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) in the United States

D9. Updated Epidemiology Of Breast Implant-associated Anaplastic Large Cell Lymphoma (BIA-ALCL) in the United States

"Breast implant-associated anaplastic large cell lymphoma diagnosis six months post breast reconstruction: a case report"

The authors report the earliest time frame (six and a half months) between exposure to textured breast implant and the development of breast implant-associated anaplastic large cell lymphoma.

Comparison of Polytech MESMO and Motiva Ergonomix Breast Implants With a Focus on Displacement Issues: A Single Surgeon's Experience in 329 Patients.

Nanotextured breast implants (classified as smooth implants by the latest ISO 14607:2018) have been described as they may reduce major textured implant-related complications such as capsular contracture and breast implant-associated anaplastic large cell lymphoma. On the other hand, micro-textured breast implants benefit from an optimal safety profile based on a much larger body of literature. To directly compare the incidence of complications between Motiva Ergonomix (Establishment Labs, Alajuela, Costa Rica) and Polytech MESMO (Polytech Health & Aesthetics GmbH, Dieburg, Germany) breast implants, especially regarding the displacement issues that might arise after breast augmentation. Consecutive patients previously operated by the same surgeon with Motiva Ergonomix and Polytech MESMO implants were included in this study. They were divided into two groups according to the type of implant. The onset of complications was assessed through survival analysis. Data were collected from 329 patients, 185 (56.2%) carrying Polytech MESMO, and 144 (43.8%) Motiva Ergonomix implants. The median follow-up was 8 months for both groups. Of the 42 women (12.8%) who experienced at least one complication, 26 belonged to the Motiva Ergonomix subgroup (p = 0.013). The most represented complications during this period resulted from displacement issues, with a clear prevalence of bottoming out in the Motiva Ergonomix cohort: 15 cases versus 0 cases in the Polytech MESMO cohort (p < 0.001). For 7 patients, a reoperation was required, more frequently for patients with Motiva Ergonomix implants (4.2% versus 0.5%; p = 0.046). Polytech MESMO devices provided a more favorable outcome. Motiva Ergonomix devices revealed a concerning incidence of displacement issues during the first post-surgery years, with no advantage over other major complications.

The Spectrum of Non-neoplastic Changes Associated With Breast Implants: Histopathology, Imaging, and Clinical Significance.

Breast implant-associated anaplastic large cell lymphoma has been recognized as a distinct entity in the World Health Organization classification of hematolymphoid neoplasms. These neoplasms are causally related to textured implants that were used worldwide until recently. Consequently, there is an increased demand for processing periprosthetic capsules, adding new challenges for surgeons, clinicians, and pathologists. In the literature, the focus has been on breast implant-associated anaplastic large cell lymphoma; however, benign complications related to the placement of breast implants occur in up to 20% to 30% of patients. Imaging studies are helpful in assessing patients with breast implants for evidence of implant rupture, changes in tissues surrounding the implants, or regional lymphadenopathy related to breast implants, but pathologic examination is often required. In this review, we couple our experience with a review of the literature to describe a range of benign lesions associated with breast implants that can be associated with different clinical presentations or pathogenesis and that may require different diagnostic approaches. We illustrate the spectrum of the most common of these benign disorders, highlighting their clinical, imaging, gross, and microscopic features. Finally, we propose a systematic approach for the diagnosis and handling of breast implant specimens in general.

Breast Implant Associated Anaplastic Large Cell Lymphoma: Evidence-Based Consensus Conference Statement From The American Association of Plastic Surgeons.

In the absence of high-quality evidence, there is a need to provide guidelines and multidisciplinary consensus recommendations on Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). The purpose of this expert consensus conference was to evaluate the existing evidence regarding the diagnosis, and management of BIA-ALCL caused by textured implants. The aim is to provide evidence-based recommendations regarding the management and prevention of BIA-ALCL. A comprehensive search was conducted in the MEDLINE, Cochrane Library, and Embase databases, supplemented by manual searches of relevant English language articles and "related articles" sections. Studies focusing on breast surgery and lymphoma associated with breast implants were included for analysis. Meta-analyses were performed and reviewed by experts selected by the American Association of Plastic Surgeons by a Delphi consensus method. 840 articles between January 2011 and January 2023 were initially identified and screened. Full-text of 188 articles were assessed. An additional 43 articles were excluded for focus, and 145 articles were included in the synthesis of results, with 105 of them being case reports or case series. The analysis encompassed a comprehensive examination of the selected articles to determine the incidence, risk factors, clinical presentation, diagnostic approaches, and treatment modalities related to BIA-ALCL. Plastic surgeons should be aware of the elevated risks by surface type, implement appropriate patient surveillance, and follow the recommendations outlined in this statement to ensure patient safety and optimize outcomes. Ongoing research on pathogenesis, genetic drivers, and preventative and prophylactic measures is crucial for improving patient care.

Our Experience in Diagnosing and Treating Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon T-cell lymphoma detected in association with textured implants. It presents as a fluid accumulation around the implant, usually years after the implantation. We present our experience in diagnosing and treating four patients with BIA-ALCL, each widely differing from the other. Data on patients' surgical history, relevant medical information, and findings on pathological slides were retrieved from their medical charts and retrospectively reviewed. Each of the four patients was diagnosed with BIA-ALCL, one after breast augmentation, one after breast reconstruction with an implant, one after breast reconstruction with a latissimus dorsi flap and implant, and the fourth after the removal of breast implants. The cases were presented to a multidisciplinary team and subsequently underwent surgery. All four are currently free of tumors, as established by a negative follow-up via positron emission tomography-computed tomography. Although the incidence of BIA-ALCL is rare, these cases emphasize the need to rule out the diagnosis of BIA-ALCL in patients with textured implants or a history of implanted textured devices who present with symptoms such as late seroma or peri-implant mass. This pathology is typically indolent and slow-growing and heightened awareness for an early diagnosis could lead to quicker intervention and enhanced patient management.

Incidental Bystander or Essential Culprit: A Systematic Review of Bacterial Significance in the Pathogenesis of Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a distinct subtype of T-cell non-Hodgkin lymphoma that arises in the context of prolonged exposure to textured breast implants. The intent of this manuscript is to explore whether the bacterial presence in biofilms on these implants is a mere incidental finding or plays a pivotal role in the pathogenesis of BIA-ALCL. Our goal is to delineate the extent of bacterial involvement, offering insights into potential underlying mechanisms, and establishing future research priorities aimed at resolving the remaining uncertainties surrounding this complex association. A comprehensive systematic review of several databases was performed. The search strategy was designed and conducted by an experienced librarian using controlled vocabulary with keywords. The electronic search identified 442 publications. After evaluation, six studies from 2015 to 2021 were included, encompassing 201 female patients aged 23 to 75. The diagnosis span post-implantation ranged from 53 to 135.6 months. Studies consistently found bacteria near breast implants in both BIA-ALCL cases and controls, with varied microbial findings. Both BIA-ALCL cases and controls exhibited the presence of specific bacteria, including Pseudomonas aeruginosa, Klebsiella oxytoca, Staphylococcus aureus, and Ralstonia spp., without any statistically significant differences between groups. The use of antiseptic and antimicrobial agents during implant insertion did not demonstrate any impact on reducing or altering the risk of developing BIA-ALCL. Our systematic review reveals that the current evidence is inadequate to link bacterial etiology as a central factor in the development of BIA-ALCL. The limitations in the existing data prevent a complete dismissal of the role of biofilms in its pathogenesis. The observed gap in knowledge underscores the need for more focused and comprehensive research, which should be structured in a multi-faceted approach. Initially, this involves the utilization of sophisticated genomic and proteomic methods. Following this, it is crucial to delve into the study of immunological reactions specifically induced by biofilms. Finally, this research should incorporate extended observational studies, meticulously tracking the evolution of biofilm development and its correlation with the emergence of BIA-ALCL. In light of the inconclusive nature of current findings, further investigation is not only justified but urgently needed to clarify these unresolved issues.

Current status of pre- or subpectoral breast reconstruction in Japan.

Breast reconstruction using silicone breast implants (SBIs) has been performed for many patients in Japan under the initiative of the Japan Oncoplastic Breast Surgery Society (JOBSS) since SBIs were first covered by insurance in 2013. A change in the lineup of available SBIs owing to the Allergan crisis caused a decrease in the availability of SBIs appropriate to Japanese breast contours. Recently, the number of immediate implant-based breast reconstructions (IBRs) was approximately 4,000 in one year and was slightly decreasing. The SBI is generally placed under the pectoralis major muscle. Because the number of patients with one-stage, implant-based operative indications is small, an acellular dermal matrix is not available in Japan, and the complication rate in one-stage, IBR is high, most immediate, IBRs are performed in two stages. The prevalence of immediate, one-stage, IBRs is approximately 10%. Fat grafting by injection using Coleman's technique is performed in many hospitals under the JOBSS initiative as a surgery combined with SBI insertion. Complications after SBI placement may be less common in Japan than those in other countries. Japanese breast reconstructive surgeons undertake preventive measures to lessen these complications according to guidelines and experts' opinions, which may contribute to the low complication rate after SBI placement. The total reported number of patients with breast implant-associated anaplastic large cell lymphoma is four, and no patients have died because of this disease. In Japan, procuring informed consent and diagnosing and treating this disease are performed according to the JOBSS guidelines.

Impact of Brentuximab Vedotin in Patients with Breast Implant-Associated Anaplastic Large Cell Lymphoma with Capsule Infiltration Requiring Chemotherapy

Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon peripheral T-cell lymphoma most frequently arising around a textured surface breast implant. It has been shown that capsule infiltration (T2, T3 and T4 of the TNM staging system) was an adverse prognostic factor. In this context, chemotherapy (with or without brentuximab vedotin [BV]) may be proposed, considering other factors such as metastatic disease or incomplete resection. Furthermore, the need for adjuvant chemotherapy in patients with stage IIA (T4N0M0) and complete en-bloc excision without residual disease is debated. Aim: To assess the management of BIA-ALCL with capsule infiltration, in particular: 1) To assess the impact of BV in those patients; 2) To evaluate the need for adjuvant chemotherapy in patients with stage IIA and complete en-bloc excision without residual disease. Methods: Since 2016, a national multidisciplinary meeting has been implemented by the French National Cancer Institute (NCI) to optimize management of patients with BIA-ALCL, particularly those with advanced disease. Meanwhile, a national registry has been set up by the LYSA, in collaboration with health authorities. Central pathological review has been carried out within the French NCI-labeled Lymphopath network. Results: From 2009 to 2023, 125 patients with BIA-ALCL were recorded, of which 111 (94 from France and 17 from Belgium) had complete data and were included in the present analysis. Overall, median age at diagnosis of BIA-ALCL was 58 years (24-82 years). Reasons for initial implantation were breast cancer reconstruction (n=54; 49%), cosmetic (n=45; 41%) or other (n=12; 10%). The median interval from first implantation to diagnosis of BIA-ALCL was 12.3 years (4-40 years). The median number of implants in the breast involved by BIA-ALCL was 2 (1-8), including at least one silicone implant in 95 (86%) patients, and at least one textured implant in all informative cases (n=102; Most often Allergan Biocell implants). At diagnosis of BIA-ALCL, 78/110 (71%) patients presented with periprosthetic effusion only, 20 (18%) had effusion and a breast mass, 6 (5.5%) had a breast mass only, and 6 (5.5%) had neither. At pathological examination of the capsule, T-stage was T1 (confined to effusion or a layer on luminal side of capsule) in 73/111 (66%) cases, T2-T3 (capsule infiltration) in 5 (4.5%) cases, T4 (lymphoma infiltrates beyond the capsule) in 32 (29%) cases, and unclassifiable in 1 case. Moreover, 18/111 (16%) patients had at least one non-breast extranodal involvement. Among the 36 patients with capsule infiltration (5 T2-T3 and 31 T4), 13 (including 11 T4) were treated with BV-CH(E)P regimen, 12 (all T4) with a CHOP/CHOP-like regimen, and 11 (including 8 T4) did not receive any chemotherapy. The main reasons for receiving chemotherapy were metastatic disease, incomplete resection, or no surgery. Patients who did not receive chemotherapy had a localized disease (3 stage IB/IC and 8 stage IIA) with complete en-bloc excision and no residual disease. Patients treated with BV-CH(E)P regimen and CHOP/CHOP-like regimen had similar characteristics without significant differences regarding age, clinical presentation, stage and surgery. After a median follow-up of 47 months from BIA-ALCL diagnosis, for BV-CH(E)P and CHOP/CHOP-like groups, the respective 4-year PFS rates were 100% and 57% (p=0.01), and the respective 4-year OS rates were 100% and 73% (p=0.07). Regarding the 11 patients who did not receive chemotherapy, 4-year PFS and OS were both 75%, which corresponds to a single event being a death without progression occurring more than 3 years after the diagnosis of lymphoma (4-year lymphoma-specific survival was 100%). Conclusions: 1) In patients with capsule infiltration requiring chemotherapy, BV-CH(E)P regimen was associated with improved PFS and OS compared with CHOP/CHOP-like regimen; 2) Patients with stage IIA and complete en-bloc excision without residual disease had favorable outcome without the need for adjuvant chemotherapy. These results should be confirmed prospectively.

Zwitterionic polymer on silicone implants inhibits the bacteria-driven pathogenic mechanism and progress of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) occurs in the capsule surrounding breast implants. Malignant transformation of T cells by bacteria-driven chronic inflammation may be underlying BIA-ALCL mechanism. Here, we covalently grafted 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymers on a silicone surface and examined its effects against BIA-ALCL pathogenesis. MPC grafting strongly inhibited the adhesion of bacteria and bacteria-causing inflammation. Additionally, cancer T cell proliferation and capsule-derived fibroblast-cancer cell communication were effectively inhibited by MPC grafting. We further demonstrated the effect of MPC against the immune responses causing BIA-ALCL around human silicone implants in micro-pigs. Finally, we generated a xenograft anaplastic T cell lymphoma mouse model around the silicone implants and demonstrated that MPC grafting could effectively inhibit the lymphoma progression. This study is the first to show that bacteria-driven induction and progression of BIA-ALCL can be effectively inhibited by surface modification of implants. STATEMENT OF SIGNIFICANCE: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a major concern in the field of plastic and reconstructive surgery. In this study, we demonstrate strong inhibitory effect of zwitterionic polymer grafting on BIA-ALCL pathogenesis and progression, induced by bacterial infection and inflammation, bothin vitroandin vivo. This study provides a molecular basis for the development of novel breast implants that can prevent various potential complications such as excessive capsular contracture, breast implant illness, and BIA-ALCL incidence, as well as for expanding the biomedical applications of zwitterionic polymers.

Breast Implant-Associated Anaplastic Large Cell Lymphoma Awareness: An Analysis of the Responses to an Institutional Campaign and Global Recall.

We performed an assessment of patient response rates and clinical outcomes to the global recall for textured breast implants and to our institution's letters informing them of their risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). A retrospective review of patients who had textured implants placed at our institution was completed. Outcome measures included patient response rates to either the global recall or our institution's letters, rate of textured implant removal, and type of subsequent revision surgery. A total of 1176 patients with textured implants were reviewed for this study. In total, 374 patients (31.8%) reached out to discuss their risk of BIA-ALCL, and 297 (25.3%) eventually presented to the clinic. One hundred twenty eight patients (34.2%) responded after the letter but before the US Food and Drug Administration (FDA) ban of macrotextured BIOCELL implants, 186 (49.7%) after the FDA ban, and 48 (12.8%) after the manufacturer's multichannel campaign. One hundred eighteen patients with textured implants (11.6%) proceeded with surgery. Most underwent exchange with smooth implants (76 patients [64.4%]) after textured implant removal. A significant portion of patients (31.8%) responded to our letters, the FDA ban, and the manufacturer's campaign. Despite the low incidence of BIA-ALCL and the ongoing recommendation for observation in the setting of no symptoms, 11.6% of our patients still elected to proceed with implant removal. Exchange to smooth implants was the most popular surgical option at 64.4%.

Consulting the Digital Doctor: Google Versus ChatGPT as Sources of Information on Breast Implant-Associated Anaplastic Large Cell Lymphoma and Breast Implant Illness.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare complication associated with the use of breast implants. Breast implant illness (BII) is another potentially concerning issue related to breast implants. This study aims to assess the quality of ChatGPT as a potential source of patient education by comparing the answers to frequently asked questions on BIA-ALCL and BII provided by ChatGPT and Google. The Google and ChatGPT answers to the 10 most frequently asked questions on the search terms "breast implant associated anaplastic large cell lymphoma" and "breast implant illness" were recorded. Five blinded breast plastic surgeons were then asked to grade the quality of the answers according to the Global Quality Score (GQS). A Wilcoxon paired t-test was performed to evaluate the difference in GQS ratings for Google and ChatGPT answers. The sources provided by Google and ChatGPT were also categorized and assessed. In a comparison of answers provided by Google and ChatGPT on BIA-ALCL and BII, ChatGPT significantly outperformed Google. For BIA-ALCL, Google's average score was 2.72 ± 1.44, whereas ChatGPT scored an average of 4.18 ± 1.04 (p < 0.01). For BII, Google's average score was 2.66 ± 1.24, while ChatGPT scored an average of 4.28 ± 0.97 (p < 0.01). The superiority of ChatGPT's responses was attributed to their comprehensive nature and recognition of existing knowledge gaps. However, some of ChatGPT's answers had inaccessible sources. ChatGPT outperforms Google in providing high-quality answers to commonly asked questions on BIA-ALCL and BII, highlighting the potential of AI technologies in patient education. Level III, comparative study LEVEL OF EVIDENCE III: 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 www.springer.com/00266 .

CD30 Lateral Flow and Enzyme-Linked Immunosorbent Assays for Detection of BIA-ALCL: A Pilot Study

Introduction: Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) commonly presents as a peri-implant effusion (seroma). CD30 (TNFRSF8) is a consistent marker of tumor cells but also can be expressed by activated lymphocytes in benign seromas. Diagnosis of BIA-ALCL currently includes cytology and detection of CD30 by immunohistochemistry or flow cytometry, but these studies require specialized equipment and pathologists’ interpretation. We hypothesized that a CD30 lateral flow assay (LFA) could provide a less costly rapid test for soluble CD30 that eventually could be used by non-specialized personnel for point-of-care diagnosis of BIA-ALCL. Methods: We performed LFA for CD30 and enzyme-linked immunosorbent assay (ELISA) for 15 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. To determine the dynamic range of CD30 detection by LFA, we added recombinant CD30 protein to universal buffer at seven different concentrations ranging from 125 pg/mL to 10,000 pg/mL. We then performed LFA for CD30 on cryopreserved seromas of 10 patients with pathologically confirmed BIA-ALCL and 10 patients with benign seromas. Results: Recombinant CD30 protein added to universal buffer produced a distinct test line at concentrations higher than 1000 pg/mL and faint test lines at 250–500 pg/mL. LFA produced a positive test line for all BIA-ALCL seromas undiluted and for 8 of 10 malignant seromas at 1:10 dilution, whereas 3 of 10 benign seromas were positive undiluted but all were negative at 1:10 dilution. Undiluted CD30 LFA had a sensitivity of 100.00%, specificity of 70.00%, positive predictive value of 76.92%, and negative predictive value of 100.00% for BIA-ALCL. When specimens were diluted 1:10, sensitivity was reduced to 80.00% but specificity and positive predictive values increased to 100.00%, while negative predictive value was reduced to 88.33%. When measured by ELISA, CD30 was below 1200 pg/mL in each of six benign seromas, whereas seven BIA-ALCL seromas contained CD30 levels &gt; 2300 pg/mL, in all but one case calculated from dilutions of 1:10 or 1:50. Conclusions: BIA-ALCL seromas can be distinguished from benign seromas by CD30 ELISA and LFA, but LFA requires less time (&lt;20 min) and can be performed without special equipment by non-specialized personnel, suggesting future point-of-care testing for BIA-ALCL may be feasible.

Smooth vs Textured Expanders: Patient Factors and Anatomic Plane Are Greater Factors in Determining First-Stage Breast Reconstruction Outcomes.

Textured implants and expanders are associated with an increased risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). As a result, plastic surgeons are utilizing smooth expanders, but many perceive these produce undesirable outcomes including infection, seroma, and lateral displacement. The aim of this study was to compare clinical outcomes of smooth and textured expanders. Breast reconstruction patients from January 2018 to May 2021 were retrospectively reviewed. Included patients underwent placement of tissue expanders at the time of mastectomy. Primary outcomes included postoperative seroma, infection, malposition, days to final reconstruction, explantation, and the need for capsulorrhaphy. In total, 233 patients were reviewed, of whom 167 met both inclusion and exclusion criteria. There was no statistically significant difference in poor outcomes comparing smooth and textured expanders. Days to final reconstruction was lower with smooth expanders per breast (P = .0424). The subpectoral group was associated with an increased likelihood of undergoing capsulorrhaphy (P = .004). Prepectoral placement was associated with more seromas (P = .0176) and infections (P = .0245). Demographic factors included older age as a protective factor for undergoing capsulorrhaphy (odds ratio [OR] = 0.962, P = .038), obesity increased the risk of infection (OR = 5.683, P = .0279) and malposition (OR = 6.208, P = .0222), and radiation was associated with malposition (OR = 3.408, P = .0246). There was no significant difference in poor outcomes between smooth and textured expanders. Patient demographics and anatomical plane placement had greater effects on infection, seroma, and the need for capsulorrhaphy compared with tissue expander texturing.

Navigating Food and Drug Administration Mandated Breast Implant Patient Literature: A Call to Increase Equitable Healthcare Access Within Plastic Surgery.

In October 2021, the US Food and Drug Administration mandated patient decision checklists and new labeling for breast implants with the goal of improving the informed decision-making process for patients considering breast implantation. Given growing concerns over breast implant-associated anaplastic large cell lymphoma, breast implant-associated squamous cell carcinoma, and breast implant illness, patients should be able to easily review these resources to make a fully informed decision when considering surgery. This study seeks to elucidate the accessibility, and therefore the utility of the newly mandated literature for the average breast implant patient. Patient decision checklists and breast implant boxed warnings were obtained from the most used breast implant manufacturers in the United States-Allergan, Mentor, and Sientra. Readability analysis of all Food and Drug Administration required documents was performed using the Flesch Reading Ease Score, Flesch Kincaid Grade Level, Gunning-Fog Index, Coleman-Liau Index, Simplified Measure of Gobbledygook, and Automated Readability Index. The overall readability of all Allergan, Mentor, and Sientra patient materials correlates with a college reading level. Documents from all 3 implant manufacturers were of a statistically significantly higher reading level than that recommended by the American Medical Association and US Department of Health and Human Services. No materials were found to be at or below the recommended sixth-grade level. The newly mandated breast implant patient decision guides are written at a college reading level. These materials should be simplified to improve health literacy shared decision making.