Diagnosis Of Breast Implant-associated Anaplastic Large Cell Lymphoma Research Articles

A Deep Learning Model to Predict Breast Implant Texture Types Using Ultrasonography Images: Feasibility Development Study.

Breast implants, including textured variants, have been widely used in aesthetic and reconstructive mammoplasty. However, the textured type, which is one of the shell texture types of breast implants, has been identified as a possible etiologic factor for lymphoma, specifically breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Identifying the shell texture type of the implant is critical to diagnosing BIA-ALCL. However, distinguishing the shell texture type can be difficult due to the loss of human memory and medical history. An alternative approach is to use ultrasonography, but this method also has limitations in quantitative assessment. This study aims to determine the feasibility of using a deep learning model to classify the shell texture type of breast implants and make robust predictions from ultrasonography images from heterogeneous sources. A total of 19,502 breast implant images were retrospectively collected from heterogeneous sources, including images captured from both Canon and GE devices, images of ruptured implants, and images without implants, as well as publicly available images. The Canon images were trained using ResNet-50. The model's performance on the Canon dataset was evaluated using stratified 5-fold cross-validation. Additionally, external validation was conducted using the GE and publicly available datasets. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (PRAUC) were calculated based on the contribution of the pixels with Gradient-weighted Class Activation Mapping (Grad-CAM). To identify the significant pixels for classification, we masked the pixels that contributed less than 10%, up to a maximum of 100%. To assess the model's robustness to uncertainty, Shannon entropy was calculated for 4 image groups: Canon, GE, ruptured implants, and without implants. The deep learning model achieved an average AUROC of 0.98 and a PRAUC of 0.88 in the Canon dataset. The model achieved an AUROC of 0.985 and a PRAUC of 0.748 for images captured with GE devices. Additionally, the model predicted an AUROC of 0.909 and a PRAUC of 0.958 for the publicly available dataset. This model maintained the PRAUC values for quantitative validation when masking up to 90% of the least-contributing pixels and the remnant pixels in breast shell layers. Furthermore, the prediction uncertainty increased in the following order: Canon (0.066), GE (0072), ruptured implants (0.371), and no implants (0.777). We have demonstrated the feasibility of using deep learning to predict the shell texture type of breast implants. This approach quantifies the shell texture types of breast implants, supporting the first step in the diagnosis of BIA-ALCL.

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.

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.

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 > 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 (<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.

Clinical recommendations for diagnosis and treatment according to current updated knowledge on BIA-ALCL

Shared strategies and correct information are essential to guide physicians in the management of such an uncommon disease as Breast Implant–Associated Anaplastic Large Cell Lymphoma (BIA-ALCL). A systematic review of the literature was performed to collect the most relevant evidence on BIA-ALCL reported cases. A panel of multidisciplinary experts discussed the scientific evidence on BIA-ALCL, and updated consensus recommendations were developed through the Delphi process. The lastest reported Italian incidence of BIA-ALCL is 3.5 per 100.000 implanted patients (95% CI, 1.36 to 5.78), and the disease counts over 1216 cases worldwide as of June 2022. The most common presentation symptom is a late onset seroma followed by a palpable breast mass. In the event of a suspicious case, ultrasound-guided fine-needle aspiration should be the first step in evaluation, followed by cytologic and immunohistochemical examination. In patients with confirmed diagnosis of BIA-ALCL confined to the capsule, the en-bloc capsulectomy should be performed, followed by immediate autologous reconstruction, while delayed reconstruction applies for disseminate disease or radically unresectable tumor. Nevertheless, a multidisciplinary team approach is essential for the correct management of this pathology.

Clinical Outcomes of Patients with Breast Implant- Associated Anaplastic Large- Cell Lymphoma (BIA-ALCL) Treated with Chemotherapy and Brentuximab Vedotin

Background BIA-ALCL is a rare form of CD30-positive, ALK-negative ALCL associated with textured breast implants. Patients with stage I BIA-ALCL have disease limited to the capsule which can be completely resected to achieve cure. Advanced stages of disease with capsular invasion, lymph node involvement and/or distant spread require more therapeutic interventions, including radiation (XRT), chemotherapy (CTX), or immunotherapy (ADC). Chemotherapy treatments are similar to those for systemic ALCL and often include anti-CD30 ADC brentuximab vedotin (BV). This study aims to compare outcomes between patients (pts) with advanced BIA-ALCL treated with adjuvant CTX and BV versus those without treatment (Tx). Methods This study is a single institution, IRB approved retrospective chart review, wherein we examined newly diagnosed pts with BIA-ALCL and review of literature between 2008 and 2022. Variables collected included age, radiologic imaging, stage, surgical procedure, pathology review, and laboratory data. Data on treatment and progression, including response to frontline CTX and BV-based therapy, was also analyzed. Overall survival (OS) was the primary endpoint of the study. R studio version 4.2.1 was used for statistical analysis. Results In a cohort of 130 pts (71 MDACC pts and 59 literature review pts) with BIA-ALCL, the median age was 53 years (range, 29-77). The indication for implants were as follows: 69 (53%) for cosmetic purpose, 45 (35%) for breast reconstruction following breast cancer, and 1 due to fibrocystic changes. Twenty-five pts with a history of breast cancer had a recorded history of Tx including CTX, radiation, and hormonal therapy. There were 61 pts (47%) with silicone implants, 30 (23%) with saline, and 3 (2%) had both silicone and saline; implant filling was not available for 36 pts (28%). In terms of types of implants: 61 (47%) had Allergan/McGhan/Inamed (A/M/I), 3 (2%) had A/M/I and implants from other companies, 1 had A/M/I and Mentor (1%), 5 (4%) had Mentor, 2 (2%) had Mentor and other companies, and 7 (5%) had implants from other companies; data was not available for 51 (39%) pts. All 82 pts for whom data was available had textured implants. The average time between implant placement and diagnosis was 12.8 years. On initial clinical presentation, 97 (75%, n=130) pts had swelling, 95 (73%, n= 130) had effusions, 22 (17%, n=130) had lymphadenopathy (LAD), and 7 (5%, n=130) had other clinical presentations such as contractures and rash. Stage included: I- 42%, II- 12%, III-7%, and IV-4%. Overall, 54 (52%) pts did not receive Tx (CTX and BV) and 50 (48%) pts did. Among pts that received no treatment (n=54), 96% had effusions and among pts who had Tx (n= 50), 74% had effusions (p=0.003). Fewer pts on the Tx arm underwent capsulectomy versus those who did not receive Tx: 17 (37.6%) vs 25 (56.8%), p= 0.001). For CTX pts 86% (n=43) pts received CHOP or CHOP-like regimens. Seven (14%) received BV only while 6 (12%) had CTX + BV. A median of 5.1 months passed between diagnosis of BIA-ALCL and starting CTX. Eighty-eight (68%) pts achieved complete remission, 6 (5%) pts were alive with disease, 7 (5%) pts died from disease and 3 (2%) pts died from unrelated diseases. Endpoint response was not available for 26 pts. Most pts who did not receive CTX had Stage I and were treated with complete capsulectomy. We compared the overall survival amongst pts with no Tx, CTX, CTX + BV, and BV. The survival probability of pts receiving CTX and CTX + BV was lower (0.9 and 0.63, respectively) as the disease was similar to systemic ALCL. Overall, there was no significant difference in OS rate (p=0.054) among all four groups of pts. Conclusion Complete surgical excision continues to play a central role in the management of pts with BIA-ALCL. Although most pts with BI-ALCL have excellent outcomes, a subset of pts with advanced stage disease has a more aggressive course and need CTX or BV. Given the smaller numbers of pts with various CTX combinations, prospective studies are required to evaluate the beneficial role of BV in pts with advanced BIA-ALCL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

TCL-495 Evaluation of Breast Implant-Associated Anaplastic Large Cell Lymphoma With Whole Exome and Genome Sequencing.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a subtype of T-cell lymphoma with much of its pathogenesis poorly understood. Mutations in the JAK/STAT pathway have been identified in a substantial proportion of cases, as well as copy number aberrations (CNAs). However, a more discrete characterization is vital to identify those with a germline predisposition to develop BIA-ALCL when exposed to a textured implant, and to identify targets for precision anti-BIA-ALCL therapeutics. To determine if there are recurrent gene mutations in BIA-ALCL patients in a cohort at a single institution. Ten patients were included that were diagnosed with BIA-ALCL between April 2015 and May 2020. Whole exome sequencing (WES) was performed on 8 tumor and normal BIA-ALCL samples and whole genome sequencing (WGS) was performed on 3 BIA-ALCL fluid samples. Samples were sequenced on an Illumina NovaSeq 6000. Data was analyzed using the Illumina DRAGEN Bio-IT Platform v3.8 workflow. This study was carried out at Barnes Jewish Hospital/Siteman Cancer Center. Patients were included if they have a pathology proven diagnosis of BIA-ALCL. Incidence and quantification of recurrent mutations in tumor samples of patients with BIA-ALCL evaluated via WES and WGS. Nearly all BIA-ALCLs showed substantial CNAs. Most patients had missense mutations in large genes with predominantly C to T transitions. Two cases had STAT3 mutations, consistent with previously reported data. Whole genome sequencing showed a critically deleted 7Mb region on chromosome 11 at 11q22.3 region in all 3 samples evaluated. This region contains the ATM gene which upon deletion in mouse models has shown an increased number of tumors. Clinically, the overall prognosis of BIA-ALCL was favorable; one patient passed from complications. There are no highly recurrent mutations in BIA-ALCL, however, 11q22.3 deletions were consistent across WGS cases and present in some exomes. Given the small sample size due to the rarity of the disease, genomic evaluation of a larger cohort is necessary to confirm this finding. Financial support for this study was provided by the Aesthetic Surgery Education Research Foundation and Barnes Hospital Foundation.

Breast Implant–associated Anaplastic Large Cell Lymphoma in Colombia: Report of a Multidisciplinary National Registry

Background: An estimated 43,390 breast augmentation surgeries (86,780 implants) and 1486 breast implant reconstructions are performed annually in Colombia, representing the second-most breast surgery destination in South America, the fourth in the western hemisphere, and the fifth country worldwide. No previous reports have evaluated the incidence of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) epidemiology or outcomes in a Hispanic population. Published data on the incidence of this disease in Colombia are unknown; therefore, a National Joint Multidisciplinary Committee was developed between the Colombian scientific societies of Mastology, Plastic Surgery, Hemato-Oncology, and the Invima (The National Food and Drug Surveillance Institute) to track national cases of BIA-ALCL. Materials and Methods: We performed a retrospective review (survey-based study) of historical cases since 2011–2019, and a prospective collection of all patients with a confirmed World Health Organization diagnosis of BIA-ALCL identified in a newly established National Registry of BIA-ALCL. The trial was approved by Institutional Review Board (IRB).

Breast Implant Associated-Anaplastic Large-Cell Lymphoma (BIA-ALCL): Data Based on the Lymphoma Study Association (LYSA) Registry. Promising Results of Brentuximab Vedotin Combined with Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) As First Line Treatment for Patient Requiring Chemotherapy

Breast Implant Associated-Anaplastic Large-Cell Lymphoma (BIA-ALCL): Data Based on the Lymphoma Study Association (LYSA) Registry. Promising Results of Brentuximab Vedotin Combined with Cyclophosphamide, Doxorubicin and Prednisone (BV-CHP) As First Line Treatment for Patient Requiring Chemotherapy

Breast implant-associated anaplastic large cell lymphoma: a case report with a history of spontaneously resolved late seroma

We report a case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), which had a history of spontaneous resorption of late seroma before diagnosis. A 47-year-old woman with a history of augmentation mammoplasty with round textured implants in January 2013 presented with a swelling on her right breast 6 years later, which was diagnosed as late seroma with suspected intracapsular rupture using ultrasonography (USG). Although aspiration was not done at the time of the initial USG, the seroma resolved spontaneously within weeks. A further workup proceeded with USG-guided aspiration followed by magnetic resonance imaging. Cytology of the aspirated fluid showed atypical cells. Cell block cytology and immunohistochemical staining confirmed the diagnosis of BIA-ALCL. En bloc resection with total capsulectomy and explantation was performed as curative surgery. Pathologic stage pT2N0M0 was confirmed and the patient was followed up without further treatment. Although the classic presentation of BIA-ALCL is known as late persistent seroma, an atypical manifestation such as spontaneous resorption may occur, as in the current case. A high level of suspicion and a thorough investigation with appropriate modalities will make it possible to detect this rare and potentially devastating disease.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): Quantifying the direct economic costs of post-treatment radiological surveillance.

e19574 Background: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) was recognised by the WHO in 2016 as a rare sub-type of peripheral T-cell, non-Hodgkin lymphoma (NHL), characterized by an indolent clinical course and excellent prognosis. Little evidence exists on the role of post-treatment imaging surveillance with variable practices across the world. Recent UK guidelines recommend that routine surveillance imaging should not be offered to BIA-ALCL patients, in line with national/international recommendations for other NHLs. The aim of this study was to quantify the direct economic costs (DEC) of post-treatment BIA-ALCL routine radiological surveillance at our institution compared to the DEC if UK guidelines were followed. Methods: Following IRB approval a retrospective analysis of a prospectively maintained database of BIA-ALCL patients at The Royal Marsden Hospital was performed. DECs were estimated using current (2020) NHS tariffs for radiological investigations. Imaging undertaken for symptomatic problems/non-BIA-ALCL related concerns was excluded. Results: Eleven patients [median age: 49 years (IQR 45-52)] were treated for BIA-ALCL between 2015-2020 following cosmetic augmentation (n = 6) or breast reconstruction (n = 5). Median time from first implant surgery to BIA-ALCL diagnosis was 11 years (IQR 8-12). Patients presented with effusion (n = 7), mass (n = 2) or effusion and mass (n = 2). One patient had neoadjuvant CHOP/brentuximab, all 11 had explantation with en bloc total capsulectomy, 1 had adjuvant CHOP. Median follow-up was 38 months (IQR 12-47) with no local or distant relapses. Two patients did not have any radiological surveillance and 1 had follow-up elsewhere. The remaining 8 patients had a combination of PET/CT (n = 10), CT (n = 2), breast ultrasound (n = 6), mammogram (n = 4) and breast MRI (n = 1) as routine imaging follow-up not guided by clinical concerns. This represents evolving practice at our institution as the UK guidelines were published in 2021. Total cost of routine imaging surveillance was £10,396 ($14,396) with median cost of £1,953 ($2,705) per patient [IQR £526-2029 ($728-2,810)]. This cost could have been saved based on current guidelines recommending no routine surveillance for patients with no symptoms or clinical concerns. Conclusions: This data demonstrates that omission of routine post-treatment imaging surveillance, as per the recent UK guidelines, would result in a median DEC saving of £1,953 ($2,705) per patient at our institution. No local or distant relapses where identified within the follow-up period, in line with the existing literature suggesting BIA-ALCL has a very low risk of relapse and excellent prognosis. These findings provide a value-based analysis to further support the recommendation not to perform routine post-treatment imaging surveillance in patients with BIA-ALCL.

Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL): Are You Covered?

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a locally aggressive T-cell lymphoma that can develop following breast implantation. In 2017, and updated in 2019, the National Comprehensive Cancer Network (NCCN) recommended total capsulectomy with implant removal as definitive therapy. The aim of this study was to evaluate the US insurance coverage for the management of BIA-ALCL and compare it to the NCCN recommendations. A cross-sectional analysis of US insurance policies for coverage of BIA-ALCL treatment was conducted. Insurance companies were selected based on their market share and state enrollment. Medical necessity criteria were abstracted from the publicly available policies. Of the 101 companies assessed, only 30 (30%) had a policy for the management of BIA-ALCL. Of those policies, all (n = 30, 100%) provided coverage of the implant removal of the breast diagnosed with BIA-ALCL. For the contralateral breast implant, 20 policies (67%) covered their removal, but significantly fewer did so if the implant was placed for cosmetic reasons vs medically necessary (n = 13 vs n = 20, 43% vs 67%; P = 0.0026). Twenty-one policies (70%) covered an implant reinsertion, but fewer would do so if the implant was cosmetic rather than medically necessary (n = 5, 17% vs 70%; P < 0.0001). There was notable intercompany variation in the coverage of BIA-ALCL treatment, some of which is unnecessarily based on whether the original reason for the breast implant was cosmetic or medically necessary. This variability may significantly reduce access to definitive treatment in patients with a BIA-ALCL diagnosis.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report

Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.

IL-10, IL-13, Eotaxin and IL-10/IL-6 ratio distinguish breast implant-associated anaplastic large-cell lymphoma from all types of benign late seromas

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is an uncommon peripheral T cell lymphoma usually presenting as a delayed peri-implant effusion. Chronic inflammation elicited by the implant has been implicated in its pathogenesis. Infection or implant rupture may also be responsible for late seromas. Cytomorphological examination coupled with CD30 immunostaining and eventual T-cell clonality assessment are essential for BI-ALCL diagnosis. However, some benign effusions may also contain an oligo/monoclonal expansion of CD30 + cells that can make the diagnosis challenging. Since cytokines are key mediators of inflammation, we applied a multiplexed immuno-based assay to BI-ALCL seromas and to different types of reactive seromas to look for a potential diagnostic BI-ALCL-associated cytokine profile. We found that BI-ALCL is characterized by a Th2-type cytokine milieu associated with significant high levels of IL-10, IL-13 and Eotaxin which discriminate BI-ALCL from all types of reactive seroma. Moreover, we found a cutoff of IL10/IL-6 ratio of 0.104 is associated with specificity of 100% and sensitivity of 83% in recognizing BI-ALCL effusions. This study identifies promising biomarkers for initial screening of late seromas that can facilitate early diagnosis of BI-ALCL.

Breast Implant-associated Anaplastic Large Cell Lymphoma in Colombia: Report of a Multidisciplinary National Registry.

Background:An estimated 43,390 breast augmentation surgeries (86,780 implants) and 1486 breast implant reconstructions are performed annually in Colombia, representing the second-most breast surgery destination in South America, the fourth in the western hemisphere, and the fifth country worldwide. No previous reports have evaluated the incidence of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL) epidemiology or outcomes in a Hispanic population. Published data on the incidence of this disease in Colombia are unknown; therefore, a National Joint Multidisciplinary Committee was developed between the Colombian scientific societies of Mastology, Plastic Surgery, Hemato-Oncology, and the Invima (The National Food and Drug Surveillance Institute) to track national cases of BIA-ALCL.Materials and Methods:We performed a retrospective review (survey-based study) of historical cases since 2011–2019, and a prospective collection of all patients with a confirmed World Health Organization diagnosis of BIA-ALCL identified in a newly established National Registry of BIA-ALCL. The trial was approved by Institutional Review Board (IRB).Results:Eighteen cases of BIA-ALCL were identified in Colombia between 2011 and 2019. Hundred percent developed as sequelae of textured implants. Six patients (33.3%) presented either a peri-implant capsule mass or axillary lymph node involvement. Seven (38.9%) required adjuvant chemotherapy most commonly with CHOP regimen. Different brands of implants were associated with our cases. One death (5.6%) was attributed to BIA-ALCL, and one (5.6%) case displayed with relapsed with bone marrow involvement requiring a bone marrow transplantation. Six cases (33.3%) were identified with advanced stage (IIB-IV). Disease-free survival of 92.3% was achieved at 30.8-month follow-up.Conclusions:Colombia has one of the highest volumes of breast surgery and use of textured surface breast implants in the world. This study is the initial report of an implant registry in South America. A high proportion of advanced disease may be a consequence of delayed presentation, lack of disease awareness, and timely access to tertiary cancer centers for diagnosis and treatment. Brands other than Allergan and Mentor were found to be associated with BIA-ALCL in our study.

En Bloc Capsulectomy for Breast Implant Illness: A Social Media Phenomenon?

En bloc capsulectomy has recently increased in prominence as a potential surgical therapy for patients with breast implant illness (BII). However, this procedure has chiefly been recommended for treating breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). This study aimed to review the current literature and evaluate the public understanding of treatment options for BII via social media to characterize any potential communication disconnect between clinicians and patients. An electronic literature review was performed to identify all available publications mentioning evidence-based support for en bloc capsulectomy as treatment for BII and BIA-ALCL. Twitter social media posts referencing BII or BIA-ALCL were analyzed from 2010 to 2019. Author identity and any mention of surgical treatment were assessed. A total of 115 publications on the subject of BII and 315 articles on BIA-ALCL were identified. En bloc resection was recommended only for patients with a diagnosis of BIA-ALCL. A total of 6419 tweets referencing BII and 6431 tweets referencing BIA-ALCL were identified. Tweets referencing BIA-ALCL were significantly more likely to be authored by physicians (25.9% vs 5.3%, P < 0.001), and tweets referencing BII were significantly more likely to mention any surgical treatment (7.8% vs 1.9%, P < 0.001) and en bloc capsulectomy (1.4% vs 0.3%, P < 0.001). This study demonstrates that a communication disconnect exists between the scientific literature and social media regarding treatment options for BII and BIA-ALCL. Physicians should be aware of these potential misconceptions to empathetically address patient concerns in a patient-centered manner.

Breast Implant-associated Anaplastic Large Cell Lymphoma: Review and Multiparametric Imaging Paradigms.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a new provisional category in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms, and its incidence is rising owing to increasing recognition of this complication of breast implant insertion. At a median of 10 years after implant insertion, the typical presenting features are sudden-onset breast swelling secondary to peri-implant effusion and less frequently mass-forming disease. Histologic features comprise pleomorphic cells expressing CD30 and negative anaplastic lymphoma kinase (ALK) receptor, similar to systemic and cutaneous ALK-negative anaplastic large cell lymphoma (ALCL). The effusion-only subtype is generally indolent and curable with surgery, unlike the more aggressive mass-forming disease, for which systemic therapy is advocated. High clinical suspicion and pertinent use of radiologic and pathology modalities are essential for timely and accurate diagnosis of BIA-ALCL. Contemporary imaging techniques including US, mammography, breast MRI, CT, and PET/CT are routinely used in breast disease and lymphomas; however, the unique behavior of BIA-ALCL presents significant diagnostic and radiologic interpretative challenges, with numerous nuanced imaging features being pertinent, and current lymphoma staging and response guidelines are not easily applicable to BIA-ALCL. The authors evaluate available evidence in this evolving field; detail key indications, strengths, and limitations of the panoply of radiologic techniques for BIA-ALCL; and propose multiparametric imaging paradigms for management of the peri-implant effusion and mass-forming or advanced disease subtypes, with the goal of accurate optimal patient care. The authors also predict a future model of multimodal assessment using novel imaging and molecular techniques and define key research directions. ©RSNA, 2020.

Evaluating the Necessity of Capsulectomy in Cases of Textured Breast Implant Replacement.

Capsulectomy has traditionally been recommended as a treatment for capsular contracture after breast augmentation. With the advent of breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL), and the Food and Drug Administration's decision to ban Biocell textured devices, this operation has taken on new importance. This review was undertaken to better inform clinical recommendations for women with textured devices. An electronic search was performed using PubMed to identify all the available literature on the subject of capsulectomy and open capsulotomy (the alternative treatment). Fifty-seven articles on this topic were identified. Capsulectomy was widely recommended for treatment of capsular contracture, although many authors recommended leaving thin capsular tissue behind in the absence of symptoms. En bloc resection was recommended only for women with a diagnosis of BIA-ALCL. No information supported a prophylactic role for capsulectomy in asymptomatic women with textured breast implants who are concerned regarding their future risk of BIA-ALCL. Routine pathologic examination in asymptomatic patients was not supported. Capsulectomy adds substantially to the surgical risk, discomfort, recovery time, and expense. Implant removal or replacement without a simultaneous capsulectomy is atraumatic and poses negligible risk. Capsulectomy introduces additional morbidity and is not mandatory for asymptomatic patients. Implant removal or exchange for smooth implants without a capsulectomy may be an acceptable choice for many women who do not demonstrate capsular pathology. However, any symptoms or surgical findings suggesting pathology warrant a capsulectomy. En bloc resections are reserved for patients diagnosed with BIA-ALCL.

Best Practices Guideline for the Pathologic Diagnosis of Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

To provide guidelines for the accurate pathologic diagnosis of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), the preoperative evaluation of the patient with suspected BIA-ALCL, and the pathologic evaluation of the capsulectomy specimen. To better inform patients and healthcare providers about BIA-ALCL, we convened to review diagnostic procedures used in the evaluation of patients with suspected BIA-ALCL. We focused on the processing of the seroma fluid/effusion surrounding the implant, the handling of capsulectomy specimens following removal of implant(s), and the preoperative evaluation of the patient with suspected BIA-ALCL. Recommendations were based on the published literature and our experience to optimize procedures to obtain an accurate diagnosis and assess for tumor invasion and the extent of the disease. Early diagnosis of BIA-ALCL is important as the disease can progress and deaths have been reported. Because the most common presentation of BIA-ALCL is swelling of the breast with fluid collection, an accurate diagnosis requires cytologic evaluation of the effusion fluid surrounding the affected implant. The first priority is cytocentrifugation and filtration of fresh, unfixed effusion fluid to produce air-dried smears that are stained with Wright-Giemsa or other Romanowsky-type stains. Preparation of a cell block is desirable to allow for hematoxylin and eosin staining and immunohistochemical analysis of formalin-fixed, paraffin-embedded histologic sections. Cell block sections can be used for polymerase chain reaction-based investigation of T-cell receptor gene rearrangement to detect clonality. Fixation and mapping of the capsulectomy specimen to select multiple representative sections are advised to assess for microscopic tumor involvement and capsular invasion. It is appropriate to assess lymph node involvement by excisional biopsy material rather than fine needle aspiration, due to propensity for focal involvement.

A Cautionary Tale and Update on Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Breast implant-associated anaplastic large T-cell lymphoma (BIA-ALCL) was first recognized by the World Health Organization in 2016. The total number of cases worldwide continues to increase, with >800 cases confirmed through a combination of the FDA, verified reports, and registries. There are 33 deaths currently reported. Typical presentation includes a late seroma containing monoclonal T cells that are CD30+ and anaplastic lymphoma kinase (ALK) negative. We present a review of the current literature and report on three cases of BIA-ALCL at our institution, which serve to illustrate our approach to diagnosis and management of this disease. In two cases, the diagnosis of BIA-ALCL was not initially confirmed due to an incomplete workup but was recognized upon explantation. The seroma fluid was sent for flow cytometry. Initially, the cells were reported as morphologically suspicious for malignancy with phenotypically normal T-cells based on standard CD3+ T-cell gating. Subsequent cytology specimens were reported as consistent with recurrent adenocarcinoma. However, upon re-gating of flow cytometry data, a population of CD30+, CD3- T-cells was noted and the diagnosis of BIA-ALCL was confirmed by immunohistochemical stains of the excised breast capsule specimen. Given the increasing incidence of this disease, as plastic surgeons we must stay informed to order the correct workup to avoid misdiagnosis and be prepared to appropriately refer affected patients to centers with multidisciplinary teams experienced in the management of BIA-ALCL.