Role of flow cytometric immunophenotyping in the diagnosis of breast implant-associated anaplastic large cell lymphoma: A 6-year, single-institution experience.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an uncommon mature T-cell neoplasm occurring in patients with textured breast implants, typically after 7-10 years of exposure. Although cytopathologic or histopathologic assessment is considered the gold standard diagnostic method for BIA-ALCL, flow cytometry (FC)-based immunophenotyping is recommended as an adjunct test. However, the diagnostic efficacy of FC is not well reported. We reviewed 290 FC tests from breast implant pericapsular fluid and capsule tissue from 182 patients, including 16 patients with BIA-ALCL over a 6-year period, calculating diagnostic rates and test efficacy. FC showed an overall sensitivity of 75.9%, specificity of 100%, and negative and positive predictive values of 95.4% and 100%, respectively. Blinded expert review of false-negative cases identified diagnostic pitfalls, improving sensitivity to 96.6%. Fluid samples had better rates of adequate samples for FC testing compared with tissue samples. Paired with FC testing of operating room (OR)-acquired fluid samples, capsulectomy FC specimens added no diagnostic value in patients with concurrent fluid samples; no cases had positive capsule FC with negative fluid FC. Fluid samples are adequate for FC testing more often than tissue. Capsule tissue FC specimens do not improve FC efficacy when paired with OR-acquired fluid FC samples and are often inadequate samples. FC is 100% specific for BIA-ALCL and can serve as a confirmatory test but should not be the sole diagnostic method. Awareness of sample-specific diagnostic pitfalls greatly improves the sensitivity of BIA-ALCL testing by FC.

Breast implant surface topography triggers a chronic-like inflammatory response.

Breast implants are extensively employed for both reconstructive and esthetic purposes. However, the safety of breast implants with textured surfaces has been questioned, owing to a potential correlation with anaplastic large-cell lymphoma and the recurrence of breast cancer. This study investigates the immune response elicited by different prosthetic surfaces, focusing on the comparison between macrotextured and microtextured breast implants. Through the analysis of intraoperatively harvested periprosthetic fluids and cell culture experiments on surface replicas, we demonstrate that macrotextured surfaces elicit a more pronounced chronic-like activation of leucocytes and an increased release of inflammatory cytokines, in contrast to microtextured surfaces. In addition, in vitro fluorescent imaging of leucocytes revealed an accumulation of lymphocytes within the cavities of the macrotextured surfaces, indicating that the physical entrapment of these cells may contribute to their activation. These findings suggest that the topography of implant surfaces plays a significant role in promoting a chronic-like inflammatory environment, which could be a contributing factor in the development of lymphomas associated with a wide range of implantable devices.

Ruptured breast implant removal because of patient anxiety in the absence of breast implant-associated anaplastic large cell lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has been regarded as a long-term problem after silicone breast implantations. We report a case in which BIA-ALCL and breast cancer were not detected preoperatively, with subsequent removal of a ruptured breast implant. A 52-year-old woman had silicone breast implants on both sides for breast augmentation 15 years ago. Right axillary lymphadenopathy and intracapsular ruptures were noted by magnetic resonance imaging. Right axillary lymph node biopsy was performed at our department of breast surgery. Flow cytometry for BIA-ALCL was also performed using the exudate around the implant. The results were negative for breast cancer and BIA-ALCL. However, taking into consideration exacerbation of breast implant rupture and the patient's anxiety about BIA-ALCL, ruptured bilateral implants were removed by total capsulectomy. The postoperative course was uneventful 1 year after the operation, and her anxiety was dispelled despite her breast deformity. Appropriate explantation and periodic examination may be required to prevent excessive anxiety.

BIA-ALCL in patients with genetic predisposition for breast cancer: our experience and a review of the literature.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is an emerging non-Hodgkin's lymphoma that occurs exclusively in patients with breast implants. The estimated risk of developing BIA-ALCL from exposure to breast implants is largely based on approximations about patients at risk. There is a growing body of evidence regarding the presence of specific germline mutations in patients developing BIA-ALCL, rising interest regarding possible markers of genetic predisposition to this type of lymphoma. The present paper focuses attention on BIA-ALCL in women with a genetic predisposition for breast cancer. We report our experience at the European Institute of Oncology, Milan, Italy, describing a case of BIA-ALCL in a BRCA1 mutation carrier who developed BIA-ALCL 5 years after implant-based post mastectomy reconstruction. She was treated successfully with an en-bloc capsulectomy. Additionally, we review the available literature on inherited genetic factors predisposing to the development of BIA-ALCL. In patients with genetic predisposition to breast cancer (mainly TP53 and BRCA1/2 germline mutations), BIA-ALCL prevalence seems to be higher and time to onset appears to be shorter in comparison to the general population. These high-risk patients are already included in close follow-up programs allowing the diagnosis of early-stage BIA-ALCL. For this reason, we do not believe that a different approach should be followed for postoperative surveillance.

[How to manage late periprosthetic fluid collections (seromas) in patients with breast implants?] / Conduite à tenir devant un sérome tardif péri-prothétique.

The widespread use of silicone implants in reconstructive and aesthetic breast surgery led to an increase in the incidence of breast implant associated anaplastic large cell lymphoma, BIA-ALCL, mainly associated with the use of macro-textured breast implants. BIA-ALCL is a serious complication presenting clinically as a late onset periprosthetic seroma. Thus, its occurrence became an alarming sign feared by most plastic surgeons. Therefore, a good knowledge with respect to early diagnosis, subsequent workup, and treatment is crucial in the management of periprosthetic seroma. The diagnosis of late onset seroma is clinically evident. Although idiopathic seroma is the most common cause, BIA-ALCL should be always eliminated. A complete workup is usually necessary. An ultrasound performed by a radiologist specialized in breast imaging followed by an ultrasound guided puncture is imperative. Consequently, the cytological and the bacteriological analysis will orient us toward the etiology (infectious, neoplastic or mechanical). A standardized management of late periprosthetic seroma does not exist, with various factors are to be taken into consideration. These include the surgeon's experience, the diagnosis, and the medical institution facilities. Although idiopathic seroma is managed by a simple puncture and drainage, other causes may require a surgical procedure with implant removal, capsulotomies, and/or total capsulectomies.

Risk of Anaplastic Large Cell Lymphoma Following Postmastectomy Implant Reconstruction in Women With Breast Cancer and Ductal Carcinoma in Situ.

This cohort study examines the risk of anaplastic large cell lymphoma (ALCL) following postmastectomy implant reconstruction among US women with breast cancer and ductal carcinoma in situ (DCIS).

Outcomes Analysis of Textured Versus Smooth Tissue Expanders in Breast Reconstruction.

INTRODUCTION: Because of concerns related to the correlation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and textured implants, the use of smooth devices in breast reconstruction has been increasing. Currently, there is a paucity of literature evaluating the safety of smooth tissue expanders (STEs), which are now being used more frequently in first-stage breast reconstruction. This study sought to compare the safety and outcomes associated with STEs compared with textured tissue expanders in prosthesis-based breast reconstruction. METHODS: A single-institution retrospective review of 394 patients undergoing tissue expander-based breast reconstruction (147 smooth and 247 textured) between 2015 and 2019 was conducted. Patient demographics, comorbidities, treatment characteristics, complications, and surgical outcomes were evaluated. Data analysis was performed using Fisher exact and t tests. RESULTS: No significant difference in demographics or complication rates were identified, including rates of hematoma, seroma, wound dehiscence, delayed wound healing, infection, tissue expander malposition, nipple necrosis, mastectomy flap necrosis, reoperation, readmission, and explantation. Average follow-up was 19 and 22 months for the smooth and textured groups, respectively. No cases of BIA-ALCL were identified in either group. CONCLUSIONS: With equivocal safety profiles and no demonstrated risk in BIA-ALCL associated with STEs, this study supports the safety of using STEs compared with textured tissue expanders in prosthesis-based breast reconstruction with the advantage in preventing BIA-ALCL and concludes that there is no role for textured breast expanders.

Smooth Versus Textured Tissue Expander Breast Reconstruction: Complications and Efficacy.

INTRODUCTION: Ongoing recognition of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and its link with textured devices has brought a paradigm shift in prosthetic-based breast reconstruction. Many institutions no longer offer textured expansion devices for staged reconstruction. However, there is a paucity of data regarding the efficacy of smooth tissue expanders (TE). We hypothesized that the time to final reconstruction and complication profile between smooth and textured TEs would be similar in breast reconstruction patients. METHODS: A retrospective chart review was performed of all patients who underwent TE breast reconstruction during a 6-year period at the Penn State Hershey Medical Center. Rates of complications treated nonoperatively and those requiring reoperation were assessed. Mechanical complications, including expander malposition and rupture, were evaluated. Time to final breast reconstruction was quantified. Mixed-effects logistic regression and linear regression models, as appropriate, were used to compare textured to smooth TEs. Patient characteristics and anatomic plane placement were adjusted for in all analyses of outcomes. RESULTS: Data were collected on 389 patients, encompassing 140 smooth and 604 textured TEs. Textured devices had an increased incidence of complications treated nonsurgically (16.7% vs 10.7%; P = 0.14). However, smooth TEs had an increased incidence of reoperation (12.1% vs 7.6%; P = 0.06). Most noteworthy was that although smooth TEs had a 40-fold increase in malposition (13.6% vs 0.3%; P < 0.001), no reoperation for this complication was warranted. Further, the time to final reconstruction was comparable between the 2 devices (textured expanders: 221 days and smooth expanders: 234 days; P = 0.15). CONCLUSIONS: Staged, implant-based reconstruction is the most common surgical approach to recreate the breast mound following mastectomy. Textured TEs were the cornerstone to this approach. Unfortunately, the association between textured devices and BIA-ALCL now mandates an alternative. We postulated that smooth expanders would compare favorably for breast reconstruction. Although our study suggests that smooth TEs suffer more malposition, this has a negligible impact on the reconstructive timeline. Thus, smooth TEs may prove beneficial when considering the risk of BIA-ALCL associated with textured devices.

Assessing Long-Term Outcomes in Breast Implant Illness: The Missing Link? A Systematic Review.

SUMMARY: The purpose of this special topic article is to explore the current state of outcomes-based literature related to breast implant illness and summarize the key understandings that emerge from the summation of existing studies. While implanted silicone devices are some of the most ubiquitous products in modern medicine, the safety of silicone breast implants has long remained under scientific scrutiny. In the era of social media and with breast implants once again under public scrutiny with the recent connection of texture silicone implants to breast implant-associated anaplastic large-cell lymphoma, the borders between breast implant illness and other implant-related diseases are becoming clouded in the public eye. The surgical management options for breast implant illness range from simple implant explantation alone to complete en bloc capsulectomies, or even secondary exploratory operations for additional capsulectomy in persistently symptomatic patients. In this review of outcomes-based studies related to breast implant illness, the authors found that a subset of patients improves with surgical intervention but limited evidence to inform most current surgical management practices. Further, the nature of this illness renders it difficult to study. A carefully designed, large, prospective, outcomes-based study is still required if an evidence-based and sound treatment approach for this condition is to be established.

Applications of Ultrasound in the Postoperative Period: A Review.

BACKGROUND: Recent advances in ultrasound technology have further increased its potential for routine use by plastic and reconstructive surgeons. METHODS: An extensive literature review was performed to determine the most common applications of ultrasound in the postoperative care of plastic and reconstructive surgery patients. RESULTS: In contrast with other available imaging modalities, ultrasound is cost-effective, rapid to obtain, eliminates the need for ionizing radiation or intravenous contrast, and has virtually no contraindications. In addition to its diagnostic capabilities, ultrasound can also be used to facilitate treatment of common postoperative concerns conveniently at the bedside or in an office setting. CONCLUSION: This article presents a review of the current applications of ultrasound imaging in the postoperative care of plastic and reconstructive surgery patients, including free flap monitoring following microsurgery, diagnosis and treatment of hematoma and seroma, including those associated with BIA-ALCL, and breast implant surveillance.

Successful Treatment of a Patient With Breast Implant-Associated Anaplastic Large Cell Lymphoma With Local Residual Disease: A Case Report.

BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a hematological malignancy that may occur in patients undergoing breast implant placement. It more commonly behaves as a solid tumor, and the criterion standard treatment consists in an en bloc capsulectomy, which may not always be possible, according to the location of the implant. When local residual disease is present, BIA-ALCL must be treated with adjuvant therapies. CASE PRESENTATION: We describe the case of a 76-year-old woman who underwent unilateral placement of a breast implant after breast cancer surgery in 2004 and developed BIA-ALCL in 2019. A multidisciplinary team managed her case, and en bloc capsulectomy was indicated for the treatment of the malignancy. The histological report showed focal neoplastic infiltration of the posterolateral margin of resection, further supported by positron emission tomography/computed tomography scan, which showed a local uptake in the right anterolateral chest wall. Therefore, adjuvant radiotherapy treatment was indicated for the management of local residual disease, alongside a stringent follow-up protocol. More than 1 year later, imaging scans show no signs of BIA-ALCL recurrence. CONCLUSIONS: Local residual disease in BIA-ALCL is bound to be a progressively more common occurrence, as awareness of BIA-ALCL increases and more cases are diagnosed worldwide. Currently, there is no established consensus on a standard approach for the treatment for patients with a higher risk of local recurrence. Our experience describes the protocol we used to successfully manage a case of BIA-ALCL with incomplete surgical margins, which hopefully can serve colleagues treating patients with similar cases.

Management of Asymptomatic Patients With Textured Breast Implants: A Survey Analysis of Members of The Aesthetic Society.

BACKGROUND: The management of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) has been well established. However, there is minimal data and significant variability in the management of asymptomatic textured implant (ATI) patients. OBJECTIVES: The purpose of this study was to survey members of The Aesthetic Society on management of ATI patients in order to understand trends in practice patterns. METHODS: Members of The Aesthetic Society were queried via an electronic survey regarding management of ATI patients. Anonymous responses were collected by QualtricsXM (SAP, Walldorf, Germany) survey software. Descriptive statistics were used to examine the data, reported as frequencies. All analyses were performed with IBM SPSS Statistics 26. RESULTS: The survey was sent to 2149 active and candidate members of The Aesthetic Society with a total of 470 responses (21.87% response rate). For ATI patients presenting with concerns regarding BIA-ALCL risk, 88.8% of respondents educate the patient with clinical follow-up and/or imaging. The other 11.2% of surgeons recommend implant removal with variability in capsulectomy technique. For ATI patients requesting surgery, 42.5% of respondents educate the patient with clinical follow-up and/or imaging. The majority of surgeons (57.6%) recommend removal of the implant, with 30% recommending total capsulectomies. CONCLUSIONS: There is considerable variability in how members of The Aesthetic Society manage ATI patients who request surgery. Future regulatory agency and professional society collaborative efforts should continue to aim for generation of high-level scientific data to aid in the counseling and management of ATI patients.

Operating room environment assessment and biofilm risk for breast implants. A case series.

AIM: Breast implant-associated anaplastic large cell lymphoma, is a rare cancer. Several theories are speculated that may constitute its etiological factors. None of them has been clearly proven. The case report we present is intended to indicate the leading cause of this disease entity. CASE PRESENTATION: Air samples taken in varying conditions at appropriate intervals by the MicroFlow Alfa 90 device in the operating room during five breast implant surgery were analyzed. Samples were taken four times during each operation. After the air was taken and delivered to the laboratory, the plates were immediately incubated under aerobic conditions. The incubation was carried out for up to 7 days. It has been shown that there is a significant difference between the total number of microorganisms during air intake carried out without and with the supply of air to purify the area in a given area by air recirculation of the operating block and cleaning it from bacteria and particles. No air colony-forming units were grown from air samples taken in the supply. However, from air samples taken without blowing, they were raised in various quantities. CONCLUSION: Laminar free airflow used in operating room conditions significantly reduces the risk of infection of the surgical site, and thus may reduce the risk of developing breast implant-associated anaplastic large cell lymphoma. KEY WORDS: BIA-ALCL ethiological factors, Biofilm, Breast implants, Laminar air flow, Surgical site infections.

Current Challenges in Breast Implantation.

Breast implantation (BI) is the most common plastic surgery worldwide performed among women. Generally, BI is performed both in aesthetic and oncoplastic procedures. Recently, the prevalence of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) or breast implant illness (BII) has aroused concerns. As a result, several countries, like Australia, Korea or the United Kingdom, introduced national registries dedicated to the safety and quality of BI surgeries. This narrative review aimed to focus on the clinical challenges, management and the current state of knowledge of BI. Both short and long-term outcomes of BI are determined by various alternatives and differences, which surgeons must consider during the planning and performing breast augmentation along with further complications or risk of reoperation. Proper preoperative decisions and aspects of surgical technique emerged to be equally important. The number of performed breast reconstructions is increasing, providing the finest aesthetic results and improving patient's quality of life. Choice of prosthesis varies according to individual preferences and anatomical variables. A newly diagnosed cases of BIA-ALCL with lacking data on prevention, diagnosis, and treatment are placing it as a compelling medical challenge. Similarly, BII remains one of the most controversial subjects in reconstructive breast surgery due to unspecified diagnostic procedures, and recommendations.

What Do Clinicians and Organizations Owe Patients With Recalled Implanted Devices or Materials?

Placement of prosthetic breast implants for augmentation or reconstruction is common. Two specific safety concerns are considered in this article: breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and complexes of symptoms known as breast implant illness. In response to a case involving a patient with concerns about BIA-ALCL, this commentary notes that triage, counseling, and treatment are guided in practice by available data in the literature. The commentary also discusses ethical considerations regarding breast implants and related illnesses.

An Unusual Case of BIA-ALCL Associated with Prolonged/Complicated Biocell-Textured Expander, followed by Smooth Round Breast Implant Exposure, and Concurrent Use of Adalimumab.

SUMMARY: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a malignancy associated with textured breast implants. BIA-ALCL is typically restricted to the periprosthetic capsule, presenting as a unilateral recurrent seroma years after placement of a textured breast implant. Current estimates suggest an incidence of one in 3300 for patients with Allergan Biocell textured implants. As of February 6, 2019, U.S. Medical Device Reporting associated with BIA-ALCL showed 457 unique cases of BIA-ALCL, with 24 "unverified and potentially inaccurate" cases associated with a nontextured implant. As of February of 2019, there were 688 reported cases to date worldwide. To date, there are no published case reports of BIA-ALCL associated exclusively with smooth implants or with smooth implants after textured expanders, and there has been no reported smooth-only case in any registry, database, or journal worldwide. The authors present a case of BIA-ALCL associated with smooth round implants and textured tissue expanders. A 56-year-old woman was treated for left stage IIA invasive ductal carcinoma with bilateral mastectomies and immediate reconstruction with bilateral subpectoral textured tissue expanders. She underwent exchange to Mentor smooth-round implants, and completed adjuvant chemotherapy. Magnetic resonance imaging and examination 4.5 years after implant placement showed no abnormal findings. The patient had left breast trauma 5 years following implant placement while taking adalimumab, and developed an open wound requiring explantation. A recurrent seroma developed, and tested positive for BIA-ALCL on cytology. Surgical pathologic examination after total capsulectomy demonstrated stage IA BIA-ALCL. To the authors' knowledge, this is the first case report of BIA-ALCL in a patient with textured expanders followed by prolonged exposure to smooth round implants.

Biocell-Initial patents versus user instructions guide: A discrepancy at the core of a crisis.

PURPOSE: Our aim is to do a comparative qualitative analysis of patents and "User Manuals" of the Biocell textured implants in order to determine if red flags were omitted when marketing and using Biocell textured implants. MATERIALS AND METHODS: We performed a systematic qualitative analysis using the NVivo software version 11 of the patents describing the Biocell textured implants prior to their approval by the FDA and of user guides published by the 3 companies owning the patents (McGhan, Inamed, Allergan). To guide our thematic analysis, we used a form of systems theory known as the complexity theory. RESULTS: Four patents related to Biocell and 2 user manuals (McGhan- Inamed and Allergan) were analyzed. Four themes emerged from the patents: invention description, mechanism of action (Tissue ingrowth), the timing of the mechanism of action and hypothetical actions on capsular contractures prevention. Of all patent's content, 34% described the invention, 29% the mechanism of action (tissue ingrowth), 1% the timing of this mechanism of action and 34% a hypothetical action against capsular contracture. Solid evidence was found on the concept of anchoring and very little on capsular contracture. On the user guide side, the main themes were indications and contraindications, surgical techniques and long-term effects. The "directed" content analysis approach of the user guides regarding the patent's themes reflected that 94% of the user guides content related to the patent thematics was about the hypothetical role on capsular contracture while only 4% was about invention description and 1.5% about tissue ingrowth. CONCLUSIONS: This analysis highlights the discrepancies between patents of Biocell textured implants and user guides for these implants. The indications of use of a treatment or device can evolve quicker than the study of its potential complications and side effects. The BIA-ALCL crisis should serve as a cautionary tale to the plastic surgery community which embraces new technologies eagerly, and sometimes precariously, in a mission to advance patient care.

Objective Comparison of FDA-Approved Breast Implant Products in the USA: 5-Year Update.

BACKGROUND: There are currently four companies offering FDA-approved breast implants: Allergan, Sientra, Mentor, and Ideal Implant. In 2015, our paper "Objective Comparison of Commercially Available Breast Implant Devices" sought to provide a unique conceptual framework to better understand the similarities and differences between FDA-approved breast implant products and tissue expanders. This paper uses the same variables, such as fill material, shape, relative dimensions, and surface coating, to aid understanding of both the surgical trainee and the operating surgeon of what devices each company offers, with a focus on how the market has evolved over the ensuing 5 years. METHODS: The product catalogs of each FDA-approved company were carefully explored to determine the current available breast implants and tissue expanders. Subsequently, flow charts were created to provide a clear and objective survey of each companies' offerings, highlighting where there are overlap and deficiencies, and where there has been contraction or growth. RESULTS: Disruptions to the industry, including both technological innovation and the recognition of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), have caused a significant shift in the details of the available permanent breast implants, breast tissue expanders, sizers, and warranty programs. CONCLUSION: As it has been in 2015, company jargon and brand names continue to make it challenging to discern the similarities and differences between company devices and programs. This project remained independent of any company's funding, support, or input, making it a uniquely objective and informative survey of the current breast implant market that should assist surgeons in decision-making regarding the breast implant procedures. 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 .