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.

The Value of Integrating Fluorescent Imaging and Immunohistochemistry for Future Anatomical Studies in Aesthetic Surgery: Lessons From the Cerebrospinal Fluid Circulatory System of Human Nerves and Brain.

BACKGROUND: During their work on the cerebrospinal fluid (CSF) circulatory system of human nerves and brain, the authors applied imaging and tissue techniques that complemented basic anatomical dissection. OBJECTIVES: The authors sought to show how integrating fluorescent imaging and basic immunohistochemistry (IHC) with facial anatomy can address current problems in aesthetic surgery. METHODS: The authors developed an algorithm and a set of principles from their work on the CSF circulatory system and applied these to 3 problems in aesthetic surgery: the functional anatomy of the vermilion-cutaneous junction; chemosis; and the functional anatomy of periosteal fixation. RESULTS: Integrating fluorescent imaging and IHC with anatomical dissection characterizes structural and functional anatomy. Fluorescent imaging helps to identify and locate easily missed structures. IHC defines cell type and function. The vermilion-cutaneous junction is defined by a major lymphatic vessel. Lymphatic flow from the medial limbus to the lateral canthus suggests the etiology of chemosis. Periosteal sites of fixation prevent shear where dural CSF vessels drain directly to subcutaneous lymphatics. CONCLUSIONS: Integrating anatomical dissection with fluorescent imaging and basic IHC characterizes structural and functional anatomy and helps to better understand many problems encountered in aesthetic surgery.

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

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

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

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

Cryolipolysis: Clinical Best Practices and Other Nonclinical Considerations.

Cryolipolysis is a nonsurgical body contouring procedure that involves cooling of fat cells to induce lipolysis while sparing surrounding structures. Plastic surgery practices are increasingly incorporating noninvasive aesthetic procedures (eg, cryolipolysis, fillers, radiofrequency, ultrasound) to offer their patients a wider range of aesthetic treatment options. Here, we report insights from 8 plastic surgeons with regard to cryolipolysis best practices from a clinical perspective and the impact of integrating this noninvasive body contouring procedure into a plastic surgery practice. The authors prefer cryolipolysis over liposuction for patients who are not amenable to surgery or those who desire to avoid downtime, also taking into consideration body mass index, skin laxity, comorbidities, and risk of contour irregularities. Patient counseling is critical for setting realistic expectations regarding outcomes and should focus on the efficacy of cryolipolysis, individual variability in results, potential side effects, time course of treatment response, and the need for multiple treatment cycles. Strategies for reaching new patients and expanding services among current cryolipolysis patients are discussed.

Synchronous Breast Implant-associated Anaplastic Large Cell Lymphoma and Invasive Carcinoma: Genomic Profiling and Management Implications.

A 59-year-old woman with a history of cosmetic implants developed ipsilateral synchronous breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) and invasive ductal carcinoma in the left breast. Each tumor was subjected to next-generation sequencing, and separate analyses revealed mutually exclusive aberrations: an activating STAT3 mutation in the lymphoma and a PIK3CA in-frame deletion in the carcinoma. The patient was treated with removal of implants, capsulectomy, partial mastectomy, sentinel node biopsy, radiotherapy, and endocrine therapy with no evidence of recurrence for 1 year. This case illustrates the importance of obtaining thorough evaluation for concomitant malignancies in the breast at the time of diagnosis of BIA-ALCL. Herein, we review the current recommendations for evaluation and management of BIA-ALCL.

Getting the Best Results in Abdominoplasty: Current Advanced Concepts.

LEARNING OBJECTIVES: After studying this article and viewing the videos, the participant should be able to: 1. Describe the safe techniques recommended for patients undergoing a lipoabdominoplasty. 2. Demonstrate safe planning techniques for marking a patient for a lipoabdominoplasty. 3. Summarize the various techniques for performing rectus plication. 4. State the current understanding of chemoprophylaxis for outpatient surgical patients. 5. Determine the appropriate placement and shape of the ideal umbilicus. SUMMARY: Abdominoplasty and lipoabdominoplasty surgery is one of the core procedures performed by plastic surgeons in the United States. As with most plastic surgery, it is part art and part science. In this article, the authors try to summarize the science behind this procedure, and point to the generally accepted artistic aspects that are currently still under debate. As this procedure has one of the highest morbidity and mortality rates in the specialty, the authors have also reviewed safe practices.

Bioengineered Approach to the Design of a Fat Graft Based on Mathematical Modeling that Predicts Oxygen Delivery.

BACKGROUND: Fat grafting is a common procedure in plastic surgery. A major limitation is unpredictable graft retention, in part caused by inadequate oxygen delivery during the early posttransfer period. METHODS: The authors present a bioengineered approach to the design of a fat graft based on mathematical theory, which can estimate the limitations of oxygen delivery. To simplify the problem, four variables were defined: (1) recipient-site oxygen partial pressure; (2) adipose tissue oxygen permeability; (3) adipose tissue oxygen consumption rate; and (4) fat graft size. Recipient-site oxygen partial pressure and adipose tissue oxygen permeability were estimated from literature, whereas adipose tissue oxygen consumption rate was measured using stirred microchamber technology. Calculations were performed in both spherical and planar geometry to calculate the maximum allowable fat graft size from an oxygen delivery standpoint. RESULTS: As expected, planar geometry is less favorable for oxygenation but represents a realistic configuration for a fat graft. Maximum allowable fat graft thickness is only approximately 1 to 2 mm at external oxygen partial pressures of 10 to 40 mm Hg; any thicker and an anoxic or necrotic core likely develops. Given a reasonably large surface area and assuming several planes of injection, the maximum allowable fat graft volume is tens of milliliters. CONCLUSIONS: A systematic bioengineered approach may help better design a fat graft. Applying principles of mass transfer theory can predict whether a fat graft has a favorable chance of surviving from an oxygen delivery standpoint and can direct the development of strategies for improved fat graft oxygenation.

Noninvasive Methods for Lower Facial Rejuvenation.

Demand for noninvasive aesthetic medicine options is increasing because of the popularity of nonsurgical procedures and industry's focus on direct-to-consumer marketing. Such techniques as nonablative and ablative lasers, intense pulsed light, radiofrequency, high-intensity focused ultrasound, and skin care with peeling agents may also be used in conjunction with surgery to optimize overall aesthetic results. To maximize benefits, the provider must have a detailed understanding of the science behind each device. Combined therapy is safe and well tolerated by many patients in an office-based setting. Although surgery remains the gold standard, nonsurgical therapy should be a portion of surgical practices.

IL-13 is produced by tumor cells in breast implant-associated anaplastic large cell lymphoma: implications for pathogenesis.

More than 500 women worldwide have developed a CD30+ T-cell lymphoma around breast implants, strongly suggesting a cause-and-effect relationship, and designated as breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The mechanism of lymphomagenesis is unknown. Recently, a bacterial biofilm containing gram-negative bacilli was discovered on the surface of breast implants associated with ALCL. We and others have described overexpression of the proto-oncogene JUNB and mutations of JAK1/2, TP53 and STAT3 in BIA-ALCL. Here we report that BIA-ALCL cell lines and anaplastic lymphoma cells in clinical specimens produce IL-13, the signature cytokine of allergic inflammation. Supporting the link of BIA-ALCL to allergic inflammation, lymphoma cells were often surrounded by eosinophils and mast cells, features typically absent in systemic ALCL. Because of the link of IL-13 to allergy, we looked for IgE and found it decorating the surface of mast cells and antigen-presenting follicular dendritic cells in capsules and lymph nodes infiltrated by anaplastic lymphoma cells, but not uninvolved capsules. Plasma cells within capsules and regional lymph nodes were identified as a possible source of IgE. Together, these findings suggest the hypothesis that an amplified immune response with features of a chronic allergic reaction in a susceptible patient underlies the pathogenesis of BIA-ALCL.

Characterization of Adipose Tissue Product Quality Using Measurements of Oxygen Consumption Rate.

BACKGROUND: Fat grafting is a common procedure in plastic surgery but associated with unpredictable graft retention. Adipose tissue (AT) "product" quality is affected by the methods used for harvest, processing and transfer, which vary widely amongst surgeons. Currently, there is no method available to accurately assess the quality of AT. OBJECTIVES: In this study, we present a novel method for the assessment of AT product quality through direct measurements of oxygen consumption rate (OCR). OCR has exhibited potential in predicting outcomes following pancreatic islet transplant. Our study aim was to reapportion existing technology for its use with AT preparations and to confirm that these measurements are feasible. METHODS: OCR was successfully measured for en bloc and postprocessed AT using a stirred microchamber system. OCR was then normalized to DNA content (OCR/DNA), which represents the AT product quality. RESULTS: Mean (±SE) OCR/DNA values for fresh en bloc and post-processed AT were 149.8 (± 9.1) and 61.1 (± 6.1) nmol/min/mg DNA, respectively. These preliminary data suggest that: (1) OCR and OCR/DNA measurements of AT harvested using conventional protocol are feasible; and (2) standard AT processing results in a decrease in overall AT product quality. CONCLUSIONS: OCR measurements of AT using existing technology can be done and enables accurate, real-time, quantitative assessment of the quality of AT product prior to transfer. The availability and further validation of this type of assay could enable optimization of fat grafting protocol by providing a tool for the more detailed study of procedural variables that affect AT product quality.

What's Your Micromort? A Patient-Oriented Analysis of Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL).

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) continues to be a rare and elusive malignancy. Because BIA-ALCL does not behave like traditional lymphomas, additional research needs to be conducted to further delineate the lymphoproliferative nature of BIA-ALCL. An estimated 35 million women worldwide have breast implants and the total reported deaths from BIA-ALCL is 12 to date. The term micromort was introduced in 1979 by Ronald Howard as a person's risk of dying as 1 in a million. Drinking 0.5 L of wine or walking 17 miles all increase your risk of death by 1 micromort. Risk of death from BIA-ALCL is 0.4 micromorts for a woman having bilateral breast implants. This information is important for counseling new patients and those presenting with delayed onset seromas.

Extended Alar Contour Grafts: An Evolution of the Lateral Crural Strut Graft Technique in Rhinoplasty.

Modification of the lower lateral cartilage complex is the sine qua non of modern rhinoplasty, and the open approach to rhinoplasty has expanded the number of techniques available to help achieve an aesthetically pleasing tip. The ideal tip has been described as having a diamond-shaped configuration, with the lateral points formed by the tip-defining points, the superior point by the supratip, and the inferior point by the columellar break point. Over the years, various techniques have been described to minimize isolation of the tip and to help achieve the ideal tip configuration: lateral crural strut grafts, alar contour grafts (i.e., rim grafts), alar strut grafts, subdomal grafts, and suturing techniques such as alar flaring sutures. The authors present their technique of the extended alar contour graft, which represents an evolution of the lateral crural strut graft and its marriage with the alar contour graft. Lateral crural abnormalities do not usually occur singularly, but rather are the result of an interplay of several factors. Nevertheless, the recurring theme of orientation and alar support to prevent isolation of the tip by extended alar grooves remains. Extended alar contour grafts are a versatile technique to optimize tip shape and orientation by combining the many positive attributes of lateral crural strut grafts and alar contour grafts.