Breast Implant-associated Anaplastic Large Cell Lymphoma: A Prospective Series of 52 Patients.

OBJECTIVE: We sought to evaluate patients at a single academic institution in a prospective manner to report patient presentation, clinical course, treatment, and outcomes in breast implant ALCL patients. BACKGROUND: Breast implant-associated anaplastic large cell lymphoma (breast implant ALCL) is an uncommon T cell lymphoma, which is associated with textured surface breast implants. The disease has received increasing attention over the last 20 years. Previous retrospective studies have begun to outline the clinical course of breast implant ALCL. METHODS: We prospectively followed women with cytologically proven breast implant ALCL from 2014 to 2019. Demographic, clinical, treatment, and outcome data were collected and descriptive statistics were performed on variables of interest. RESULTS: We identified 52 women with pathologically confirmed breast implant ALCL. Implants were placed for augmentation in 61.5% of women and reconstruction in 36.5% of women. All of the 41 patients with known implant information had implants with textured surface. The majority of patients presented with delayed seroma (69.2%) and without systemic symptoms (86.5%). Most patients with staging information presented with Stage IA disease. Patient outcomes were excellent with 2 disease recurrence (3.8%) and all patients ultimately achieved complete remission. CONCLUSIONS: Further evaluation of the prospective and growing database of patients with breast implant ALCL will further improve our understanding of the disease and its clinical course. Robust participation in the breast implant ALCL PROFILE registry will improve our knowledge of long-term outcomes after implant placement. Finally, increasing awareness for patients and providers will lead to earlier diagnosis and improved outcomes for patients.

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

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

Neuronal waste management: new roles for autophagy genes in the extrusion of protein aggregates and in longevity.

A decline in macroautophagic/autophagic activity with age contributes to the accumulation of damaged molecules and is associated with the impairment of neuronal functions and the onset of age-related diseases, particularly neurodegenerative disorders. To learn about the neuronal-specific roles of autophagy genes in aging, we specifically inhibited autophagy genes pan-neuronally in C. elegans, which leads to unexpected positive impacts on neuronal homeostasis including polyQ aggregate load and organismal lifespan. These improvements are independent of canonical, degradative autophagy in neurons and instead correlate with an increase in the secretion of large, extracellular vesicles, known as exophers. We found that the ATG-16.2 WD40 domain, a conserved domain critical for at least some noncanonical autophagy functions of ATG16L1 in mammalian cells, is required for the increased exopher biogenesis, reduction in polyQ aggregate load, and lifespan extension induced by neuronal inhibition of early-acting autophagy genes. Our study suggests that noncanonical functions of ATG-16.2, and potentially other early-acting autophagy genes, may play a role in neuronal exopher formation and C. elegans aging, extending beyond their canonical degradative functions in the autophagy process.

Autophagy protein ATG-16.2 and its WD40 domain mediate the beneficial effects of inhibiting early-acting autophagy genes in C. elegans neurons.

While autophagy genes are required for lifespan of long-lived animals, their tissue-specific roles in aging remain unclear. Here, we inhibited autophagy genes in Caenorhabditis elegans neurons, and found that knockdown of early-acting autophagy genes, except atg-16.2, increased lifespan, and decreased neuronal PolyQ aggregates, independently of autophagosomal degradation. Neurons can secrete protein aggregates via vesicles called exophers. Inhibiting neuronal early-acting autophagy genes, except atg-16.2, increased exopher formation and exopher events extended lifespan, suggesting exophers promote organismal fitness. Lifespan extension, reduction in PolyQ aggregates and increase in exophers were absent in atg-16.2 null mutants, and restored by full-length ATG-16.2 expression in neurons, but not by ATG-16.2 lacking its WD40 domain, which mediates noncanonical functions in mammalian systems. We discovered a neuronal role for C. elegans ATG-16.2 and its WD40 domain in lifespan, proteostasis and exopher biogenesis. Our findings suggest noncanonical functions for select autophagy genes in both exopher formation and in aging.