Breast Implant-Associated Anaplastic Large-Cell Lymphoma in Brazil: What Are We Missing?

BACKGROUND: Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) has been diagnosed in more than 1000 patients in more than 30 countries, although only a few cases have been reported in Latin America and the Caribbean to date. As the second-largest global market for breast implants with a predominance of textured-surface implants, Brazil is a major global market for cosmetic augmentations, making it unlikely that cases of BIA-ALCL are actually scarce. METHODS: A local and voluntary registry of patients with BIA-ALCL was initiated in 2018. All patients diagnosed with BIA-ALCL were confirmed by the World Health Organization criteria. Implant characteristics, disease symptoms, treatment, and oncologic outcomes were assessed. RESULTS: Fourteen cases of BIA-ALCL in a Brazilian population were identified in the Paraná state. Disease-specific diagnostic tests were omitted before surgical intervention in 50 percent of patients. With additional cases from a literature review, the treatment and outcomes of 29 cases of BIA-ALCL in Brazil were assessed. CONCLUSIONS: Compared with other populations, these initial observations suggest that awareness of the disease by the local breast surgery community remains low and that a number of cases may remain undiagnosed. Lack of preoperative diagnostic testing compromises disease treatment, oncologic outcomes, and both short- and long-term surveillance.

Retinoic acid and VEGF delay smooth muscle relative to endothelial differentiation to coordinate inner and outer coronary vessel wall morphogenesis.

RATIONALE: Major coronary vessels derive from the proepicardium, the cellular progenitor of the epicardium, coronary endothelium, and coronary smooth muscle cells (CoSMCs). CoSMCs are delayed in their differentiation relative to coronary endothelial cells (CoEs), such that CoSMCs mature only after CoEs have assembled into tubes. The mechanisms underlying this sequential CoE/CoSMC differentiation are unknown. Retinoic acid (RA) is crucial for vascular development and the main RA-synthesizing enzyme is progressively lost from epicardially derived cells as they differentiate into blood vessel types. In parallel, myocardial vascular endothelial growth factor (VEGF) expression also decreases along coronary vessel muscularization. OBJECTIVE: We hypothesized that RA and VEGF act coordinately as physiological brakes to CoSMC differentiation. METHODS AND RESULTS: In vitro assays (proepicardial cultures, cocultures, and RALDH2 [retinaldehyde dehydrogenase-2]/VEGF adenoviral overexpression) and in vivo inhibition of RA synthesis show that RA and VEGF act as repressors of CoSMC differentiation, whereas VEGF biases epicardially derived cell differentiation toward the endothelial phenotype. CONCLUSION: Experiments support a model in which early high levels of RA and VEGF prevent CoSMC differentiation from epicardially derived cells before RA and VEGF levels decline as an extensive endothelial network is established. We suggest this physiological delay guarantees the formation of a complex, hierarchical, tree of coronary vessels.