Melanoma with peripheral globules: clinical, molecular and dermatoscopic features

• Grant number: 22/12558-5
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2023
• End date: October 31, 2025
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Juliana Casagrande Tavoloni Braga
• Grantee: Juliana Casagrande Tavoloni Braga
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated researchers: Ana Flavia Aquen de Moraes ; Clóvis Antonio Lopes Pinto ; Dirce Maria Carraro ; Giovana Tardin Torrezan ; Tatiana Cristina Moraes Pinto Blumetti

Abstract

The morphology and biology of nevi with peripheral globules are described as active radial growth phase and benign specially in younger individuals, whereas those of melanomas with peripheral globules remain unclear.Our primary study, published in "JAAD - Journal of American Academy of Dermatology" (doi: 10.1016/j.jaad.2022.04.031) described the morphologic and dermoscopic diferences of nevi with peripheral globules and melanomas. A total of 401 melanocytic lesions with peripheral globules (41 melanomas) were included in this retrospective study. We concluded that melanocytic lesions displaying peripheral globules are at the greatest risk of melanoma if located on the lower extremity and if lesions reveal any of the following structures: blotch, atypical dots and globules or atypical vessels.The appearance of melanoma has a multifactorial etiology, the interaction between intrinsic and extrinsic factors is strongly associated with the development of melanoma. From a genetic point of view, melanoma is one of the most mutating cancers in terms of somatic changes. The melanoma genome classification by The Cancer Genome Atlas in 2015 characterized melanoma with 4 molecular subtypes: BRAF-mutated, RAS-mutated, NF1-mutated and triple negative type. This classification corresponds to most types of "classic" melanomas. Still in relation to the greater risk for the development of melanoma throughout life, our cells undergo thousands of replications, which increases the risk for somatic mutations that can lead to disordered growth. During the process of cell replication, chromosomes are exposed to a loss of genetic material and, to prevent and correct this process, there are telomeres. Repeated cycles of cell replication led to telomere shortening and signal senescence, resulting in cell apoptosis. This is a protective mechanism against disordered cell proliferation and possible tumor cell development.Advances in molecular research on this tumor have revolutionized the treatment of advanced disease. Currently with broader genetic panels that allow the evaluation of different mutations capable of guiding and predicting therapeutic failure. Additionally, molecular analysis can complement the anatomopathological diagnosis of ambiguous lesions and contribute to the understanding of evolutionary and clinical biological differences observed between the different subtypes of melanoma.The primary objective of this project is to describe the morphological, dermoscopic findings and the mutational profile (through the analysis of BRAF, NRAS, KIT and TERT genes) of melanocytic lesions with peripheral globules, seeking to differentiate benign melanocytic lesions from cutaneous melanoma. The purpose of this project is to recognize risk factors for the development of cutaneous melanoma and assist in its early and accurate diagnosis through the description of the dermoscopic pattern and better understanding of the tumorigenesis of this neoplasm, with the description of the profile of somatic mutations.The secondary objective is to prove the conduct algorithm proposed in the initial study (doi: 10.1016/j.jaad.2022.04.031), through prospective analysis.With these results, we hope to help in the prevention and early diagnosis of melanoma with peripheral blood cells in individuals of different age groups, seeking to improve the survival of patients with this tumor in addition to reducing the costs of the health system resulting from late diagnosis. (AU)