RESUMEN
AIMS: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. METHODS AND RESULTS: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. CONCLUSIONS: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Persona de Mediana Edad , Biopsia con Aguja Gruesa/métodos , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Estudios Retrospectivos , Anciano , Adulto , Carcinoma Intraductal no Infiltrante/patología , Carcinoma Intraductal no Infiltrante/cirugía , Carcinoma Intraductal no Infiltrante/diagnóstico por imagen , Carcinoma Intraductal no Infiltrante/diagnóstico , Mama/patología , Mama/cirugía , Mama/diagnóstico por imagen , Mamografía/métodos , Esclerosis/patologíaRESUMEN
CDH1 (E-cadherin) bi-allelic inactivation is the hallmark alteration of breast invasive lobular carcinoma (ILC), resulting in its discohesive phenotype. A subset of ILCs, however, lack CDH1 genetic/epigenetic inactivation, and their genetic underpinning is unknown. Through clinical targeted sequencing data reanalysis of 364 primary ILCs, we identified 25 ILCs lacking CDH1 bi-allelic genetic alterations. CDH1 promoter methylation was frequent (63%) in these cases. Targeted sequencing reanalysis revealed 3 ILCs harboring AXIN2 deleterious fusions (n = 2) or loss-of-function mutation (n = 1). Whole-genome sequencing of 3 cases lacking bi-allelic CDH1 genetic/epigenetic inactivation confirmed the AXIN2 mutation and no other cell-cell adhesion genetic alterations but revealed a new CTNND1 (p120) deleterious fusion. AXIN2 knock-out in MCF7 cells resulted in lobular-like features, including increased cellular migration and resistance to anoikis. Taken together, ILCs lacking CDH1 genetic/epigenetic alterations are driven by inactivating alterations in other cell adhesion genes (CTNND1 or AXIN2), endorsing a convergent phenotype in ILC.