Diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification.

AIMS: Rhabdomyosarcomas currently are classified into one of four subtypes (alveolar, embryonal, spindle cell/sclerosing, or pleomorphic) according to their morphological, immunohistochemical, and molecular genetic features. The alveolar subtype is characterised by a recurrent translocation involving PAX3 or PAX7 and FOXO1; identification of this translocation is important for appropriate classification and prognostication. In this study, we aimed to explore the diagnostic utility of FOXO1 immunohistochemistry for rhabdomyosarcoma classification. METHODS/RESULTS: A monoclonal antibody targeting a FOXO1 epitope retained in the fusion oncoprotein was used to study 105 rhabdomyosarcomas. FOXO1 was positive for expression by immunohistochemistry in all 25 alveolar rhabdomyosarcomas, with 84% showing diffuse expression in greater than 90% of neoplastic cells; the remainder of alveolar rhabdomyosarcomas displayed at least moderate staining in a minimum of 60% of lesional cells. Apart from three spindle cell rhabdomyosarcomas showing heterogeneous nuclear immunoreactivity in 40-80% of tumour cells, the 80 cases of embryonal, pleomorphic, and spindle cell/sclerosing rhabdomyosarcoma were negative for FOXO1 expression (96.3% specific) when using a threshold of nuclear staining in 20% of neoplastic cells to determine positivity. Variable cytoplasmic staining was present in a fraction of all rhabdomyosarcoma subtypes. Nonneoplastic lymphocytes, endothelial cells, and Schwann cells also showed variably intense nuclear anti-FOXO1 immunoreactivity. CONCLUSION: Taken together, our findings suggest that FOXO1 immunohistochemistry is a highly sensitive and relatively specific surrogate marker of the PAX3/7::FOXO1 fusion oncoprotein in rhabdomyosarcoma. Cytoplasmic immunoreactivity, expression in nonneoplastic tissues, and limited nuclear staining of nonalveolar rhabdomyosarcomas represent potential pitfalls in interpretation.

Long-Term Outcomes in Prepectoral versus Subpectoral Two-Stage Implant-Based Breast Reconstruction after Nipple-Sparing Mastectomy.

BACKGROUND: Implant-based breast reconstruction remains the most often used method following mastectomy, but data are lacking regarding differences in complications and long-term patient-reported outcomes for two-stage subpectoral versus prepectoral reconstruction. This study sought to better understand the risks and impact of these reconstructive approaches on overall satisfaction. METHODS: Patients who underwent unilateral or bilateral nipple-sparing mastectomy and two-stage implant-based reconstruction from 2014 to 2019 were identified from the electronic medical records and contacted via email to complete the BREAST-Q survey. Overall satisfaction was measured by the question, "How happy are you with the outcome of your breast reconstruction?" using a six-point Likert scale. Patients were grouped into subpectoral or prepectoral cohorts. Complications were evaluated retrospectively. Only patients who were at least 6 months from their final reconstruction were included in the analysis. RESULTS: Of the 582 patients contacted, 206 (35%) responded. The subpectoral ( n = 114) and prepectoral ( n = 38) groups did not differ significantly by demographic or treatment characteristics. BREAST-Q scores were also comparable. Complication rates were similar, but prepectoral patients had a significantly higher rate of capsular contracture (16% versus 4%, P < 0.05). Bivariate ordered logistic regression identified prepectoral implant placement, having any postoperative complication, and capsular contracture as predictors of less overall happiness. CONCLUSIONS: The authors' study suggests that prepectoral patients may have slightly higher complication rates but are as satisfied as subpectoral patients after at least a year of follow-up. Further studies should investigate risk factors for capsular contracture, how the risk changes over time, and how the risk affects patient satisfaction.