Glomerulonephritis after Alemtuzumab Treatment for Multiple Sclerosis: A Report of Two Cases.

Introduction: Alemtuzumab, a humanized monoclonal antibody indicated for the treatment of adult patients with active relapsing-remitting multiple sclerosis (MS), has been associated with increased risk of autoimmune adverse events, including thyroid disorders, immune thrombocytopenia, and renal diseases. Renal immune-mediated adverse events, which have been reported in 0.3% of patients treated with alemtuzumab in MS clinical trials, typically occur within 39 months after the last drug administration. However, no consensus has been reached regarding the management of patients who develop glomerulonephritis after treatment with alemtuzumab. Case Presentation: We report the cases of two young adults with MS who developed biopsy-proven severe glomerulonephritis after alemtuzumab treatment. Both patients, including a 32-year-old female patient who developed membranous nephropathy and a 31-year-old male who developed drug-induced podocytopathy, were treated successfully with the calcineurin inhibitor tacrolimus followed by the anti-CD20 antibody rituximab. Conclusion: Regular renal function monitoring is required in patients who may rarely develop glomerulonephritis following treatment with alemtuzumab. There is no clear consensus on case management. In both cases, immunosuppressive therapy, which was necessary due to disease severity, resulted in successful remission, highlighting the potential utility of this approach.

Conventional and digital Ki67 evaluation and their correlation with molecular prognosis and morphological parameters in luminal breast cancer.

Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73-0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (rs = 0.46, p < 0.01) compared to the conventional method (rs = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.