Treatment with CD19-directed CAR T cells has evolved as a standard of care for multiply relapsed or refractory large B-cell lymphoma (r/r LBCL). A common side effect of this treatment is the immune-effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can occur in up to 30-40% of patients treated with axicabtagene ciloleucel (axi-cel), usually within the first 4 weeks post dosing, and usually responding well to steroids. Here, we describe a case of progressive central neurotoxicity occurring 9 months post axi-cel in a patient with r/r LBCL having undergone a prior alloHCT. Despite extensive systemic and intrathecal immunosuppression neurological deterioration was inexorable and eventually fatal within 5 months. High CAR T cell DNA copy numbers and higly elevated levels of IL-1 and IL-6 were found in the CSF as clinical symptoms emerged, and CAR T cell brain infiltration was observed on autopsy, suggesting that CAR T cells played a major pathogenetic role. This case of unexpected devastating late neurotoxicity warrants intensified investigation of neurological off-target effects of CD19-directed CAR T cells and highlights the need for continuous monitoring for late toxicities in this vulnerable patient population.

Introduction Parietal cell/oncocytic gastric carcinomas are very rare and various aspects of this group remain unclear. The human epithelial growth factor receptor 2 (HER2) status of these tumours is largely unknown. Methods We performed a systematic electronic search of the literature and clinicopathological presentation of two cases including first-time complete assessment of HER2 status. Thirty-two patients with a mean age of 64.3 years, 87.5% of whom were male, were included in this review. Findings Half of the cases were recorded in Asia. Median follow-up was 24 months. There was no predominant site of development, while underlying histological abnormalities were present in 25%. At initial presentation, lymph node involvement was evident in 46.6% while distant metastatic disease was present in 9.3%. Presentation at stage I occurred in 55.6%. Potentially curative surgical/interventional treatment was intended in 90.6%. Recurrence occurred in 6.6%, while death was recorded in 19.2%, with cancer-related deaths reaching 11.5%. The one- and three-year survival rates were 84.2% and 79%, respectively. Our two cases displayed negative HER2 expression. Conclusions This systematic review demonstrates that this group of malignancies is very rare but possibly underdiagnosed. The disease commonly presents at early stage, mainly affecting middle-aged men. The prognosis is generally favourable even in cases of advanced disease. The HER2 expression and its correlation with the outcomes need to be further explored.

Choroid plexus papillomas (CPPs) are primary neuroectodermal neoplasms that usually arise in the fourth ventricle in adults. In this study, we present 12 patients with CPP arising from the cerebellopontine angle (CPP-CPA) and/or of the cerebellomedullary angle (CPP-CMA) that were treated in our department. Patients who underwent surgery for the treatment for CPP-CPA/CMA from January 2004 to March 2020 were identified by a computer search of their files from the Department of Neurosurgery, Tübingen. CPPs were classified according to their location into type 1 (tumor portion only in the CPA,), type 2 (tumor portions only in the CMA), and type 3 (tumor portions both in the CPA and CMA). Patients were evaluated for initial symptoms, previous therapies in other hospitals, extent of tumor resection, recurrence rate, and complications by reviewing patient documents. Of approximately 1500 CPA lesions, which were surgically treated in our department in the last 16 years, 12 patients (mean age 42 ± 19 years) were found to have CPP-CPA/CMA. Five were male, and seven were female patients. Gross total resection was achieved in nine cases, and a subtotal resection was attained in three cases. Tumor recurrence in the same location after the first surgery in our hospital was observed in 2 patients after 15 and 40 months of follow-up, and in another patient, distant metastases (C3/4 and L3 levels) were observed. Surgical removal of CPP is the treatment of choice, but additional therapeutic options may be necessary in case of remnant tumor portions, recurrence, or malignant transformation.