Background:Immune-related adverse effects (irAEs) often occur during immune checkpoint inhibitor (ICI) therapy. In the nervous system, the incidence of irAEs ranges from 0.1-12%, with 80% occurring within the first 4 months of ICI application. For complications of the nervous system, adequate diagnosis is made by signs, symptoms, imaging and cerebrospinal fluid. If severe irAEs occur, ICIs should be discontinued and patients should be treated with high-dose glucocorticoids, immunoglobulins, or immunosorbent therapy with systemic support. Patients who develop severe neurologic irAEs have a poorer prognosis.Case Description:In this article, we report 2 cases of encephalopathy induced by anti-programmed cell death protein 1 (PD-1) monoclonal antibodies at the initial diagnoses. Our findings may help clinicians to differentiate between encephalopathy caused by immunotherapy and other neurological disorders. Case 1 was a 24-year-old male patient who had undergone PD-1 immunotherapy to treat olfactory neuroblastoma. After the 6th course of therapy, he began to develop persistent epilepsy, which decreased significantly after high doses of glucocorticoid and immunosorbent therapy were administered. Based on his medical history and laboratory examination results, PD-1-induced encephalopathy was the most likely diagnosis. Case 2 was a 67-year-old female patient who had been treated with PD-1/programmed death ligand-1 therapy for lung adenocarcinoma. She began to have headaches after 1 cycle of treatment, and her cognitive function gradually decreased with the continuation of immunotherapy.Conclusions:These case reports show the difficulty in distinguishing PD-1-induced encephalopathy from other neurological disorders, especially paraneoplastic neurological syndromes. If not treated properly, patients' lives may be endangered. Thus, early identification and early treatment are very important.

Abstract BACKGROUND CIC-rearrangements most commonly occur in patients with Ewing-like sarcomas, an emerging class of round cell sarcomas. CIC sarcoma has considered being a new entity in CNS tumors by cIMPACT-NOW conform classification of tumors of soft tissue and bone. However, not all patients harbor CIC fusion are sarcoma cases. Herein, we firstly report a case of primary CNS diffuse large B-cell lymphoma (DLBCL) harboring CIC-rearrangement with a novel partner. METHODS CIC fusions were screened in the tumor tissue or peripheral blood from 3,961 cases with different types of cancer excluded patients with sarcomas. Comprehensive genomic profiling with a 539 cancer-related genes panel was administrated based on next generation sequencing (NGS) which is adept in finding novel fusion mutations. The pathology diagnosis of every case was confirmed via hematoxylin and eosin (H&E) stained. RESULTS Among the whole 3,961 cases, 3 CIC-rearrangements were observed. One case has been reported yet, one was a patient with lung adenocarcinoma, the last one was a patient harboring POU2F2 (Exon5) -CIC (Exon 11) with CNS arisen tumor, primary DLBCL. Literature review revealed only CIC-LEUTX was reported not only in sarcomas, but also in anaplastic ganglioglioma and CNS embryonal tumors. The partners of CIC sarcomas included DUX4, NUTM1, NUTM2A, FOXO4 and LEUTX, and whether specific partner affected biology of CIC-rearrangement tumors. CONCLUSIONS CIC-rearrangement arises in another type of brain cancer besides glioma and embryonal tumor, primary CNS DLBCL. Observation of novel partner provides new basis for further study of biology function of them in CIC fusions. Our study also indicates the presence of a specific tumor type with distinct histopathology driven by CIC fusions can be classified via CIC molecular pathology.

Abstract BACKGROUND Pituitary gland metastasis is a rare disease which represents only 1% of pituitary gland lesions. Intracranial solitary pituitary metastasis tends to be misdiagnosed as pituitary adenoma, resulting in a delayed anti-tumor treatment. METHODS Five cases of patients with pituitary gland metastasis recorded between 2014 and 2018 in our hospital were investigated with reference to patient demographics, symptoms at presentation, radiological and histological findings, management and outcomes. RESULTS Five patients (4 male and 1 female) were included and the median age was 48 years (range: 21 to 66). In those five cases, central nervous system related symptoms were the first sign of malignancy, including visual loss (5 in 5 patients), visual field defects (5 in 5 patients), apituitarism (5 in 5 patients), headache (4 in 5 patients), hypothroidism (4 in 5 patients) and diabetes insipidus (2 in 5 patients). All patients received total or partial hypophysectomy and pathologically revealed metastatic adenocarcinoma in 4 patients and metastatic squamous carcinoma in 1 patient. Further examinations by Computed Tomography (CT) or Positron Emission Computed Tomography (PET) indicated lung as primary site in five cases. EGFR mutation and ROS1 fusion were found in 3 and 1 adenocarcinoma patient, respectively, through gene detection of tissue. Postoperative radiotherapy (5 patients), target therapy (4 patients) and chemotherapy (1 patient) were given as subsequent treatment. During the follow-up, four patients died and the overall survival was 2, 8, 28 and 30 months, respectively. CONCLUSION We found that pituitary symptoms usually presented as the first sign of malignancy in intracranial solitary pituitary metastasis. Lung is the most frequently primary site, particularly in adenocarcinoma with driver gene mutation. Patients may benefit from multidiscipline treatment, including resection of pituitary metastasis combined with radiotherapy and targeted therapy.