Immune microenvironment of medulloblastoma: The association between its molecular subgroups and potential targeted immunotherapeutic receptors

Medulloblastoma (MB) is considered the commonest malignant brain tumor in children. Multimodal treatments consisting of surgery, radiation, and chemotherapy have improved patients’ survival. Nevertheless, the recurrence occurs in 30% of cases. The persistent mortality rates, the failure of current therapies to extend life expectancy, and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches. Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections. Recently, MBs have been segregated into four molecular subgroups: Wingless-activated (WNT-MB) (Group 1); Sonic-hedgehog-activated (SHH-MB) (Group 2); Group 3 and 4 MBs. These molecular alterations follow specific gene mutations and disease-risk stratifications. The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival. However, the need to explore new therapies targeting specific receptors in MB microenvironment became essential. The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells. Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment, and their role are still under investigation. In this review, we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment, with an overview of the recent investigations and clinical trials     

A case of “smoldering” immune‐mediated thrombotic thrombocytopenic purpura manifesting as recurrent cardioembolic stroke

Prompt recognition and treatment for thrombotic thrombocytopenic purpura (TTP) are critical to prevent the irreversible manifestations of this rare and quickly fatal hematologic disorder. Untreated TTP is typically a rapid‐onset disease with mortality exceeding 90% within days in the absence of appropriate treatment. In the current report, we describe a case of immune‐mediated TTP (iTTP) in a 62‐year‐old man manifesting as longstanding thrombocytopenia, recurrent cardioembolic strokes, and valvular thrombogenesis over a period of 3 years. We provide correlative evidence to support the potential contribution of adalimumab, a TNFα inhibitor, to the development of iTTP. We offer several educational insights regarding the identification of atypical presentations of iTTP owing to the longstanding disease course and numerous clinical comorbidities seen in this patient.     

Successful management of dural venous sinus thrombosis secondary to ulcerative colitis in a pediatric patient: A case report

Cerebral venous sinus thrombosis secondary to inflammatory bowel disease is a clinically rare and challenging entity with serious sequela. We preset a case of a 15-year-old female patient who was recently diagnosed with ulcerative colitis and had been suffering from headache for 4 days duration. During the diagnostic workup, computed tomography (CT) venography revealed Dural venous sinus thrombosis in the left transverse sinus extending into the left sigmoid sinus and the upper third of the left internal jugular vein as well as into the sinus confluence with non–occlusive filling defects in the superior sagittal sinus. Anticoagulant therapy with enoxaparin was initiated and the patient is being monitored in an outpatient setting regularly. Post-discharge disease course was uneventful. CT venography performed after 3 months illustrated partial recanalization of both left transverse and sigmoid sinuses. CVST is a rare extraintestinal manifestation of ulcerative colitis with significant morbidity and mortality which requires a high level of suspicion to establish a clear diagnosis. In spite the fact that CVST is rare, it should be ruled out in inflammatory bowel disease patients with new onset seizures, headache, along with focal, and non–focal neurologic symptoms.