RESUMO
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal lymphoma exclusively occurring within the central nervous system. Inflammatory brain lesions as "sentinel lesions" of PCNSL are very rare. We present a rare case of PCNSL with preceding inflammatory lesions in an immunocompetent patient who underwent two biopsies, one craniotomy and two genetic testing. CASE REPORT: A 66-year-old male patient presented with left limb weakness and ataxia. Brain magnetic resonance imaging showed a contrast-enhancing lesion with perifocal brain edema in the near midline of right frontal lobe. Histological examination of a brain biopsy specimen revealed inflammatory lesion characteristics with infiltration of T-cell dominant lymphocytes and few B-cell. Given that the patient developed cerebral hematoma after biopsy, lesion resection by craniotomy was performed. An excised sample demonstrated mixed T-cell and B-cell infiltrating inflammatory lesions. Four months after total resection of the right frontal lobe lesion, another lesion appeared in the left frontal parietal lobe, which was diagnosed as diffuse large B-cell lymphoma by biopsy. In addition, genetic testing of the lesions at two different locations was performed, and the results showed that the inflammatory lesions had the same three gene (RELN, PCLO, and CREBBP) mutations as PCNSL. Interestingly, the three mutated genes are associated with tumor. CONCLUSION: Our present case is the first to demonstrate inflammatory brain lesions heralding PCNSL from genetic and pathological perspectives. This may help clinicians to select new auxiliary diagnostic methods for timely diagnosis of patients with suspected PCNSL.
Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Masculino , Humanos , Idoso , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/diagnóstico por imagem , Neoplasias do Sistema Nervoso Central/genéticaRESUMO
The Omicron variant of SARS-CoV-2 has rapidly become the dominant infective strain and the focus efforts against the ongoing COVID-19 pandemic. Here we report an extensive set of structures of the Omicron spike trimer by its own or in complex with ACE2 and an anti-Omicron antibody. These structures reveal that most Omicron mutations are located on the surface of the spike protein, which confer stronger ACE2 binding by nearly 10 folds but become inactive epitopes resistant to many therapeutic antibodies. Importantly, both RBD and the closed conformation of the Omicron spike trimer are thermodynamically unstable, with the melting temperature of the Omicron RBD decreased by as much as 7{degrees}C, making the spiker trimer prone to random open conformations. An unusual RBD-RBD interaction in the ACE2-spike complex unique to Omicron is observed to support the open conformation and ACE2 binding, serving the basis for the higher infectivity of Omicron. A broad-spectrum therapeutic antibody JMB2002, which has completed Phase 1 clinical trial, is found to interact with the same two RBDs to inhibit ACE2 binding, in a mode that is distinguished from all previous antibodies, thus providing the structural basis for the potent inhibition of Omicron by this antibody. Together with biochemical data, our structures provide crucial insights into higher infectivity, antibody evasion and inhibition of Omicron.
