Metastatic brain lymphomas, which belong to secondary central nervous system lymphomas, usually originate from primary tumors of the bone marrow, testis, or orbit. Gastrointestinal lymphomas commonly metastasize to the lung or heart. We report here a case of brain hemorrhage due to metastasis from primary gastrointestinal diffuse large B-cell lymphoma (DLBCL). A 30-year-old male presented with headache. He was diagnosed to have gastrointestinal lymphoma 6 months earlier, and treated with gastrointestinal surgery. Pathological diagnosis was DLBCL. A PET-CT scan immediately after gastrointestinal surgery demonstrated no brain metastasis. On admission to the ward, imaging of the brain showed right temporoparietal hematoma. In the ward, the patient deteriorated with impaired consciousness. Repeat brain imaging showed enlargement of the hematoma. He underwent right temporoparietal craniotomy for the removal of a hematoma, and tumor nodules adherent to the cortex was found. Pathology confirmed a metastatic DLBCL in the brain. Literature review showed that this was the first reported case of brain hemorrhage from metastatic lymphoma. Metastatic central nervous system lymphoma should be considered as a differential diagnosis in patients with a history of gastrointestinal lymphoma presenting with neurological symptoms.

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.