Microenvironment-dependent growth of preneoplastic and malignant plasma cells in humanized mice.

Most human cancers, including myeloma, are preceded by a precursor state. There is an unmet need for in vivo models to study the interaction of human preneoplastic cells in the bone marrow microenvironment with non-malignant cells. Here, we genetically humanized mice to permit the growth of primary human preneoplastic and malignant plasma cells together with non-malignant cells in vivo. Growth was largely restricted to the bone marrow, mirroring the pattern in patients with myeloma. Xenografts captured the genomic complexity of parental tumors and revealed additional somatic changes. Moreover, xenografts from patients with preneoplastic gammopathy showed progressive growth, suggesting that the clinical stability of these lesions may in part be due to growth controls extrinsic to tumor cells. These data demonstrate a new approach to investigate the entire spectrum of human plasma cell neoplasia and illustrate the utility of humanized models for understanding the functional diversity of human tumors.

Intracranial hypotension after trauma.

INTRODUCTION: Intracranial hypotension (IH) occurs typically spontaneous and is a potentially life-threatening condition characterized by symptoms varying from postural headache to coma, with classical magnetic resonance imaging (MRI) findings. CASE DESCRIPTION: We report two cases of clinically relevant trauma-related IH and review of the literature. One patient with a cerebral trauma presented unilateral mydriasis and coma resolved by the Trendelenburg position (-20°) as urgency intervention. In the second patient, IH was caused by a lesion of the brachial plexus after a motor vehicle accident. DISCUSSION AND CONCLUSION: A history of mild or moderate trauma in association with prolonged postural or permanent headache may indicate IH. Posttraumatic IH is rare, nevertheless life-threatening in case of misdiagnosis. Intracranial hypotension in a trauma context is rarely described and difficult to diagnose. The change from tipical supine 30° to Trendelenburg position (0-20°) can be a life-saving manoeuver in these patients.