SOX3 is critical for the development of the pituitary, brain, and face, and SOX3 mutations may lead to hypopituitarism, intellectual disability, and craniofacial abnormalities. Common SOX3 mutations are duplications and deletions of the whole or part of SOX3, yet only a few cases with point mutations were reported by far. We present a case with growth retardation, small penis, and learning difficulty. Further assessment confirmed growth hormone deficiency, hypogonadotropic hypogonadism (HH), and borderline intellectual disability. He also responded well to gonadotropin-releasing hormone stimulation test, which suggests defects in the hypothalamus, contrary to previous studies that reported defects in the pituitary. A pathogenic frame-shift mutation of SOX3 was found. A heterogeneous missense mutation in SEMA3A was identified in this patient as well, which may also contribute to the development of HH. As far as we know, this is the first report that a frame-shift mutation of SOX3 constitutes rare genetic causes of HH and growth hormone deficiency. Whether mutations in these two genes act synergistically in the pathogenesis of the patient’s phenotype remains to be further investigated. We believe that our case extends the phenotypic spectrum and genetic variability of SOX3 mutation.

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There are great needs to explore more efficient and low-cytotoxic treatment for refractory/relapsed (R/R) or old acute myeloid leukemia (AML) patients without FLT3-ITD mutation. We observed the procedures and outcomes of 13 such patients subsequently treated by sorafenib in our departments. Five of them used low-dose cytorabine concomitantly and 8 patients took sorafenib alone as induction therapy. Five patients achieved complete remission (CR) and the needed time ranged from 31 to 100 days. Four patients achieved CR by concomitantly using low-dose cytorabine and sorafenib, but only one patient achieved CR by taking sorafenib alone. The difference of CR induction rates between the two groups was significant. Sorafenib was then prescribed as the maintenance treatment to these AML patients achieving CR until adverse event happening or stem cell transplantation received. Only one patient developed adverse event of grade 3 during the maintenance with sorafenib and it was relieved by withdrawal of the drug. The event free survival with sorafenib ranged from 2 to 20 months. The median survival time of these CR patients was 520 days since the beginning of taking sorafenib. The median survival time of those not achieved CR with sorafenib was 344 days. But we found no significant differences of survival time between those achieving and not achieving CR. Our results of the observation suggested a group of R/R or geratic AML patients unfit for intensive chemotherapy induction and without FLT3-ITD mutation may well respond to single sorafenib treatment. The combination of low-dose cytarabine with sorafenib improved the response rate comparing with using sorafenib alone. This treatment is safe and the survival time is acceptable for such formidable patients.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by clonal expansion of CD1a+/CD207+ cells in lesions. The most frequent sites involved are bone and, less commonly, lymph nodes, lungs, and skin. The thymus or heart is rarely involved with LCH. In this case, we present a 73-year-old woman with a mediastinal mass. Histopathology after thymectomy identified this mass as type AB thymoma; notably, subsequent immunohistochemical tests showed lesions of LCH scattered in the region of thymoma. 18-Fluorodeoxyglucose PET/CT (18-FDG-PET/CT) was performed to make an overall assessment of the extent of this disease, which demonstrated suspicious cardiac involvement of LCH. This report highlights the importance of differentiating abnormalities of the thymus or mediastinal mass from LCH and the necessity of comprehensive evaluation for patients with LCH.