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ObjectiveTo investigate the clinicopathological characteristics, molecular genetic characteristics and prognosis of extraventricular neurocytoma located in the sellar/suprasellar region.MethodsSeven archived tumor samples derived from 4 patients with neurocytoma in the sellar/suprasellar region were collected from the First Affiliated Hospital of Fujian Medical University and the Affiliated Hospital of Qingdao University and retrospectively analyzed for clinical manifestations, imaging features, and histopathological features. Neuronal and pituitary biomarkers and molecular features were detected in these tumor tissues by immunohistochemistry and FISH or Sanger sequencing. The related literature was reviewed.ResultsThree patients were female, while 1 was male, with an average age of 35.5 years (range: 27 to 45 years). The initial manifestations were mainly headache and blurred vision in both eyes. The first MRI examination showed marginally enhancing masses in the intrasellar or intra- to suprasellar region. The diagnosis of pituitary adenomas was based on imaging features. The levels of pituitary hormones were normal. Histologically, the tumor cells were arranged in a sheet-like, monotonous architecture and were uniform in size and shape with round to oval, exquisite and hyperchromatic nuclei, which densely packed close to one another and were separated only by a delicate neuropil background. There was no evident mitosis, necrosis or microvascular proliferation. The three cases of recurrent tumors were highly cellular and showed increased mitotic activity. Immunohistochemically, the tumor cells were positive for syn, CR, CgA, and vasopressin and were focally positive for NeuN, TTF-1, NF, CK8, vimentin, and S100 proteins. Other markers, including IDH1, BRAF VE1, Olig-2, and EMA, were negative. Pituitary transcription factors and anterior pituitary hormones were negative. Molecular genetic testing showed that the tumor cells lacked IDH gene mutations, LOH of 1p/19q, MYCN amplification, and EGFR alteration. With a median follow-up of 74.5 months (range 23 to 137 months), 3 patients relapsed at 11, 50, and 118 months after the initial surgery.ConclusionThe morphological features and immunophenotypes of neurocytoma in the sellar/suprasellar region are similar to those of classic central neurocytoma. The prognosis is relatively good. Gross-subtotal resection and atypical subtype may be related to tumor recurrence.

Background Female Dent disease 1 patients with low-molecular-weight proteinuria (LMWP) due to CLCN5 gene mutation were rarely reported, and these cases that the people were also with Turner syndrome (TS) were even hardly documented before. Case presentation Here we report a 3-year and 11-month old Chinese girl with short stature who had a karyotype of 46,X,i(X)(q10) and a de novo pathogenic variant in the CLCN5 gene on the short arm of X chromosome. Laboratory examinations showed that the patient had LMWP, hypercalciuria, hypophosphatemia, delayed bone age, and genital dysplasia. Conclusion The combination of i(X)(q10) and CLCN5 mutation causes the deletion of the wild-type CLCN5 allele that results in Dent-1 and TS. To the best of our knowledge, this is the first case that a female CLCN5 mutation hemizygote is diagnosed with Dent-1 and Turner syndrome due to isochromosome X. Also, our case has indicated that the prevalence of the situation may be largely underestimated because of the mild signs of females with Dent-1.

Long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and development of endometrial carcinoma (EC). Here, using RNA sequencing analysis, we systemically screened and identified the lncRNA eukaryotic translation initiation factor 1A, X-linked (EIF1AX)-AS1, which is aberrantly downregulated in clinical EC tissues and closely correlated with tumor type. EIF1AX-AS1 markedly inhibited EC cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, EIF1AX-AS1 interacts with EIF1AX mRNA and poly C binding protein 1 (PCBP1), which promote EIF1AX mRNA degradation. Intriguingly, by interacting with internal ribosome entry site-related protein Y-box binding protein 1 (YBX-1), EIF1AX promotes c-Myc translation through the internal ribosome entry site pathway. c-Myc promotes EIF1AX transcription and thus forms a feed-forward loop to regulate EC cell proliferation. Taken together, these data reveal new insights into the biology driving EC proliferation and highlights the potential of lncRNAs as biomarkers for prognosis and future therapeutic targets for cancer.

Dysregulation of eukaryotic translation initiation factor 1A, X-linked (EIF1AX), has been implicated in the pathogenesis of some cancers. However, the role of EIF1AX in endometrial carcinoma (EC) remains unknown. We investigated the EIF1AX expression in EC patients and assessed its tumorigenesis-associated function and nucleocytoplasmic transport mechanism in vitro and in vivo. The results indicated that the cytoplasmic EIF1AX expression showed a gradual increase when going from endometrium normal tissue, simple endometrial hyperplasia, complex endometrial hyperplasia, and endometrial atypical hyperplasia to EC, while vice versa for the nuclear EIF1AX expression. In addition, the cytoplasmic EIF1AX expression was positively correlated with histologic type, high International Federation of Gynecology and Obstetrics (FIGO) grade, advanced FIGO stage, deeper infiltration, high Ki67 index, and shorter recurrence-free survival in EC patients. In vitro, short hairpin RNA-mediated EIF1AX depletion or SV40NLS-mediated EIF1AX import into the nucleus in multiple human EC cells potently suppressed cell migration and invasion, epithelial-mesenchymal transition, and lung metastasis. Moreover, exportin 1 induced the transport of EIF1AX from the nucleus to the cytoplasm that could be inhibited by leptomycin B treatment or the mutation in the EIF1AX location sequence. These results demonstrate that cytoplasmic EIF1AX may play a key role in the incidence and promotion of EC, and thus, targeting EIF1AX or its nucleocytoplasmic transport process may offer an effective new therapeutic approach to EC.

Objective To explore the clinical and pathologic features of ovarian juvenile granulosa cell tumors (JGCTs). Methods Clinical data, histopathologic observations, immunohistochemical results, FOXL2 mutation status, and follow-up information of 7 JGCT cases were studied. Results The patients most commonly presented with abdominal distension and pain (5 cases), followed by precocious puberty (1 case) and a pelvic mass (1 case). Six patients had stage I disease, and 1 had stage IV disease. The microscopic examinations typically showed lobular growth punctuated by variably sized and shaped follicles. Rare features included a reticular-cystic appearance mimicking a yolk sac tumor (2 cases), a lobular appearance similar to a sclerosing stromal tumor (1 case), strands and cords (1 case), pseudopapillary appearance (2 cases), spindle cell appearance (1 case), microcystic appearance (1 case), hobnail cells (1 case), and rhabdomyoid cells (1 case). No FOXL2 mutation was encountered. After a median follow-up of 53 months, only 1 patient with a strongly diffuse TP53-positive tumor died of the disease, and 2 successfully had babies. Conclusions JGCT is a rare neoplasm with a wide morphologic spectrum and is easily confused with other tumors. Familiarity with the characteristics, rare atypical appearances, and immunohistochemical results may aid in obtaining a correct diagnosis.

Objective To evaluate the expression and prognostic significance of ALDH1A1 in gastric neuroendocrine carcinoma. Materials and methods Immunohistochemical stains of ALDH1A1 were evaluated in 67 cases of gastric neuroendocrine carcinoma. The findings were correlated with clinicopathologic variables and overall survival. Results Immunohistochemistry revealed positive cytoplasmic immunoreactivity in 35 of 67 (52.2%) tumors and strongly positive immunoreactivity in 14 of 67 (20.9%). Strongly positive ALDH1A1 expression, but not positive staining, was significantly associated with lymph node status, lymphovascular invasion, and ki-67 index (P = 0.039, 0.045, and 0.045, respectively). Kaplan‐Meier survival curves and log-rank tests showed significantly poorer prognoses in cases of high ALDH1A1 expression compared to cases of low ALDH1A1 expression or the negative control group (MST, 17 vs. 52 months; P = 0.026). Multivariate analysis showed that high ALDH1A1 expression, lymph node metastasis, and lymphovascular invasion had significant associations with decreased overall survival (P = 0.029, 0.008, and 0.005, respectively). Conclusions High ALDH1A1 expression may be a prognostic indicator of survival in patients with gastric neuroendocrine carcinoma.

Background Protein phosphorylation & dephosphorylation are ubiquitous cellular processes that allow for the nuanced and reversible regulation of protein activity. Protein phosphatase 2A (PP2A) is a multifunction phosphatase that is well expressed in all cell types of kidney during early renal development, though its functions in kidney remains to be elucidated. Methods PP2A conditional knock-out mice was generated with PP2A fl/fl mice that were crossed with Podocin-Cre mice. The phenotype of Pod-PP2A–KO mice (homozygous for the floxed PP2A allele with Podocin-Cre) and littermate PP2A fl/fl controls (homozygous for the PP2A allele but lacking Podocin-Cre) were further studied. Primary podocytes isolated from the Pod-PP2A-KO mice were cultured and they were then employed with sing label-free nano-LC − MS/MS technology on a Q-exactive followed by SIEVE processing to identify possible target molecular entities for the dephosphorylation effect of PP2A, in which Western blot and immunofluorescent staining were used to analyze further. Results Pod-PP2A–KO mice were developed with weight loss, growth retardation, proteinuria, glomerulopathy and foot process effacement, together with reduced expression of some slit diaphragm molecules and cytoskeleton rearrangement of podocytes. Y box protein 1 (YB-1) was identified to be the target molecule for dephosphorylation effect of PP2A. Furthermore, YB-1 phosphorylation was up-regulated in the Pod-PP2A–KO mice in contrast to the wild type controls, while total and un-phosphorylated YB-1 both was moderately down-regulated in podocytes from the Pod-PP2A-KO mice. Conclusion Our study revealed the important role of PP2A in regulating the development of foot processes and fully differentiated podocytes whereas fine-tuning of YB-1 via a post-translational modification by PP2A regulating its activity might be crucial for the functional integrity of podocytes and glomerular filtration barrier. Graphic abstract Electronic supplementary material The online version of this article (10.1186/s12964-019-0402-y) contains supplementary material, which is available to authorized users.

Ependymoma with cartilaginous metaplasia with or without bone formation is exceedingly rare. Only eight cases have been reported in the literature. We report a case of ependymoma with cartilaginous and osseous metaplasia in a 5-year-old boy. Microscopically, the tumor was composed of neoplastic ependymal tissue and mature cartilage and bone. Immunohistochemically, glial fibrillary acidic protein and epithelial membrane antigen were positive for ependymoma cells but negative for cartilage and bone. Recurrence occurred after 15-month follow-up. The patient deteriorated rapidly and died after 1 month. Reviewing 8 reported cases and our latest case, we found that 3 cases of ependymoma with cartilaginous metaplasia were treated with radiotherapy. Six cases had recurrence from 6 months to 8 years and 2 cases died on the day of operation. These findings suggest that ependymoma with cartilaginous metaplasia might have more aggressive clinical behavior.