Deep Sylvian fissure meningiomas: A case report.

BACKGROUND: Deep Sylvian meningiomas are rare and difficult to diagnose when small tumours lead to various symptoms. The difficulty associated with surgery is underestimated. Our case involved a mass (11 mm × 12 mm × 12 mm in size) in the right Sylvian fissure. It is the smallest deep Sylvian meningioma known and might be more easily misdiagnosed than previous examples. CASE SUMMARY: A well-enhanced mass in the right Sylvian fissure of a 26-year-old male with a three-month history of seizure was identified via magnetic resonance imaging. The patient underwent operations twice for seizure control. During the first operation, the tumour was surrounded by the second segment of the middle cerebral artery and its numerous perforators. Partial resection had to be selected due to mild arterial damage. After the first operation, the patient presented with simple partial seizure. During reoperation, we isolated the anatomical structure near the tumour and the tumour over and removed it from its dorsal side by piecemeal resection. CONCLUSION: This case reported the smallest deep Sylvian meningioma according to a literature review. Preoperative diagnosis is a crucial step due to deep Sylvian meningioma firmly adhering to the middle cerebral artery and its perforators. Adequate preparation is crucial to ensure the success of surgery.

Signaling protein signature predicts clinical outcome of non-small-cell lung cancer.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.

Overexpression of GPNMB predicts an unfavorable outcome of epithelial ovarian cancer.

OBJECTIVE: Glycoprotein non-metastatic protein B (GPNMB) is a transmembrane glycoprotein that is expressed at higher levels in several malignant human tissues than those in matched normal tissues. Thus, GPNMB may serve as an attractive therapeutic target of cancer treatment. In this study, the prognostic value of GPNMB expression was examined in tumors derived from a cohort of patients with epithelial ovarian cancer (EOC). METHODS: GPNMB expression in matched formalin-fixed and paraffin-embedded tissue samples was evaluated by immunohistochemistry (IHC), whereas GPNMB mRNA expression in fresh-frozen biopsy tissues was detected using real-time quantitative PCR (qPCR). Meanwhile, the correlations of GPNMB expression with the clinical characteristics of EOC were assessed. Besides, survival data were analysed using Kaplan-Meier and Cox regression analyses, respectively. RESULTS: GPNMB expression was remarkably upregulated in EOC tissues compared with that in normal ovarian controls at both mRNA and protein levels. In addition, abundant GPNMB expression in EOC was correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001), residual tumor (P = 0.036), and lymph node metastasis (P = 0.004). Furthermore, results of univariate and multivariate analyses indicated that GPNMB expression level was an independent prognostic factor of the progression-free survival (PFS) and overall survival (OS) (P < 0.001 and P < 0.001, respectively) for EOC patients. CONCLUSION: Upregulated GPNMB levels in EOC patients are associated with dismal prognosis. Moreover, findings in the current study indicate that GPNMB is a potentially useful prognostic predictor of the therapeutic approaches for EOC.

Diverse endometrial mRNA signatures during the window of implantation in patients with repeated implantation failure.

High endometrial receptivity in the window of implantation (WOI) is essential for successful implantation. However, a diagnostic tool with high specificity for impaired endometrial receptivity remains to be developed. We collected endometrium specimens during the WOI from patients with RIF and women who conceived after one IVF/ICSI attempt. We conducted mRNA microarray on the samples followed by relevant comparative and functional analysis. Microarray analysis revealed 357 dysregulated mRNAs between the two groups. The majority of these mRNAs were found to encode membrane proteins by Gene Ontology (GO) analysis. The major functional biological pathways associated with the down-regulated mRNAs were cytokine-cytokine receptor interaction, the p53 signalling pathway and the complement and coagulation cascades. Up-regulated mRNAs were found mainly to participate in pathways such as PPAR signalling, hematopoietic cell lineage, phosphatidylinositol signalling system, ECM-receptor interaction and notch signalling. AQP3, DPP4 and TIMP3 whose expression patterns were down-regulated in RIF patients both by microarray and real-time PCR had a high correspondence with previous studies demonstrating that these genes may contribute to the defects in endometrial receptivity in RIF patients. Overall, these RIF-associated mRNAs may help devise new diagnostic tools for endometrial receptivity.

Endometrial MicroRNA Signature during the Window of Implantation Changed in Patients with Repeated Implantation Failure.

BACKGROUND: At present, a diagnostic tool with high specificity for impaired endometrial receptivity, which may lead to implantation failure, remains to be developed. We aimed to assess the different endometrial microRNA (miRNA) signatures for impaired endometrial receptivity by microarray analysis. METHODS: A total of 12 repeated implantation failure (RIF) patients and 10 infertile patients, who conceived and delivered after one embryo transfer attempt, were recruited as RIF and control groups, respectively. Endometrial specimens from the window of implantation (WOI) were collected from these two groups. MiRNA microarray was conducted on seven and five samples from the RIF and control groups, respectively. Comparative, functional, and network analyses were performed for the microarray results. Quantitative real-time polymerase chain reaction (PCR) was performed on other samples to validate the expression of specific miRNAs. RESULTS: Compared with those in the control group, the expression levels of 105 miRNAs in the RIF group were found to be significantly up- or down-regulated (at least 2-fold) by microarray analysis. The most relevant miRNA functional sets of these dysregulated miRNAs were miR-30 family, human embryonic stem cell regulation, epithelial-mesenchymal transition, and miRNA tumor suppressors by tool for annotations of microRNA analysis. Network regulatory analysis found 176 miRNA-mRNA interactions, and the top 3 core miRNAs were has-miR-4668-5p, has-miR-429, and has-miR-5088. Expression levels of the 18 selected miRNAs in new samples by real-time PCR were found to be regulated with the same trend, as the result of microarray analysis. CONCLUSIONS: There is a significant different expression of certain miRNAs in the WOI endometrium for RIF patients. These miRNAs may contribute to impaired endometrial receptivity.

BMPR2-pSMAD1/5 signaling pathway regulates RUNX2 expression and impacts the progression of dedifferentiated chondrosarcoma.

Bone morphogenetic protein receptors (BMPRs) are multifunctional proteins; they have indispensible roles in the process of BMP signaling. However, their function in dedifferentiated chondrosarcoma is uncertain. It has been reported that BMPR2 is associated with chondrosarcoma. Moreover, the detection of BMPR2 is more frequent in dedifferentiated chondrosarcomas (DDCS) than in conventional chondrosarcomas (CCS). BMPR2, phospho-SMAD1/5 (pSMAD1/5), and runt-related transcription factor 2 (RUNX2) expressions were found to be associated with the pathological grades of chondrosarcoma and could be a promising target of treatment outcome. Moreover, BMPR2 was found to induce the RUNX2 expression via pSmad1/5. Knockdown of BMPR2 and pSmad1/5 results in the downregulation of RUNX2 expression in DDCS cells, while the upregulation of BMPR2 and Smad1/5 in CCS cells leads to increased RUNX2 expression. The luciferase reporter gene assay suggested that BMPR2 can induce the RUNX2 expression at the transcriptional level. By chromatin immunoprecipitation (ChIP) and electrophoresis mobility shift assay (EMSA), it was found that pSmad1/5 combined directly to RUNX2. The in vivo tumorigenicity assay in mice showed that the inhibition of BMPR2 or Smad1/5 in DDCS cell line reduced tumor growth, while the upregulation of BMPR2 or Smad1/5 in CCS cell line increased tumor growth. Furthermore, a BMPR signaling inhibitor, LDN-193189, was introduced to investigate its role as a potential drug to treat DDCS. Taken together, the present-study results suggest that BMPR2-pSmad1/5 signaling pathway has an important role in regulating not only the RUNX2 expression but also the tumorigenesis of DDCS.

Postoperative recurrence of desmoid tumors: clinical and pathological perspectives.

BACKGROUND: The clinical features and the pathological changes of desmoid tumors were studied to point out the key factors affecting the recurrence. METHODS: The clinical data and specimens of 56 patients who underwent desmoid tumor resection from 2003 to 2008 were reviewed. Possible clinical factors related to the postoperative recurrence were analyzed statistically. The specimens round the lesions were studied histopathologically. RESULTS: The overall recurrence rate was 39.3%. The postoperative recurrence rate of the patients with negative surgical margins and no tumor invasion of the major vessels and nerves was low (P < 0.05). However, the desmoid tumors could destroy the cortical bone and invade the medullary cavity. CONCLUSIONS: Desmoid tumors were pathologically benign, which could extensively invade tissues around the lesions. The invasion of major vessels and nerves and quality of surgical margins are the key factors for the high postoperative recurrence rate.

[Dieulafoy disease of the bronchus: 3 cases report with literature review].

OBJECTIVES: To improve the understanding of bronchial Dieulafoy disease by summarizing the clinical and literature reported cases. METHODS: The clinical data of 3 patients with bronchial Dieulafoy disease diagnosed by pathology from January 1, 2007 to May 31, 2012 in our hospital was collected and summarized. The data of 19 cases from literature case report regarding bronchial Dieulafoy disease both in Chinese and English were also reviewed through databases including Wanfang Data, National Knowledge Infrastructure, National Center for Biotechnology Information and Ovid Technologics from January 1, 2005 to May 31, 2012. The clinical characteristics, diagnosis and treatment of all the 22 cases were summarized and analyzed. RESULTS: The average age of the 22 cases with bronchial Dieulafoy disease was (47 ± 15) years, and the preponderance was in male adults (16/22). Right lung (16/22) was more commonly involved than the left lung (4/22), and rarely in both lungs (2/22). Eight cases had smoking history, and 10 cases had underlying diseases such as tuberculosis.Sudden onset of massive hemoptysis was a common manifestation. Massive or lethal hemorrhage was often caused by biopsy injury. The abnormality of bronchial Dieulafoy disease was usually demonstrated as nodular lesions within the lumen of the bronchus.However, It was unable to determine their originating of the anomalous arteries in half of the cases(11/22). Most anomalous arteries confirmed by pathology were branched from bronchial artery (9/22), and rarely from pulmonary artery (2/22). The definitive diagnosis was made by pathological examination.Selective bronchial artery embolization and pulmonary lobectomy were the major therapeutic strategies, but bleeding may relapse after bronchial artery embolization, and lobectomy of the lung was a cure approach. CONCLUSIONS: Bronchial Dieulafoy disease should be differentiated in patients with massive and unexplained hemoptysis.It takes a very high risk for biopsy, which rarely needs to be implemented. Bronchial arteriography and selective bronchial artery embolization should be promptly carried out to avoid life-threatening hemoptysis.Lobectomy could be an alternative choice for a cure.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

Diffuse pulmonary lymphangiomatosis: a case report with literature review.

Diffuse pulmonary lymphangiomatosis (DPL) is a rare disease that is characterized by diffuse proliferation of abnormal pulmonary lymphatic channels. DPL occurs mostly in children and young adults and often undergoes a progressive clinical course, eventually causing deterioration of the lung. Both the clinical diagnosis and treatment of DPL remain a challenge. Here, we report a case of DPL in a 53-year-old Chinese woman with comprehensive investigations including pulmonary function tests, computer tomography (CT), bronchoscopy and histological examination of the lung biopsy, and review the literature.

[Gastrointestinal mesenchymal tumors: a clinical pathologic and immunohistochemical study of 210 cases].

OBJECTIVE: To study the clinical pathologic and immunohistochemical features of gastrointestinal mesenchymal tumors (GIMTs), and to investigate the value of molecular markers in GIMTs clinical differentiation diagnosis. METHODS: The clinical and pathological data of 210 cases of GIMTs, collected from Jan. 1987 to Dec. 2005 in our hospital, were investigated retrospectively. GIMTs were rediagnosed by using standard immunostaining technique in paraffin-embedded tissue. The expression level of CD117, CD34, Desmin, SMA and PS100 were detected by immunohistochemical method. RESULTS: Among 210 cases of GIMTs, 127 cases were Gastrointestinal stromal tumors (GISTs) (60.5%), 33 leiomyomas and leiomyosarcomas (15.7%), 27 neurogenic tumours (12.8%), and 23 miscellaneous tumors (11.0%). The incidences of GIST, leiomyoma and leiomyosarcoma were similar among men and women. Men were more likely to develop neurogenic tumors and miscellaneous tumors than women. Of all the GISTs, 51.2% cases originated from stomach, 19.7% from small intestine, 11.0% from esophagus, 10.2% from colon and rectum. The most common location of leiomyomas and leiomyosarcomas was esophagus (45.5%). The most common location of neurogenic tumors was retroperitoneum (74.1%). Common symptoms of GISTs included digestive tract hemorrhage in 36 cases (28.3%), abdominal pain in 27 cases (21.3%) and abdominal mass in 24 cases (18.9%). Other GIMT cases except GISTs had no first symptom of digestive tract hemorrhage. It was noticed that 79.5% of GISTs had no obvious invasion, and 72.7% of leiomyomas and leiomyosarcomas had no obvious invasion. 33.3% of neurogenic tumors invaded the adjacent organs or tissues. No metastases had been found in other GIMT cases except GISTs. The neoplastic cells of GISTs were composed of various percentage of spindle (72.5%), epithelioid (11.8%) and mixed-type cells (15.7%). The percentage of spindle cells in leiomyomas and leiomyosarcomas was 94. The immunohistochemical results of GISTs showed that the positive rate of CD117 was 93.7%, CD34 was 69.3%, Desmin was 13.4%, SMA was 12.6%, and PS100 was 10.2%. The immunohistochemical results of leiomyomas and leiomyosarcomas showed that the positive rate of Desmin was 78.5%, SMA was 63.6%, while as the expressions of CD117, CD34, and PS100 were negative. Diffuse strong positive staining of PS100 was observed in 88.9% of neurogenic tumor patients. CONCLUSIONS: GISTs are the most common tumors among GIMTs. GISTs are different from neurogenic tumors, leiomyomas and leiomyosarcomas in initial symptom, tumor location, biological behavior and immunophenotype. Immunohistochemistry plays an important role in differentiating GISTs from leiomyomas and neurogenic tumors.

[The pilot study of the effect of paclitaxel by local slow delivery on intimal hyperplasia of vascular anastomosis after vascular graft bypass].

OBJECTIVE: To develop a new way to prevent restenosis in the anastomotic site due to intimal hyperplasia after vascular graft bypass (VGB) in peripheral arteries. METHODS: Five mongrel dogs received bilateral iliac-femoral VGB and their arteries between the graft were ligated and cut off under general anaesthesia. The mixture of the paclitaxel and fibrin gel (FG) were randomly sprayed onto one side of grafts including distal and proximal anastomotic site, and the fibrin gel served as control were sprayed onto the other one. The bilateral grafts including distal and proximal anastomotic site were harvested four weeks postoperationally and the anastomotic sites were observed grossly, pathologically and by electron microscopy. The intimal thickness and area of each anastomotic site were measured, then the data were analysed statistically. RESULTS: The bilateral grafts of all dogs were patent and the neointima of all anastomotic sites have been seen grossly. The neointimal thickness and area of the experimental side were significantly reduced compared with the control side (P < 0.05). Scanning electron microscopy showed that the anastomotic intima of the experimental side was covered with one layer of intact and regular endothelium cells with deposition of little blood components, but the anastomotic intima of the control side was covered with irregular endothelium cells and deposited with a lot of blood cells and fibrins. Transmission electron microscopy showed the anastomotic intima of the control side that rich in vascular smooth muscle cells and the matrix of the intima was composed of regular collagenous fibers, and that of the experimental side consisted of several types of cells with a lot of foreign particles in the matrix. CONCLUSION: It is safe and effective to locally use low dose of paclitaxel carried by FG in the prevention of vascular anastomotic site intimal hyperplasia. Paclitaxel molecules can penetrate the graft wall and stay in the anastomotic intima more than four weeks postoperationally.

[Clinicopathologic analysis of 141 cases of metastatic carcinoma in bone].

OBJECTIVE: To study the clinicopathologic features of metastatic carcinoma in bone and to evaluate the role of immunohistochemistry in delineation of possible primary sites. METHODS: One hundred and forty-one cases of metastatic carcinoma in bone encountered during the period from 1998 to 2004 in People's Hospital, Peking University, were reviewed retrospectively. The clinical information, radiographic features and pathologic findings were analyzed. Immunohistochemical study for antigens including cytokeratins, prostatic specific antigen, thyroglobulin, thyroid transcription factor 1 and gross cystic disease fluid protein 15, was performed in 51 cases possessing skeletal metastasis with unknown primary. RESULTS: Skeletal metastasis occurred more commonly in males (male to female ratio = 1.7:1). The age of patients ranged from 23 to 86 years (mean age = 56.5). The presenting symptoms included pain and dysfunction in the affected bones. The locations of skeletal metastasis were as follows: spine (58), pelvic bone (46), long bone (34) and others (3). Twenty-three cases harbored multiple bony lesions. Radiographically, 99 cases (70.2%) of skeletal metastasis were detected by X-rays, including 85 cases (85.9%) showing lytic changes. The primary sites of the tumor could be determined by clinicopathologic correlation in 90 cases (63.8%) and were unknown in the remaining 51 cases. Upon immunohistochemical study, the primary sites were determined in another 40 cases. Overall, the primary sites were identified in 130 cases (92.2%), which included lung (37), female genital system and breast (25), kidney (18), gastrointestinal system (17), liver (12), thyroid (11), prostate (7), bladder (2) and skin (1). CONCLUSIONS: Skeletal metastasis occurs more often in elderly males. Axial bones (spine and pelvis) are usually affected. Lung and female genital system are frequent the primary sites. Immunohistochemical study is useful in cases with occult primary.