Unusual morphologic features of low-grade endometrial stromal sarcoma: A case report.

BACKGROUND: Endometrial stromal tumours are uncommon tumours of the uterus. They mainly occur in perimenopausal women. Tumours with typical clinicopathological features do not usually pose diagnostic problems. However, rare clinicopathological features can occur, and clinicians without significant experience may have difficulty diagnosing these tumours and managing these patients. METHODS: Herein, we report a case of endometrial stromal sarcoma that occurred in a 25-year-old woman. The pathological features, immunophenotype, treatment and prognosis were discussed. RESULTS: The tumour revealed morphological heterogeneity, and there were similar proliferative-type endometrial stromal cells, an extensive amount of mature adipose tissue, and prominent rhabdomyoblastic and smooth muscle cells. Histopathological and immunohistochemical studies confirmed low-grade endometrial stromal sarcoma with smooth muscle, adipocytic and rhabdomyoblastic differentiation (approximately 60% were differentiated tissues). The final treatment of the tumour was total abdominal hysterectomy with bilateral salpingo-oophorectomy. There was no evidence of recurrence for 109 months postoperatively. CONCLUSIONS: We found that low-grade endometrial stromal tumours with extensive adipocytic and prominent rhabdomyoblastic differentiation are misdiagnosed because they are infrequent. They must be differentiated from rhabdomyosarcoma with accurate identification of adipocytes, and long-term follow-up is needed.

Low-grade oncocytic tumor of kidney harboring TSC/MTOR mutation: clinicopathologic, immunohistochemical and molecular characteristics support a distinct entity.

Low-grade oncocytic tumor (LOT) has recently been described as a distinct renal tumor. LOT shows consistent morphologic features and a CK7-positive/CD117-negative immunophenotype. To examine the clinicopathological, immunohistochemical, and molecular features of LOT, we searched our institutional archives and identified seven cases of LOT. All patients were female, with a mean age of 66 years (range 44-79 years). The average tumor size was 3.2 cm (range 1.6-5.5 cm). Macroscopically, the tumors showed tan-brown and solid cut surfaces. Microscopically, the tumors showed compact nested to solid growth pattern, three cases with areas of edematous stroma containing loosely connected small clusters, cords or dispersed single tumor cells. The tumor cells had uniformly round to oval nuclei with eosinophilic cytoplasm, and showed perinuclear halos. Two cases focally had nuclear irregularities and binucleated cells were occasionally seen in three cases. Immunohistochemically, diffuse positivity for CK7 and lack of CD117 expression were present in all cases. All of the tumors were negative for CD10, CK20, vimentin, CA9, TFE3, TFEB, HMB45, and Melan-A. All tumors were positive for MTOR and negative for Cathepsin-K. FH and SDHB were retained. Next generation sequencing identified genetic variations in the MTOR pathway related genes: TSC1 (4/7), TSC2 (5/7), and MTOR (1/7). All patients were alive and without disease progression, after a mean follow-up of 43 months (range 6-89 months). LOT is an uncommon eosinophilic renal neoplasm with unique morphological and characteristic immunophenotypic features, and may represent an emerging separate renal entity characterized by mutations in the TSC/MTOR pathway.

Pinin promotes tumor progression via activating CREB through PI3K/AKT and ERK/MAPK pathway in prostate cancer.

Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown. In the study, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and modulated cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells, accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of CREB, which was reversed by CREB inhibition. More important, PNN activated CREB via PI3K/AKT and ERK/MAPK pathway. Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it is a potential therapeutic target for prostate cancer treatment.

Primary adrenal diffuse large B cell lymphoma arising within an adrenal myelolipoma: A case report and review of the literature.

Adrenal myelolipoma (AML) is a benign tumor that consists of mature adipose tissue and bone marrow elements. We report a case of a 57-year-old woman who presented with complaint of lower abdominal discomfort. Computed tomography scan of abdomen and pelvis revealed a mass in the left adrenal measuring 2.0 cm which was radiologically considered to be AML. Pathological evaluation of the lesion showed foci of lymphoid aggregate in a background of AML that were confirmed to be diffuse large B cell lymphoma by immunohistochemistry and gene rearrangement. To our knowledge, this collision tumor has not been reported previously. The clinical, radiological, pathological features, and treatment are discussed.

AFP-producing Xp11 translocation renal cell carcinoma: Case report and review of the literature.

Alpha-fetoprotein (AFP) is a useful tumor marker for hepatocellular carcinomas and yolk sac tumors. Rare extrahepatic visceral malignancies may be associated with AFP production and those exhibiting a hepatoid differentiation by morphology and immunohistochemical are classified as hepatoid adenocarcinoma. Renal cell carcinoma (RCC) producing AFP is a rare entity. To date, only one case of AFP-producing Xp11 translocation RCC has been reported. We reported another case of Xp11 translocation RCC, in which the tumor cells displayed strong immunostaining for AFP, HepPar1, and GPC-3. Additionally, the other published cases are reviewed.

Up-Regulation of RIP3 Alleviates Prostate Cancer Progression by Activation of RIP3/MLKL Signaling Pathway and Induction of Necroptosis.

BACKGROUND: The receptor-interacting protein kinase 3 (RIP3/RIPK3) was recently found to be a critical regulator of programmed necrosis/necroptosis. However, the biological role and clinical significance of RIP3 in prostate cancer remain obscure. METHODS: Western blotting and QRT-PCR were performed to detect the level of RIP3 in prostate cancer cells. Fixed cancer tissue and normal tissue specimens were subjected to immunohistochemical analysis of RIP3. Cell migration and invasion abilities were evaluated by transwell assays. In vitro proliferative ability was examed by MTS. And in vivo nude mice model were used to evaluate the effect of RIP3 ectopic expression on proliferative capability. Cell cycle of prostate cancer cells were analyzed by flow cytometry. Changes in some related proteins caused by RIP3 overexpression were explored using Western blotting. RESULTS: RIP3 was significantly down-regulated in prostate cancer cell lines and clinical prostate tumor samples. And over-expressing RIP3 suppressed the migration and invasion of prostate cancer cells. Two important matrix metalloproteinases MMP2, MMP9 which enables the destruction of the histological barrier of tumor cell invasion and three mesenchymal markers Vimentin, fibronectin, and N-cadherin were under-expressed due to the overexpression of RIP3, but the E-cadherin level which is the epithelial marker was increased. Furthermore, our results also showed that RIP3 can inhibit the proliferation and tumorigenicity of prostate cancer cells both in vitro and in vivo by phosphorylating MLKL, which were reversed by MLKL inhibitor treatment, indicating that necroptosis was involved in cell death. CONCLUSION: Taken together, these findings indicated that RIP3 is responsible for the progression of prostate cancer, suggesting that RIP3 might have the potential to be a prognostic marker or a therapeutic target against prostate cancer.

TFE3 rearranged epithelioid hemangioendothelioma of bone: A clinicopathological, immunohistochemical and molecular study of two cases.

Epithelioid hemangioendothelioma (EHE) is a rare malignant angiocentric vascular neoplasm. Around 90% of classic EHE has a t(1;3)(p36;q25) that results in a WWTR1-CAMTA1 fusion gene, a histologically distinctive subset of EHE has been recently shown to have a t(10;14)(p13;q42)that results in a different fusion gene, YAP1-TFE3. Twenty-one cases of TFE3 Rearranged Epithelioid Hemangioendothelioma have been reported in the literature, and only two cases occurred in bone. In the report, we report additional two cases occurred in the femur and skull and review the related literature.

Evaluation of PD-L1 biomarker for immune checkpoint inhibitor (PD-1/PD-L1 inhibitors) treatments for urothelial carcinoma patients: A meta-analysis.

INTRODUCTION: Newly published results of clinical trials has demonstrated immune checkpoint inhibitors as robust antitumor agents for urothelial carcinoma patients. However, searching for predictive biomarkers is still on the way. Previous clinical trials used PD-L1 as biomarkers, however, whether it can predict the objective response rate and overall survival is controversial. This is the first and latest study to pool the newest data in order the evaluate PD-L1 biomarker. RESULT: Nine studies were included and 1,436 urothelial carcinoma patients were included. We evaluated PD-L1 biomarker for atezolizumab, nivolumab, durvalumab, avelumab, and pembrolizumab treatments. Patients with higher PD-L1 expression have significantly higher objective response rate compared with the lower ones. PD-L1 predicted the one year overall survival of PD-L1 inhibitors but not PD-1 inhibitors. Only one year overall survival of durvalumab was significantly associated with PD-L1 expression. CONCLUSION: PD-L1 can be used as a biomarker for objective response rate, while PD-L1 cannot predict the overall survival.

Downregulation and subcellular distribution of HER2 involved in MDA-MB-453 breast cancer cell apoptosis induced by lapatinib/celastrol combination.

PURPOSE: To investigate the effect and related molecular mechanisms of lapatinib/celastrol combination or single-agent treatment in HER2/neu-overexpressing MDA-MB-453 breast cancer cells. METHODS: The effects of treatment with lapatinib, celastrol or their combination on cell growth were determined using MTT assay. Drug synergy was determined using the combination index (CI) methods derived from Chou-Talalay equations using CalcuSyn software. Apoptotic morphology was observed by fluorescence microscope with Hoechst 33258 staining. Changes of apoptotic and growth pathways-related proteins were analysed by Western blot. The expression of HER2 of cell surface was performed by flow cytometry. Subcellular distribution of HER2 was observed by immunofluorescence study. RESULTS: Combination celastrol and lapatinib produced strong synergy in growth inhibition and apoptosis in comparison to single-agent treatment in HER2/neu-overexpressing MDA-MB-453 cells. Interestingly, compared with celastrol treatment alone, lapatinib/celastrol combination induced more HER2 membrane protein downregulation and ectopic to cytoplasm and nucleus in MDA-MB-453 cells. CONCLUSION: The combination of celastrol and lapatinib could be used as a novel combination regimen which provides a strong anticancer synergy in the treatment of HER2/neu-overexpressing cancer cells.

Incidence and Antimicrobial Sensitivity Profiles of Normal Conjunctiva Bacterial Flora in the Central Area of China: A Hospital-Based Study.

Objective: To study the distribution and patterns of resistance to antimicrobial agents of normal conjunctival bacteria. Materials and Methods: Conjunctival specimens were collected from 8,224 patients and then cultured, which underwent antimicrobial susceptibility test following standard methods. Patients with infectious symptoms such as erythema or oedema and those using systemic or topical antibiotics within 1 month were excluded. Results: In this study, the incidence of isolated bacteria was 24.2%. The middle aged group of 41-65 years presented the lowest rate of bacterial isolation which was 19.4%, while the highest isolation rate (83.1%) was found in patients in the age range of 0-6 years. In every age group, the incidence of bacterial isolation in men was higher than that in women. The top 3 most commonly isolated micro-organisms were Staphylococcus epidermidis (39.7%), Streptococcus pneumoniae (4.5%), and Staphylococcus aureus (2.7%), of which about 83.1% S. aureus were isolated in the group of 0-6 years. We found that coagulase-negative Staphylococcus (CONS) were more resistant to penicillin, macrolides, clindamycin and sulfonamides with the rate ranging from 57.9 to 90.8%, which were highly susceptible to vancomycin, linezolid, rifampin, tetracyclines, and aminoglycosides. Contrasting to CONS, the general resistance rate of S. aureus was significantly lower. Additionally, Streptococcus was susceptible well to the majority of antimicrobial agents, while highly resistant to macrolides and tetracyclines with the rate >80%. Conclusions: In conclusion, our study revealed the incidence and antimicrobial sensitivity profiles of normal conjunctiva bacterial flora in the central area of China, which could be useful in the prevention of ocular infections. Importantly, our data could be used to guide the selection of appropriate prophylactic agents.

Immunohistochemistry and Fluorescence In Situ Hybridization Can Inform the Differential Diagnosis of Low-Grade Noninvasive Urothelial Carcinoma with an Inverted Growth Pattern and Inverted Urothelial Papilloma.

Urothelial carcinoma (UC) comprises a heterogeneous group of epithelial neoplasms with diverse biological behaviors and variable clinical outcomes. Distinguishing UC histological subtypes has become increasingly important because prognoses and therapy can dramatically differ among subtypes. In clinical work, overlapping morphological findings between low-grade noninvasive UC (LGNUC), which exhibits an inverted growth pattern, and inverted urothelial papilloma (IUP) can make subclassification difficult. We propose a combination of immunohistochemistry (IHC) and molecular cytogenetics for subtyping these clinical entities. In our study, tissue microarray immunohistochemical profiles of Ki-67, p53, cytokeratin 20 (CK20) and cyclinD1 were assessed. Molecular genetic alterations such as the gain of chromosomes 3, 7 or 17 or the homozygous loss of 9p21 were also assessed for their usefulness in differentiating these conditions. Based on our analysis, Ki-67 and CK20 may be useful for the differential diagnosis of these two tumor types. Fluorescence in situ hybridization (FISH) can also provide important data in cases in which the malignant nature of an inverted urothelial neoplasm is unclear. LGNUC with an inverted growth pattern that is negative for both Ki-67 and CK20 can be positively detected using FISH.

Development of a nomogram to predict non-organ-confined bladder urothelial cancer before radical cystectomy.

PURPOSE: To create a preoperative prediction model for estimating the risk of non-organ-confined (pT3-4 or pN+) bladder urothelial cancer (NOC-BUC) in patients with clinically OC-BUC (cT1-2N0M0). METHODS: The study involved 248 consecutive patients who had undergone radical surgery for clinically OC-BUC at a tertiary cancer center between 2003 and 2011. Logistic regression analysis was used to develop a prediction model for estimating the risk of pathological NOC disease. Prespecified predictors included age, gender, recurrent frequency, tumor size and number, hydronephrosis, and pathological characteristics at transurethral resection (T-stage, tumor grade, lymphovascular invasion (LVI), and carcinoma in situ). Discrimination ability was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: Overall, 39.1 % of the patients with clinically OC-BUC had NOC disease at the time of radical surgery. In multivariate analysis, recurrent frequency, tumor size, hydronephrosis, and three pathological features at transurethral resection (T-stage, tumor grade, and LVI) were significantly associated with disease extent. The final prediction model included seven variables after backward elimination and achieved a bootstrap-corrected AUC of 0.79. Internal validation showed good calibration and clinical usefulness of the nomogram. CONCLUSIONS: Based on readily available clinicopathological parameters, we developed a nomogram for predicting NOC tumor in clinically OC-BUC. Despite reasonable performance in internal validation, the prediction model should be assessed in external dataset before applied in clinical setting.

A combined clinicopathologic analysis of 658 urothelial carcinoma cases of urinary bladder.

OBJECTIVE: To study the clinicopathological features of patients with urothelial carcinoma of the urinary bladder (UCB), and analyze the association of clinicopathological characteristics with tumor recurrence and progression. METHODS: Altogether 658 UCB cases in Fudan University Shanghai Cancer Center were collected from January 2006 to December 2010. The histopathologic materials and the clinical records were reviewed. Univariate and multivariate analyses were preformed to detect the association. RESULTS: The mean age of the patients was 61.97 +/- 12.97 years (range, 20-90 years). Male to female ratio was about 5:1. A total of 517 cases (78.6%) were superficial at the time of diagnosis (stage Ta/T1). The mean follow-up period was 22.36 +/- 24.92 months. Twenty-five patients lacking follow-up information were excluded in calculating recurrence and progression rates, the recurrence rate was about 37.0% (234/633), and progression rate about 6.2% (39/633). Three variables (grade, tumor growth pattern, and pathological stage) were found to be significant risk factors for tumor progression in univariate and multivariate analyses (P < 0.05). CONCLUSIONS: Most of the newly diagnosed UCB cases may be superficial diseases. Grade, tumor growth pattern, and pathological stage are associated with tumor progression of UCB.

[Assessment of eco-environmental vulnerability of Hainan Island, China].

Based on the assessment method of environmental vulnerability constructed by SOPAC and UNEP, this paper constructed an indicator system from three sub-themes including hazard, resistance, and damage to assess the eco-environmental vulnerability of Hainan Island. The results showed that Hainan Island was suffering a middling level eco-environmental hazard, and the main hazards came from some intensive human activities such as intensive agriculture, mass tourism, mining, and a mass of solid wastes thrown by islanders and tourists. Some geographical characters such as larger land area, larger altitude range, integrated geographical form, and abundant habitat types endowed Hainan Island higher resistance to environmental hazards. However, disturbed by historical accumulative artificial and natural hazards, the Island ecosystem had showed serious ecological damage, such as soil degradation and biodiversity loss. Comprehensively considered hazard, resistance, damage, and degradation, the comprehensive environmental vulnerability of the Island was at a middling level. Some indicators showed lower vulnerability, but some showed higher vulnerability.

[Ecological quality of Beijing urban area from 1996 to 2005].

From the aspects of four ecological themes, i.e., ecological element, ecological process, ecological function and ecological destruction, an indicator framework including 16 indicators was developed to make an integrated assessment on the ecological quality of Beijing urban area. The weights of the indicators were determined by the methods of entropy weight, optimal state weight, and worst state weight, and the ecological element index (EEI), ecological process index (EPI), ecological function index (EFI), ecological destruction index (EDI), and composite ecological index (CEI) were computed by a weighted sum method and served as effective tools for analyzing the evolvement of the ecological quality of Beijing urban area from 1996 to 2005. The results showed that during the period of 1996-2005, the EEI of Beijing urban area did not display visible improvement and maintained a low level, far from the ideal state. The EPI and EFI increased dramatically, and approached to the ideal state in 2005. The EDI fluctuated within a low level, far from ideal state, and did not show an evolutionary trend. The CEI improved year after year, but was still low and did not reach the ideal state. The EPI, EFI, and CEI increased rapidly with economic development when the GDP per capita was less than US $ 3,000, but the decrease was decelerated after the GDP exceeded US $ 3,000. The EEI and EDI were less affected by economic development, but mainly restrained by the natural conditions and global and regional eco-environmental evolvement.

[Chief physician Lian Yu-lin's experience on treatment of cervical spondylosis by classification].

In clinical teaching practice of over 30 years, professor LIAN Yu-lin combines physiological, pathological and anatomic knowledge with TCM treatment based on syndrome differentiation, forming own unique theoretical system. This paper introduces LIAN's experience on treatment of cervical spondylosis in detail, and location of cervical vertebra three lines and determination of needling depth and reinforcing-reducing manipulation based on clinical manifestations of various types of cervical spondylosis, and combination of long needle with short needle, deep needling with superficially needling, stressing the main point and having a definite object. This is an effective pathway for treatment of cervical spondylosis.