The success rate of small renal mass core needle biopsy and its impact on lowering benign resection rate.

BACKGROUND: Small renal mass (SRM) biopsy remains under-utilized due to stigma. Meanwhile, the alarmingly high benign findings in resected kidney masses highlight the need for improved preoperative diagnosis and patient selection. METHODS: The purpose of this study is to review the success rate of SRM biopsy and to evaluate its impact on patient management. A total of 168 percutaneous image-guided core needle biopsies (CNBs) of SRMs were retrieved at a tertiary academic center between 2015 and 2019. Subsequent treatment choices, side effects and outcomes were retrospectively reviewed. RESULTS: The diagnostic rate of CNB was 86.9%. Benign neoplasms accounted for a significant portion (14.3%) of SRM. Renal cell carcinomas (RCCs) were the most common diagnoses (69.6%) as expected. In biopsy-resection correlation, the positive predictive value of CNB was 100%. Tumor typing and subtyping by CNB were highly accurate, 100% and 98.3% respectively. Nuclear grading for clear cell RCC was accurate in 83.8% cases. The CNB results had significant impact on treatment. Most patients with RCCs underwent either resection (54.1%) or ablation (33.9%), in contrast to observation in benign neoplasms (90.5%). Most importantly, the benign resection rate (3.2%) in this series was much lower than the national average. CONCLUSION: CNB provided accurate diagnoses for the majority of SRMs and revealed benign diagnoses in a subset of clinically suspicious lesions. Employment of CNB in suspicious SRM may help avoid overtreatment for benign lesions.

Activation of Notch1 synergizes with multiple pathways in promoting castration-resistant prostate cancer.

Metastatic castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific mortality. Defining new mechanisms that can predict recurrence and drive lethal CRPC is critical. Here, we demonstrate that localized high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediate-risk prostate cancer, express high levels of nuclear Notch homolog 1, translocation-associated (Notch1) receptor intracellular domain. Chronic activation of Notch1 synergizes with multiple oncogenic pathways altered in early disease to promote the development of prostate adenocarcinoma. These tumors display features of epithelial-to-mesenchymal transition, a cellular state associated with increased tumor aggressiveness. Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in combination with multiple pathways altered in prostate cancer are metastatic and resistant to androgen deprivation. Our study provides functional evidence that the Notch1 signaling axis synergizes with alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for advanced prostate cancer.

[Diagnostic Utility of LEF1 Immunostain in Cytology Specimens of Solid Pseudopapillary Neoplasm of Pancreas].

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare neoplasm. Diagnosis of SPN requires an integrated approach with aid of radiology, biopsy, cytology, and immunohistochemical stains. Although morphological features in combination with nuclear positivity of ß-catenin IHC have been the gold standard of SPN diagnosis, but overlapping morphology and immunohistochemical findings with other entities in differential diagnoses such as pancreatic neuroendocrine tumors and pancreatic ductal adenocarcinoma make the diagnosis of SPN difficult particularly in limited cytology specimens. Lymphoid enhancer-binding factor 1 (LEF1), a key player in the Wnt signaling pathway, has shown promising diagnostic utility in SPN in recent literatures. METHODS: In this retrospective study, we evaluated the diagnostic utility of LEF1 IHC in SPN in cytology specimens. LEF1 IHC was performed and compared with ß-catenin, synaptophysin, and chromogranin immunostains in 13 SPN and 23 pancreatic neuroendocrine tumors (PanNETs) cytology cases with retrievable cell blocks. RESULTS: LEF1 was positive in 13 of 13 (100%) SPNs and was negative in all PanNETs (0%). CONCLUSION: LEF1 shows 100% sensitivity and specificity in cytology specimens for SPN and can be valuable immuno-stain in the diagnosis of SPN in cytology cell blocks.

Conjunctival scrape cytology findings in patients with chronic graft-versus-host disease following allogeneic bone marrow transplantation.

OBJECTIVE: To describe the conjunctival scrape cytology findings in patients with chronic graft-versus-host disease (GVHD). STUDY DESIGN: Conjunctival scrape cytology was performed to find the cause of conjunctivitis in 20 patients with chronic conjunctival GVHD. All patients had chronic ocular symptoms such as foreign body sensation, burning, tearing and red eye. Twenty age-matched bone marrow transplant recipient without GVHD were included as a control group. RESULTS: Scraping yielded a sufficient number of cells. Cytologic findings included atypical epithelial cells; loss of goblet cells; epithelial cells with vacuolated or coarse, granular cytoplasm; squamous metaplasia; and a prominent inflammatory background. CONCLUSION: Conjunctival scrape cytology yields a sufficient number of cells in conjunctival GVHD. This method is useful for the diagnosis of complications associated with conjunctival GVHD and may be helpful in evaluating the response to treatment options.

Touch preparation for rapid onsite evaluations of renal mass biopsies: concordance rate, pearls, and pitfalls.

INTRODUCTION: Core needle biopsy (CNB) of renal masses has not been commonly performed because of the perceived low sensitivity until recent years. Rapid onsite evaluation (ROSE) using touch preparations (TPs) has the potential to improve the yield of CNB, although it can be challenging because of the diverse morphology of various types of renal tumors and native cells. MATERIALS AND METHODS: We retrospectively reviewed percutaneous CNBs of renal masses with ROSE using TPs. ROSE findings were correlated with diagnoses on CNBs. RESULTS: Among the 165 cases identified between August 2016 and August 2019, CNB led to definitive diagnoses in 82.4% (136 of 165) cases. These included renal cell carcinomas (RCCs) (n = 113, 68.5%), benign neoplasms (n = 14, 8.5%), urothelial carcinomas (n = 6, 3.6%), metastatic carcinomas (n = 2, 1.2%) and 1 case of lymphoma (0.6%). Eight cases were indeterminate, including 2 cases positive for oncocytic neoplasm, 2 cases suspicious for RCC, and 4 cases with atypical features. Twenty-one (12.7%) CNBs were negative for tumor. ROSE interpretations for these cases were: malignant (n = 18, 10.8%); positive for neoplasm (n = 6, 3.6%); atypical/lesional/adequate not otherwise specified (n = 113, 68.5%); negative (n = 19, 11.5.0%); and unsatisfactory (n = 9, 5.5%). The overall concordance rate between ROSE and the final CNB diagnoses was 87.3%. CONCLUSIONS: Renal mass CNBs revealed a subset of non-surgical conditions in addition to RCCs. ROSE using TPs showed a high concordance rate with CNB results. Proximal tubular cells, macrophages, and angiomyolipomas are common pitfalls, whereas vacuolated cytoplasm and background are helpful features to confirm low-grade RCCs.

Intravitreal infliximab in experimental endotoxin-induced uveitis.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of ocular inflammation and the level of TNF-alpha is increased in ocular fluids of patients with uveitis. Intravenous infliximab, a monoclonal antibody against TNF-alpha, has been used for the treatment of uveitis with promising preliminary results. The aim of this study was to evaluate the effect of intravitreal injection of infliximab on experimental uveitis. METHODS: Thirty-three white New Zealand rabbits were divided randomly into three groups. Group 1 (n=5) received intravitreal injection of 1 mg/0.1 cc infliximab plus 0.1 cc normal saline, group 2 (n=14) received intravitreal injection of 2 microg Salmonella typhimurium endotoxin plus 1 mg/0.1 cc infliximab, and group 3 (n=14) animals received intravitreal endotoxin 2 microg/0.1 cc plus normal saline 0.1 cc. Inflammation was evaluated by clinical examinations on days 1, 3, 5, and 7 after the injections; measuring the protein concentration and inflammatory cell content of the aqueous humor; and histopathologic examination. RESULTS: No inflammation occurred in group 1 animals. There was a statistically significant difference between group 2 and 3 animals with regard to clinical examination on the third, fifth, and seventh postinjection days. The differences between groups 2 and 3 were significant with regard to aqueous cell counts and protein content at day 7 (p=0.02 and p=0.001, respectively). Histopathologic examination results showed less inflammation in group 2 animals compared to group 3 animals (p=0.009). CONCLUSIONS: The results provide evidence that intravitreal injection of infliximab suppresses ocular inflammation in a rabbit model of severe endotoxin-induced uveitis.

Somatic SMARCB1 Mutation in Sporadic Multiple Meningiomas: Case Report.

Background: Multiple intracranial meningiomas account for <10% of all meningiomas. Familial multiple meningiomas have been linked to germline mutations in two genes: neurofibromatosis type 2 (NF2) and SWIch/Sucrose Non-Fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1). Sporadic multiple meningiomas have been associated with somatic NF2 mutations and, to date, there has been no case related to somatic SMARCB1 mutations. Here, we describe the first case. Case Report: A 45-year-old female suffered a head trauma while snowboarding. Subsequent to her injury, she experienced persistent headache, nausea, vomiting, dizziness, and flashing lights in the right eye. Magnetic resonance imaging (MRI) of her brain revealed multiple intracranial meningiomas. She underwent a two-staged craniotomy to remove frontal/parietal/temporal and occipital extra-axial tumors. Pathology confirmed the masses as meningiomas, WHO Grade I. Tumor genetic testing was positive for SMARCB1 mutation but blood genetic testing was negative for SMARCB1 mutation. Conclusion: In sporadic multiple meningiomas, somatic NF2 mutations are usually the suspected genetic alternations. Our case illustrates that somatic SMARCB1 mutation is another genetic risk factor for sporadic multiple meningiomas, albeit rare.

Receptor activator of NF-κB (RANK)-mediated induction of metastatic spread and association with poor prognosis in renal cell carcinoma.

BACKGROUND: Inhibition of the receptor activator of NF-κB ligand (RANKL) has become a standard of care supportive treatment to prevent skeletal related events in cancer patients. Moreover, RANKL inhibition has been implicated with better survival outcome in lung cancer, while RANKL expression induces tumor progression and metastatic spread in vivo in breast cancer. Whether RANK/RANKL may have an impact on the pathogenesis of clear cell renal cell carcinoma (ccRCC) is currently unknown. PATIENTS AND METHODS: A retrospective tissue micro array (TMA)-study was carried out determining the expression of RANK/RANKL in primary tumors of 306 ccRCC patients. Additionally, 24 ccRCC cell lines were employed for in vitro analyses of the RANK/RANKL axis including cell proliferation, migration and anchorage independent growth. RESULTS: RANK (+) vs. RANK (-) tumors had both worse cancer specific survival (CSS) (6.3 vs. 1.3 years; p < 0.001) and recurrence free survival (RFS) (9.9 vs. 5.8 years; p < 0.001). RANK (+) (HR 2.21; p < 0.001) was an independent prognostic factor for CSS and RFS (HR 4.98; p < 0.001). RANKL treatment resulted in increased proliferation, soft agar growth, and colony formation of RANK (+) RCC cell lines, which could be reversed by treatment with an NF-κB inhibitor and with a combination of osteoprotegrin and RANKL in vitro. CONCLUSIONS: RANK is expressed in ccRCC tissue, correlates with clinicopathological features, survival outcome, and when stimulated with RANKL can induce ccRCC progression in vitro. Consequently, RANKL inhibition combined with standard of care treatment may be a promising approach to improve ccRCC patient's survival.

Q Fever Presented as a Large Retroperitoneal Pseudotumoral Mass.

BACKGROUND: Q fever is an infection caused by Coxiella burnetii, an intracellular organism. Acute infection is most often a benign and asymptomatic process; however, some individuals may go on to develop subacute and persistent localized symptomatic Q fever. As such, the clinical and histopathologic findings of Q fever are widely variable and may be missed if clinical suspicion is not high. CASE PRESENTATION: Herein we report the first case of C. burnetii infection presenting as an isolated retroperitoneal mass. A 61-year-old male underwent axillary-bifemoral bypass surgery. His postoperative course was complicated by the discovery of a large retroperitoneal mass. CONCLUSION: Clinical and histopathologic findings of Coxiella burnetii infection are variable and can be deceiving. These are often nonspecific, especially in its persistent localized infectious stages.

Low CD38 Identifies Progenitor-like Inflammation-Associated Luminal Cells that Can Initiate Human Prostate Cancer and Predict Poor Outcome.

Inflammation is a risk factor for prostate cancer, but the mechanisms by which inflammation increases that risk are poorly understood. Here, we demonstrate that low expression of CD38 identifies a progenitor-like subset of luminal cells in the human prostate. CD38lo luminal cells are enriched in glands adjacent to inflammatory cells and exhibit epithelial nuclear factor κB (NF-κB) signaling. In response to oncogenic transformation, CD38lo luminal cells can initiate human prostate cancer in an in vivo tissue-regeneration assay. Finally, the CD38lo luminal phenotype and gene signature are associated with disease progression and poor outcome in prostate cancer. Our results suggest that prostate inflammation expands the pool of progenitor-like target cells susceptible to tumorigenesis.

p53 Mutation Directs AURKA Overexpression via miR-25 and FBXW7 in Prostatic Small Cell Neuroendocrine Carcinoma.

UNLABELLED: Prostatic small cell neuroendocrine carcinoma (SCNC) is a rare but aggressive form of prostate cancer that is negative for androgen receptor (AR) and not responsive to hormonal therapy. The molecular etiology of this prostate cancer variant is not well understood; however, mutation of the p53 (TP53) tumor suppressor in prostate neuroendocrine cells inactivates the IL8-CXCR2-p53 pathway that normally inhibits cellular proliferation, leading to the development of SCNC. SCNC also overexpresses Aurora kinase A (AURKA) which is considered to be a viable therapeutic target. Therefore, the relationship of these two molecular events was studied, and we show that p53 mutation leads to increased expression of miR-25 and downregulation of the E3 ubiquitin ligase FBXW7, resulting in elevated levels of Aurora kinase A. This study demonstrates an intracellular pathway by which p53 mutation leads to Aurora kinase A expression, which is critically important for the rapid proliferation and aggressive behavior of prostatic SCNC. IMPLICATIONS: The pathogenesis of prostatic SCNC involves a p53 and Aurora Kinase A signaling mechanism, both potentially targetable pathways.

Effect of povidone-iodine concentration and exposure time on bacteria isolated from endophthalmitis cases.

PURPOSE: To determine the in vitro susceptibility of post-cataract surgery endophthalmitis bacterial isolates to different concentrations of povidone-iodine at different exposure times. SETTING: Poostchi Ophthalmology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. DESIGN: Experimental study. METHODS: Ocular-fluid samples obtained from patients diagnosed with postoperative endophthalmitis were submitted to a microbiology laboratory for culture. One milliliter of microbial isolate suspension with a McFarland standard turbidity of 0.5 was mixed with 1 mL of 1%, 2%, 5%, and 10% povidone-iodine solutions. After 1 minute, 5 minutes, and 15 minutes of exposure at 37°C, each solution was transferred to appropriate culture media and incubated at 37°C for 24 hours. RESULTS: Organisms were isolated in 30 (68%) of the 44 patients evaluated. Coagulase-negative Staphylococcus was identified in 14 cases (47%), Streptococcus species in 8 cases (27%), Staphylococcus aureus in 5 cases (17%), Bacillus cereus in 2 cases (6%), and Pseudomonas aeruginosa in 1 case (3%). Higher povidone-iodine concentrations and longer exposure times were more effective than lower povidone-iodine concentrations or shorter exposure in preventing growth of bacterial isolates. The most effective regimens were 5% povidone-iodine for 15 minutes and 10% povidone-iodine for at least 5 minutes. With a high bacterial load, 13% of bacterial isolates remain viable after exposure to 10% povidone-iodine, even with a long exposure time. CONCLUSION: Results indicate that using 5% povidone-iodine for 15 minutes or 10% povidone-iodine for 5 minutes can prevent the growth of most post-cataract surgery endophthalmitis bacterial isolates.