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Objectives To explore the presence of neutrophil extracellular traps (NETs) in inflamed temporal artery biopsies (TABs) of patients with GCA. Methods Ten patients with GCA [five with limited and five with associated generalized vascular involvement, as defined by 18F-fluorodeoxyglucose PET with CT (PET/CT)] and eight with PMR were studied. The presence, location, quantitation and decoration of NETs with IL-6, IL-1β and IL-17A were assessed in TABs at the time of disease diagnosis by tissue immunofluorescence and confocal microscopy. Paired serum levels of IL-6 and IL-17A were also evaluated in all patients. Results All temporal artery biopsies from GCA, but not PMR, patients had NETs located mainly in the adventitia, adjacent to the vasa vasorum. NETs decorated with IL-6 were present in 8/10 TABs of GCA patients, of whom 5 were PET/CT(+) and 3 PET/CT(–) patients. IL-17A(+) NETs were observed in all GCA patients. IL-1β(+) NETs were not detected in any GCA patient. No relation was found between serum IL-6 and IL-17A levels and NETs containing IL-6 and/or IL-17A. Conclusions NETs bearing pro-inflammatory cytokines are present in inflamed GCA-TABs. Future studies with a larger number of patients from different centres will show whether the findings regarding neutrophils/NETs in the TAB are consistent and disclose their clinical impact.

Poromas, and their malignant counterparts, porocarcinomas, harbor recurrent translocations involving YAP1-MAML2, YAP1-NUTM1, and infrequently WWTR1-NUTM1; YAP1-NUTM1 being the most common in porocarcinomas. NUT immunohistochemistry (IHC) can be used to identify NUTM1-translocated tumors. This study sought to investigate potential novel NUTM1-fusion partners among NUT IHC-positive poromas and porocarcinomas.Thirteen NUT IHC-positive poroid tumors (four poromas and nine porocarcinomas) were identified within a multi-institutional international cohort. Next-generation sequencing (NGS) assessed for NUTM1 fusion partners.NGS detected a NUTM1 fusion in 12 of 13 cases: YAP1-NUTM1 (11/12 cases) and WWTR1-NUTM1 (1/12 cases). Two of the cases (2/12) with NUTM1 fusion were not called by the NGS algorithm but had at least one read-spanning YAP1-NUTM1 break point upon manual review. A NUTM1 fusion was not identified in one case; however, the sample had low RNA quality. The following fusion events were identified: YAP1 exon 4::NUTM1 exon 3 in six cases, YAP1 exon 6::NUTM1 exon 2 in one case, YAP1 exon 3::NUTM1 exon 3 in three cases, WWTR1 exon 3::NUTM1 exon 3 in one case, and YAP1 exon 8::NUTM1 exon 3 fusion in one case.While no novel NUTM1 fusion partners were identified within our cohort, 12 of 13 cases had discoverable NUTM1 fusions; YAP1-NUTM1 fusion was detected in 11 cases (92%) and WWTR1-NUTM1 in 1 case (8%). These data corroborate findings from other recent investigations and further substantiate the utility of NUT IHC in diagnosing a subset of poroid neoplasms. In addition, two of our cases harbored fusions of YAP1 exon 6 to NUTM1 exon 3 and YAP1 exon 8 to NUTM1 exon 2, which have not been reported before in poroid neoplasms and indicate novel break points of YAP1.

Originally described in a rare subset of poorly differentiated squamous cell carcinomas termed NUT carcinomas

Epithelioid fibrous histiocytoma (EFH) is a rare cutaneous neoplasm, which is characterized by the presence of rearrangements involving the ALK gene. Although EFH was long considered a variant of fibrous histiocytoma, the identification of its unique genetic signature confirmed that it represents a distinct entity. The aim of the present study was to examine a cohort of ALK-immunoreactive EFH cases to further characterize gene fusion partners. Next generation sequencing detected ALK fusions in 11 EFH cases identified in the pathology archives of two different institutions. The most common fusion partner was DCTN1 (N = 4) followed by CLTC (N = 2) and VCL (N = 2), while the remaining cases harbored fusions involving SPECC1L, PPFIBP1, and PRKAR1A. In one case no fusion was detected by NGS and FISH despite suitable sample quality. Notably, IHC demonstrated positive ALK expression and the level of aligned ALK reads was comparable to the fusion-positive cases. To the best of our knowledge, this is the first report of CLTC as a fusion partner in EFH. The two CLTC rearranged cases in our cohort also represent the first two EFH cases in the literature that involve exon 19 of ALK, instead of exon 20. These findings underscore the remarkable plasticity of ALK as an oncogenic driver and further expand the list of its potential fusion partners in EFH. Lastly this is also the first report of ALK-immunoreactive EFH with no underlying fusion suggesting a fusion independent transcription mechanism as seen in other tumors.

Castleman disease is a rare benign lymphoproliferative disorder that includes a spectrum of distinct histopathological entities. The differential diagnosis of Castleman disease is broad and includes lymphomas, HIV-related lymphadenopathy, autoimmune disorders, and inflammatory liposarcoma. When Castleman disease occurs in the retroperitoneum, the distinction from the inflammatory variant of well-differentiated liposarcoma can be very challenging in small biopsies. Herein we report a case of Castleman disease that presented as a retroperitoneal mass and expressed MDM2 and CDK4 by immunohistochemistry. To our knowledge, this is the first report of Castleman disease staining positively for MDM2/CDK4, and it underscores how immunohistochemistry can potentially serve as a pitfall when differentiating this rare entity from retroperitoneal sarcomas.

Dedifferentiated liposarcoma is a nonlipogenic sarcoma of variable histological grade that frequently arises in association with a well-differentiated liposarcoma. Dedifferentiation occurs in approximately 10% of well-differentiated liposarcomas and is most commonly encountered in the retroperitoneum. Dedifferentiated liposarcoma of the upper respiratory tract is an extremely rare occurrence. Herein, we report a very rare case of low-grade dedifferentiated liposarcoma of the pharynx that presented as a polyp mimicking a benign process clinically and microscopically. We discuss the relevant molecular findings and review the current literature.

Exosomes are extracellular vesicles, enriched in biomolecular cargo consisting of nucleic acids, proteins, and lipids, which take part in intercellular communication and play a crucial role in both physiologic functions and oncogenesis. Bladder cancer is the most common urinary malignancy and its incidence is steadily rising in developed countries. Despite the high five-year survival in patients diagnosed at early disease stage, survival substantially drops in patients with muscle-invasive or metastatic disease. Therefore, early detection of primary disease as well as recurrence is of paramount importance. The role that exosomal biomarkers could play in bladder cancer patient diagnosis and surveillance, as well as their potential therapeutic applications, has not been extensively studied in this malignancy. In the present review, we summarize all relevant data obtained so far from cell lines, animal models, and patient biofluids and tissues. Current literature suggests that urine is a rich source of extracellular vesicle-derived biomarkers, compared with blood and bladder tissue samples, with potential applications in bladder cancer management. Further studies improving sample collection procedures and optimizing purification and analytical methods should augment bladder cancer diagnostic, prognostic, and therapeutic input of extracellular vesicles biomarkers in the future.

Leukocyte guidance by chemical gradients is essential for immune responses. Neutrophils are the first cells to be recruited to sites of tissue damage where they execute crucial antimicrobial functions. Their trafficking to these loci is orchestrated by several inflammatory chemoattractants, including chemokines. At the molecular level, chemoattractant signaling is regulated by the intracellular trafficking of the corresponding receptors. However, it remains unclear how subcellular changes in chemokine receptors affect leukocyte migration dynamics at the cell and tissue level. Here we describe a methodology for live imaging and quantitative analysis of chemokine receptor dynamics in neutrophils during inflammatory responses to tissue damage. These tools have revealed that differential chemokine receptor trafficking in zebrafish neutrophils coordinates neutrophil clustering and dispersal at sites of tissue damage. This has implications for our understanding of how inflammatory responses are self-resolved. The described tools could be used to understand neutrophil migration patterns in a variety of physiological and pathological settings and the methodology could be expanded to other signaling receptors.

It is common knowledge that there are patients who have an uncomplicated cataract surgery with an actual improvement of their visual acuity, but they are dissatisfied with their final visual capacity. It is hypothesized that patients’ preoperative expectations play a significant role in their postoperative perceptions. A systematic review of the recent literature regarding preoperative expectations of patients before lens extraction surgery and their postoperative perceptions as regards the visual outcome was performed based on the PubMed, Medline, Google Scholar, American Academy of Ophthalmology, Nature and Springer databases in September 2017 and data from 14 descriptive and 7 comparative studies were included in this narrative review. The objective of this review is the determination of the relationship between preoperative expectations and postoperative perception of visual outcome, as well as the investigation of predictors of patient satisfaction by understanding the factors that determine preoperative patient expectations. A considerable number of studies evaluate patient expectations before cataract surgery and compare them with postoperative patient perceptions. In conclusion, the final patient’s postoperative perception could be affected both by the actual outcome of the operation and by patient preoperative expectations. Ocular and systemic comorbidity, unrealistic expectations, preoperative spectacle independence, the cost of surgery, and a previous cataract surgery as well as the level of health literacy and age could influence preoperative expectations and predict more accurately patient satisfaction. Taking these factors into consideration could allow surgeons to control the expectations with an extensive preoperative counseling.

Purpose To develop an algorithm for the Fourier analysis of posterior corneal videokeratographic data and to evaluate the derived parameters in the diagnosis of Subclinical Keratoconus (SKC) and Keratoconus (KC). Methods This was a cross-sectional, observational study that took place in the Eye Institute of Thrace, Democritus University, Greece. Eighty eyes formed the KC group, 55 eyes formed the SKC group while 50 normal eyes populated the control group. A self-developed algorithm in visual basic for Microsoft Excel performed a Fourier series harmonic analysis for the posterior corneal sagittal curvature data. The algorithm decomposed the obtained curvatures into a spherical component, regular astigmatism, asymmetry and higher order irregularities for averaged central 4 mm and for each individual ring separately (1, 2, 3 and 4 mm). The obtained values were evaluated for their diagnostic capacity using receiver operating curves (ROC). Logistic regression was attempted for the identification of a combined diagnostic model. Results Significant differences were detected in regular astigmatism, asymmetry and higher order irregularities among groups. For the SKC group, the parameters with high diagnostic ability (AUC > 90%) were the higher order irregularities, the asymmetry and the regular astigmatism, mainly in the corneal periphery. Higher predictive accuracy was identified using diagnostic models that combined the asymmetry, regular astigmatism and higher order irregularities in averaged 3and 4 mm area (AUC: 98.4%, Sensitivity: 91.7% and Specificity:100%). Conclusions Fourier decomposition of posterior Keratometric data provides parameters with high accuracy in differentiating SKC from normal corneas and should be included in the prompt diagnosis of KC.