Loss of SMARCE1 expression is a specific diagnostic marker of clear cell meningioma: a comprehensive immunophenotypical and molecular analysis

Clear cell meningioma (CCM) is a rare grade II histopathological subtype that usually occurs in young patients and displays high recurrence rate. Germline SMARCE1 mutations have been described in hereditary forms of this disease and more recently in small syndromic and sporadic CCM series. The diagnostic value of SMARCE1 in distinguishing between CCM and other meningioma variants has not been yet established. The aim of our study was to investigate the status of SMARCE1 in a series of CCMs and its morphological mimickers. We compared the performance of an anti‐SMARCE1 antibody and the molecular analysis of the SMARCE1 gene in a retrospective multicenter series of CCMs. All CCMs lossed SMARCE1 immunoexpression. Bi‐allelic inactivating events were found by NGS‐based sequencing in all of these cases, except for one, which was incompletely explored, but had a wild‐type sequence. We then validated the anti‐SMARCE1 antibody specificity by analyzing additional 305 pediatric and adult meningiomas of various subtypes and 15 non‐meningioma clear cell tumors by SMARCE1 immunohistochemistry. A nuclear immunostaining was preserved in all other meningioma variants, as well as non‐meningioma clear cell tumors. In conclusion, our series showed, for the first time, that SMARCE1 immunostaining is a highly sensitive biomarker for CCM, useful as a routine diagnostic biomarker.     

Unusual case of urothelial carcinoma disguised as xanthogranulomatous pyelonephritis and causing reno-colic fistula: Case report and review of literature

Xanthogranulomatous pyelonephritis is a rare and aggressive form of chronic pyelonephritis, it can occur at all age groups but is more common in women than in men, supposedly relating to the increased incidence of urinary tract infections and chronic nephrolithiasis in woman. Computed tomography (CT) findings are very helpful in making the correct diagnosis, but the definitive diagnosis is still based on histology, as there are many differential diagnoses such as renal cell carcinoma and renal tuberculosis. The complications of this type of pyelonephritis are due to the involvement of adjacent organs. The most frequent ones are Psoas abscess, perinephric abscess, and sepsis. Nephrocutaneous and renocolic fistulas are less common. We report a case of a 61-year-old male, who presented to emergency for left-sided lumbar pain for whom radiological investigations confirmed a renocolic fistula complicating xanthogranulomatous pyelonephritis. The diagnosis of XGP was proven by histopathological examination of the nephrectomy specimen slides, but there was also association with an underlying malignant squamous differentiation consistent with urothelial carcinoma, which was not evident on CT. XGP is a rare variant of chronic pyelonephritis with known imaging features. The treatment of choice is nephrectomy and histopathological examination is required for final diagnosis, as there may be associated renal malignancy.     

Interaction of CD154 with different receptors and its role in bidirectional signals

In addition to its classical receptor, CD40, it is now well established that CD154 also binds αIIbβ3, α5β1, and αMβ2 integrins. Although these integrins are all members of the same family, they bind CD154 differently. The current investigation aims to analyze the interaction of CD154 with α5β1 and αMβ2 and investigate its role in bidirectional signals in various human cell lines. Results obtained herein indicate that the CD154 residues involved in the interaction with α5β1 are N151 and Q166, whereas those involved in αMβ2 binding are common to residues required for CD40, namely Y145 and R203. Soluble CD40/CD154 or αMβ2/CD154 complexes do not interfere with the binding of CD154 to α5β1‐positive cells, but inhibit the binding of CD154 to CD40‐ or αMβ2‐positive cells, respectively. Ligation of CD154 on CD154‐positive cells with soluble CD40, αIIbβ3, α5β1, or αMβ2 stimulates intracellular signaling, including MAPK phosphorylation. Given that CD154 exists as a trimer, our data strongly suggest that CD154 may bind concomitantly to two receptors of the same or different family, and biologically activate cells expressing both receptors. The characterization of CD154/receptor interactions helps the identification of new therapeutic targets for the prevention and/or treatment of CD154‐associated autoimmune and inflammatory diseases.     

Molecular epidemiology of invasive and non-invasive group B Streptococcus circulating in Serbia

Streptococcus agalactiae (group B Streptococcus, GBS) remains the leading cause of invasive diseases in neonates and an important cause of infections in the elderly. The aim of this study was to access the prevalence of GBS genito-rectal colonisation of pregnant women and to evaluate the genetic characteristics of invasive and non-invasive GBS isolates recovered throughout Serbia.A total of 432 GBS isolates were tested for antimicrobial susceptibility, capsular polysaccharide (CPS) types and the presence of the hvgA gene. One hundred one randomly selected isolates were further characterized by clustered regularly interspaced short palindromic repeats (CRISPRs) analysis and/or multilocus sequence typing (MLST).The prevalence of GBS colonization in pregnant women was 15%. Overall, six capsular types (Ia, Ib, II to V) were identified, the most common being III (32.2%) and V (25.2%). The hiper-virulent clone type III/ST17 was present in 43.1% and 6.3% (p?<?0.05) of paediatric and adults isolates, respectively. Comparative sequence analysis of the CRISPR1 spacers content indicated that a few clones comprised the vast majority of the tested GBS isolates. Thus, it was estimated that dominant clones recovered from infants were CPS III/ST17 in late-onset infections (19/23; 82.6%), and Ia/ST23 in early-onset disease (44.4%). Conversely, genotype CPS V/ST1 was the most prevalent in adults (4/9; 25.4%). All isolates were susceptible to penicillin. Macrolide resistance (23.1%) was strongly associated with the ermB gene and constitutive resistance to clindamycin (63.9%). The majority of strains was resistant to tetracycline (86.6%), mostly mediated by the tetM gene (87.7%). GBS isolates of CPS V/ST1 and CPS III/ST23 were significantly associated with macrolide and tetracycline resistance, respectively.In conclusion, hyper-virulent CPS III/ST17 and V/ST1 were recognized as dominant GBS clones in this study.     

Complex vesicovaginal fistula. Report of 55 cases]

OBJECTIVE: To specify the clinical and therapeutic peculiarities of complex vesico-vaginal fistulas. MATERIAL AND METHODS: 55 cases of complex vesico-vaginal fistulas are reported. After the clinical diagnostic all the patients had an intravenous excretory urogram. The fistulas were classified according to the Benchekroun classification. RESULTS: The mean age was 34 years (17-70 years). The diagnostic was made clinically in all the patients. Thirteen patients had an abnormal intravenous excretory urogram. The treatment was made by a vaginal way in 45 patients, by an abdominal way in three patients and by a mixed way in two patients. Four patients had an urinary diversion and one refused the treatment. Among the 50 patients whose fistula was treated, 44 (88%) were continent whom 26 (52%) after one operation, 15 (30%) after two operations and three (6%) after three operations. CONCLUSION: The complex vesico-vaginal fistulas as all the vesico-vaginal fistulas are diagnosed clinically. The intravenous excretory urogram is indispensable to search an associated ureteral lesion. The treatment is surgical and usually needs the interposition of a vascularised graft.