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Myointimoma is an uncommon, benign soft-tissue tumor derived from the intimal cells of blood vessels. Since little is known about this rare tumor entity, our aim is to describe an additional case and to perform the first literature review on this topic. A 49-year-old Caucasian man presented with a 12-month history of a palpable, firm, solitary lesion involving the glans penis. On physical examination, there was a 1 cm palpable, endophytic well-circumscribed nodule located to the left side of glans penis, close to the coronal sulcus, with disease-free external urethral orifice. The patient was submitted to complete excisional biopsy. A skin rhombus measuring 1.1 × 0.8 × 0.3 cm was removed and the biopsy sample, fixed in 10% formaldehyde, sent to Pathology. At the 18-month follow-up visit, the patient was clinically disease free. Histopathology revealed a multinodular intravascular proliferation of the corpus spongiosum. This myointimal proliferation comprised bland predominantly spindle cells in an abundant fibromyxoid stroma. Immunostains for smooth muscle actin (1A4), cytokeratins (AE1/AE3, CAM5.2), and CD34 were carried out using the avidin-biotin complex (ABC) immunoperoxidase method. Lesional cells displayed positivity for smooth muscle actin and negativity for cytokeratins and CD34. Myointimoma is confirmed to be a penile benign lesion that may be adequately treated with excisional biopsy. Even after incomplete or marginal removal, the penile lesion has been shown to remain stable overtime or regress. Differential diagnosis is essential to exclude similar histologic entities that could be more aggressive or have possible systemic implications.

Simple Summary Urothelial bladder cancer (BC) is one of the most fatal cancers, with a dismal five-year survival rate of 5% in patients with metastatic disease. Clinically relevant benefits of immunotherapy in advanced or metastatic bladder cancer have led to Food and Drug Administration (FDA) approval of immune checkpoint inhibitors (ICIs) as second- or first-line therapy in patients unresponsive to or ineligible for standard treatment. The advantage of ICIs is being investigated in various stages of BC, either as monotherapy or in combination with other drugs. In this review we discuss the role of ICIs in BC, highlighting their current clinical application and outlining future therapeutic perspectives. Abstract Bladder cancer (BC) is the most common malignancy of the genitourinary tract, with high morbidity and mortality rates. Until recently, the treatment of locally advanced or metastatic urothelial BC was based on the use of chemotherapy alone. Since 2016, five immune checkpoint inhibitors (ICIs) have been approved by the Food and Drug Administration (FDA) in different settings, i.e., first-line, maintenance and second-line treatment, while several trials are still ongoing in the perioperative context. Lately, pembrolizumab, a programmed death-1 (PD-1) inhibitor, has been approved for Bacillus Calmette–Guérin (BCG)-unresponsive high-risk non-muscle invasive bladder cancer (NMIBC), using immunotherapy at an early stage of the disease. This review investigates the current state and future perspectives of immunotherapy in BC, focusing on the rationale and results of combining immunotherapy with other therapeutic strategies.

Our understanding of aetiological factors associated with urinary bladder cancer has radically improved over the last decades. Cigarette smoking is considered the most important risk factor, even in the industrialised world, while various occupational and environmental exposures to chemicals are also held responsible. The link between bladder cancer and schistosomiasis, highly prevalent in sub-Saharan Africa, Sudan, Egypt, and Yemen, provides input for investigating and potentially preventing bladder carcinogenesis. Growing concern regarding environmental diseases prompts investigation into the historical milestones that have helped disentangle the relationships between health and environment.

Background and objectives: Angiosarcomas are uncommon and extremely aggressive malignancies derived from vascular endothelial cells. Although they can occur anywhere in the body and at any age, they are more frequently found in the skin of the head and neck regions and in the elderly. Few cases have been recorded in deep soft tissues and in parenchymal organs. Angiosarcomas of the urinary bladder are exceedingly rare. They usually arise in adult patients with a history of radiation therapy, cigarette smoking, or exposure to chemical agents (e.g., vinyl chloride). Despite multidisciplinary treatment approaches combining surgery, radiotherapy, and chemotherapy, prognosis is dismal. Materials and Methods: We describe a case of a 78-year-old Caucasian man presenting with a vesical mass incidentally discovered with abdominal computerized tomography (CT). He underwent transurethral resection of the bladder (TURB), and histology was compatible with angiosarcoma. Results: The patient had been a heavy smoker and his medical history included therapeutic irradiation for prostate cancer eight years previously. Radical cystoprostatectomy was feasible, and pathologic examination of the surgical specimen confirmed angiosarcoma involving the urinary bladder, prostate, and seminal vesicles. Post-operative peritonitis resulted in progressive multi-organ failure and death. Conclusions: Angiosarcoma primary to the urinary bladder is seldom encountered, however, it should be considered in the differential diagnosis of vesical tumors, especially in elderly men with a history of pelvic radiotherapy.

Brain-Derived Neurotrophic Factor (BDNF) and its rs6265 single nucleotide polymorphism (SNP) play an important role in post-stroke recovery. We investigated the correlation between BDNF rs6265 SNP and recovery outcome, measured by the modified Barthel index, in 49 patients with stroke hospitalized in our rehabilitation center at baseline (T0) and after 30 sessions of rehabilitation treatment (T1), moreover, we analyzed the methylation level of the CpG site created or abolished into BDNF rs6265 SNP. In total, 11 patients (22.4%) were heterozygous GA, and 32 (65.3%) and 6 (12.2%) patients were homozygous GG and AA, respectively. The univariate analysis showed a significant relationship between the BDNF rs6265 SNP and the modified Barthel index cut-off (&chi, 2(1, N = 48) = 3.86, p = 0.049), considering patients divided for carrying (A+) or not carrying (A&minus, ) the A allele. A higher percentage of A&minus, patients obtained a favorable outcome, as showed by the logistic regression model corrected by age and time since the stroke onset, compared with the A+ patients (OR: 5.59). At baseline (T0), the percentage of BDNF methylation was significantly different between GG (44.6 &plusmn, 1.1%), GA (39.5 &plusmn, 2.8%) and AA (28.5 &plusmn, 1.7%) alleles (p &lt, 0.001). After rehabilitation (T1), only patients A&minus, showed a significant increase in methylation percentages (mean change = 1.3, CI: 0.4&ndash, 2.2, p = 0.007). This preliminary study deserves more investigation to confirm if BDNF rs6265 SNP and its methylation could be used as a biological marker of recovery in patients with stroke undergoing rehabilitation treatment.

Erdafitinib is the first orally administered pan-fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the Food and Drug Administration (FDA).Specifically binding to FGFR family (FGFR-1 to FGFR-4), erdafitinib leads to reduced cell signaling and cellular apoptosis. Coupled with the ability to bind to vascular endothelial growth factor 2 (VEGFR-2), KIT, Fms-related tyrosine kinase 4 (FLT4), platelet-derived growth factor receptor α and β (PDGFR-α and PDGFR-β), RET and colony-stimulating factor 1 receptor (CSF-1 R), erdafitinib has further reported antitumor features causing cell killing.In this review, we provide a comprehensive overview of erdafitinib chemical structure, pharmacologic properties, and current knowledge of clinical efficacy in the treatment of locally advanced or metastatic urothelial carcinoma. This treatment, recently approved in the U.S., is available for adult patients harboring FGFR2/FGFR3 genetic alterations who progressed within 12 months of an adjuvant or neoadjuvant chemotherapy regimen including platinum or progressed during or after prior a chemotherapy regimen including platinum.

Background Inverted urothelial papilloma (IUP) of the upper urinary tract is an uncommon benign tumour that occasionally presents as a polypoid mass causing urinary obstruction. Histologically, IUP is characterised by a proliferating urothelium arranged in cords and trabeculae, in continuity with overlying intact epithelium, and extending into the lamina propria in a non-invasive, endophytic manner. Cytological atypia is minimal or absent. Top differential diagnoses include urothelial carcinoma with inverted growth pattern and florid ureteritis cystica. Although urothelial carcinomas of the upper urinary tract with prominent inverted growth pattern commonly harbour microsatellite instability, the role of the mutator phenotype pathway in IUP development is still unclear. The aim of this study was to describe two additional cases of IUP of the upper urinary tract, along with an extensive literature review. Case presentation We observed two polypoid tumours originating in the renal pelvis and the distal ureter, respectively. Both patients, a 76-year-old woman and a 56-year-old man, underwent surgery because of the increased likelihood of malignancy. Histology was consistent with IUP and patients are alive and asymptomatic after long-term follow-up (6 years for the renal pelvis lesion and 5 years for the ureter lesion). The tumours retained the expression of the mismatch-repair protein MLH1, MSH2, and PMS2 whereas loss of MSH6 was found in both cases. Conclusions When completely resected, IUP does not require rigorous surveillance protocols, such as those for urothelial carcinoma and exophytic urothelial papilloma. It is therefore important for the surgical pathologist to be aware of this rare entity in order to ensure correct patient management.

Metastatic prostate cancer is the most common cancer in males and the fifth cause of cancer mortality worldwide. Despite the major progress in this field, leading to the approval of novel anti-androgens, the prognosis is still poor. A significant number of patients acquire an androgen receptor splice variant 7 (AR-V7), which is constitutively activated and lacks the ligand-binding domain (LBD) while maintaining the nuclear localization signal and DNA-binding domain (DBD). This conformational change, even in the absence of the ligand, allows its retention within the nucleus, where it acts as a transcription factor repressing crucial tumor suppressor genes. AR-V7 is an important oncogenic driver and plays a role as an early diagnostic and prognostic marker, as well as a therapeutic target for antagonists such as niclosamide and TAS3681. Anti-AR-V7 drugs have shown promise in recent clinical investigations on this subset of patients. This mini-review focuses on the relevance of AR-V7 in the clinical manifestations of castration-resistant prostate cancer (CRPC) and summarizes redemptive therapeutic strategies.

Inflammation is inherent in prostatic diseases and it is now accepted that it may facilitate cellular proliferation in both benign and malignant conditions. The strong relationship between prostatic inflammation and pathogenesis of benign prostatic hyperplasia (BPH) is supported by epidemiologic, histopathologic and molecular evidence. Contrariwise, the role of inflammation in prostate carcinogenesis is still controversial, although current data indicate that the inflammatory microenvironment can regulate prostate cancer (PCa) growth and progression. Knowledge of the complex molecular landscape associated with chronic inflammation in the context of PCa may lead to the introduction and optimization of novel targeted therapies. In this perspective, evaluation of the inflammatory component in prostate specimens could be included in routine pathology reports.

The current WHO/ISUP classification and grading system subdivides urothelial tumours into prognostically distinct categories. Understanding the molecular pathways involved in bladder cancer development can improve patient stratification and management. This study aims to investigate the relationship between Snail, Slug and E-cadherin expressions and clinico-pathological features of non-muscle invasive bladder carcinoma (NMIBC). All patients attending the same urological centre from January to May 2002, who were pathologically diagnosed with NMIBC, were enrolled in this longitudinal cohort study. E-cadherin, Snail and Slug protein expressions were assessed by immunohistochemical analysis and compared with follow-up data. The main outcome measures were recurrence and progression rates. The cohort under investigation included 43 patients (38 men and 5 women, mean age 67.7 ± 10.6 years). High-grade (HG) carcinomas were 20/43, with 10 invasive cases (pT1). Low-grade (LG) carcinomas were 23/43, with no invasive cases (pTa). Among the eight HGpTa cases with recurrence, strong Snail expression was detected in six (75%). Out of the 17 LGpTa patients who experienced recurrence, 12 (70.6%) showed strong positivity for Snail. Among the 10 HGpT1 cases, recurrence was observed in 4, of which, 3 (75%) stained intensely for Snail. The Kaplan-Meier curves showed significantly different recurrence rates for patients with strong or weak Snail reactivity (p = 0.027). E-cadherin and Slug expression did not correlate with any of the parameters considered. On multivariate analysis, Snail expression was recognised as an independent prognostic factor for tumour recurrence (p = 0.003). In our study population, Snail immunohistochemical overexpression proved to be related to tumour recurrence in patients affected by NMIBC.