Multifocality in Testicular Cancer: Clinicopathological Correlations and Prognostic Implications.

There are limited data regarding the significance of multifocality in testicular cancer patients. This study evaluated the relationship between multifocality and clinicopathological features determined at the time of radical orchiectomy. The study involved 280 consecutive patients who underwent radical orchiectomy between 2018 and 2023. Multifocality was defined as a distinct tumor focus characterized by a group of malignant cells > 1 mm, clearly differentiated from the primary tumor mass. Uni- and multivariate logistic regression analyses were employed to investigate the association between multifocality and histopathological parameters along with potential risk factors for clinical stages II + III. Multifocality was identified in 44 (15.7%) patients. Significantly smaller primary tumors were observed in subjects with multifocality (20.0 mm vs. 30.0 mm, p = 0.0001), while those exhibiting monofocality presented a markedly elevated rate of tumors exceeding 4 cm (40.3% vs. 18.2%, p = 0.005). Furthermore, multifocality was associated with a significantly higher rate of primary tumors < 2 cm (52.3% vs. 29.2%, p = 0.003). Univariate logistic regression analysis revealed a substantial decrease in the likelihood of multifocality occurrence in seminoma patients with tumors > 4 cm (OR = 0.38, p = 0.017). Meanwhile, in multivariate logistic regression, multifocality did not emerge as a significant risk factor for clinical stages II + III in either seminoma (p = 0.381) or non-seminoma (p = 0.672) cases. Our study suggests that multifocality holds no substantial prognostic relevance for clinically advanced disease in testicular cancer patients. The findings indicate that multifocality is associated with smaller primary tumors, particularly those measuring less than 2 cm.

Inflammatory Myofibroblastic Tumour of the Urinary Bladder in a Middle-Aged Man-A Case Report of an Unusual Localization of a Rare Tumour.

Inflammatory myofibroblastic tumour (IMT) is a rare tumour with an intermediate biological behaviour. It usually occurs in children and adolescents, primarily in the abdomen or lungs. Histopathologically, IMT consists of spindle cells, i.e., myofibroblasts, and a variable inflammatory component. Localization in the urinary bladder is rare. We are presenting a rare case of IMT in the bladder in a middle-aged man treated by partial cystectomy. A 62-year-old man consulted a urologist because of haematuria and dysuric disturbances. A tumorous mass was detected by an ultrasound in the urinary bladder. CT urography described the tumorous mass at the dome of the urinary bladder measuring 2 × 5 cm. A smooth tumorous mass was cystoscopically observed at the dome of the urinary bladder. Transurethral resection of the bladder tumour was performed. Histopathological analysis of the specimen identified spindle cells with a mixed inflammatory infiltrate; immunohistochemical findings showed positivity for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA) and vimentin. A histopathological diagnosis of IMT was established. It was decided that the patient would undergo a partial cystectomy. A complete excision of the tumour from the dome of the urinary bladder with surrounding healthy tissue was performed. Histopathological and immunohistochemical findings of the sample confirmed the diagnosis of IMT, without the presence of the tumour at the surgical margins. The postoperative course went smoothly. IMT is a rare tumour in adults, especially localised in the urinary bladder. IMT of the urinary bladder is difficult to distinguish from urinary bladder malignancy both clinically and radiologically, as well as histopathologically. If the location and size of the tumour allow it, bladder-preserving surgeries such as partial cystectomy represent a reasonable modality of operative treatment.

The Association of Polymorphisms in Genes Encoding Antioxidant Enzymes GPX1 (rs1050450), SOD2 (rs4880) and Transcriptional Factor Nrf2 (rs6721961) with the Risk and Development of Prostate Cancer.

Background and Objectives: Mounting evidence implicates oxidative damage in prostate carcinogenesis, contributing to modifications of macromolecules that drive cellular malignant transformation. Functional single-nucleotide polymorphisms (SNPs) of enzymes involved in redox homeostasis can disrupt pro-oxidant-antioxidant balance, leading to accumulation of reactive oxygen species and oxidative damage. We investigated the potential role of genetic polymorphisms of antioxidant enzymes glutathione peroxidase 1 (GPX1 rs1050450) and superoxide dismutase 2 (SOD2 rs4880) and regulatory antioxidant protein nuclear factor erythroid 2-related factor 2 (Nrf2 rs6721961) in the susceptibility to prostate cancer development (PC) and prognosis. Materials and Methods: We conducted a case-control study consisting of 235 patients with PC and 240 controls. Gene polymorphisms were determined by quantitative polymerase chain reaction (qPCR) and polymerase chain reaction with confronting two-pair primers (PCR-CTTP) methods. Multiple risk models were composed to inspect the separate and mutual effect of multiple genes and in combination with acquired contributory factors on the risk of PC development. Results: Independently, carriers of at least one SOD2*C allele had increased risk of PC development, which was significantly further amplified in advanced statistical models. When tested in combination, individuals with both SOD2*C allele and Nrf2*C/C genotype were also at increased risk of PC development, which was augmented when combined with acquired contributory factors. During the mean 75 ± 25 months of follow-up, investigated gene polymorphisms did not affect overall survival. Conclusion: Our results suggest that these gene polymorphisms could be used as risk biomarkers of PC evolution.

Clinicopathological and fluorescence in situ hibridisation analysis of primary testicular diffuse large B-cell lymphoma: a single-centre case series.

Primary testicular diffuse large B-cell lymphoma (PT-DLBCL) represents a rare and aggressive extranodal non-Hodgkin's lymphoma (NHL) with some specific features that differ from other NHLs. Formalin fixed, paraffin wax embedded (FFPE) samples of 21 PT-DLBCLs and 30 comparative patients with DLBCL were analysed. All PT-DLBCL patients were treated with rituximab-containing regimens, intrathecal prophylaxis (10 patients), and irradiation of the contralateral testis (9 patients). FFPE samples were additionally analysed by immunohistochemistry (Bcl-2, c-Myc protein expression) and fluorescence in situ hybridisation (FISH) (BCL2 and MYC). The patients with PT-DLBCL (median age 48.5 years), had low frequency of B symptoms (28.6%) and were often diagnosed in I and II Ann Arbor clinical stage (66.0%). The majority of PT-DLBCL (80.9%) had a non-germinal centre B-cell-like immunophenotype. Immunohistochemical staining showed increased c-Myc protein expression in the PT-DLBCL group compared to the control group (p = 0.016). MYC rearrangement was detected in 1 of 14 (7.0%), and MYC amplification in 3 of 14 (21.0%) patients. One of the 14 cases (7.0%) in the PT DLBCL group showed BCL2 rearrangement, and four of 14 (28.05%) cases showed BCL2 amplification. Complete remission (CR) was achieved in 75.0% of PT-DLBCL patients who had superior survival compared to those who did not achieve CR (median 48 vs. 21 months, p = 0.012). Patients with PT-DLBCL express some immunohistochemical, biological, and clinical features that might differentiate them from nodal and extranodal DLBCL patients, indicating the need for a more personalised treatment approach.

Testosterone and dihydrotestosterone levels in the transition zone correlate with prostate volume.

BACKGROUND: There is still no consensus regarding intraprostatic androgen levels and the accumulation of androgens in the hyperplastic prostatic tissue. The current opinion is that intraprostatic dihydrotestosterone (DHT) concentrations are maintained but not elevated in benign prostatic hyperplasia (BPH), while there is no similar data concerning intraprostatic testosterone (T). METHODS: Tissue T (tT) and tissue DHT (tDHT) concentration were determined in 93 patients scheduled for initial prostate biopsy. The criteria for biopsy were abnormal DRE and/or PSA > 4 ng/mL. Total prostate volume (TPV) was determined by transrectal ultrasound (TRUS). During TRUS- guided prostate biopsy, 10-12 samples were collected from the peripheral zone (PZ) and two additional samples were collected from the transition zone (TZ). The samples from the TZ were immediately frozen in liquid nitrogen at -70°C, and transported for tissue androgen determination, using liquid chromatography mass spectrometry (LC-MS). RESULTS: Pathological analysis revealed that prostate cancer (PCa) was present in 45 and absent in 48 patients. In the whole group, there were 42 men with small prostate (TPV < 30 mL) and 51 with enlarged prostate (TPV ≥ 31 mL). The overall average tT level was 0.79 ± 0.66 ng/g, while the average tDHT level was 10.27 ± 7.15 ng/g. There were no differences in tT and tDHT level in prostates with and without PCa. However, tT and tDHT levels were significantly higher in larger, than in smaller prostates (tT: 1.05 ± 0.75 and 0.46 ± 0.29 ng/g, and tDHT: 15.0 ± 6.09 and 4.51 ± 2.75 ng/g, respectively). There were strong correlations between tT and TPV (r = 0.71), and tDHT and TPV (r = 0.74). CONCLUSIONS: The present study confirmed that both T and DHT accumulated in the stroma of enlarged prostates; the degree of accumulation correlated with prostate volume.

Partial versus radical nephrectomy for pT1a renal cancer in Serbia.

PURPOSE: To assess the treatment outcome of pT1a renal tumors, comparing overall survival (OS) in patients treated with radical nephrectomy (RN) and partial nephrectomy (PN), and to examine the rate of utilization of PN in a tertiary institution in Serbia. METHODS: Included were patients treated for pT1a kidney tumors with open RN or open PN during 1996-2013. The inclusion criterion was the pathological tumor stage T1a. Exclusion criteria were higher pathological stages, metastatic presentation, or imperative indications for partial nephrectomy. Patients were followed-up every 3 to 4 months for the first year after surgery, every 6 months until the 5th year, and annually thereafter. RESULTS: 286 patients were included in the study, and PN was performed in 177 (61.9%) of them, whereas RN was performed in the remaining 109 (38.1%). The median follow- up for the entire group was 42.0 months (interquartile range 74.5). There were no statistically significant differences between groups in cancer-specific survival (CSS) (log-rank=0.506; p=0.477). Patients selected for RN were more likely to be older, symptomatic at presentation, and have larger tumors. There was no statistically significant difference in OS between the two groups (log-rank=2.616; p=0.106). In 1996, 20% of the patients were treated with PN; this number increased to 88% in 2013. CONCLUSION: We did not find OS advantage for PN compared to RN in the setting of a developing country. The use of PN is increasing and is now utilized for ∼90% of pT1a renal tumors.

GSTM1-null and GSTA1-low activity genotypes are associated with enhanced oxidative damage in bladder cancer.

OBJECTIVES: To examine the association between gene variants of the detoxifying and antioxidant enzymes glutathione transferase M1 (GSTM1) and glutathione transferase A1 (GSTA1) and the extent of oxidative damage in patients with transitional cell carcinoma (TCC) of the urinary bladder. METHODS: GSTM1 deletion polymorphism was identified by polymerase chain reaction, and the restriction fragment length polymorphism method was used for the single nucleotide polymorphism of GSTA1. Enzyme immunoassay was used to determine markers of DNA (8-hydroxy-2'-deoxyguanosine, 8-OHdG) and lipid (8-epiprostaglandin F2α) oxidative damage in the urine of 80 TCC patients and 60 age-matched controls. RESULTS: Urinary 8-OHdG and 8-epi-prostaglandin F2α concentrations in TCC patients were significantly higher than in controls (P=0.043 and 0.001, respectively). GSTM1 and GSTA1 polymorphisms influence vulnerability to both DNA and lipid oxidation, with the GSTM1-null gene variant having a more pronounced effect. A significant effect of combined GSTM1 and GSTA1 genotypes on the extent of oxidative damage was found only for 8-OHdG (P=0.018). In addition, TCC patients with the most malignant tumors exhibited significantly higher frequencies of GSTM1-null or GSTA1-low activity genotypes, associated with a twofold increase in urinary 8-OHdG concentration (P=0.044). CONCLUSIONS: Our results suggest that absent GSTM1 or reduced GSTA1 antioxidant activity may increase the accumulation of oxidative DNA damage, thereby contributing to the malignant potential of TCC.

Renal cancer and Wegener's granulomatosis: a case report.

Wegener's granulomatosis (WG) is a systemic disorder characterized by necrotizing vasculitis involving the respiratory tract, and in most cases, the kidneys. The most common manifestation of WG in the kidneys is segmental necrotizing glomerulonephritis. The presence of a renal mass as a manifestation of WG is rare. We report a patient with WG in whom a CT scan revealed an infiltrating mass in the lower portion of the left kidney. After surgical exploration, we performed an open radical nephrectomy. Histopathology showed clear cell type renal cell carcinoma (RCC). RCC associated with WG has been reported in only a few cases, and in most of them, the diseases started simultaneously, suggesting common pathogenetic pathways. Long-term immunosuppressive treatment is a known risk factor in the development of malignancies, so occurrence of RCC in WG has been proposed as a side effect of cyclophosphamide treatment. Furthermore, it is important to make a differential diagnosis between RCC and pseudotumors in WG as they cannot be distinguished solely on basis of imaging findings. Due to the higher risk of urologic malignancies, more frequent checkups and screening of WG patients should be considered.

Metastasis of lobular breast carcinoma to the cervix.

Breast cancers without previous dissemination occasionally result in hematogenous metastases in gynecologic organs, particularly in the cervix. This case report examines a multimodally treated lobular breast cancer patient who was 52 months later diagnosed with malignancy in the uterus. After a tumor was detected at the endocervical and isthmic part of the uterus, a complete hysterectomy with bilateral salpingo-oophorectomy was carried out. The malignant cells were highly positive for carcino-embrional antigen and gross cystic disease fluid protein-15, sensitive breast cancer markers. In conclusion, as breast carcinoma can metastasize to atypical places (cervix, endometrium, etc.), regular surveillance of patients should include gynecologic control.