Urogenital Tumors Research Articles

Pathology and molecular pathology of carcinoma of the penis

Penile carcinoma exhibits significant geographic variation in incidence, ranking 30thglobally among newly diagnosed cancers with an annual rate of 0.84 cases per 100,000 men. Particularly high incidence rates of up to 2.2 are seen in Latin America, Asia, and Africa, largely due to ahigh prevalence of HPV, lower circumcision rates, and inadequate hygiene standards.The 2022 WHO classification of urogenital tumors continues to differentiate penile carcinomas based on their HPV status; however, the subdivision of numerous subtypes especially of the HPV(+) carcinomas was abandoned. This article aims to present current knowledge on the carcinogenesis of HPV(+) and HPV(-) penile carcinomas and their precursor lesions as well as updates from the latest WHO classification.Approximately 50% of penile carcinomas are caused by infection with high-risk HPV subtypes, with positive p16 immunohistochemistry serving as agood surrogate marker for HPV(+) tumors. HPV(-) carcinomas frequently show TP53 mutations and are associated with apoorer prognosis.While localized penile carcinomas have arelatively good prognosis, survival rates in metastatic cases remain poor. Neither microsatellite instability nor mismatch-repair deficiency appear to play arole, but up to 62.2% of tumors express PD-L1. Currently, immune checkpoint inhibitors such as Avelumab and Ipilimumab, along with antibody-drug conjugates targeting TROP2 and Nectin‑4, are being tested in clinical trials, potentially leading to the approval of targeted therapies for metastatic penile carcinoma in the future.

Cell-Free Carbonic Anhydrase IX mRNA in Urine as Biomarker for Urogenital Cancers: The Relationship Between Urinary Extracellular RNA and Tumor-Cell-Associated RNA.

Circulating tumor cells and cell-free nucleic acids are novel diagnostic, prognostic and predictive tools for non-invasive and cost-effective cancer detection in liquid biopsy. Carbonic anhydrase IX (CAIX) has been proposed as a biomarker in urogenital tumors and urine sediment. Our aim was to evaluate CAIX full-length percentage (CAIX FL%) in urine-cell-free RNA (cfRNA) and its relationship with tumor-cell-associated RNA (TC-RNA). CAIX FL% was quantified by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in patients with prostate, kidney or bladder carcinoma. When cfRNA and TC-RNA were analyzed, CAIX FL% was significantly higher in urine samples from cancer patients than from controls. Using a 10% cutoff for CAIX FL%, specificity, sensitivity, positive and negative predictive values, as well as accuracy for TC-RNA were higher than for cfRNA in all urogenital cancers, but varied according to tumor type. CAIX FL% distribution in TC-RNA differed significantly (p < 0.001) between control and tumor samples (37.5% and 96.2%, respectively); similar results were obtained for each tumor type. Additionally, the 10% cutoff showed a 77.9% concordance between TC-RNA and cfRNA. In conclusion, urine is proposed as an alternative biofluid for investigating CAIX FL% in urogenital cancers, and this parameter can be reliably measured as cfRNA and TC-RNA with different predictive capabilities depending on tumor type.

Systematic Characterization of Splicing Dysregulation in Pan Solid Tumor Transcriptome.

Splicing dysregulation arising from spliceosomal mutations contributes to disease progression and treatment resistance, mostly in hematologic malignancy. Whereas spliceosomal mutations are less common in solid tumors, splicing disorders are pervasive and proven to promote tumorigenesis. However, there is a lack of systematic understanding of the overall splicing dysregulation patterns and how widespread different patterns occur within or across solid tumor lineage. To address these questions, a computational method called SMNPLS (Sparse Multi-Network Regularized Partial Least Squares) is developed to uncover the pan-cancer splicing dysregulation landscape by extracting joint modular patterns from paired matrices of splicing factors (SFs) expressions and alternative splicing events (ASEs). Six unique patterns illustrated by ASE-SF co-modules are summarized, which involve 1,570 ASEs and altered expression of 170 SFs, covering 40% of TCGA solid tumors. Cross-cancer commonalities of splicing dysregulation are observed among digestive system neoplasms, renal-associated tumors, and urogenital tumors. By contrast, brain tumors demonstrate a distinct splicing pattern with the highest ASE-SF correlation. In addition, some new splicing regulatory relationships are identified that are potentially oncogenic. Overall, the study characterizes the full spectrum of splicing dysregulation patterns, indicating the similarity and specificity of splicing-derived pathogenesis across 31 human solid tumors.

Comprehensive Genomic Analysis of Puerarin in Inhibiting Bladder Urothelial Carcinoma Cell Proliferation and Migration.

Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218μmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

PET/MRI in Urogenital System Tumors: How Helpful is it?

PET/MRI in Urogenital System Tumors: How Helpful is it?

Dual-Energy Computed Tomography in Urological Diseases: A Narrative Review.

Dual-Energy computed tomography (DECT) with its various advanced techniques, including Virtual Non-Contrast (VNC), effective atomic number (Z-eff) calculation, Z-maps, Iodine Density Index (IDI), and so on, holds great promise in the diagnosis and management of urogenital tumours. In this narrative review, we analyze the current status of knowledge of this technology to provide better lesion characterization, improve the staging accuracy, and give more precise treatment response assessments in relation to urological tumours.

Occurrence of cancer in people with intellectual disabilities in Germany.

1595 Background: Intellectual disability (ID) affects about 1% of the general population, involving approximately 1 million people in Germany. People with ID experience shorter life expectancies and one of the most common causes of death include malignancies (20%). In addition to life-style factors, possibly genetic mutations causing ID may contribute to oncogenesis. Whether individuals with ID have a higher-than-expected risk of cancer in Germany remains unknown. Methods: A cross-sectional study was conducted using nationwide outpatient health insurance data in Germany from 2019. The data set included 438 028 people with ID and 65 762 146 people without ID (0-107 years, male/female). After matching for age, sex, and district code, data from 437 802 people with ID (4.23 % with cancer) and 4 378 020 without ID (5.06 % with cancer) aged 0-95 years were analyzed. Univariate odds ratios estimated the association between ID and cancer occurrence for various cancer diagnoses (ICD-10: C00-C97). The study was approved by the ethics committee of the Berlin Medical Association (Eth-11/23). Results: Across all cancer types, people with ID showed lower risks for a cancer diagnosis than those without ID (Odds Ratio [OR] 0.83; 95% Confidence Interval [95% CI] 0.82-0.84); p &lt; .0001 for all data. Certain cancer types occurred more often, such as malignant neoplasms of the brain (C71; OR 2.80; 95% CI 2.58-3.03), other parts of the central nervous system (C72; OR 2.45; 95% CI 1.76-3.34), the testicles (C62; OR 1.80; 95% CI 1.68-1.93), the ovary (C56; OR 1.26; 95% CI 1.13-1.4), the corpus uteri (C54; OR 2.02; 95% CI 1.86-2.19), leukemia of unspecified cell type (C95; OR 1.86; 95% CI 1.67-2.06) and other leukemia of specified cell type (C94; OR 1.81; 95% CI 1.43-2.25). However, other entities such as malignant melanomas (C43; OR 0.55; 95% CI 0.51-0.59), prostate cancer (C61; OR 0.59; 95% CI 0.56-0.62), tumors in the respiratory system (C30-39; OR 0.69; 95% CI 0.64-0.74) and the breast (C50; OR 0.82; 95% CI 0.79-0.85) occurred less often. Conclusions: People with ID showed a decreased risk for being diagnosed with cancer. This may be caused by lower exposition to certain risk factors in some cancer types such as skin or lung cancers. Difficulties in accessing the health care system and lower cancer screening rates leading to fewer diagnoses may partly explain the results. Later recognition of cancer in a more advanced stage of the disease may be associated with premature deaths and lead to lower prevalence rates. Certain oncological diseases such as malignant neoplasms of the central nervous system, urogenital tumors and hematological neoplasms require a special focus in prevention and therapy. Medical services, screening programs and patient education for people with ID need to be established, adapted and expanded to meet the needs of people with ID and to reach this highly vulnerable population group for guideline-based oncological screening and treatment.

Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities.

The fifth edition of the World Health Organization (WHO) classification for urogenital tumors, released in 2022, introduces some novelties in the chapter on renal epithelial tumors compared to the previous 2016 classification. Significant changes include the recognition of new disease entities and adjustments in the nomenclature for certain pathologies. Notably, each tumor entity now includes minimum essential and desirable criteria for reliable diagnosis. This classification highlights the importance of biological and molecular characterization alongside traditional cytological and architectural features. In this view, immunophenotyping through immunohistochemistry (IHC) plays a crucial role in bridging morphology and genetics. This article aims to present and discuss the role of key immunohistochemical markers that support the diagnosis of new entities recognized in the WHO classification, focusing on critical topics associated with single markers, in the context of specific tumors, such as the clear cell capillary renal cell tumor (CCPRCT), eosinophilic solid and cystic renal cell carcinoma (ESC-RCC), and so-called "other oncocytic tumors", namely the eosinophilic vacuolated tumor (EVT) and low-grade oncocytic tumor (LOT). Their distinctive characteristics and immunophenotypic profiles, along with insights regarding diagnostic challenges and the differential diagnosis of these tumors, are provided. This state-of-the-art review offers valuable insights in biomarkers associated with novel renal tumors, as well as a tool to implement diagnostic strategies in routine practice.

Urogenital tumors following kidney transplantation-monocentric analysis of incidences and overview of urological preventive measures

Urogenital tumors are among the most common solid malignancies after kidney transplantation (TX). We analyzed the incidence and mortality of urogenital tumors after kidney TX in our own patient population as well as answered the question of recommended follow-up necessity and frequency in this cohort. Retrospective monocentric data collection of tumor diseases and the most common urogenital tumors after kidney TX at the Transplant Center Dresden between 2010 and 2020 was done. From this, we derived recommendations for auseful follow-up concept. Atotal of 13% (93/710) of kidney TX patients developed aneoplasm. Older patients (60.1 ± 10.6 vs. 53.8 ± 12.5; p < 0.001), with higher Charlson scores (≥ 4: 68% vs. 46%; p < 0.001) and aprevious tumor history (18% vs. 8%; p < 0.001) were more likely to develop aneoplasm after transplantation. In the multivariate analysis, previous tumor history was found to be an independent predictor of tumor development after renal transplantation (OR 2.2; 95%-KI [1.2-4.1]; p = 0.01). Urogenital tumors accounted for 30% (28/93) of all malignancies. Renal cell carcinoma of the native kidney was the most common (n = 12) neoplasm, followed by prostate cancer (n = 9). Most solid malignancies after kidney TX arise from the urinary tract. Due to their frequency, there is an urgent need for specialized urological therapy and long-term follow-up care. Even before listing for TX, risk factors can be recognized and individual concepts for follow-up care can be developed.

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature.

Eosinophilic solid and cystic renal cell carcinoma is now defined in the 5th edition of the 2022 World Health Organization classification of urogenital tumors. To perform morphologic, immunohistochemical, and preliminary genetic studies about this new entity in China for the purpose of understanding it better. The study includes 18 patients from a regional tertiary oncology center in northern China (Tianjin, China). We investigated the clinical and immunohistochemical features of these cases. The mean age of patients was 49.6 years, and the male to female ratio was 11:7. Macroscopically, 1 case had the classic cystic and solid appearance, whereas the others appeared purely solid. Microscopically, all 18 tumors shared a similar solid and focal macrocystic or microcystic growth pattern, and the cells were characterized by voluminous and eosinophilic cytoplasm, along with coarse amphophilic stippling. Immunohistochemically, most of the tumors had a predominant cytokeratin (CK) 20-positive feature, ranging from focal cytoplasmic staining to diffuse membranous accentuation. Initially, we separated these cases into different immunohistochemical phenotypes. Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling. Group 2 (4 of 18; 23%) was negative for NF2, probably implying a germline mutation of NF2. Group 3 (7 of 18; 38.5%) consisted of the remaining cases. One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

The role of microRNA-186 in urogenital tumors

The role of microRNA-186 in urogenital tumors

Oral Anticoagulants Beyond Warfarin.

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.

Anisomycin inhibits the activity of human ovarian cancer stem cells via regulating antisense RNA NCBP2-AS2/MEK/ERK/STAT3 signaling.

Ovarian cancer stem cells (OCSCs) are the main cause of relapse and drug resistance in patients with ovarian cancer. Anisomycin has been shown to be an effective antitumor agent, but its mechanism of action in ovarian cancer remains elusive. CD44+/CD133+ human OCSCs were isolated from human ovarian cancer tissues. OCSCs were interfered with using anisomycin and specific small-interfering RNA (siRNA). Microarray assay, MTT, in vivo tumorigenic experiments, transwell assay, cell cycle assay, colony formation assay, angiogenesis assay, and hematoxylin and eosin staining were used to detect the mechanism of anisomycin with respect to inhibiting the activity of OCSCs. Expression of the NCBP2-AS2/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK)/signal transducer and activator of transcription 3 (STAT3) pathway was examined using western blotting, a quantitative real-time PCR (RT-qPCR) and immunofluorescence staining. Bioinformatics analysis was used for predictive analysis of NCBP2-AS2 expression in urogenital tumors. Microarray analysis showed that treatment with anisomycin significantly decreased the expression of antisense RNA NCBP2-AS2 in OCSCs. In vitro cellular experiments showed that interfering with endogenous antisense RNA NCBP2-AS2 using siRNA distinctly inhibited the proliferation, migration and angiogenesis of OCSCs, whereas in vivo animal experiments revealed decreased tumorigenesis in nude mice. Moreover, the results of RT-qPCR and western blotting demonstrated that both anisomycin treatment and NCBP2-AS2 silencing led to significant reductions in the mRNA and protein expression levels of NCBP2-AS2, MEK, ERK and STAT3. From a bioinformatic point of view, antisense RNA NCBP2-AS2 exhibited significantly differential expression between urogenital tumors and normal controls, and a similar expression pattern was found in the genes NCBP2, RPL35A, DNAJC19 and ECE2, which have similarity to NCBP2-AS2. Anisomycin suppresses the in vivo and in vitro activity of human OCSCs by downregulating the antisense RNA NCBP2-AS2/MEK/ERK/STAT3 signaling pathway, whereas the antisense RNA NCBP2-AS2 and genes with similarity have the potential to serve as markers for clinical diagnosis and prognosis of urogenital tumors.

New WHO classification 2022: urinary bladder cancer

The new World Health Organization (WHO) classification of urogenital tumors is still primarily based on anatomic location, but is also a hierarchical taxonomic classification without separate chapters for tumors of the upper urinary tract and the urethra. It clarifies aspects regarding grading and noninvasive entities. It consolidates the use of the Paris system for urinary cytology as well as various subtypes/special types of neoplasms, and incorporates general concepts of the 5th edition of the WHO blue book. In addition to mesenchymal tumors, well-differentiated neuroendocrine tumors and neuroendocrine carcinomas are addressed in separate chapters. Papillary non-invasive low- and high-grade carcinomas and carcinoma in situ remain, while dysplasia and urothelial proliferation of unknown malignant potential (UPUMP) are no longer treated as separate entities. Former variants of urothelial carcinoma are now called subtypes and aberrant differentiation and special types are more precisely defined.

Pulmonary metastases in urogenital cancers: Surgical treatment and outcomes

IntroductionMetastasis is remaining one of the major problems in cancer treatment. Like many other malignancies, urogenital tumors originating from kidney, prostate, testes, and bladder tend to metastasize to the lungs.The aim of this retrospective study is to evaluate the operative results and prognosis of pulmonary metastasectomy in patients with primary urogenital tumors. MethodsThis study was approved by the local ethical committee. We retrospectively analyzed the surgical and oncological results of patients who underwent lung resections for urogenital cancer metastases in our department between 2002 and 2018. Demographic data and clinicopathological features were extracted from the medical records. Survival outcomes according to cancer subtypes and early postoperative results of VATS and thoracotomy were analyzed. Results22 out of 126 patients referred for pulmonary metastasectomy to our department had metastases from urogenital tumors. These patients consisted of 17 males and five females. Their metastasis originated from renal cell carcinoma (RCC; n=9), bladder tumor (n=7), testis tumors (n=4), and prostate cancer (n=2). There was no intraoperative complication. Postoperative complications were seen in 2 patients. ConclusionsAlthough pulmonary metastasectomy in various types of tumors is well known and documented, the data is limited for metastases of urogenital cancers in the literature. Despite the limitations of this study, we aim to document our promising results of pulmonary metastasectomy in patients with primary urogenital tumors and wanted to emphasize the role of minimally invasive approaches.

Synthesis and evaluation of radioiodinated estrogens for diagnosis and therapy of male urogenital tumours.

The preparation of 24 estrogens, their estrogen receptor (ER) affinity and studies of radioiodinated estrogen binding to ER-positive male bladder tumor cells (HTB9) are described. The estrogens with the highest affinity were selected using fluorescence anisotropy assays. A 2,2,2-trifluoroethyl group at the 11β-position caused particularly promising affinity. (Radio)iodination was performed on the 17α-vinyl group. Binding studies on HTB9 cells revealed picomolar affinities of radioconjugates 19 and 31, indicating promising ability for targeting of urogenital tumors.

Dry and wet experiments reveal the significant role of FUT11 in clear cell renal cell carcinoma.

Renal cancer is one of the most common urogenital tumors worldwide. Although numerous traditional and relatively new therapeutic strategies have been adopted for clear cell renal cell carcinoma (ccRCC) patients, their effects are not satisfactory enough for the improvement of patients. The pathogenesis and progression of ccRCC requires further investigations. Using a series of bioinformatic analyses, the expression levels, clinical relevance, and prognostic potential of FUT11 as well as its correlations with immune cells in ccRCC were investigated. The mRNA and protein expression levels of FUT11 in renal cancer cell lines and human tissues were determined using quantitative real-time-polymerase chain reaction (RT-PCR) and Western blot analyses. MTT, colony formation, Edu, and wound healing assays were performed to explore the function of FUT11 in renal cancer cell lines. The immunohistochemical staining of human and mouse tissues was performed to reveal the correlations between the expression levels of FUT11 and the infiltration level of immune cell subtypes. Using mouse xenograft models, the role of FUT11 was further investigated in-vivo. The data mining and corresponding analyses indicated that the expression levels of FUT11 were elevated in renal cancer and independently correlated with the prognosis of ccRCC patients. The cibersort and ssGSEA algorithms revealed differential infiltration levels of immune cells between the patients with distinct expression levels of FUT11; these results were verified by the consequent human renal cancer tissues and animal models. The MTT, colony formation, EdU, and wound healing assays showed that the decreased expression level of FUT11 could promote the proliferation and migration of renal cancer cell lines. The animal models-based analysis showed similar results. In conclusion, this study identified a novel important molecule correlated with the prognosis of ccRCC patients and revealed its immune-related role and its function in the proliferation and migration of renal cancer cells. This study might provide a novel basis for the treatment of renal cancer.

Histopathological study of childhood tumors of the urogenital system

Background: Malignancies form one of the important causes of pediatric morbidity as well as mortality. These malignancies are increasingly becoming more important causes of pediatric mortality as deaths from other causes such as infections, malnutrition, and heart diseases are decreasing due to advances in field of pediatric medicine. Urogenital tumors form one of the important causes of pediatric urology consultations. This study was done to describe the spectrum and clinicopathologic features of childhood tumors of the urogenital tract in our institution. Aims and Objectives: The aims of this study were as follows: (1) To study the histopathology of childhood tumors of the urogenital system. (2) To describe the clinical, gross, and microscopic features of these tumors. Materials and Methods: This was a retrospective study conducted in the Department of Pathology of Christian Medical College, Vellore, in which children below 18 years of age, in whom biopsies or resections of tumors of the urogenital system was done, were included on the basis of a predefined inclusion and exclusion criteria. Slides of all such specimens were retrieved from the archives of General Pathology. The clinical features were recorded from cases papers. Microscopic and immunohistochemistry findings were studied. Data analysis was done using SPSS 16.0. Descriptive data were reported and compared. Categorical variables were reported using frequency and percentage. Continuous variables were reported using mean ± standard deviation or median (interquartile range) as appropriate. Results: In our study of 100 pediatric patients with urogenital tumors, there were 55 boys (55%) and 45 girls (45%) amongst the studied cases with a M: F ratio of 1:0.81. The most common type of urogenital neoplasm in pediatric age group was found to be Wilms tumor which was seen in 55 (55%) patients. The other common histopathological findings were mature cystic teratoma (13%), mixed germ cell tumor (7%), yolk sac tumor (6%), and rhabdomyosarcoma (6%). Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell renal carcinoma were less common and were seen in one patient (1%) each. Conclusion: Urogenital tumors in pediatric age groups form one of the important causes for pediatric urology consultation. In our study Wilms tumor was most common urogenital tumors followed by mature cystic teratoma, mixed germ cell tumor, yolk sac tumor, rhabdomyosarcoma, and immature teratoma.

Clinical implications of liquid biopsies in urogenital tumors: a narrative review

Background and Objective: Liquid biopsy is a minimally invasive method for cancer management, with diagnostic, prognostic and predictive applications, which can overcome some of the limitations of tissue biopsy. The aim of this review is to present the available literature on the clinical implications of liquid biopsy use in urogenital tumors, specifically in prostate cancers (PCs) and bladder cancers (BCs).

Gonadal tumor development in 46,XX disorders of gonadal development.

Differences/disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. The aim of this study is to report the histological characteristics and immunoexpression patterns of gonadal parenchyma in patients with 46,XX testicular and ovotesticular DSD, with a focus on the detection of germ cell malignancies. Inclusion criteria were SRY-negative 46,XX testicular and ovotesticular DSD with available samples from gonadal biopsy or gonadectomy for the review of histological findings. Gonadal histology was assessed on hematoxylin and eosin-stained sections and immunohistochemical analysis. Histopathological criteria from the last World Health Organization classification of urogenital tumors were used to identify undifferentiated gonadal tissue, gonadoblastoma, and dysgerminoma. Median age at first histological evaluation of gonadal samples was 1.46 years (range: 0.16-16 years). Totally 15 patients were classified as ovotesticular and only 1 as testicular DSD. Most individuals had bilateral ovotestes (12/15). No histological alterations were found in the ovarian parenchyma, while signs of dysgenesis were seen in all cases of testicular parenchyma. In 4/15 ovotesticular DSD, a prepubertal biopsy failed to identify ovarian parenchyma. We detected early prepubertal preinvasive and invasive malignancies in this cohort (five patients had undifferentiated gonadal tissue, five gonadoblastoma, and one dysgerminoma). 46,XX disorders of gonadal development are historically considered at a low risk for germ cell cancer, and the need for assessment of gonadal histology has been questioned. The finding of early germ cell malignancies in our cohort brings awareness and needs further research.