Search Results (1,148)

Background/Objectives: Prostate cancer remains one of the most common malignancies in men, and prognosis remains particularly challenging in patients with lymph node metastases. Cyclooxygenase-2 (COX-2), an inducible enzyme involved in inflammation and tumor progression, has been investigated as a potential prognostic biomarker and therapeutic target, but its expression in lymph node metastases remains unclear. While COX-2 overexpression in primary prostate tumors has been reported, its expression in lymph node metastases has not been thoroughly investigated. Therefore, this study aimed to compare COX-2 expression in primary prostate tumors and corresponding lymph node metastases and to evaluate its association with clinicopathological characteristics and survival. Methods: This study included 77 treatment-naïve patients with prostate cancer and histologically confirmed lymph node metastases who underwent radical prostatectomy with extended lymphadenectomy. COX-2 expression was assessed using immunohistochemistry in paired samples from primary tumors and corresponding lymph node metastases. Statistical comparisons were conducted using the Mann–Whitney U test and survival analyses were performed using Kaplan–Meier curves with the log-rank test. Results: COX-2 expression was detected in both primary tumors and lymph node metastases, with no significant difference in staining intensity between the two sites. High COX-2 expression in primary tumors was significantly associated with a higher percentage of involved lymph nodes (30.0% vs. 11.8%, p = 0.026), elevated postoperative PSA levels (1.98 vs. 0.10 ng/mL, p = 0.007), and reduced surgical radicality (11.1% vs. 63.2%, p = 0.008). Moreover, elevated COX-2 expression in both primary and metastatic tissues correlated with worse five-year overall survival (41.7% vs. 92.8%, p = 0.033; and 40.0% vs. 95.6%, p < 0.001, respectively). Conclusions: High COX-2 expression is associated with adverse clinicopathological features and poorer survival in lymph node–positive prostate cancer. The association of COX-2 expression with the extent of lymph node involvement and survival suggests that COX-2 may have prognostic value in this setting. However, the present findings do not establish a causal role of COX-2 in disease progression or lymphangiogenesis. Further studies are warranted to validate the prognostic significance of COX-2 and to clarify its potential biological and therapeutic relevance in lymph node–positive prostate cancer. Full article

Background/Objectives: Nutritional status and adipose tissue-derived mediators have been implicated in the development and clinical characteristics of epithelial ovarian carcinoma; however, studies integrating circulating adipokines, adipokine receptor expression, and nutritional status remain limited. This study aimed to evaluate circulating adipokine concentrations, adipokine receptor expression, nutritional status parameters, and their associations with clinically relevant features and disease stage in women with epithelial ovarian carcinoma. Methods: A total of 151 women were included, comprising 43 patients with epithelial ovarian carcinoma, 89 with benign ovarian tumors, and 19 healthy controls. The nutritional status parameters included body composition, dietary intake, and serum glucose concentration. Circulating adipokines were quantified by ELISA, whereas adipokine receptor expression was evaluated by automated immunohistochemistry in patients with available tumor tissue. Associations with clinicopathological variables were assessed using correlation analyses and multivariable regression models. Results: Compared with women with benign ovarian tumors, women with epithelial ovarian carcinoma had significantly lower circulating leptin concentrations, whereas their circulating resistin concentrations were significantly higher than in healthy controls. In multivariable analysis, lower leptin and higher resistin concentrations were associated with clinical disease classification, while lower leptin was also associated with advanced-stage disease. Visceral fat was associated with clinical disease classification. In addition, AdipoR1 expression was significantly more frequent in malignant than in benign ovarian tumors. Conclusions: Circulating leptin and resistin, visceral fat, and AdipoR1 expression were associated with clinically relevant characteristics across the study groups. Together, these findings provide a more comprehensive characterization of the metabolic and inflammatory alterations associated with epithelial ovarian carcinoma and may contribute to the identification of potential clinically relevant markers. Full article

Background: Homeobox transcription factors regulate developmental programs, cellular plasticity, and tumor progression, yet the role of H2.0-like homeobox (HLX) in prostate cancer (PCa) remains poorly defined. We investigated the clinical significance of HLX and its relationship to the pro-metastatic transcription factor TBX2. Methods: Transcriptomic and clinical datasets from TCGA, MET500, and SU2C/PCF cohorts were analyzed to assess HLX expression, clinicopathologic associations, and its relationship with TBX2. Functional studies in human PCa cell lines included TBX2 gain- and loss-of-function, HLX knockdown, chromatin immunoprecipitation (ChIP), and expression analyses. Shared HLX- and TBX2-associated pathways were evaluated by Reactome enrichment analysis, and Hallmark Gene Set Enrichment Analysis compared castration-resistant prostate cancer (CRPC) bone metastases with high versus low HLX expression (GSE77930; n = 5/group). In vivo relevance was assessed in an orthotopic TBX2 dominant-negative PCa xenograft model. Results: Human PCa datasets showed that HLX expression was elevated in PCa versus normal prostate tissue and associated with higher Gleason grade, lymph node involvement, aggressive molecular subtypes, and shorter disease-free survival. HLX expression also positively correlated with TBX2 across human PCa cohorts. HLX- and TBX2-associated transcriptional programs converged on extracellular matrix organization, cell adhesion, NOTCH, and VEGF-MAPK signaling pathways. Furthermore, HLX-high CRPC bone metastases were enriched for epithelial–mesenchymal transition, NOTCH, TGF-β, inflammatory, angiogenic, hypoxic, and KRAS signaling pathways. Mechanistic studies showed that HLX knockdown suppressed extracellular matrix-associated genes and key NOTCH pathway components. ChIP demonstrated direct TBX2 binding to the HLX promoter, and genetic modulation of TBX2 expression established HLX as a downstream target of TBX2. Consistent with these findings, reduced HLX expression in orthotopic TBX2 dominant-negative xenografts was associated with loss of metastatic progression. Conclusions: HLX is a candidate biomarker of aggressive PCa and a direct transcriptional target of TBX2. These findings identify a previously unrecognized TBX2–HLX regulatory axis associated with metastatic transcriptional programs and aggressive disease in advanced PCa. Full article

The role of adamalysins (ADAMs) has been widely described in many processes related to carcinogenesis, angiogenesis, inflammation, metastasis, and metabolic disorders. Despite numerous studies, their role in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the expression of selected ADAM genes in colorectal cancer tissue and corresponding surgical margins. In addition, for a subgroup of patients, the expression of selected proteins from the ADAM family was assessed. The final study group consisted of 67 patients who underwent elective surgery for colorectal cancer. The relative expression of the ADAM10, 12, 17, and 28 genes was expressed as relative quantification (RQ) and determined by real-time quantitative PCR (RT-qPCR) in tumor tissue and surgical margins. In addition, for a subgroup of 45 patients, the expression of ADAM10, 12, and 17 proteins was assessed by ELISA. Associations between ADAM expression and clinicopathological parameters were analyzed statistically. ADAM12 gene expression was significantly higher in tumor than in margin tissue (median RQ: 0.995 vs. 0.251; p = 0.003), whereas ADAM28 RQ was significantly higher in the margin (median RQ: 0.400 vs. 0.204; p = 0.021). No significant differences were observed in the expression of the ADAM10, ADAM12, ADAM17, or ADAM28 genes based on tumor stage, sex, substance use, BMI, or age, except for nominally higher ADAM12 gene expression in patients over 65 years of age (p = 0.033). Among patients under 65 years of age with cardiovascular disease (CVD), ADAM28 RQ in tumor tissue was significantly higher than in those without CVD (p < 0.05). In obese patients with CVD, a markedly increased expression of ADAM28 in tumor tissue was observed, regardless of age (1.469 vs. 0.132; p < 0.005). Significant positive correlations were observed between the ADAM10 and ADAM17 RQ, and between the ADAM10 and ADAM28 RQ, in both tumor and marginal tissues (all adjusted p < 0.01). No significant correlations were found between gene expression and corresponding protein levels for ADAM10, ADAM12, or ADAM17. ADAM10, 12, 17, and 28 are poor biomarkers for colorectal cancer, but their significance may increase in patients with comorbid metabolic disorders. The lack of correlation between protein expression and gene expression suggests the contribution of post-transcriptional and post-translational regulatory mechanisms, which justifies further research. Full article

Background/Objectives: Distinguishing parathyroid carcinoma from parathyroid adenoma remains a major diagnostic challenge because these tumors frequently share similar clinical, biochemical, radiological, and histopathological features. Accurate diagnosis is essential for appropriate surgical management, highlighting the need for reliable adjunctive biomarkers. This study evaluated the diagnostic value of tumor angiogenesis, quantified by microvessel density (MVD), for differentiating parathyroid carcinoma from parathyroid adenoma and its association with clinicopathological characteristics. Methods: This retrospective study included 50 patients with primary hyperparathyroidism who underwent surgery at a tertiary endocrine surgery center, including 10 parathyroid carcinomas and 40 parathyroid adenomas. Tumor angiogenesis was assessed by immunohistochemical staining, and MVD was quantified in vascular hot spots using standardized methods. Receiver operating characteristic (ROC) analysis evaluated the diagnostic performance of MVD, while correlations with clinicopathological parameters were analyzed. Results: Parathyroid carcinoma demonstrated significantly higher MVD than parathyroid adenoma (median 901.14 vs. 431.24; p < 0.001). ROC analysis showed excellent diagnostic performance, with an area under the curve of 0.917. Higher MVD was positively associated with Ki-67 expression, preoperative parathyroid hormone and calcium levels, and tumor weight, indicating a close relationship between angiogenesis, tumor proliferation, biochemical disease severity, and tumor burden. No significant associations were observed with age or preoperative phosphate levels. Conclusions: Quantitative assessment of MVD is a promising adjunctive immunohistochemical biomarker for distinguishing parathyroid carcinoma from parathyroid adenoma. Incorporating MVD into conventional histopathological evaluation may improve diagnostic confidence, particularly in morphologically challenging cases. Larger multicenter studies are warranted to validate these findings and further establish the clinical utility of MVD. Full article

Background/Objectives: Angiogenesis plays a central role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Transvaginal Doppler ultrasonography (TVDUSG) offers a non-invasive means of assessing hemodynamic changes associated with neoplastic transformation. This study aimed to evaluate the diagnostic performance of uterine artery (UA) Doppler parameters across the full cervical disease spectrum and their associations with adverse prognostic features and clinicopathological features in CC. Methods: This prospective observational cohort study enrolled 170 patients who were divided into four groups: controls, CIN 1, CIN 2–3, and CC. All underwent TVDUSG prior to treatment. Pulsatility index (PI), resistance index (RI), peak systolic velocity (PS), end-diastolic velocity (ED), PS/ED ratio, ED/PS ratio, and time-averaged maximum velocity were recorded. ROC curve analysis was performed to assess diagnostic performance. Results: PI and RI increased progressively from controls to CC, while ED declined across groups (all p < 0.001). In patients with CC, PI correlated with tumor volume and was elevated in those with advanced-stage, parametrial and lymph node involvement (all p < 0.001). ROC analysis revealed strong diagnostic performance for PI in distinguishing CC from controls (AUC = 0.861, sensitivity 80.0%, specificity 80.4%); however, PI showed limited ability to distinguish cervical cancer specifically from high-grade CIN (AUC = 0.593). Conclusions: UA Doppler parameters, particularly PI, are associated with cervical neoplastic severity and adverse prognostic features in CC. TVDUSG may serve as a practical, non-invasive adjunct in the preoperative evaluation of cervical neoplasia, especially where advanced imaging is unavailable. Full article

Background/Objectives: Chronic inflammation in the tumor microenvironment (TME) promotes immune evasion and metastasis in breast cancer, where the IL-23/IL-17 axis is a key mediator. We investigated the expression of IL-23 in breast cancer and identified a small natural molecule therapeutically targeting this axis. Methods: IL-23 expression and its clinicopathological significance were assessed in a Moroccan breast cancer cohort and the METABRIC dataset. A High-throughput virtual screening of Allium sativum L. compounds was conducted to target the IL-23/IL-17 axis. In vitro, the selected candidate, IL-23RI, was evaluated for its effects on IL-17A and IFNγ production in human PBMCs using flow cytometry, as well as on the migration of MCF-7 and MDA-MB-231 breast cancer cells using wound-healing assays. Results: IL-23 was found to be overexpressed in aggressive breast cancer subtypes and correlated with unfavorable clinicopathological features and a poor prognosis. Elevated IL-23 expression was associated with an immunosuppressive TME, characterized by increased inhibitory immune checkpoints and immunosuppressive chemokines. In silico, IL-23RI demonstrates a high binding affinity for the IL-23 receptor, with a docking score of −7.482 kcal/mol and a binding free energy of −48.80 kcal/mol, stabilized by five hydrogen bonds. In vitro, IL-23RI selectively suppressed IL-17A production by CD4⁺ T cells without affecting IFNγ secretion by both CD4⁺ and CD8⁺ T cells. Furthermore, IL-23RI significantly inhibited the migration of MCF-7 and MDA-MB-231 breast cancer cells. Conclusions: These findings establish the IL-23/IL-17 axis as a critical therapeutic target and present IL-23RI as a promising dual-function agent for breast cancer treatment, concurrently modulating immunity and inhibiting tumor cell migration. Full article

Background and Clinical Significance: Proliferative fasciitis (PF) is an infrequent benign fibroblastic/myofibroblastic proliferation that may closely resemble a soft tissue sarcoma, creating a diagnostic dilemma out of proportion to its biological behaviour. Because no single clinical, histological or immunohistochemical feature is diagnostic, accurate classification depends on the integration of complementary findings. We describe a challenging case of PF involving the lower leg and present a practical clinicopathological approach to its evaluation. Case Presentation: A 34-year-old man presented with a painless subcutaneous nodule on the lateral aspect of the left lower leg, discovered incidentally. Clinical examination suggested a benign superficial soft-tissue lesion, and because no features raised suspicion for malignancy, complete excision was performed without preoperative imaging. Gross examination revealed a 1.9 × 1.6 × 0.7 cm fascial-based lesion composed of spindle cells and scattered ganglion-like cells within a variably myxoid stroma. Focal nuclear pleomorphism, typical mitotic activity (2 mitoses/10 high-power fields), and limited extension into adjacent adipose tissue broadened the differential diagnosis. Immunohistochemistry demonstrated focal SMA positivity, weak focal desmin and S100 expression, absence of CD31 and CD34 staining, and a low Ki-67 proliferative index (approximately 2–3%). Negative surgical margins, together with integration of the clinical presentation, gross findings, histomorphology, and immunophenotype, supported the diagnosis of proliferative fasciitis. The patient remains free of local recurrence four months after surgery. Conclusions: PF should be considered in the differential diagnosis of superficial spindle-cell proliferations showing deceptively aggressive histological features. Careful clinicopathological correlation remains the cornerstone of diagnosis and helps distinguish this benign entity from its malignant mimics. The clinicopathological framework proposed in this report may assist pathologists in the systematic evaluation of similar diagnostically challenging lesions. Full article

Background/Objectives: Breast cancer is the most frequent malignant neoplasm in women and presents marked biological heterogeneity. The androgen receptor (AR) has emerged as a biomarker with important prognostic and therapeutic implications, its effect varying according to the molecular subtype. The objective of this study was to analyze AR expression in breast carcinoma samples and its relationship with the different molecular subtypes and clinicopathological variables. Methods: An observational, descriptive, cross-sectional, and prospective study was conducted based on the immunohistochemical analysis of 215 formalin-fixed, paraffin-embedded breast carcinoma samples. AR expression was digitally evaluated as the percentage of positive tumor cells after incubation with an anti-AR monoclonal antibody. Results: A high frequency of AR expression was demonstrated in the cohort, with a median of 53.3%. There were statistically significant differences between molecular subtypes (p < 0.001), detecting greater expression in luminal tumors and markedly low levels in triple-negative breast cancer (TNBC) (median 0.41%). A significant negative correlation was evidenced between AR expression and the Ki-67 proliferation index (ρ = −0.272; p < 0.001), both in the overall sample and in the TNBC subgroup. Conclusions: The androgen receptor is associated with specific molecular subtypes and lower tumor proliferation, suggesting a less aggressive phenotype and supporting its role as a biological biomarker and potential therapeutic target in the management of breast cancer. Full article

Integrins are heterodimeric transmembrane receptors that mediate bidirectional signaling and regulate cell–cell and cell–extracellular matrix interactions. Integrin αvβ6 is an epithelial-associated integrin that has emerged as a promising molecular target for PET/CT imaging using integrin αvβ6-directed radiotracers such as ⁶⁸Ga-Trivehexin, and, most recently, for antibody–drug conjugate therapy in epithelial malignancies. Unexpected physiological and incidental uptake within the pituitary gland has been reported in integrin αvβ6-targeted PET studies, including uptake in morphologically normal pituitary glands and pituitary neuroendocrine tumors (PitNETs). However, the histological basis of integrin αvβ6 expression in the human pituitary gland remains poorly understood. The aim of this study is to characterize the immunohistochemical expression of integrin αvβ6 in normal human pituitary tissue and PitNETs and to evaluate its potential implications for integrin αvβ6-targeted imaging and theranostic applications. Five complete adult pituitary glands obtained at autopsy and 28 PitNETs were examined by immunohistochemistry for integrin αvβ6. Staining distribution, intensity, and cellular localization were assessed in the adenohypophysis, neurohypophysis, and Rathke’s cleft remnants. PitNETs were classified according to transcription factor expression (PIT1, TPIT, and SF1). Among the 28 PitNETs, 17 were SF1-lineage (60.7%), three were PIT1-lineage (10.7), two were TPIT-lineage (7.1%), three lacked a dominant transcription factor (10.7%), and three showed plurilineage expression (10.7%). Integrin αvβ6 expression was evaluated semiquantitatively according to staining intensity and the percentage of positive tumor cells. In normal pituitary glands, integrin αvβ6 immunoreactivity was predominantly membranous and localized to larger adenohypophyseal cells irrespective of transcription factor lineage or hormone phenotype. Strong expression was also observed in the epithelial lining cells of Rathke’s cleft remnants, whereas the neurohypophysis lacked detectable integrin αvβ6 expression. Among the 28 PitNETs, integrin αvβ6 expression was detected in 20 cases (71.4%). Positive tumors demonstrated variable staining intensity and extent, ranging from 20% to 100% positive tumor cells. By lineage, integrin αvβ6 expression was detected in 13 of 17 SF1-lineage tumors (76.5%), one of three PIT1-lineage tumors (33.3%), and zero of two TPIT-lineage tumors (0%). Additionally, all three tumors lacking a dominant transcription factor (100%) and all three plurilineage tumors (100%) demonstrated integrin αvβ6 expression. Eleven integrin αvβ6-positive tumors showed expression in ≥50% of tumor cells, and six exhibited strong or diffuse immunoreactivity. Integrin αvβ6 expression in adenohypophyseal cells and Rathke’s cleft remnants provides a histological explanation for physiological pituitary uptake observed on αvβ6-targeted PET/CT imaging. The high prevalence of integrin αvβ6 expression in PitNETs, particularly in a subset demonstrating strong and diffuse immunoreactivity, suggests potential applicability of integrin αvβ6-targeted molecular imaging and theranostic approaches, including both radioligand- and antibody-based strategies. However, these applications remain investigational and require further validation in preclinical and clinical studies. At the same time, physiological integrin αvβ6 expression in normal anterior pituitary tissue may limit imaging specificity and should be considered when developing integrin αvβ6-targeted radioligand therapies. Further clinicopathological and imaging correlation studies are warranted to define the diagnostic and therapeutic role of integrin αvβ6-targeted approaches in PitNETs. Full article

Background/Objectives: The PIM kinase family, comprising three serine/threonine kinase isoforms (PIM1, PIM2, and PIM3), plays a fundamental role in various cancer types, where they are frequently described as regulators of proliferation, survival, and metabolic pathways. Acute leukemia is a group of hematological malignancies characterized by the uncontrolled clonal proliferation of hematopoietic stem cells, encompassing myeloid (AML) and lymphoblastic (ALL) lineages, which together present limited therapeutic options and poor clinical outcomes. This study investigated the correlation between PIM kinase signaling pathways and the clinicopathological features, molecular pathway interactions, and cytogenetic risk stratification of patients with acute leukemia. Methods: Microarray data and clinical information from AML and ALL patients were retrieved from the Gene Expression Omnibus database. The expression levels of PIM1, PIM2, and PIM3 were assessed across leukemia subtypes and cytogenetic risk groups using ANOVA or Kruskal–Wallis tests, with Bonferroni post hoc correction, performed in R (v4.5.1). A transcriptome-wide co-expression analysis was conducted using Spearman’s rank correlation to identify genes correlated with each PIM isoform. Subsequently, Gene Set Enrichment Analysis (GSEA) was performed on pre-ranked gene lists using the clusterProfiler (v4.16.0) package and Hallmarks of Cancer gene signatures, with pathway significance determined by Benjamini–Hochberg-adjusted FDR < 0.05. Results: Transcriptomic analysis revealed distinct expression patterns of the PIM kinase family between AML and ALL subtypes, identifying PIM3 as the predominantly dysregulated isoform, marked by significant overexpression across both lineages. Risk-stratified analysis further demonstrated that PIM expression is highly context-dependent, exhibiting dynamic variation across cytogenetic risk groups. Functional enrichment analysis highlighted a potential functional redundancy and compensatory mechanisms among PIM isoforms, with enriched pathways predominantly associated with stress tolerance, hypoxia adaptation, and inflammatory signaling, rather than classical proliferative signatures. Conclusions: Collectively, these findings position the PIM kinase family as a dynamically regulated axis in acute leukemia, deeply integrated with cytogenetic risk profiles and stress-adaptation mechanisms. The consistent upregulation of PIM3 and its correlation with inflammatory and hypoxic signatures suggest a potential role in facilitating tumor survival within adverse microenvironments. Full article

Incontinentia pigmenti (IP) is a rare, X-linked dominant genodermatosis caused by mutations in the IKBKG gene and characterized by sequential cutaneous stages following the lines of Blaschko. The highly inflammatory initial vesiculobullous stage frequently mimics severe neonatal infections, such as herpes simplex or bullous impetigo, leading to potentially dangerous diagnostic delays and unnecessary antimicrobial therapies. The objective of this report is to highlight the utility of multimodal medical imaging and clinico-pathologic correlation in the rapid diagnosis of early-stage IP. We present the case of a full-term female neonate presenting on the third day of life with a rapidly disseminating blistering eruption, initially treated as a widespread infectious process. A multimodal diagnostic approach was applied, incorporating bedside clinico-dermoscopic evaluation of the infant and her mother (who reported a history of early miscarriages), followed by neonatal skin biopsy, immunohistochemistry (S-100, MART-1), and subsequent genetic testing. Dermoscopy of the neonate’s transitional lesions revealed early dermal melanophage accumulation, while maternal evaluation exposed pathognomonic residual Blaschko-linear dyspigmentation featuring a distinct “pepper-like” dermoscopic pattern. Histopathology demonstrated classic eosinophilic spongiosis, intraepidermal vesicles, and early pigment incontinence. Genetic testing confirmed recurrent IKBKG exon 4–10 deletion. Crucially, this rapid diagnosis facilitated immediate targeted ophthalmologic screening, detecting asymptomatic stage 2B retinal vasculopathy. Integrating noninvasive dermoscopy with precise histopathologic correlation offers a rapid, highly effective framework to distinguish early IP from neonatal blistering infections. Timely multimodal imaging is crucial for triggering immediate multidisciplinary screening, effectively preventing severe, irreversible vision-threatening complications. Full article

Background/Objectives: Antibody–drug conjugates (ADCs) targeting Nectin-4 (enfortumab vedotin) and TROP-2 (sacituzumab govitecan) have transformed the management of advanced urothelial carcinoma (UC), but evidence on their molecular targets in rare non-urothelial bladder carcinomas (N-UC) is scarce. We evaluated the immunohistochemical expression of TROP-2 and Nectin-4 in muscle-invasive UC and N-UC and assessed their association with tumour stage, nodal status and overall survival. Methods: In this retrospective single-centre study, 111 consecutive patients with primary muscle-invasive bladder carcinoma (73 UC, 38 N-UC including squamous, adenocarcinoma, neuroendocrine and sarcomatoid variants) were analysed. TROP-2 and Nectin-4 expression was quantified using the H-score; positivity was defined as ≥15. Marker expression was correlated with clinicopathological characteristics and overall survival (OS) using chi-squared, linear-by-linear, log-rank, and Cox regression analyses. Results: TROP-2 positivity was observed in 46.6% of UC and 36.8% of N-UC (p = 0.925); Nectin-4 positivity in 17.8% and 28.9%, respectively (p = 0.275). Among positive cases, TROP-2 H-scores were higher in N-UC than in UC (mean 109 vs. 70; Mann–Whitney p = 0.045; Cliff’s delta 0.37, 95% CI 0.05–0.66); as no adjustment for multiple testing was applied, this difference is regarded as nominally significant and exploratory. Nectin-4 H-scores were numerically higher in UC (mean 82 vs. 53) but did not reach statistical significance (p = 0.84). Across the cohort, TROP-2 expression increased with advancing T stage (linear-by-linear p = 0.026) and was associated with nodal involvement (p = 0.043). Nectin-4 showed no significant stage association. Sarcomatoid carcinomas were negative for both markers. Median OS was 41 months in UC versus 19 months in N-UC (p = 0.668). Neither marker independently predicted OS, whereas advanced T stage (p = 0.003) and nodal involvement (p = 0.021) were significantly associated with poorer survival; T stage remained independently prognostic in multivariable analysis. Conclusions: TROP-2 and Nectin-4 are expressed at comparable rates in muscle-invasive UC and rare N-UC, except in sarcomatoid variants. TROP-2 expression increased with advancing tumour stage, suggesting stage-dependent regulation in muscle-invasive disease. Therefore, both markers should be interpreted as potential therapeutic targets whose expression can be demonstrated in these tumours, rather than as prognostic biomarkers or as validated predictive biomarkers of ADC response; because no patient received an ADC, the present study cannot determine whether expression predicts clinical benefit, and this distinction requires prospective, treatment-linked evaluation that includes patients with N-UC. Full article

Oligodendroglioma-like morphology, classically recognized by round nuclei, optically clear cytoplasm, and perinuclear halos, is one of the most familiar patterns in neuropathology but also one of the most diagnostically misleading. Although historically associated with oligodendroglioma, this phenotype is now recognized across a wide spectrum of neoplastic and non-neoplastic central nervous system lesions, including adult-type diffuse gliomas, ependymal tumors, pediatric-type low-grade gliomas, glioneuronal and neurocytic tumors, metastatic clear-cell neoplasms, demyelinating disease, and subacute infarcts. The 2021 WHO Classification of CNS Tumors has consolidated a diagnostic framework in which histology remains indispensable, but no longer sufficient, for tumor classification. In this setting, oligodendroglioma-like morphology should be interpreted as a morphological clue that prompts a differential diagnosis and guides ancillary testing rather than as a definitive diagnostic category. This review provides a practical integrated approach to CNS tumors and tumor-like lesions with oligodendroglioma-like or clear-cell morphology. We summarize the major diagnostic mimics of oligodendroglioma, highlighting first-line immunohistochemical panels, and proposing a tiered molecular workflow to identify the conditions in which genome-wide DNA methylation profiling becomes essential. Particular emphasis is placed on clinico-pathological correlation and on red flags that should prompt reconsideration of a conventional oligodendroglioma diagnosis. Full article

Background/Objectives: Paragangliomas (PGLs) are rare neuroendocrine tumors, and data describing them from a medical oncology perspective are limited. We characterized clinicopathological features, tumor localization, and treatment outcomes. Methods: We retrospectively analyzed 43 patients with PGL at a single medical oncology department. The primary endpoint was recurrence-free survival (RFS), defined as time to first recurrence or death from any cause; overall survival (OS), objective response rate (ORR), disease control rate (DCR), and prognostic associations were secondary. Results: Median age was 44 years, 60.5% were female, and tumors were sympathetic (extra-adrenal) in 55.8% and parasympathetic (head and neck) in 39.5%. After a median follow-up of 116.8 months, 40 patients (93.0%) underwent resection, among whom 14 RFS events occurred (13 recurrences, 1 unrelated death). Median RFS and OS were not reached (60-month RFS, 67.1%; 120-month OS, 83.3%). Among nine patients receiving first-line systemic therapy (eight response-evaluable), ORR was 12.5% and DCR 37.5%. In exploratory univariable analysis, a Ki-67 index ≥ 3% correlated with recurrence (time-averaged hazard ratio, 4.53; 95% CI, 1.55–13.19; p = 0.006), alongside an R1 resection margin (not significant after Bonferroni correction). Conclusions: These findings may support further evaluation of Ki-67 within risk-adapted surveillance but do not replace germline testing. Full article