Background: Kidney tumors comprise a biologically diverse and diagnostically challenging group of neoplasms. Many entities share overlapping morphologic features despite having distinct molecular profiles. Although histomorphology remains the cornerstone of diagnosis, molecular biomarker testing has become increasingly important for accurate classification, recognition of emerging entities, identification of hereditary cancer syndromes, and therapeutic decision-making. Focus of the Review: This narrative review provides a practical, pathology-oriented framework for molecular biomarker testing in kidney tumors. It integrates immunohistochemistry, fluorescence in situ hybridization, polymerase chain reaction-based methods, and next-generation sequencing with morphologic assessment. Particular attention is given to diagnostically relevant alterations involving VHL, TFE3, TFEB, MET, FH, ELOC, and ALK, genes encoding SDH subunits, and components of the mTOR signaling pathway, together with commonly used immunohistochemical surrogates. The prognostic and predictive roles of selected biomarkers, including their potential value in hereditary risk assessment and treatment selection, are also discussed. Practical limitations, such as limited biopsy material, intratumoral heterogeneity, and technical variability, are considered. Conclusions: Molecular biomarker testing is reshaping kidney tumor pathology by supporting an integrated diagnostic approach that complements, rather than replaces, careful morphologic evaluation. Its appropriate use can improve diagnostic accuracy, refine clinical stratification, and facilitate the recognition of emerging renal tumor entities with hereditary or therapeutic relevance. Future developments are expected to include methylation profiling, transcriptomic classifiers, liquid biopsy platforms, and artificial intelligence-assisted interpretation.

High-grade serous carcinoma is categorized based on p53 mutation status. A relationship is known to exist between p53 mutations and p53 immunoexpression patterns, including overexpression, complete absence, cytoplasmic, and wild-type patterns. The ubiquitin ligases WWP1 and PARC, known to regulate p53 activation, are hypothesized to influence the pathogenesis of serous ovarian tumors. This retrospective study examined 7 low-grade serous carcinomas, 38 high-grade serous carcinomas, and 15 serous cystadenomas, with immunohistochemical analyses performed for WWP1, PARC, and p53. High-grade serous carcinoma cases were classified into wild-type, cytoplasmic, complete absence, or overexpression categories based on p53 immunohistochemistry. PARC and WWP1 expressions were compared across p53 categories and diagnoses. Results showed a statistically significant reduction in WWP1 and PARC expression in serous carcinomas, with the most pronounced loss observed in high-grade cases. Among morphologically classified high-grade carcinomas, 17 overexpression, 11 complete absence, 6 wild-type, and 4 cytoplasmic p53 cases were identified. A statistically significant relationship was found between PARC, WWP1, and p53 status. Higher expression levels of PARC and WWP1 were detected in p53 wild-type cases, whereas lower expression levels were associated with cases exhibiting p53 overexpression and complete absence. This study suggests that PARC and WWP1 play a role in the pathogenesis of high-grade serous ovarian carcinoma, potentially mediated by p53, making them promising targets for treatment and prognostic markers in serous ovarian cancer.

Aims: Plasmacytoid urothelial carcinoma (PUC) is an aggressive morphological subtype characterized by discohesive single‐cell infiltration and frequent loss of epithelial adhesion. Although p63 is widely regarded as a reliable urothelial lineage marker in conventional urothelial carcinoma, its expression may be reduced or absent in plasmacytoid tumours, creating an important diagnostic pitfall. This multi‐institutional study aimed to characterize the clinicopathological and immunohistochemical profile of PUC, with particular emphasis on p63 immunoreactivity and its relationship to adhesion‐related markers and other diagnostically relevant immunophenotypes. Methods and results: A total of 93 cases initially diagnosed as PUC were retrospectively reviewed across multiple centres. After histopathological re‐evaluation, 70 confirmed cases were included. Immunohistochemical analysis was performed for p63, e‐cadherin, p120 catenin, TRPS1, HER2/Neu . The cohort comprised 70 patients with a median age of 66.5 years (IQR, 59.8–72.0) and a strong male predominance of 85.7% (60/70). Most specimens were obtained from transurethral resections (64.3%, 45/70) and radical cystectomy specimens (34.3%, 24/70). The median tumour size was 3.0 cm (IQR, 1.0–5.0), and the median proportion of plasmacytoid differentiation was 80% (IQR, 20–100). Morphologically, tumours were classified as classic plasmacytoid in 65.7% (46/70), pleomorphic in 22.9% (16/70) and desmoplastic in 11.4% (8/70). Concurrent variant histology was identified in 21.4% (15/70), most commonly micropapillary (12.9%, 9/70) and sarcomatoid (7.1%, 5/70) components. Lymphovascular invasion was present in 51.4% (36/70), and concomitant carcinoma in situ was detected in 35.7% (25/70). Immunohistochemically, p63 expression was retained in only 10.0% of tumours (7/70). HER2 membranous overexpression was observed in 58.6% (41/70), while loss of E‐cadherin expression was highly prevalent (84.3%, 59/70). Aberrant p120 catenin expression was common, with cytoplasmic localization in 72.9% (51/70) and complete loss in 17.1% (12/70). TRPS1 immunostaining was available in 54 tumours and was negative in 92.6% of evaluable cases (50/54). Conclusion: PUC demonstrates a distinctive immunophenotype characterized by frequent loss of p63 and disruption of the e‐cadherin/p120 adhesion complex. Recognition of p63 attenuation, together with adhesion‐related markers and HER2 status, provides a useful diagnostic framework for distinguishing this aggressive subtype from conventional urothelial carcinoma and its mimickers.