Renal papillary necrosis (RPN) is an uncommon but important cause of hematuria in patients with sickle cell trait. We report a 28-year-old female with sickle cell trait and beta thalassemia who developed recurrent, transfusion-dependent gross hematuria. Despite extensive imaging, endoscopic evaluation, and conservative management, bleeding persisted. Ureteroscopy demonstrated findings consistent with RPN. The patient required intensive multidisciplinary care and 21 units of packed red blood cells. Hematuria ultimately resolved following treatment with oral epsilon-aminocaproic acid. This case highlights the potential severity of RPN in sickle cell trait and supports consideration of antifibrinolytics as salvage therapy in refractory cases.

The annual incidence of papillary thyroid cancer(PTC) has shown a steady increase in the number of cases. Advances in minimally invasive surgical techniques and the growing frequency of late-stage diagnoses have collectively heightened the complexity of PTC management and treatment. Tumor necrosis factor receptor-associated factor-interacting protein (TRAIP) ,which has been implicated in the progression of various malignancies,remains inadequately characterized in terms of its expression patterns and functional roles in papillary thyroid carcinoma. In this study, we implemented a comprehensive experimental strategy integrating tissue-based analyses, cellular functional assays, and in vivo animal models. We constructed a protein-protein interaction network and established stable cell lines with TRAIP overexpression, knockdown, knockout, and mutation. These models were subsequently analyzed using Western blotting and co-immunoprecipitation (co-IP) assays. Experimental results demonstrated significantly upregulated TRAIP expression in PTC. Silencing TRAIP markedly inhibited PTC cell proliferation and migratory potential. BRAF, a critical oncogene in PTC pathogenesis, exhibited a positive correlation with TRAIP expression both in vitro and in vivo. TRAIP was shown to regulate BRAF ubiquitination and was linked to MAPK pathway activation. However, mutation-based studies indicated that BRAF degradation did not occur via TRAIP-dependent ubiquitination. Furthermore, TRAIP was found to physically interact with both TRAF2 and BRAF, with TRAF2 displaying a higher binding affinity for TRAIP than BRAF. Overexpression of TRAIP reduced the interaction between TRAF2 and BRAF, whereas TRAF2 independently mediated BRAF ubiquitination.These findings demonstrate that TRAIP attenuates TRAF2-mediated BRAF ubiquitination, thereby promoting MAPK pathway activation in PTC cells, which subsequently enhances their proliferation and migration.

A20, encoded by tumor necrosis factor alpha-induced protein 3 (TNFAIP3), is a key negative regulator of NF-κB signaling with context-dependent functions in cancer. Its role in renal cell carcinoma (RCC), particularly clear-cell RCC (ccRCC), remains incompletely defined.

Objective: The 2022 WHO classification introduced differentiated high-grade thyroid carcinoma (DHGTC) as a distinct category characterized by high-grade features despite maintained differentiation. Therefore, this study aims to evaluate its clinical characteristics, treatment responses, and the prognostic impact of the Ki-67 proliferation index in this patient population. Methods: We retrospectively reviewed 3100 patients with differentiated thyroid carcinoma (DTC) between 2017 and 2024. From this baseline pool, a total of 56 patients (1.8%) were identified and re-classified as DHGTC based on mitotic count (≥5/2 mm[2]) and/or tumor necrosis. Additionally, 69 DTC patients (2.2%) with an elevated Ki-67 index (>5%) identified from the same baseline pool-representing an overlapping group with the DHGTC cohort-were analyzed to evaluate its clinical significance. Results: In the DHGTC group, tumor necrosis was present in 87.5% and high mitotic activity in 19.6% of cases. While all DHGTC patients were classified as high-risk under 2025 American Thyroid Association (ATA) guidelines, 42.8% showed biochemical or structural incomplete response at the last follow-up and 28.6% required additional salvage interventions. In the broader DTC cohort, Ki-67 ≥ 15% was significantly associated with older age, larger tumor size, extensive invasion, and poorer treatment response (p < 0.05). However, within the DHGTC subset, Ki-67 ≥ 15% was only significantly associated with increased lymphovascular invasion and more extensive surgery. Conclusions: DHGTC carries a significant burden of aggressive histopathological features and a high risk of structural disease persistence or recurrence. While an elevated Ki-67 index (≥15%) serves as an adverse marker in general DTC, its additional prognostic value within the high-grade DHGTC cohort remains inconclusive, potentially obscured by limited statistical power due to small subgroup sizes.

ASPSCR1::TFE3-rearranged renal cell carcinoma (RCC) represents the most common subtype of TFE3-rearranged RCC, yet clinicopathologic and prognostic data remain limited. We analyzed 30 cases confirmed by fluorescence in situ hybridization or RNA-based next-generation sequencing, representing the largest single-center series to date. The cohort demonstrated an overwhelming female predominance, with a median age of 23.6 years. Microscopically, tumors exhibited diverse histological patterns, including papillary, nested, or tubular architectures, with papillary structure being the most prevalent. Tumor cells characteristically showed abundant clear to eosinophilic cytoplasm with discrete cell borders. Psammoma bodies were frequently present. Rare morphologic patterns included TFEB-rearranged RCC-like and cystic changes that, to our knowledge, have not been reported previously. Immunohistochemically, all tested tumors showed nuclear TFE3 positivity, with variable PAX8 expression, weak or absent staining for epithelial markers (CK7 and EMA), and negativity for melanocytic markers (HMB45 and Melan-A). PD-L1 was positive in 4 of 18 cases. Over 5-173 months of follow-up, the 5-year disease-free survival (DFS) rate was 37.9%, while the corresponding overall survival (OS) rate was 61.4%, with 3 patients developing recurrences and 16 developing metastases. Univariate analysis linked larger tumor size (> 4 cm), grossly solid appearance, tumor necrosis, psammoma bodies, microvascular tumor thrombi, high Ki-67 (≥ 5%), advanced stage (≥ III), and synchronous metastasis to worse prognosis. On multivariate analysis, tumor necrosis was independently associated with shorter DFS. Our findings expanded the clinicopathologic, immunohistochemical, molecular, and prognostic spectrum of ASPSCR1::TFE3-rearranged RCC and underscored the importance of precise morphologic and molecular assessment for risk stratification.

A decade into the formal adoption of the World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading system for clear cell renal cell carcinoma (CCRCC) and papillary renal cell carcinoma (PRCC), newer grading concepts, innovative approaches and some issues have emerged. A comprehensive review of the literature on the WHO/ISUP grading system and other grading approaches for CCRCC and PRCC was conducted. Updates and issues are presented on the following: (1) validation studies on WHO/ISUP grading; (2) grade elements including heterogeneity, grades 1 versus 2, types of multinucleated tumour cells, 'grade spectrum' of spindle cells, impact of sarcomatoid change in grade 4 RCC, percent (%) high grade, % sarcomatoid change and rhabdoid change versus sarcomatoid change; (3) grade applications including observer agreement, needle biopsy grade accuracy (correlation with nephrectomy grade) and grading of multifocal RCCs; (4) grade in papillary tumours including heterogeneity and on small (≤1.5 cm) neoplasms; and (5) novel grading or risk categories including incorporation of necrosis into grading and pattern or architectural-based grading. Practice guidance for some of the issues is provided when feasible or where data are sufficient. This review highlights the recent updates and controversies in the use of WHO/ISUP grading and on novel approaches to grading for CCRCC and PRCC. This review may serve as a best practice guide in addressing some of the grading issues and will help identify gaps in our understanding and use of grading for CCRCC and PRCC that can inform future research.

Differentiated thyroid carcinomas (DTC), including papillary thyroid carcinoma (PTC) and follicular carcinoma (FC), account for most thyroid malignancies and are generally associated with excellent prognosis. However, a subset of DTC demonstrate aggressive clinical behavior characterized by increased recurrence, distant metastasis (DM), radioactive iodine (RAI) resistance, and reduced survival. Identification of these tumors is critical for appropriate risk stratification and management. A number of pathologic features have been shown to predict aggressive behavior, including vascular invasion (VI), capsular invasion (CI), and extrathyroidal extension (ETE), as well as high-grade histologic features such as increased mitotic activity and tumor necrosis. In the 2022 World Health Organization (WHO) Classification for Endocrine and Neuroendocrine Tumours, high-grade features are acknowledged as prognostically significant, and DTC meeting these criteria are classified as high grade differentiated thyroid carcinoma (HGDTC), a category with a prognosis similar to PDTC. In addition, certain histologic subtypes of PTC, including the tall cell, hobnail, and columnar cell subtypes, have traditionally been associated with more aggressive clinical outcomes. However, the prognostic significance of histologic subtype alone remains debated, as tumor behavior is often influenced by the presence of invasive features and high-grade morphology. Recent advances in molecular profiling have further refined risk stratification. While the independent prognostic significance of the BRAFV600E mutation remains controversial, TERT promoter mutations have consistently been associated with aggressive tumor biology, including DM, RAI resistance, and decreased survival. Importantly, the coexistence of BRAFV600E and TERT promoter mutations identifies a subset of thyroid carcinomas with particularly poor outcomes. This review summarizes the key pathologic and molecular features associated with aggressive behavior in DTC, highlighting their diagnostic criteria, prognostic significance, and implications for clinical management. Comprehensive pathologic evaluation integrating morphologic and molecular findings remains essential for accurate risk stratification and multidisciplinary care of patients with thyroid carcinoma.

5-Aminolevulinic acid (5-ALA) induces tumor-selective accumulation of protoporphyrin IX (PpIX), enabling fluorescence-guided visualization of malignant tissue. In urologic oncology, the most established application is photodynamic diagnosis (PDD) during transurethral resection of non-muscle-invasive bladder cancer, in which fluorescence can identify occult carcinoma in situ and additional papillary lesions; however, specificity may decline in the presence of inflammation, recent instrumentation, or intravesical therapy. Renal applications are emerging: oral 5-ALA before partial nephrectomy can highlight some renal tumors, but fluorescence is often heterogeneous, can overlap with normal parenchyma, and is affected by histologic subtype, necrosis, blood attenuation, and device-dependent optics. Evidence in upper tract urothelial carcinoma and prostate cancer remains preliminary, with small cohorts and practical challenges in endoscopic or robotic workflows, alongside systemic adverse events such as hypotension and photosensitivity. This review synthesizes clinical and preclinical studies of 5-ALA-based fluorescence guidance across bladder, kidney, upper tract, and prostate malignancies, focusing on where the technology is ready for practice versus where it remains investigational. We discuss common pitfalls in interpretation and implementation and outline future directions, including quantitative fluorescence and spectroscopy, standardized dosing and imaging protocols, and prospective multicenter trials linking fluorescence guidance to residual disease, recurrence, margin status, and patient-centered outcomes.

Renal-pelvic fibroepithelial polyps (FEPs) are rare benign mesodermal lesions that can radiologically and clinically mimic urothelial carcinoma, sometimes prompting radical surgery. We reviewed five consultation cases of renal pelvis or proximal-ureter FEPs, integrating histology, immunohistochemistry, and targeted molecular testing. Patients were all females, tumors measured 3.3-9.0 cm (mean 5.2 cm), and four arose in the renal pelvis with variable ureteral extension. Three patients underwent nephroureterectomy for presumed malignancy. Histologically lesions shared a polypoid architecture with fibrovascular cores lined by benign -appearing urothelium; stromal cellularity separated lesions into hypercellular (patients 1-2) and hypocellular stromal patterns. Hypocellular lesions displayed fibrocollagenous stroma with bland spindle cells and were lined by benign urothelium. Hypercellular examples showed epithelioid smooth muscle type or primitiveappearing-stromal proliferations with occasional mitoses and focal Ki-67 elevation but lacked significant atypia, necrosis, infiltrative growth, or lymphovascular invasion. Immunoprofiles confirmed urothelial epithelial differentiation (AE1/AE3, GATA3, PAX8) with areas of anastomosing cords and pyelitis cystica and variable stromal labeling for desmin, CD10, ER, and PR; myogenin/MyoD1 were negative. A fusion/cancer gene- NGS panel (including GLI1 and NCOA1/2) was negative in the tested case. No recurrences were observed with mean followup of 24 months. We emphasize distinguishing features from papillary urothelial carcinoma, mixed -epithelialstromal tumor/smooth muscle adenoma-like renal tumor (SMART), rhabdomyosarcoma, and -translocation associated mesenchymal neoplasms, noting that focal -fibroadenoma like- stromal areas can occur in FEPs. Recognition of the confined polypoid growth beneath intact urothelium, bland cytology, supportive immunohistochemistry, and selective molecular testing when stromal atypia raises concern, can avoid misclassification and unnecessary radical surgery.

Solid papillary carcinoma (SPC) is a rare disease of the breast and usually shows favorable biology, with or without invasion. We experienced an SPC with invasion and aggressive biology, and report its characteristic image findings in this article. A 54-year-old woman with breast cancer, histologically diagnosed at another hospital, was admitted to our hospital for a left femoral neck fracture and underwent orthopedic surgery. During the admission, the patient requested that we operate on her breast cancer. Mammography showed a well-circumscribed mass with pleomorphic and linear calcifications, the latter not pointing toward the nipple. Ultrasound clarified many small cystic areas and multiple echogenic spots in the tumor. Magnetic resonance imaging of the mass showed low signal on T1-weighted images, weak high signal on fat-suppressed T2-weighted images, and a slow/plateau pattern on dynamic studies. Core needle biopsy pathologically led to the diagnosis of SPC with invasion. The patient, therefore, underwent a mastectomy and a sentinel node biopsy. Postoperative pathological study showed no lymph node metastasis but aggressive characteristics such as nuclear grade 3, estrogen receptor negativity, and an extremely high Ki-67 labelling index of 80%. The patient, unfortunately, developed skin flap necrosis, had sudden visual deterioration due to the worsening of diabetic retinopathy, and has been unable to receive postoperative adjuvant chemotherapy for more than 3 months. Diagnostic physicians should note that linear calcifications in the mass pointing toward non-nipple directions should be an important diagnostic clue for SPC of the breast. Diagnostic physicians should further note that many small cystic components in the mass are also important diagnostic image findings for SPC of the breast.