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.

Small renal masses (SRMs), typically defined as tumors ≤4 cm, are generally considered indolent and often managed with active surveillance. However, metastasis can occur even in small tumors. We report a 76-year-old man with a 26-mm renal mass and a periduodenal lesion initially suspected as pancreatic invasion. EUS-FNA suggested metastatic renal cell carcinoma. Nephrectomy revealed a 17-mm papillary RCC with high nucleolar grade (WHO/ISUP grade 2), tumor necrosis, venous invasion, and lymph node metastasis. This case underscores that biological aggressiveness may outweigh tumor size and that atypical imaging findings warrant careful evaluation.

Selpercatinib (Retevmo) is a selective rearranged during transfection (RET) kinase inhibitor approved for RET-altered malignancies, including thyroid carcinoma. Hepatic enzyme elevations have been reported; however, biopsy-proven drug-induced liver injury (DILI) associated with selpercatinib is uncommon. We report a case of a 59-year-old woman with recurrent papillary thyroid carcinoma who developed progressive gastrointestinal symptoms followed by severe hepatocellular transaminitis approximately four weeks after initiating selpercatinib (160 mg twice daily). Laboratory evaluation demonstrated marked aminotransferase elevation (aspartate aminotransferase: 525 U/L and alanine aminotransferase: 639 U/L) with mild hyperbilirubinemia (total bilirubin: 2.1 mg/dL), and aminotransferases peaked above 800 U/L during hospitalization. Comprehensive workup for alternative etiologies, including viral hepatitis and autoimmune hepatitis (negative antinuclear antibody and smooth muscle antibody with normal immunoglobulin levels), was unrevealing, and abdominal imaging showed no acute abnormalities. Liver biopsy demonstrated sparse portal lymphocytic inflammation with intact bile ducts and prominent centrilobular (zone 3) hepatocellular necrosis accompanied by macrophages and eosinophils, consistent with DILI. Selpercatinib was discontinued, resulting in progressive biochemical improvement with aminotransferases declining to <100 U/L within approximately four months. Given oncologic necessity, selpercatinib was reintroduced at a reduced dose (40 mg daily) without recurrence of severe transaminitis. This case highlights that selpercatinib can cause clinically significant hepatocellular DILI and underscores the diagnostic value of liver biopsy in distinguishing DILI from autoimmune hepatitis, particularly when considering safe dose modification and rechallenge.

Papillary thyroid carcinoma, columnar cell subtype (PTC-CC) is a PTC characterized by nuclear pseudostratification and elongation. High-grade differentiated thyroid carcinoma is a novel classification of the WHO classification, defined by mitotic count ≥5/2 mm2 and/or tumor necrosis, which may exhibit CC morphology and can be termed as high-grade PTC-CC (HGPTC-CC). In this multicenter retrospective study, we conducted a detailed clinicopathologic review in a retrospective cohort of 71 PTC-CC and HGPTC-CC. HGPTC-CC was common among tumors showing columnar cell morphology, accounting for 46% (33/71) of the entire cohort. Compared with PTC-CC, HGPTC-CC was significantly associated with male sex, infiltrative tumors, angioinvasion, microscopic extrathyroidal extension (ETE), positive resection margin, and advanced pT stage. Furthermore, HGPTC-CC had significantly shortened disease-specific survival (DSS), distant metastasis-free survival (DMFS), and regional recurrence-free survival (RRFS). The 10-year DSS was 95% and 57%, the 10-year DMFS was 87% and 26%, and the 10-year RRFS was 85% and 55% for PTC-CC and HGPTC-CC, respectively. Among tumors with known BRAFV600E and RASQ61R status, BRAFV600E mutation was detected in 40% (19/47), whereas RASQ61R was identified in 15% (6/39). HGPTC-CC was associated with a significantly higher percentage of RASQ61R (PTC-CC 4%, HGPTC-CC 36%). In conclusion, a significant percentage (46%) of PTC-CCs are high-grade. HGPTC-CC is associated with adverse clinicopathologic features and poor outcomes. The impression of PTC-CC as an aggressive PTC subtype may be attributed to the high prevalence of high-grade histology in these tumors. Careful examination for mitoses and necrosis is required for accurate diagnosis and prognostication in PTC-CC.

Cystic breast lesions are commonly encountered on breast ultrasound, encompassing a spectrum from simple benign cysts to complex mixed solid and cystic lesions with malignant potential. Accurate sonographic characterization using ACR BI-RADS v2025 criteria is essential to guide clinical management, avoid unnecessary biopsies, and reduce patient anxiety. This review examines the sonographic features of cystic breast lesions across the pathological spectrum, including simple cysts, fat necrosis, abscesses, papillomas, and malignant subtypes such as medullary, papillary, and mucinous carcinomas. Key ultrasound techniques - including harmonic imaging, Doppler evaluation, and elastography - are discussed in the context of optimizing lesion characterization and differentiating benign from malignant cystic lesions. Despite these advances, image interpretation remains operator-dependent and challenging, particularly when malignancies mimic benign cystic features. Ultrasonomics emerged as a promising quantitative approach, extracting high-dimensional imaging features related to lesion shape, texture, and intensity to enable objective, reproducible assessment of lesion heterogeneity beyond visual interpretation. When combined with machine learning algorithms, ultrasonomics enhances lesion classification and diagnostic consistency. Building upon this framework, AI-based decision support systems analyze multiple sonographic parameters simultaneously, reducing interobserver variability and helping stratify malignancy risk in indeterminate or mixed solid and cystic lesions demonstrating suspicious features such as irregular walls, mural nodules, or internal vascularity. Clinical studies demonstrate AI can reduce unnecessary biopsies without compromising cancer detection rates. The integration of advanced ultrasound techniques, ultrasonomics, and AI-based decision support represents a meaningful advancement in the objective evaluation of cystic breast lesions, supporting more accurate risk stratification and optimized patient management.

Epithelioid angiosarcoma (EA) is a malignant tumor of endothelium origin that most commonly arises in the deep soft tissues of extremities but may occasionally be primary in skin, adrenal gland, and bone. A 72-year-old male presented with a painless enlargement of his thyroid for more than 10 days before hospitalization. A walnut-sized mass in the right thyroid was found simultaneously by palpation and Color Doppler Ultrasound. After a total thyroidectomy was performed, a mass with a size of 4.5 cm × 3.5 cm was found at the lower pole of the right thyroid gland. Histologically, the tumor was diffusely distributed in a sheet-like pattern, with tumor cells being epithelioid. There was extensive coagulative necrosis while no components of papillary carcinoma, follicular carcinoma and insular poorly differentiated carcinoma were noticed. CD31 and vimentin were positive for immunostaining. The diagnosis of primary epithelioid angiosarcoma of right thyroid was then given to the patient. Eleven months after the operation, the patient died from brain metastasis. It is suggested that primary epithelioid angiosarcoma of thyroid, as an extremely rare tumor, have no characteristic clinical manifestations, laboratory and imaging examinations, and the diagnosis mainly depend on its unique clinical pathological features. Although extensive surgical resection is the preferred treatment, the prognosis is still very poor.

ObjectivesDuctal carcinoma in situ (DCIS) is typically detected as microcalcifications on mammography but can occasionally present as a mass-forming lesion. This study examined the histopathologic features of DCIS and its histologic subtypes diagnosed on biopsies for radiologically detected mass lesions and evaluated their correlation with imaging findings and surgical outcomes.MethodsWe retrospectively reviewed 38 biopsies diagnosed as DCIS and its subtypes that were performed for radiologically detected mass lesions. Each lesion was assessed for architectural patterns, nuclear grade, necrosis, calcifications, estrogen receptor (ER) status, and coexisting benign lesions. Subsequent excision outcomes were available for 30 lesions to evaluate the presence of invasive carcinoma and mass-forming correlates. Statistical analyses were performed.ResultsInvasive carcinoma was found in 13 of 38 lesions (34%) upon excision. Among 25 non-invasive tumors, 15 (60%) had a benign lesion accounting for the mass. DCIS with desmoplastic stromal fibrosis (n = 4) showed a significantly higher nuclear grade (P = .0451). Specific DCIS morphological subtypes-including encapsulated papillary carcinoma, solid papillary carcinoma, papillary DCIS, and cystic apocrine DCIS-were identified as plausible causes of mass-forming lesions. No statistically significant histologic predictors of invasive carcinoma on excision were identified in our limited study cohort.ConclusionsDCIS with associated desmoplastic stromal fibrosis, along with some specific histologic subtypes, can cause mass-forming lesions on imaging. Histologic features alone are not reliable predictors of coexisting invasive carcinoma. Careful pathologic-radiologic correlation, including attention to benign mass-forming correlates, is essential for accurate diagnosis and clinical management.