Search Results (148)

Background/Objectives: Lymph node metastasis within the prostatic anterior fat pad (PAFP) is uncommon but may refine nodal staging when pelvic lymph node dissection and PSMA PET/CT are negative. Case Presentation: A 58-year-old man with PSA 59 ng/mL, negative digital rectal examination, and a PI-RADS 5 anterior lesion underwent transperineal MRI/US fusion biopsy, showing an acinar adenocarcinoma (Gleason score 5 + 5 = 10, ISUP grade group 5) confined to anterior cores. 18F-PSMA-1007 PET/CT showed intense intraprostatic uptake (SUVmax 55.2) without nodal or distant disease. Retropubic radical prostatectomy, bilateral extended pelvic lymph node dissection (ePLND), and separate PAFP submission were performed. Final pathology showed a 38 mm bilateral anterior tumor involving 35% of the prostate, focal anterior extraprostatic extension, negative margins, absent seminal vesicle and bladder neck invasion, perineural and lymphovascular invasion, and no cribriform or intraductal carcinoma. All 15 pelvic nodes were negative. One of two PAFP nodes contained a 3 mm PSA-positive metastasis without extranodal extension, resulting in pT3aN1 staging. Postoperative PSA persistence prompted radiotherapy plus androgen deprivation therapy; PSA was 0.01 ng/mL at 6 months. Conclusions: In very-high-risk anterior prostate cancer, separate PAFP evaluation may provide clinically relevant staging information when PSMA PET/CT and pelvic lymph nodes are negative. This case highlights the PAFP as a potential site of occult regional nodal disease. Full article

Background: Reliable assessment of cervical lymph node metastases remains a key challenge in the management of oral squamous cell carcinoma (OSCC). While elective ipsilateral neck dissection (ND) is widely accepted, the benefit of contralateral ND and the influence of tumor site on metastatic risk remain incompletely defined. This study aimed to evaluate patterns of lymphatic metastases, the diagnostic accuracy of preoperative staging, and the therapeutic relevance of ipsilateral and contralateral ND. Methods: A retrospective single-center cohort study was conducted including 287 patients with histologically confirmed OSCC treated between 2013 and 2019. Patterns of lymph node metastases were analyzed with respect to tumor localization and clinicopathological factors. Multivariate binary logistic regression was performed to identify predictors of cervical lymph node metastases. The diagnostic accuracy of preoperative staging was evaluated using histopathological findings as the reference standard. Results: Tumor localization and histopathological grading significantly influenced the occurrence of lymph node metastases. OSCC of the maxilla demonstrated a significantly lower observed rate of cervical and occult metastases compared with other tumor sites. Occult metastases were detected in 16.9% of primary tumor cases, with only two contralateral occult metastases observed. The calculated number needed to treat (NNT) was 6 for ipsilateral elective ND and 74 for contralateral elective ND. Preoperative staging showed limited diagnostic accuracy, with a negative predictive value of 0.83 and a positive predictive value of 0.65. Conclusions: Elective ipsilateral ND remains an essential component in the surgical management of OSCC due to the considerable rate of occult metastases and the limited reliability of preoperative staging. In contrast, the benefit of contralateral elective ND appears limited in patients without midline-crossing tumors. Maxillary OSCC and well-differentiated tumors demonstrated a significantly lower metastatic risk, supporting a more individualized risk-adapted approach to neck dissection in selected cases. Full article

Fever of unknown origin (FUO) remains a persistent diagnostic challenge in clinical medicine despite significant advances in laboratory testing and imaging techniques. The definition of FUO has evolved since the original criteria proposed in 1961 and currently refers to persistent fever exceeding approximately 38.2–38.3 °C without a definitive diagnosis after an adequate diagnostic evaluation. Gastrointestinal diseases represent an important but often underrecognized group of conditions associated with FUO. The aim of this review is to synthesize current evidence on the gastroenterological causes of FUO, with particular emphasis on pathophysiological mechanisms, diagnostic strategies, and therapeutic management. The analysis highlights the role of inflammatory, infectious, and neoplastic gastrointestinal disorders in the etiology of prolonged fever. Key mechanisms involve systemic inflammatory responses mediated by cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor, as well as immune processes associated with the gut-associated lymphoid tissue (GALT) and interactions between intestinal microbiota and host immunity. Among the most frequently reported gastroenterological causes of FUO are inflammatory bowel diseases, intra-abdominal infections and abscesses, hepatobiliary disorders, pancreatitis, and gastrointestinal malignancies. Diagnostic evaluation requires a stepwise approach integrating laboratory testing, microbiological studies, imaging modalities, and endoscopic procedures, with advanced techniques such as computed tomography and fluorodeoxyglucose positron emission tomography improving detection of occult inflammatory or neoplastic processes. Therapeutic management is primarily guided by the identification of the underlying cause, while empirical treatment should be carefully considered to avoid masking diagnostic clues. A better understanding of the gastrointestinal mechanisms underlying FUO and the development of more efficient diagnostic algorithms may improve clinical outcomes and reduce the number of undiagnosed cases. Full article

Background and Clinical Significance: SWI/SNF chromatin remodeling complex-deficient malignancies constitute an aggressive group of undifferentiated tumors defined by inactivation of core subunits including SMARCA4 (BRG1) or SMARCB1 (INI1). In the head and neck, these tumors predominate in the sinonasal tract; oral cavity presentations are exceedingly rare, with reported cases predominantly representing metastatic disease. Peri-implant gingival masses in clinical practice are overwhelmingly reactive, but their occasional malignant nature mandates timely biopsy and thorough pathologic workup. We report the first comprehensively molecularly characterized case of a peri-implant gingival SWI/SNF complex-deficient tumor with confirmed biallelic SMARCA4 inactivation. Case Presentation: A 75-year-old man presented with a one-week history of a rapidly enlarging exophytic erythematous peri-implant gingival mass in the right posterior mandible (region 44–47). Incisional biopsy demonstrated an undifferentiated high-grade tumor with epithelioid, plasmablastoid, and focally rhabdoid morphology with necrosis. Immunohistochemistry showed complete loss of BRG1 (SMARCA4) with retained INI1 (SMARCB1), EMA positivity, Ki-67 of approximately 100%, and negativity across all lineage-specific markers (hematolymphoid, epithelial, melanocytic, endothelial, squamous). Comprehensive next-generation sequencing (Oncomine Comprehensive Assay Plus) confirmed biallelic SMARCA4 inactivation via a truncating nonsense mutation (p.Trp1346Ter; VAF 73.85%) combined with copy number loss, establishing the molecular mechanism underlying BRG1 protein loss. Co-occurring alterations included homozygous CDKN2A/CDKN2B deletion, MTAP loss (9p21.3), clonal TP53 and KEAP1 mutations, and intermediate–high tumor mutational burden (13.3 mutations/Mb) with microsatellite stability. The patient initiated carboplatin–paclitaxel and achieved a partial response at one month with further shrinkage by four months. This case illustrates a rare oral cavity manifestation of SWI/SNF complex deficiency arising in a peri-implant location, with a diagnostic workup that required integration of immunohistochemistry and molecular profiling for definitive characterization. The MTAP deletion co-occurring with homozygous CDKN2A/B loss identifies a potentially actionable synthetic lethal vulnerability to MAT2A and PRMT5 inhibitors currently under clinical investigation. An occult primary site could not be fully excluded due to absence of a dedicated staging workup. Conclusions: Rapidly enlarging peri-implant gingival masses should prompt timely biopsy and SWI/SNF marker testing when histology is high-grade and lineage-ambiguous. NGS-based molecular profiling confirms diagnosis, elucidates mechanism, and reveals actionable targets in this rare tumor class. Full article

Background and Clinical Significance: Lymph node metastases from carcinoma of unknown primary origin (CUP) are a rare and diagnostically challenging entity, particularly when arising from thoracic malignancies with atypical clinical presentations. This study aims to illustrate the essential nature of multidisciplinary integration, with a particular emphasis on the role of the pathologist in identifying occult thoracic tumors. Case Presentation: We report three cases of patients presenting with cervical or systemic lymphadenopathy as the initial clinical manifestation. Comprehensive diagnostic workups included advanced imaging (CT, MRI, and PET), comprehensive histopathological analysis, and next-generation sequencing of circulating tumor DNA. Case one and case two were diagnosed as occult primary non-mucinous lung adenocarcinomas, based on the integration of morphological features and immunohistochemical co-expression of TTF-1 and Napsin A, despite the absence of identifiable lung lesions. One case harbored an ALK rearrangement, guiding effective targeted therapy with alectinib. Case three involved metastatic pleural epithelioid mesothelioma, which presented with systemic lymphadenopathy and was initially misclassified as metastatic adenocarcinoma. Diagnosis was confirmed by the loss of BAP1 expression by immunohistochemistry and the detection of a BAP1 S160fs*1 mutation, emphasizing the role of molecular pathology. Conclusions: Lymphadenopathy as the first manifestation of thoracic malignancy is a rare but clinically significant occurrence. In such atypical presentations, pathologists play a pivotal role in diagnosis, often leading the process when clinical or radiological clues are minimal or absent. Accurate histopathological assessment is essential to establish a correct diagnosis and guide appropriate therapy. A multidisciplinary approach remains the cornerstone of diagnostic precision in CUP cases. Full article

Upper tract urothelial carcinoma (UTUC) presents distinct diagnostic and therapeutic challenges because of its rarity, anatomic constraints, frequent understaging at biopsy, and risk of systemic recurrence after radical nephroureterectomy. Current perioperative management is driven primarily by clinicopathologic risk factors, which may be insufficient to identify occult molecular residual disease (MRD) or to determine which patients are most likely to benefit from systemic therapy. This narrative review summarizes available evidence on circulating tumor DNA (ctDNA) in UTUC and related urothelial carcinoma settings, classifies the level of evidence supporting each application, and proposes a research framework for prospective evaluation. The strongest UTUC-specific evidence supports ctDNA as a prognostic biomarker associated with recurrence risk, whereas predictive validity for selecting chemotherapy, immune checkpoint inhibitors, antibody-drug conjugates, targeted therapy, or surveillance intensity remains unproven. Evidence from muscle-invasive bladder cancer, including ctDNA-correlative and ctDNA-guided perioperative trials, provides biologic rationale but should not be directly translated into routine UTUC care without disease-specific validation. We outline key implementation questions, including target population, assay selection, timing, false-positive and false-negative results, lead-time bias, and integration of plasma ctDNA with utDNA. Prospective UTUC-specific trials are needed to determine whether ctDNA-guided perioperative strategies improve survival, reduce unnecessary toxicity, and are cost-effective. Full article

Background/Objectives: Peritoneal metastases represent a common manifestation of advanced gastrointestinal malignancies and are associated with poor survival. Their early detection is essential for adequate tumor staging, prognosis, and treatment selection, especially to avoid unnecessary surgery. Intraoperative peritoneal lavage has been established as a diagnostic tool to detect occult peritoneal disease. However, reported techniques, analytical methods, and detection rates vary considerably. The objective of this review was to summarize current approaches to intraoperative peritoneal lavage, evaluate different detection methods, and assess their clinical relevance. Methods: A literature search was performed using the PubMed database for studies published between 2015 and 2025. The search terms “intraoperative peritoneal lavage” or “peritoneal fluid cytology” were used. Studies were included if they evaluated peritoneal lavage as a diagnostic method for detecting malignant cells, including all primary tumors and disease stages. Articles focusing on lavage as a therapeutic intervention or lacking methodological details were excluded. Results: Physiological saline solution was used for lavage in all included studies, with volumes ranging from 10 to 1000 mL. Sampling was predominantly performed immediately after abdominal access in various abdominal sites. Detection methods varied widely, with conventional cytology being most frequently used, while molecular techniques were used in a smaller number of studies. Positive detection rates showed broad variations and were higher in advanced tumor stages. Conventional cytology showed limited detection rates compared to molecular approaches. Conclusions: Intraoperative peritoneal lavage remains a valuable but methodologically heterogeneous diagnostic tool with limited detection rates when relying on conventional cytology alone. Molecular techniques seem to improve the detection rate of occult peritoneal disease but require further standardization and validation before routine clinical implementation. The technique of peritoneal lavage should be standardized by implementing an international consensus including lavage sites, volume of applied fluid, and detection method. Full article

Background/Objectives: Image-guided percutaneous thermal ablation is an established local treatment for selected patients with liver metastases, provided that accurate tumor targeting and adequate ablation margins can be achieved. However, lesion detection, target delineation, and intraprocedural margin verification remain challenging in post-chemotherapy or previously treated lesions that may become morphologically inconspicuous or radiologically occult. Catheter-assisted C-arm (cone-beam) CT hepatic arteriography (CBCT-HA) improves intraprocedural visualization of tumor vascularity and supports streamlined workflows within the angiography suite, yet it may underestimate tumor extent in lesions with limited or absent angiographic conspicuity. This pictorial essay illustrates the feasibility and added value of integrating preprocedural PET/CT with intraprocedural CBCT-HA for liver tumor ablation. Methods: Representative clinical cases of percutaneous liver tumor ablation guided by PET–CBCT-HA fusion are presented. Preprocedural PET/CT datasets were rigidly registered and fused with intraprocedural CBCT-HA to support tumor detection, target delineation, ablation planning, and real-time intraprocedural margin assessment. The complementary roles of metabolic and angiographic imaging were evaluated qualitatively across different clinical scenarios. Results: PET–CBCT-HA fusion improved detection and delineation of viable tumor components that were occult or insufficiently defined on CBCT-HA alone, particularly in post-chemotherapy or previously treated lesions. Conversely, CBCT-HA identified angiographically evident lesions not apparent on PET/CT. The combined approach enabled confident target definition, biologically informed ablation planning, and immediate post-ablation verification of metabolic and angiographic coverage, supporting margin-oriented intraprocedural decision-making. Conclusions: By integrating complementary metabolic and vascular information into a single-session workflow, PET–CBCT-HA fusion represents a multimodal guidance strategy that enhances lesion visualization and intraprocedural margin assessment. This approach may improve local tumor control in complex post-treatment and oligometastatic liver disease. Full article

Background and Objectives: Pulmonary neuroendocrine carcinomas (NECs) are characterized by aggressive clinical behavior and heterogeneous postoperative outcomes. Early recurrence, often reflecting occult micrometastatic disease, remains a key determinant of prognosis and is insufficiently captured by conventional staging systems. We hypothesized that the lactate dehydrogenase-to-albumin ratio (LAR), as an integrative tumor–host biomarker, may provide biologically informed risk stratification in this setting. Materials and Methods: We conducted a multicenter retrospective cohort study including 88 patients with resected small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC). Preoperative LAR and comparator inflammatory indices were evaluated. The primary endpoints were disease-free survival (DFS) and overall survival (OS), with early recurrence (≤12 months) as a prespecified secondary endpoint. Time-dependent receiver operating characteristic analyses, Cox proportional hazards models, and logistic regression analyses were applied within a predefined analytical framework. Results: Using a cut-off derived from 12-month DFS (LAR = 45.58), elevated LAR was associated with significantly shorter DFS (median 12.3 vs. 26.1 months; p = 0.018) and OS (median 20.7 vs. 52.8 months; p = 0.010). In multivariable analyses, LAR remained independently associated with both DFS (HR 1.012, 95% CI 1.001–1.023; p = 0.037) and OS (HR 1.016, 95% CI 1.005–1.027; p = 0.003). Elevated LAR was also associated with an increased risk of early recurrence (adjusted OR 4.656, 95% CI 1.520–14.262; p = 0.007). In time-dependent receiver operating characteristic (ROC) analyses, LAR demonstrated the highest overall discriminatory performance across evaluated biomarkers and showed a statistically significant advantage over neutrophil-to-lymphocyte ratio (NLR) for 24-month OS. Conclusions: Preoperative LAR captures a clinically relevant tumor–host phenotype associated with early disease progression and adverse survival outcomes in resected pulmonary NECs. As a biologically integrative and readily accessible biomarker, LAR may complement existing risk stratification strategies in this heterogeneous disease context. Prospective validation and integration into multimodal risk models are warranted. Full article

Background: Neuroendocrine neoplasms are frequently diagnosed after the detection of liver metastases, often when the primary tumor remains occult. Accurate non-invasive differentiation of neuroendocrine liver metastases (NELMs) from other focal hepatic lesions is therefore crucial. This study aimed to characterize the magnetic resonance imaging (MRI) features of NELMs using hepatocyte-specific contrast agents and to identify a potential radiologic “signature” that may suggest a neuroendocrine origin. Methods: This retrospective study included three cohorts: patients with histologically confirmed NELMs (n = 51; 146 lesions), patients with colorectal cancer liver metastases (n = 18; 46 lesions), and patients with benign hepatic hemangiomas (n = 28; 51 lesions). All subjects underwent standardized liver MRI with Gd-EOB-DTPA. Lesions were evaluated for size, diffusion-weighted imaging characteristics, apparent diffusion coefficient values, arterial-phase enhancement, T2-weighted signal, hepatobiliary-phase appearance, and hemorrhagic components. Statistical analyses included univariate and multivariate testing and receiver operating characteristic curve analysis. Results: NELMs commonly demonstrated arterial hyperenhancement, diffusion restriction, and variable T2 and hepatobiliary-phase signal heterogeneity. Compared with colorectal metastases and hemangiomas, NELMs showed distinctive patterns, particularly higher rates of hepatobiliary-phase heterogeneity and arterial enhancement. Lesion size, ADC metrics, T2 heterogeneity, and hemorrhage were significant discriminators. Conclusions: Hepatocyte-specific MRI enables identification of characteristic imaging features of NELMs. An integrated assessment of morphologic, diffusion, and hepatobiliary-phase findings may facilitate early recognition of neuroendocrine metastases, even when the primary tumor is unknown, improving diagnostic confidence and clinical management. Full article

Background: Laryngeal cancer (LC), a common subtype of head and neck cancers (HNC), is most frequently represented by laryngeal squamous cell carcinoma (LSCC). Prognosis largely depends on early detection; however, traditional prognostic tools, including tumor-node-metastasis (TNM) staging, often show limited predictive accuracy. Artificial intelligence (AI), including machine learning (ML), natural language processing, and deep learning (DL), has emerged as a promising approach to improving cancer diagnosis, prognosis, and treatment planning by analyzing clinical data and medical imaging. Objective: This systematic review assesses the role of AI in prognosis, recurrence prediction, and treatment outcomes in LC. Methods: PubMed, MEDLINE, Scopus, Web of Science, IEEE Xplore, and ScienceDirect were searched up to January 2025. A total of 1062 records were identified; after title/abstract screening and full-text assessment, 29 studies were included. Eligible studies involved adult patients with LC and applied AI to diagnose, prognose, predict recurrence, or assess treatment outcomes using human datasets. Study quality and risk of bias were evaluated using the QUADAS-2 and QUIPS. Results: The 29 included studies were mostly retrospective, with sample sizes ranging from 10 to 63,000 patients. Most focused on LSCC, with a higher prevalence in males. The studies utilized various AI techniques, including deep learning models such as convolutional neural networks (CNNs) and DeepSurv, as well as ML algorithms like random survival forest, gradient boosting machines, random forest, k-nearest neighbors, naïve Bayes, and decision trees. AI models demonstrated strong prognostic performance, surpassing Cox regression and TNM staging in predicting survival and recurrence. Several studies reported outcomes related to treatment, such as chemotherapy response, occult lymph node metastasis, and the need for salvage surgery. Methodological quality varied, with biases related to patient selection and confounding factors. Conclusions: AI has the potential to improve prognosis estimation, recurrence prediction, and treatment outcome assessment in LC. However, although AI can be a helpful addition to clinical decision-making, more prospective studies, external validation, and standardized evaluation are necessary before these technologies can be confidently adopted in everyday clinical practice. Full article

Decisions regarding the use of adjuvant systemic therapy in genitourinary (GU) malignancies—including bladder, kidney, and prostate cancers—are currently driven by clinicopathologic risk factors, which incompletely capture individual risk of residual disease. Consequently, patient selection for adjuvant treatment remains imprecise, leading to both overtreatment of cancers unlikely to recur and undertreatment of those with occult residual disease. Circulating tumor DNA (ctDNA), a minimally invasive liquid biopsy biomarker for minimal residual disease, has emerged as a promising tool to refine adjuvant treatment decision-making. Detection of ctDNA reflects persistent tumor-derived genomic material and often precedes radiographic recurrence, whereas ctDNA negativity is consistently associated with favorable oncologic outcomes. In this review, we summarize the evolving evidence supporting the use of ctDNA to guide adjuvant therapy decisions in bladder, kidney, and prostate cancers. This is not a comprehensive review on all of the potential applications of ctDNA in these malignancies. Rather, we aim to highlight disease-specific, adjuvant-guiding applications, including post-neoadjuvant and post-cystectomy decision-making in bladder cancer and emerging proof-of-concept data in renal cell carcinoma, and explore the potential application of ctDNA in the post-prostatectomy setting. Collectively, these data suggest that ctDNA may enable a paradigm shift toward biologically informed escalation and de-escalation of adjuvant therapy across GU malignancies, while underscoring the need for prospective validation in biomarker-driven clinical trials. Full article

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related mortality globally. While multi-modal artificial intelligence (AI) models offer significant predictive potential, their translation into routine clinical practice is delayed by the “black box” nature of complex algorithms and the fragmentation of heterogeneous data. We present LANTERN-XGB, a hierarchical machine learning workflow designed to bridge this gap by generating interpretable “digital human avatars” for precision oncology. The methodology employs a multi-stage scalable tree boosting system (XGBoost) architecture utilizing shapley additive explanations (SHAP) for rigorous hierarchical feature selection, missing value management, and patient-specific decision support. The workflow was developed and benchmarked using a retrospective cohort of 437 patients with clinical N0 NSCLC, followed by validation on a prospective dataset (n = 100) and an independent external dataset (n = 100). The pipeline integrates diverse data modalities to predict occult lymph node metastasis (OLM). LANTERN-XGB identified a robust consensus signature driven by non-linear interactions among CT textural fragmentation, PET metabolic heterogeneity, tumor density distribution, and systemic clinical modulators. Exploratory transcriptomic pathway analysis (GSVA) revealed that high-risk predictions strongly correlate with systemic molecular dysregulation, such as the enrichment of immune-inflammatory signaling and metabolic stress pathways. The model achieved robust discrimination in external validation (AUC ≈ 0.77), performing comparably to state-of-the-art nomogram benchmarks. Crucially, the LANTERN-XGB framework demonstrated superior utility in handling diagnostic ambiguity; local force plots allowed for the correct reclassification of “borderline” prediction by visualizing feature interactions that standard linear models fail to capture. LANTERN-XGB provides a validated, open-source framework that successfully balances predictive power with clinical transparency. By empowering clinicians to visualize and verify the logic behind AI predictions, this workflow offers a pragmatic path for integrating reliable multi-modal avatars into daily medical decision-making. Full article

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. Full article

Background: Indeterminate renal masses (IRMs) frequently require biopsy for characterization and often lead to unnecessary surgical interventions. ⁸⁹Zr-girentuximab is a positron emission tomography (PET) radiopharmaceutical targeting carbonic anhydrase IX, a biomarker overexpressed in clear-cell renal cell carcinoma (ccRCC). This real-world experience demonstrates the impact of ⁸⁹Zr-girentuximab PET on the clinical management of patients with IRM and its role in differentiating primary and metastatic ccRCC from other etiologies. Methods: This prospective single-center study, part of an expanded access program (NCT06090331), investigated patients with IRM on conventional imaging who underwent ⁸⁹Zr-girentuximab PET/computed tomography (PET/CT). Qualitative and quantitative PET/CT features of each lesion were assessed. Pathologic or clinical diagnosis was determined for all lesions. Referring physicians were surveyed to evaluate the impact of PET on patient management. Results: Seven male patients (age range, 57–78 years) were included; four had ccRCC (including two with metastatic disease) and three had oncocytoma (including one with Birt-Hogg-Dubé syndrome). Across all 32 lesions identified, ⁸⁹Zr-girentuximab PET/CT accurately characterized each lesion based on pathologic or clinical diagnosis. ⁸⁹Zr-girentuximab PET/CT identified ccRCC tumor thrombi in the inferior vena cava and renal vein branches (SUV_max 12.0–13.0), a perinephric deposit (SUV_max 36.4), and intramuscular (SUV_max 103.0), pulmonary (SUV_max 4.0–10.5), and osseous (SUV_max 10.2) metastases. ⁸⁹Zr-girentuximab PET/CT enabled the diagnosis of oncocytomatosis in one patient and detected a renal lesion with positive uptake that was occult on MRI. According to referring physicians, ⁸⁹Zr-girentuximab PET/CT changed clinical management in six of seven patients and improved patient care in all cases. Conclusions: ⁸⁹Zr-girentuximab PET/CT provides a noninvasive tool for characterizing indeterminate renal masses and metastatic ccRCC and may improve clinical problem-solving in complex scenarios. Full article