Search Results (3,660)

Background: Iodinated contrast media are essential for oncologic imaging but raise specific safety concerns because cancer patients are often exposed to repeated contrast-enhanced computed tomography, nephrotoxic drugs, immune-modulating therapies, and, in selected cases, radioiodine-dependent diagnostic or therapeutic pathways. Methods: We performed a narrative review based on an exploratory search followed by a focused search targeting iodinated contrast use in oncology-related settings. Studies were included if they addressed renal risk and post-contrast acute kidney injury, hypersensitivity and acute adverse reactions, or thyroid dysfunction with radioiodine-related implications. We also considered clinically relevant studies on drug interactions, isotope studies, and laboratory confounding. Results: The evidence base was methodologically heterogeneous, with renal safety as the predominant domain. Kidney injury after contrast-enhanced imaging in cancer patients appeared frequently multifactorial, supporting the broader concept of post-contrast acute kidney injury rather than automatic attribution to contrast alone. Hypersensitivity reactions to modern nonionic iodinated contrast media were generally uncommon, with severe reactions rare, although immune-modulating therapies may alter risk. Thyroid-related effects were usually transient but relevant in patients with thyroid autonomy and in differentiated thyroid carcinoma, where contrast exposure may affect scintigraphy and radioiodine planning. Conclusions: In oncology, iodinated contrast use requires individualized, field-specific risk stratification instead of reflexive avoidance. Full article

Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTCs) remain highly lethal gastrointestinal malignancies because of late presentation, marked molecular heterogeneity, and limited durable benefit from conventional systemic therapy. This narrative review summarizes recent advances in both diseases, focusing on practice-informing clinical trials, biomarker-driven treatment strategies, and translational insights into tumor biology and resistance. In PDAC, progress includes refinement of perioperative management, broader germline and somatic testing, recognition of DNA damage repair-deficient subsets, and development of KRAS-directed therapies and rational combination strategies. In BTCs, especially intrahepatic cholangiocarcinoma, comprehensive molecular profiling has expanded precision oncology through actionable alterations such as FGFR2 rearrangements, IDH1 mutations, HER2 amplification/overexpression, BRAF V600E, NTRK fusions, and MSI-high/dMMR status. Immunotherapy has a clearer role in selected BTC populations, whereas in PDAC benefit remains largely restricted to rare biomarker-defined subsets. Across both diseases, circulating tumor DNA is emerging as a promising tool for prognostication, minimal residual disease assessment, response monitoring, and early resistance detection. Contemporary care increasingly depends on early molecular profiling, individualized treatment sequencing, and integration of targeted therapies, biomarker-guided immunotherapy, and clinical trials. Full article

Angioedema (AE) is a frequent symptom reported by dermatologists and allergists, as well as by general practitioners and physicians in other specialties. Hereditary angioedema (HAE) is an ultra-rare condition, whereas the majority of AE episodes in daily medical practice are secondary to an underlying condition or drug intake. This review discusses the most common causes of acquired angioedema, presents selected aspects of its pathogenesis in the context of available diagnostic tests, and provides an account of reports on possible management options. Acquired angioedema (AAE) poses an actual challenge both in terms of its diagnosis and management. Its variable etiology warrants a diagnostic approach aimed at the exclusion of underlying cancers, lympho- and myeloproliferative diseases, monoclonal gammopathies, as well as autoimmune and infectious conditions. Apart from its variable etiology, the management of AAE is further complicated by the lack of approved and standardized prophylaxis and treatment schemes. Therefore, an appropriate diagnostic approach is required for the efficient prevention of AAE symptoms and the detection of possible underlying pathologies. Full article

Since the first approval of CTLA-4 blockade for melanoma, immune checkpoint inhibitors (ICIs) have expanded into a major class of cancer therapy, with more than 100 FDA-approved oncological indications across metastatic and earlier-stage disease settings, including use as monotherapy and in combination regimens. Preclinical research has largely focused on myocarditis and atherosclerosis, but a wider set of phenotypes, such as non-inflammatory left ventricular dysfunction (NILVD), arrhythmias, and vasculitis, can be observed, and they are rarely connected within a single mechanistic model. We aim to build a systems-oriented, mechanistic framework of the most widely studied biological processes; it will link the main checkpoint pathways to relevant cardiac and vascular cell types, molecular pathways, immune synapses, and candidate biomarkers. We searched PubMed, Scopus, and Web of Science using combinations of terms for immune checkpoint inhibition and cardiovascular-immune-related adverse events that provide mechanistic insight into cardiac-immune-related adverse reactions (irAEs). An AI-assisted semantic clustering approach was used only to organize the included literature. The integrated framework identifies PD-1/PD-L1 as the dominant mechanistic hub linking T-cell activation, endothelial recruitment, myocardial injury, and vascular inflammation. Across phenotypes, a shared immune core involving checkpoint pathways, cytokine signaling, and leukocyte trafficking coexists with phenotype-restricted mediators that may bias injury toward myocarditis, vascular inflammation, conduction-system disease, or NILVD. KEGG analyses support the enrichment of T-cell receptor signaling, Th17 differentiation, JAK-STAT signaling, cytokine–cytokine receptor interaction, and lipid and atherosclerosis pathways. Candidate biomarkers emerging from the reviewed literature include troponin, IL-6, CXCL9/CXCL10/CXCL13, S100A family proteins, ROCK2, HLA-linked susceptibility signals, and T-cell receptor clonality markers. The AI-assisted clustering broadly recapitulated the expert-defined thematic structure while identifying finer semantic neighborhoods within the literature. This framework provides a support map for further hypotheses about toxicity patterns with current and next-generation checkpoint strategies on the cardiac system, while AI-assisted clustering provides a complementary method for organizing the literature rather than an independent source of biological inference. Full article

Objectives: This study aims to describe a rare case of oral metastasis from small-cell neuroendocrine carcinoma originating from the lung and to perform a systematic review of the cases reported in the literature. Methods: We present the case of a patient with oral metastasis from small-cell neuroendocrine carcinoma of the lung. The patient presented at the clinical examination with severe pain in the attached gingiva in the 3.5 region, extracted one month earlier, despite prolonged antibiotic therapy. A systematic review of the literature was conducted using the PubMed, Scopus and Web of Science databases, in accordance with the PRISMA 2020 guidelines for systematic reviews. Results: A biopsy of the affected area was performed. The histological and immunohistochemical analysis revealed a fragment with features compatible with a secondary lesion with probable origin from the lung. In addition, a review of the existing English-language literature was carried out and revealed a total of six cases of oral metastasis. Conclusions: Oral metastases from small-cell neuroendocrine carcinoma are rare but have been reported in the literature. The gold standard for diagnosis remains histological examination. Full article

Background/Objectives: Penile squamous cell carcinoma (SCC) is a rare but aggressive malignancy in which survival declines sharply once regional lymph nodes are involved. Neoadjuvant therapy is recommended for clinically node-positive disease to improve resectability and address micro-metastatic spread; however, the supporting evidence remains limited. We systematically reviewed contemporary data on neoadjuvant strategies for penile SCC, including cytotoxic chemotherapy, radiotherapy, immunotherapy, and molecularly targeted agents. Methods: A systematic search of MEDLINE, EMBASE, ClinicalTrials.gov, and CENTRAL was conducted from inception to January 2026 in accordance with MECIR guidance. Eligible studies included patients with histologically confirmed penile cancer treated with neoadjuvant intent prior to curative surgery. Primary outcomes were objective response rate (ORR), pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Data were synthesised narratively by treatment modality. Results: Forty-two studies met the inclusion criteria (32 chemotherapy, five radiotherapy, five immunotherapy, three targeted therapy). The evidence base was dominated by retrospective cohorts with limited prospective phase II data and no completed randomised trials. Across chemotherapy studies, the median reported ORR was 50% (range 29–90%), with pCR/ypN0 rates ranging 10–25%. Median reported PFS and OS were approximately 11 and 18 months, respectively, with durable survival concentrated among responders undergoing complete surgical consolidation. Radiotherapy data were sparse and heterogeneous. Early-phase immunotherapy combinations reported higher short-term response and pCR signals than historical chemotherapy, though the results were based on small single-arm cohorts. Molecularly targeted systemic monotherapy demonstrated modest activity. Conclusions: Neoadjuvant taxane–platinum-based chemotherapy remains the guideline-supported standard for cN2-3 penile SCC, supported by phase II and retrospective data but limited by methodological heterogeneity and absence of randomised evidence. Emerging combination immunotherapy strategies show promising efficacy signals and warrant prospective validation within biomarker-informed trial frameworks. Full article

Objective: This study aims to evaluate the additional diagnostic value of systematic (SBx) and perilesional biopsies (PBx) compared with targeted biopsy (TBx) in patients with mpMRI-detected PI-RADS 3-4–5 lesions. Methods: We performed a retrospective analysis of 208 men with PI-RADS ≥ 3 lesions who underwent mpMRI–ultrasound fusion biopsy at a single institution. Clinically significant prostate cancer (csPCa; ISUP ≥ 2) was identified in 155 patients (74.5%), who constituted the study cohort. All patients underwent a standardized biopsy protocol consisting of 3–5 TBx cores, 3 PBx cores sampled within a 10 mm radius of the index lesion, and 10 SBx cores using the KOELIS Trinity^® system. Detection rates of csPCa and ISUP grade upgrading were analyzed and stratified by PI-RADS category. Results: TBx csPCa detection rates increased progressively with PI-RADS score: 39% for PI-RADS 3, 50% for PI-RADS 4, and 60% for PI-RADS 5 lesions. PBx showed a 42.5% detection rate of csPCa in PI-RADS 3 and 58% and 85.3% of csPCa in PI-RADS 4 and 5 respectively, whereas SBx detected 34.5% of csPCa in PI-RADS 3, 46% of csPCa in PI-RADS 4, and 60.5% of csPCa in PI-RADS 5. Despite these detection rates, PBx and SBx rarely provided clinically meaningful upgrading over TBx findings. ISUP grade upgrading occurred in only 7.3% of PBx cases and 1.8% of SBx cases in PI-RADS 5 lesions, with similarly low upgrading rates observed in PI-RADS 3–4 lesions. Conclusions: In patients with high-grade lesions like PI-RADS 4–5, TBx alone identifies the vast majority of csPCa, while SBx and PBx contribute minimal additional diagnostic or grading benefit. These findings support biopsy de-escalation strategies in high-risk mpMRI settings to reduce unnecessary sampling and procedure-related morbidity. On the other hand, in the PI-RADS 3 subgroup, omitting non-targeted sampling (SBx and/or PBx) may lead to underdiagnosis of higher-grade tumors not captured by TBx alone, potentially resulting in substantial changes in therapeutic strategy and, consequently, patient prognosis. Full article

Background/Objectives: Merkel cell polyomavirus (MCPyV) is a ubiquitous virus strictly associated with Merkel cell carcinoma (MCC), a rare and aggressive skin cancer. MCPyV oncogenic properties are associated mainly with early protein expression, integration, and LT truncation. MCPyV can also interact with DNA Damage Response (DDR) mechanisms, contributing to oncogenesis and tumor progression. In this work, we investigated the correlation between MCPyV and MCC and evaluated the mRNA expression profiles of DDR genes in virus-positive and -negative tumors. Methods: A total of 19 formalin-fixed paraffin-embedded biopsies were acquired from patients diagnosed with MCC. After DNA and RNA extraction, the DNA was used for MCPyV detection via qPCR and for sequencing analysis of the early, late, and non-coding control viral regions and the extracted RNA was used for MCPyV transcripts, miRNA detection and for the evaluation of several DDR genes expression such as ATM, ATR, CHK1, CHK2, H2AX, Rad51, p53, and p21, in MCPyV-positive and -negative samples via reverse transcription, PCR, and qPCR. Results: MCPyV presence was detected in 11/19 samples, all characterized by viral integration, LT truncation, and early region expression only. Furthermore, higher mRNA levels of DDR genes were observed in MCPyV-positive tumors compared with the negative ones. Conclusions: Our findings support the role of MCPyV in MCC formation and suggest its involvement in the transcriptional regulation of DDR genes, which may influence tumor progression. Understanding the molecular interplay between MCPyV and the DDR may guide future research into plausible novel diagnostic and therapeutic strategies for virus-induced tumors. Full article

Immunotherapy with immune checkpoint inhibitors (ICIs) has profoundly transformed the therapeutic landscape of lung cancer. Although ICIs are generally associated with a more favorable toxicity profile compared with traditional chemotherapy, rare and potentially severe immune-related adverse events (irAEs) may occur, sometimes posing significant diagnostic challenges. We report a case of macrophage activation syndrome (MAS) following a single administration of the anti-PD-L1 antibody atezolizumab in a patient with advanced non-small-cell lung cancer (NSCLC). A 62-year-old woman was diagnosed in February 2024 with stage IIIB NSCLC according to the 8th TNM classification. The patient was deemed ineligible for radiotherapy because of previous thoracic irradiation for breast cancer. First-line therapy with carboplatin plus pemetrexed was administered from March to June 2024, resulting in stable disease; this was followed by pemetrexed maintenance from July to October 2024, at which time thoracic disease progression was documented. Second-line treatment with atezolizumab was initiated in November 2024. Ten days after the first infusion, the patient was admitted to the emergency department for fever and confusion. Laboratory investigations revealed markedly elevated C-reactive protein and hyperferritinemia. Despite empirical antibiotic therapy, fever and thrombocytopenia persisted. Bone marrow biopsy demonstrated findings consistent with MAS. Corticosteroid therapy with prednisone at 1 mg/kg was promptly initiated under rheumatologic supervision, leading to a rapid clinical and biochemical improvement. During tapering, inflammatory markers relapsed when prednisone was reduced to below 12.5 mg/day. Given the occurrence of a grade 4 (CTCAE v5.0) immune-related adverse event, atezolizumab was permanently discontinued. The patient remains in follow-up without radiological evidence of disease progression. This case highlights the diagnostic challenge of MAS secondary to ICIs, which may initially present with nonspecific symptoms such as fever, confusion, and elevated inflammatory markers. Early recognition and timely initiation of high-dose corticosteroids were essential for effective management and full recovery. Clinicians should maintain a high index of suspicion for MAS among rare but severe hematologic irAEs during immunotherapy. Full article

Y-box binding protein 1 (YB-1; encoded by YBX1) is a multifunctional DNA- and RNA-binding protein implicated in cell cycle regulation, DNA repair, stress adaptation, and therapy resistance. Elevated YBX1 expression has been associated with aggressive disease across multiple cancer types; however, its pan-cancer genomic and clinical correlates, and the extent to which these reflect proliferative activity versus genomic instability, remain incompletely defined. Here, we performed an integrative pan-cancer analysis across 53 independent datasets spanning 33 tumour types, incorporating transcriptomic (YBX1 mRNA), proteomic (RPPA), genomic, and clinical data. We found that YBX1 is rarely altered at the genomic level, whereas its mRNA expression is highly variable within tumour cohorts. Tumours with high YBX1 mRNA expression consistently exhibited conserved transcriptional programmes enriched for cell cycle, mitotic, RNA processing, and signalling pathways, patterns that were also reflected at the protein level by concordant pathway associations with elevated YB-1 abundance. These molecular features co-occurred with clinicopathological characteristics indicative of aggressive disease. High YBX1 mRNA expression was associated with increased mutation burden, chromosomal alteration burden, hypoxia, and homologous recombination deficiency at the pan-cancer level, with similar molecular associations observed in tumours stratified by elevated YB-1 protein levels. The association between YBX1 expression and chromosomal alteration burden was largely attenuated after accounting for proliferative activity, particularly G2/M-associated transcriptional programmes used as a proxy for mitotic activity. While the relationship with mutation burden was heterogeneous across tumour types, this pattern suggests that links between YBX1 expression and chromosomal instability primarily reflect shared proliferative and mitotic tumour biology rather than an independent genomic instability programme. Clinically, high YBX1 mRNA expression was associated with advanced disease stage, higher histologic grade, reduced progression-free survival, and poorer overall survival. Elevated YB-1 protein levels were also associated with advanced disease stage and poorer survival outcomes and demonstrated a similar, although non-significant, directional trend with histologic grade. Collectively, these findings demonstrate that elevated YBX1 expression marks proliferative and clinically aggressive tumour states within which genomic instability-related features arise in a context-dependent manner, providing a clarified pan-cancer framework for interpreting YB-1-associated tumour biology. Full article

Background: Primary thyroid lymphoma (PTL) is a rare malignancy, accounting for less than 5% of thyroid cancers and less than 2% of extranodal lymphomas. It predominantly affects older women and is strongly associated with autoimmune thyroiditis, particularly Hashimoto’s thyroiditis. Diagnosis is often challenging due to non-specific clinical, imaging, and cytological findings, and the role of surgery has progressively shifted from therapeutic to primarily diagnostic. Methods: We conducted a retrospective single-center case series including nine patients treated for PTL between 2015 and 2025 at a tertiary referral endocrine surgery center. An analysis was conducted on clinical presentation, pre-existing thyroid disease, diagnostic work-up, histopathological subtypes, treatment strategies and outcomes. All patients underwent preoperative ultrasound and fine-needle aspiration cytology (FNAC); surgical intervention was performed to confirm cytology results, when cytology was inconclusive or when compressive symptoms were present. Results: The cohort included six females and three males, with a median age of 65.2 years. Four patients had Hashimoto’s thyroiditis and three had multinodular goiter. FNAC was diagnostic or suggestive of lymphoma in three cases only, and surgical biopsy or thyroidectomy for a definitive diagnosis was performed in eight cases. One case started follow-up after cytology and flow cytometry. Histological subtypes were heterogeneous, including diffuse large B-cell lymphoma, Burkitt’s lymphoma, Hodgkin lymphoma, follicular lymphoma, high-grade B-cell lymphoma, and MALT lymphoma. Seven patients received combined chemoimmunotherapy. A complete response was obtained in eight patients, with a minimum follow-up of three years; one patient died of unrelated causes. Conclusions: PTL remains a rare and diagnostically challenging thyroid malignancy. FNAC alone is frequently insufficient, and surgical biopsy retains an important role in cases with high clinical suspicion or compressive symptoms. While surgery has limited therapeutic value, a multidisciplinary approach and timely, tailored treatment are crucial to achieving favorable outcomes. Full article

Background: Adult survivors of childhood cancer face a significant risk for treatment-related late effects that may impair health-related quality of life (HRQoL). Incorporating longitudinal changes in patient-reported symptoms beyond treatment-based risk factors may enhance the prediction of HRQoL. Methods: Survivors (n = 576) dually enrolled in the St. Jude Lifetime Cohort Study and Childhood Cancer Survivor Study reported 37 symptoms across 10 domains at three time points over 20 years to ascertain longitudinal symptom change patterns. HRQoL was subsequently assessed using SF-36 scores. Prediction models were developed using Bayesian Information Criterion Elastic Net (BIEN), first including demographic, diagnosis, and treatment variables, then adding symptom change patterns. Prediction of suboptimal HRQoL (score < 40) was evaluated using 10-fold cross-validated area under the receiver operating characteristic curve values (AUC). Results: Participants (median baseline age 26.7 years, 52% female, 90% non-Hispanic white, 41% leukemia, and 30% Hodgkin/non-Hodgkin lymphoma survivors) most frequently reported symptom domains of sensory, pain, and anxiety (50–60% at any time point), followed by depression and memory (40–50%). Consistent absence throughout follow-up was the most common pattern (41.7–98.1%), while patterns requiring symptom presence at ≥1 time point were less common (0.0–16.7%), and persistent presence throughout follow-up was rare (0.0–6.8%). Across 10 SF36-HRQoL scores, symptom-enhanced models improved prediction over non-symptom models (AUCs 0.75–0.85 vs. 0.56–0.66; p-values < 0.001). Conclusions: Longitudinal symptom change patterns substantially improved future HRQoL prediction, achieving prediction accuracy that may be of clinical effectiveness. This supports regular symptom assessment and further research towards symptom-informed risk stratification in survivorship care. Full article

Soft tissue sarcomas (STS) comprise a rare and highly heterogeneous group of mesenchymal-derived malignancies, accounting for less than 1% of all cancers and characterized by diverse histologic and molecular subtypes. Despite their low incidence, STS account for a disproportionate burden of cancer-related morbidity and mortality, largely driven by their risk of metastatic dissemination. Early detection of metastatic spread is a cornerstone of preoperative staging, treatment planning, and postoperative monitoring in patients with STS. Although conventional imaging modalities remain fundamental for surveillance of metastatic disease, they may fail to accurately detect metastatic sites and provide limited insight into tumor biology. Advances in precision medicine have positioned liquid biopsy as a minimally invasive approach for the analysis of tumor-derived material, facilitating characterization of tumor biology and identification of prognostic biomarkers. Circulating tumor cells (CTCs) represent intact and viable tumor cells that provide unique genomic and phenotypic traits that could not be assessed using acellular tumor-derived material. They have emerged as promising biomarkers for monitoring disease progression, assessing treatment response, and stratifying prognosis. Particularly, their clinical value as prognostic biomarkers has been established in epithelial-derived malignancies. Despite these advances, the role of CTCs in STS remains largely investigational, mainly due to STS heterogeneity and the lack of standardized protocols for detection across platforms. Therefore, this narrative review summarizes the biomolecular mechanisms underlying CTCs in STS, including the role of phenotypic plasticity in tumor intravasation, anoikis resistance and its interaction with the tumor microenvironment, and stem cell-like phenotypes in tumor initiation at distant sites. Furthermore, we discuss current methodologies for CTC detection, highlighting emerging approaches developed to address the limitations of conventional methods. Finally, we provide a critical overview of subtype-specific detection strategies, as well as their clinical implications in treatment response monitoring and prognostic assessment. Full article

Background: The clinical impact of familial history on the prognosis of non-medullary thyroid cancer (NMTC) remains controversial. This study aimed to investigate whether familial NMTC (fNMTC) is associated with different patterns of response-to-therapy evolution over time compared to sporadic NMTC (sNMTC), using a dynamic risk stratification (DRS) approach. Methods: We analyzed 665 sNMTC cases and 130 fNMTC cases. Response to therapy was assessed at the first follow-up (6–12 months after initial therapy) and at the last outcome. Univariate and multivariate analyses were used to assess the role of family history as a modifier of response reclassification, independently of established prognostic factors. Results: A significant difference in the dynamic pattern of response evolution was observed between fNMTC and sNMTC (p = 0.003), with familial cases showing higher response variability. Among patients with an initial excellent response (n = 558), familial status remained the only independent predictor of losing excellent response (OR 3.3, 95% CI 1.54–7.12; p = 0.002). The worsening in fNMTC was primarily driven by transitions to indeterminate or biochemical incomplete responses (12.3% vs. 4.2%, p = 0.006), while structural progression remained rare and similar between groups (2.5% vs. 1.3%, p = 0.33). Regarding recovery, 50.2% of patients with an initial non-excellent response achieved an excellent response, with no significant difference between familial and sporadic cases (61.2% vs. 47.3%, p = 0.1). An intermediate-to-high ATA risk class was independently associated with a lower probability of achieving an excellent response (OR 0.45, 95% CI 0.25–0.91; p = 0.01). Conclusions: These findings suggest that “Excellent Response” is more fragile in a familial context. Familial NMTC might require prolonged and vigilant biochemical surveillance, even when cases appear to be in full remission. Full article

Background and Objectives: Incidental gallbladder cancer (IGBC) is an uncommon but clinically important diagnosis after cholecystectomy for presumed benign biliary disease. This study aimed to determine the incidence of invasive IGBC in a large cholecystectomy cohort and to describe its clinicopathological profile, stage-specific management pathway, and exploratory univariable survival associations. Materials and Methods: We retrospectively reviewed all cholecystectomies performed between January 2010 and December 2025 at a tertiary referral center (n = 19,798). Patients with known preoperative gallbladder cancer and those with incomplete data precluding reliable staging or survival assessment were excluded. Only invasive IGBC was analyzed; dysplasia and carcinoma in situ were excluded a priori. Overall survival (OS) was defined from index surgery to death from any cause, and disease-free survival (DFS) was assessed in patients with non-metastatic disease at baseline. Survival was estimated using Kaplan–Meier methods, and associations with survival outcomes were explored using univariable Cox regression. Results: IGBC was identified in 43 patients (0.22%). Adenocarcinoma predominated, pT2 was the most frequent pathological stage, and 11 patients (25.6%) had pT3–T4 disease. Staged re-resection was performed in 12 patients (27.9%). Median OS was 48.0 months (95% CI, 34.0–62.0), and median DFS in the M0 cohort was 80.0 months (95% CI, 9.5–150.5). The 2-, 4-, and 6-year OS rates were 78.2%, 48.3%, and 38.8%, respectively; the corresponding DFS rates were 70.4%, 59.3%, and 50.8%. In exploratory univariable analyses, pathological T stage showed the most consistent unadjusted association with OS and DFS, whereas margin positivity, perineural invasion, lymphovascular invasion, and increasing tumor size were associated with worse DFS. Conclusions: Although rare, IGBC may present with advanced pathological features despite presumed benign disease. These findings support meticulous pathological assessment, structured postoperative staging, and risk-adapted multidisciplinary management. Given the limited sample size and exploratory, unadjusted analyses, survival associations should be interpreted cautiously. Full article