Frontiers in Oncology最新文献

Background: Primary hepatic carcinosarcoma is a rare, aggressive tumour with both carcinomatous and sarcomatous components. Limited documented cases hinder comprehensive understanding, making diagnosis, treatment, and management particularly challenging for clinicians.

Case: A 62-year-old female, with prior cervical squamous cell carcinoma 7 years ago, underwent right hemihepatectomy, cholecystectomy, and diaphragmatic resection in 2025. Grossly, a 180 mm white hepatic tumour with a large cystic cavity was seen adherent to the diaphragm, extending to the resection margin (R2), while the hepatic resection margin was clear (R0). Histology confirmed hepatic carcinosarcoma (pT4), comprising cholangiocarcinoma (CK7, BerEP4+), hepatocellular carcinoma (Glypican-3+), and squamous carcinoma (p63, p40+). Sarcomatous areas included rhabdomyosarcomatous (Desmin, Myogenin, MyoD1+), leiomyosarcomatous (SMA+), and chondrosarcomatous (S100+) differentiation. PLAP and CD117 positivity suggested germ cell-like features. There is no distinct separation between the carcinomatous and sarcomatous components. Molecular profiling revealed a KIAA1549::BRAF fusion alongside oncogenic variants: TERT c.-124C>T (VAF 0.60) and TP53 c.811G>A p. (Glu271Lys) (VAF 0.90). Targeted panel sequencing showed no other actionable mutations. MSI readout was 2.5%, confirming microsatellite stability (MSS).

Outcome: Multidisciplinary review at tertiary centres confirmed the rarity and grave outlook. The patient developed early recurrence with thoraco-abdominal deposits, venous thromboembolism, and pleural effusion. Paclitaxel-carboplatin chemotherapy was commenced with dose modifications for hepatotoxicity, complicated by infusion reactions, mild neuropathy, and mucositis.

Conclusion: This case underlines the extreme morphological and molecular heterogeneity of hepatic carcinosarcomas, the rapid progression despite surgery, and the limited systemic treatment options available for such rare tumours.

Introduction: Angiomyolipoma (AML) is a mesenchymal tumor composed of blood vessels, smooth muscle, and adipose tissue, and is generally considered benign. However, epithelioid angiomyolipoma (eAML) is a rare and aggressive variant with metastatic potential. Molecular characterization utilizing the tuberous sclerosis complex (TSC)-mTOR pathway is beneficial in advanced disease. This report describes the clinical course, histopathological findings, and molecular analysis of a patient with metastatic eAML.

Methods: A 59-year-old Japanese man with no personal or family history of tuberous sclerosis (TSC) was admitted to the hospital with gradually worsening back pain and initially diagnosed with clear cell renal cell carcinoma (ccRCC). He underwent nephrectomy, followed by hepatic recurrence treated with pazopanib and subsequent axitinib. Both were discontinued due to intolerance, and the two remaining liver metastases were surgically resected. Histopathological examination of the resected lesions revealed eAML. After several recurrences and resections, unresectable hepatic and pulmonary metastases eventually developed.

Results: Comprehensive genomic profiling (CGP) using the resected liver metastasis specimen identified two somatic TSC2 mutations: a frameshift mutation (p. P677fs*21; variant allele frequency [VAF] 0.0789) and a nonsense mutation (p. S1469*; VAF 0.0736), suggesting biallelic loss of TSC2. Based on these findings, everolimus, a mammalian/mechanistic target of rapamycin (mTOR) inhibitor, was recommended, which markedly reduced the size of the metastatic lesions and was continued for 24 months until disease progression without severe adverse events.

Discussion: This case suggests that CGP can help identify actionable alterations in eAML, such as TSC2 mutations, to guide personalized therapy with mTOR inhibitors.

Introduction: Hydronephrosis is typically considered a hallmark radiographic finding of urinary tract obstruction, expected to develop within 7 days of onset. However, this timeline may not apply universally. We report a rare case of delayed-onset hydronephrosis in the context of borderline end-stage renal dysfunction following radical nephrectomy in a patient with metastatic renal cell carcinoma (RCC), emphasizing the limitations of imaging in the early diagnosis of obstruction.

Case presentation: A 59-year-old male patient with metastatic renal cell carcinoma underwent right cytoreductive nephrectomy for an 8.5-cm renal mass with significant retroperitoneal lymphadenopathy and pulmonary metastases. Preoperative imaging showed mild left-sided hydronephrosis, and baseline renal function was preserved [estimated glomerular filtration rate (eGFR) 68 mL/min/1.73 m²]. Postoperatively, the patient immediately began experiencing a rapidly progressive decline in renal function, with eGFR falling to 15 mL/min/1.73 m² and serum potassium rising to 7.0 mmol/L. Repeat imaging performed 8 days following initial decline was unremarkable, with findings consistent with prior scans. Subsequent nuclear medicine studies confirmed delayed perfusion and obstructive physiology in the solitary kidney. A nephrostomy tube was placed 15 days following the decline, leading to rapid improvement in renal function (eGFR 44 mL/min/1.73 m² by POD 41).

Discussion: This case illustrates the potential for clinically significant obstruction to occur in the absence of early hydronephrotic changes on imaging. We hypothesize that hyperacute progressive obstruction may lead to rapid intrarenal pressure stabilization, limiting capsular stretch and delaying radiographic findings. The absence of pain and significant radiographic hydronephrosis contributed to diagnostic delay.

Conclusions: The absence of hydronephrosis on imaging cannot exclude obstruction, particularly in patients with a solitary functional kidney and high-risk features such as retroperitoneal malignancy. Early clinical deterioration should prompt a high index of suspicion and further diagnostic evaluation to prevent irreversible renal injury.

Background: Cronobacter sakazakii is an emerging Gram-negative opportunistic pathogen, mostly associated with severe neonatal infections. In adults, infections are rare and usually occur in immuno-compromised or elderly patients. Urinary tract infections caused by C. sakazakii in oncological adults are extremely uncommon.

Case: We report a 66-year-old Caucasian male with acute myeloid leukaemia (AML) with a history of bladder carcinoma. The patient was admitted to the Haematology ward with fever (38.5°C), dysuria, pyuria, abdominal pain, and diarrhoea. He was already undergoing treatment at our Institute for AML and had completed the third cycle of liposomal daunorubicin/cytarabine (Vyxeos) 23 days prior to admission. Urine culture revealed C. sakazakii infection, confirmed on two different culture media. Blood and stool cultures were negative. The isolate was fully susceptible to all tested antibiotics. Empirical therapy with piperacillin/tazobactam was initiated, leading to rapid resolution of fever and urinary symptoms. Follow-up urine cultures after one week were negative, and the patient was discharged.

Conclusions: This case highlights a rare urinary tract infection caused by C. sakazakii in an immunocompromised adult. Conventional culture-based methods, with confirmation on two different media, enabled accurate identification of the pathogen. Prompt empirical antimicrobial therapy resulted in rapid clinical improvement and complete recovery. Reporting such cases contributes to awareness of this emerging pathogen in adult oncological patients and underscores the importance of culture-based diagnosis to guide effective management.

Background: The differential diagnosis of an adrenal mass is critical for clinical management. We report a case that expanded the spectrum of a rare disease and present a novel diagnostic trap for both pathologists and clinicians.

Methods: Histopathological, immunohistochemical (CD68, CD163, ALK), and molecular (FISH) analyses were performed on a right adrenal tumor from an 81-year-old male.

Results: The tumor was diagnosed as ALK-positive histiocytosis. Uniquely, it presented as a primary adrenal mass with unusual morphology. The tumor cells showed marked anaplasia and emperipolesis. Apart from classic xanthogranuloma areas, the tumor exhibited hypercellular and hypocellular zones. Neoplastic cells in the hypercellular regions displayed anaplastic features, including a high nuclear-to-cytoplasmic ratio, prominent nucleoli, and observable mitotic figures. In contrast, neoplastic cells in the hypocellular areas were cytologically bland within a myxoid stroma. Neoplastic cells were positive for macrophage markers CD68, CD163 and ALK. Fluorescence in situ hybridization (FISH) demonstrated ALK gene rearrangements. The patient was disease-free after 8 months.

Conclusion: To our knowledge, this is the first documentation of primary ALK-positive histiocytosis in the adrenal gland. The presence of anaplastic features poses a high risk of misdiagnosis as a sarcoma or carcinoma, potentially leading to overly aggressive therapy. Therefore, we advocate for the inclusion of this entity in the differential diagnosis of adrenal neoplasms and recommend routine ALK testing in similar challenging cases to guide precise management and avoid therapeutic errors.

Background: Latin America and the Caribbean (LAC) have higher prostate cancer (PCa) mortality rates than other regions, possibly due to disparities in detection and treatment, as well as differences in tumor biology and behavior. This scoping review aimed to identify studies conducted in LAC that evaluated potential biomarkers associated with PCa.

Methods: A search was conducted in PubMed, Scopus, Embase, LILACS, and Web of Science, including original studies conducted in LAC that evaluated the presence of potential biomarkers in relation to PCa. Due to the heterogeneity of the studies, a descriptive analysis of the data was performed.

Results: A total of 138 articles were included, evaluating 342 potential biomarkers across 17 countries/territories of LAC. Articles were classified into one or more of the following categories of potential biomarkers: risk of developing PCa (n=74), screening, early detection, and diagnosis (n=13), prognosis (n=48), treatment (n=10) and others (n=12). The countries with the most publications were Brazil, Mexico, and Chile.

Conclusion: Most studies analyzed the relationship between various potential biomarkers and the risk of developing PCa as well as its prognosis. The majority of studies came from continental countries with lower percentages of African ancestry and lower PCa mortality rates, highlighting the need to strengthen research in LAC while improving access to healthcare. Systematic review registration.

Introduction: Colorectal neoplasia is a significant global health burden. Early detection is critical for improving clinical outcomes. However, developing a noninvasive strategy for routine detection of colorectal neoplasia remains challenging. This study evaluated the diagnostic performance of a combined SDC2/SFRP2/TFPI2 gene methylation stool DNA test for detecting colorectal cancer (CRC) and advanced adenoma (AA).

Methods: A multicenter, case-control study was conducted involving 409 patients with CRC, 82 patients with AA, and 495 control participants between July 2022 and March 2024. Stool samples were collected from all participants and analyzed for SDC2, SFRP2, and TFPI2 methylation using quantitative fluorescent polymerase chain reaction (PCR). To evaluate the detection efficacy of the SDC2/SFRP2/TFPI2 methylation assay in comparison to conventional methods, fecal occult blood test (FOBT) and serum carcinoembryonic antigen (CEA) levels were measured in 110 CRC patients and 100 healthy individuals at Tianjin Medical University General Hospital.

Results: The stool DNA test demonstrated high sensitivity for CRC (94.13%, 95% CI: 91.42-96.03) and AA (59.76%, 95% CI: 48.94-69.70), with 94.74% specificity (95% CI: 90.30-97.21) in the normal controls. Notably, the SDC2 marker displayed zero false positives among 98 digestive system cancer cases within the control groups, while SFRP2 and TFPI2 showed 8.16% and 10.2% false-positive rates, respectively. The stool DNA test accurately identified CRC, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.9343, and AA, with an AUC of 0.7729. Furthermore, positive stool DNA test results were significantly associated with distal cancer, ulcerative type, deeper tumor infiltration, flat-type AA, and lesions with high-grade dysplasia (P < 0.05). Among the 110 patients with CRC and 100 healthy controls, the AUC values for FOBT, CEA, and stool DNA were 0.7532, 0.6732, and 0.9399, respectively. The integration of all three detection methods achieved the highest detection efficacy (AUC = 0.9725).

Conclusion: The combined methylation assay of SDC2, SFRP2, and TFPI2 outperformed FOBT and CEA in detecting CRC and AA, although further optimization is required for AA detection. Its high specificity and compatibility with routine screening procedures underscore its potential as a tool for detecting colorectal neoplasia.

Objective: This study aimed to develop an explainable fusion model that integrates intratumoral, peritumoral, and habitat features derived from MRI to evaluate its feasibility for predicting the WHO/ISUP nuclear grade of clear cell renal cell carcinoma (ccRCC).

Methods: We retrospectively enrolled 154 patients with pathologically confirmed ccRCC and partitioned them into a training set (n = 108) and an independent test set (n = 46). On contrast-enhanced T1-weighted images, regions of interest were manually delineated layer-by-layer along the tumor margin and expanded outward by 1 mm, 2 mm, 3 mm, 4 mm and 5 mm to derive peritumoral regions. Tumor habitat regions were identified using the K-means clustering algorithm. After extraction and selection of radiomic features, radiomics and habitat models were constructed using five machine learning algorithms. These effective features were then integrated into a nomogram. Model performance was assessed by plotting receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). Model calibration and clinical utility were evaluated using calibration curves and decision curve analysis (DCA). Model interpretability was enhanced by employing Shapley Additive exPlanations (SHAP).

Results: Three habitat subregions were identified within tumors. The integrated habitat region(Habitat) model demonstrated the highest performance among the evaluated habitat models, with AUCs of 0.894 and 0.877 in the training and test sets, respectively. The Peri2mm model achieved AUCs of 0.884 and 0.839, outperforming other peritumoral ranges. Therefore, the 2-mm peritumoral margin was considered a potentially optimal analysis range in this cohort.When the integrated habitat region signature was combined with intratumoral features, 2-mm peritumoral features and the independent clinical predictor (corticomedullary enhancement level) in a nomogram, predictive performance was further improved, achieving AUCs of 0.934 and 0.912. SHAP bee swarm and force plots provided intuitive visualization of the habitat model's decision-making process.

Conclusion: The nomogram, which integrates intratumoral, peritumoral and habitat radiomic features derived from MRI, demonstrated excellent performance for noninvasive preoperative prediction of WHO/ISUP nuclear grade in ccRCC and holds promise as an adjunctive tool for individualized therapy planning and prognostic assessment. However, its clinical application requires further external validation.

Background: Hepatocellular carcinoma (HCC) is a lethal malignancy. Lipid metabolic reprogramming influences therapy response, but its prognostic value is undefined.

Methods: From TCGA and GEO data, we derived an 8-gene lipid metabolism-related risk score (LMrisk) via LASSO regression. Its associations with tumor immunity and drug sensitivity were analyzed. The lead gene, LPCAT1, was functionally assessed in vitro.

Results: The LMrisk signature robustly stratified patient survival in both cohorts. Integrated analysis identified LPCAT1 as a hub gene. Its overexpression in HCC cells potently enhanced proliferation, migration, and invasion.

Conclusion: LPCAT1 is a vital prognostic biomarker and putative therapeutic target in HCC.

Objective: To investigate the therapeutic effect and mechanism of Pulsed ultrasound stimulated microbubbles to form thrombus and enhance the effect of high-intensity focused ultrasound (HIFU) for ablation of vascular tumors.

Methods: After EOMA cells were inoculated subcutaneously in mice to form a hemangioendothelioma model, the mice were treated with HIFU alone, pulsed ultrasound combined with microbubbles therapy(PUCM) and the combination of the two methods(PUCM+HIFU) by Contrast ultrasound imaging, HE staining, CD31 immunofluorescence staining to detect the successful establishment of the model and the therapeutic effect. The effect of different treatment groups on apoptosis was detected by TUNEL staining. qRT-PCR, ELISA, CD31 and VEGF immunofluorescence staining were used to detect the changes of cytokines related to thrombosis and angiogenesis. The safety of the treatment was verified through HE staining of important organs and blood biochemical tests.

Results: We successfully established hemangioendothelioma model, and the characteristics of CEUS are consistent with clinical findings. Pulsed ultrasonic stimulation of microbubbles can form thrombus. Further, PUCM+HIFU exhibits safety and significantly higher ablation effect and promotes apoptosis and necrosis of tumor cells. In addition, PUCM+HIFU can effectively lower the secretion of cytokines related to angiogenesis.

Conclusion: In this study, a new therapeutic approach for vascular tumors was proposed, pulsed ultrasound stimulated microbubbles to form thrombus in vascular tumors and then combined with high-intensity focused ultrasound to treat vascular tumors. The combined therapy can better ablate vascular tumors and reduce the formation of blood vessels in the tumors. It is expected to provide a new scheme for the clinical treatment of vascular tumors.