Complete androgen insensitivity syndrome (CAIS) is a rare X-linked recessive disorder due to androgenreceptor mutations, characterised by a 46,XY karyotype, female phenotype, and undescended testes. This reportaims to illustrate the clinical management and the rare synchronous pathology of multiple gonadal tumors in a 60-year-old phenotypic female with long-standing CAIS.

Patients diagnosed with metastatic colorectal cancer (mCRC) face a constrained therapeutic landscape following the failure of initial treatment. This multicenter, single-arm, phase II trial (NCT06202001) aimed to assess the efficacy and safety of a novel second-line regimen comprising trifluridine/tipiracil (TAS-102), irinotecan, and bevacizumab. Patients with mCRC resistant to prior fluoropyrimidine and oxaliplatin-based chemotherapy were enrolled. Based on a preceding phase I trial, patients received biweekly cycles of oral TAS-102 (30 mg/m² twice daily, days 1-5), intravenous irinotecan (150 mg/m²), and intravenous bevacizumab (5 mg/kg). The primary outcome measure was the objective response rate (ORR). From October 2023 to August 2024, 60 patients were enrolled. As of December 2024, the ORR was 18.3% (2 complete and 9 partial responses), and the disease control rate (DCR) was 83.3%. The median progression-free survival (PFS) was 6.6 months (95% CI, 4.39-8.81), and the median overall survival (OS) was 17.3 months (95% CI, 13.55-21.05). Subgroup analyses indicated that prior resection of the primary tumor was associated with significantly longer median OS (21.9 vs. 16.2 months; p = 0.048) and PFS (8.9 vs. 5.2 months; p = 0.004). The most frequently reported treatment-related adverse events (TRAEs) were nausea (100%), neutropenia (86.7%), and anemia (83.3%). The predominant grade 3/4 TRAEs included neutropenia (48.3%), febrile neutropenia (8.3%), and diarrhea (6.7%). In conclusion, the combination of irinotecan, TAS-102, and bevacizumab shows encouraging efficacy and a manageable safety profile as a second-line therapy for mCRC, meriting further investigation.

ObjectiveOral squamous cell carcinoma is the most common malignant tumor occurring in the head and neck region. Current treatment principles are based on radical surgery, supplemented by radiotherapy and chemotherapy. However, the 5-year survival rate for patients remains approximately 50%. Therefore, further research into the molecular mechanisms underlying oral squamous cell carcinoma development is needed to identify more effective treatment methods.MethodsIn this study, immunohistochemical techniques were used to quantitatively analyze the expression levels of E-cadherin, vimentin, CD206, programmed cell death receptor 1 (PD-1), and programmed cell death ligand 1 (PD-L1) in 45 pathological sections of oral squamous cell carcinoma. The results showed that the expression levels of vimentin, CD206, and programmed cell death ligand 1 were significantly associated with overall survival. Additionally, Cox multivariate analysis indicated that the M2 macrophage marker, CD206, is an independent risk factor for poor prognosis in oral squamous cell carcinoma. Furthermore, correlation analysis revealed that E-cadherin expression was negatively correlated with vimentin, CD206, and programmed cell death ligand 1 expression levels. Vimentin expression was positively correlated with programmed cell death receptor 1 and programmed cell death ligand 1 expressions.ResultsImmunohistochemical examination indicated that M2 macrophages are an independent risk factor for poor prognosis in oral squamous cell carcinoma and are closely associated with overall survival. Furthermore, they may influence the development and progression of oral squamous cell carcinoma tumors by inducing epithelial-mesenchymal transition in oral squamous cell carcinoma tumor cells. Third, programmed cell death ligand 1 expression has an adverse impact on oral squamous cell carcinoma prognosis and is significantly correlated with the expression levels of CD206, E-cadherin, and vimentin.ConclusionsThis study indicates that programmed cell death receptor 1/programmed cell death ligand 1 and CD206 expressions are independent risk factors for poor oral squamous cell carcinoma prognosis; however, whether programmed cell death receptor 1/programmed cell death ligand 1 expression influences the occurrence and development of oral squamous cell carcinoma through M2 macrophages requires further investigation.

Tumors foster an immunosuppressive microenvironment to evade the antitumor immune response. However, the influence of intratumoral immunosuppressive steroids on tumor-infiltrating natural killer (NK) cells and their implications for effective immunotherapy has remained largely unexplored. Here, we report that the functional enrichment of glucocorticoid cortisol signaling in the lung tumor microenvironment (TME) impairs NK cell anti-tumor cytotoxicity and exacerbates hypoxic stress. Cancer-associated fibroblasts (CAFs) and macrophages convert inactive cortisone to active cortisol, while T cells, fibroblasts, myeloid cells, macrophages, and cancer cells contribute to de novo steroid biosynthesis, collectively establishing a steroid-rich niche. Pharmacological inhibition of the glucocorticoid receptor (GR) in vivo alleviates cortisol-mediated immune suppression, resulting in reduced tumor growth and enhanced cytotoxicity of tumor-infiltrating NK cells. To overcome the cortisol-induced dysfunction of solid tumor targeting immunotherapy, we engineered chimeric antigen receptor (CAR) -NK cells specific to the Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (highly expressed in lung tumors) and rendered them cortisol-resistant by genetic deletion of the cortisol receptor gene NR3C1. In cortisol-rich niches, cortisol-resistant CAR-NK cells sustained antitumor cytotoxicity. Mechanistically, NR3C1 deletion relieved cortisol-mediated suppression of PI3K-AKT-NF-κB signaling, restored anti-tumor activity, and markedly reduced hypoxic stress. In lung metastasis models, cortisol-resistant CAR-NK cells achieved superior tumor control and significantly reduced tumor burden compared with conventional CAR-NK cells. Together, these findings identify local cortisol signaling as a critical barrier to solid tumor immunotherapy and establish cortisol-resistant CAR-NK cells as a promising strategy for targeting steroidogenic solid tumors, which can be combined with therapeutic glucocorticoids.

Objective: To investigate the clinical characteristics and treatment outcomes of parameningeal rhabdomyosarcoma (PM-RMS) of the head and neck in children, and to analyze the risk factors influencing prognosis. Methods: Clinical data of children with PM-RMS admitted to Beijing Tongren Hospital of Capital Medical University between September 2009 and September 2023 were collected. The cohort included 27 males and 26 females, aged from 4 to 191 months. Overall survival and event-free survival rates were calculated using the Kaplan-Meier method. Log-rank test was used for univariate analysis and Cox regression model for multivariate analysis. Results: The predominant pathological subtypes were embryonal (30 cases, 56.6%) and alveolar (21 cases, 39.6%). There were 23 cases in stage Ⅱ, 16 cases in stage Ⅲ, and 14 cases in stage Ⅳ. According to risk stratification, there were 9 cases with low-risk, 24 with intermediate-risk, 8 with high-risk, and 12 with the invasion of central nervous system. The median follow-up time was 36 months (range: 4-152 months). The overall survival rate was 67.9% (36/53) and the 5-year overall survival rate was 53.6%. All patients received chemotherapy and 43 patients received radiotherapy. Univariate analysis revealed that lymph node metastasis (χ2=4.82, P=0.028), distant metastasis (χ2=8.63, P=0.003), and absent of radiotherapy (χ2=4.18, P=0.041) were significantly associated with poor prognosis. Multivariate analysis identified distant metastasis (HR=4.888, 95%CI: 1.345-17.769, P=0.016) and absent of radiotherapy (HR=5.155, 95%CI: 1.637-16.130, P=0.005) as independent risk factors for prognosis.Conclusion: Pediatric PM-RMS of the head and neck is highly malignant, prone to distant metastasis, and associated with a poor prognosis. Radiotherapy can improve local control rates in affected children.

Objective: To assess the real-world data of thyroid cancer patients with neoadjuvant treatment of anlotinib, and to evaluate the clinical efficacy, safety and correlation with molecular characteristics. Methods: Patients with locally advanced thyroid cancer were treated with neoadjuvant therapy with 10 mg anlotinib from April 2021 to June 2025. Statistical analysis was performed on patient demographics, molecular characteristics, changes in target lesions before and after targeted therapy, treatment-related adverse events, imaging CT values, and surgical rates. Results: A total of 24 patients were enrolled, including 21 of papillary carcinoma, 2 of high-grade differentiated thyroid cancer, and 1 of follicular carcinoma with medullary carcinoma. Eighteen were treatment-naïve patients, and 6 were relapsed patients after treatment. Fifty percent of patients were in the T4b stage. Of 24 patients, 17 underwent genetic testing, and mutations were detected in 15 patients, including 8 with mutations in two genes and 2 with mutations in three genes. Six patients had an ECOG performance status of 0 score, 8 patients with 1 score, and 10 patients with 2 scores. There were 6 patients of partial response, 18 of stable disease, and no progressive disease patients. The objective response rate was 25% and the disease control rate was 100%. The CT value of imaging was significantly reduced after targeted therapy (t=2.589, P=0.017). Among of the 24 patients, 16 (66.67%) underwent surgery. The surgical conversion rate in T4b stage patients was 75%(9/12). The average medication cycle was 5.91 cycles. The main treatment-related adverse events were hypertension (6/24), proteinuria (3/24), and palmar-plantar erythrodysesthesia syndrome (5/24). Adverse events were grade Ⅰ-Ⅱ, and no Ⅲ-Ⅳ grade adverse events occurred. The average follow-up time was 24.79 months. Conclusion: Anlotinib can be used as a preoperative neoadjuvant treatment for patients with locally advanced thyroid cancer, and the initial dose of 10 mg can ensure both efficacy and safety.

Objective: To investigate the diagnostic and prognostic value of CSPG4 and SFRP1 expression in esophageal basaloid squamous cell carcinoma (EBSCC). Methods: EBSCC cases in pathological diagnostic reports from Zhongshan Hospital, Fudan University from 2001 to 2023 were collected. Three senior pathologists independently reviewed the slides, and 81 cases of EBSCC and 55 conventional esophageal squamous cell carcinomas (ESCC) with consistent diagnoses were collected. Immunohistochemical staining for CSPG4 and SFRP1 was performed. The sensitivity and specificity of CSPG4 and SFRP1 expression in diagnosing EBSCC, as well as their correlation with prognosis, were analyzed. Results: Among the 81 EBSCC and 55 conventional ESCC cases, there were no significant differences in patient gender, age, or surgical resection time (P>0.05). The expression levels of CSPG4 and SFRP1 were significantly higher in EBSCC than in conventional ESCC (P<0.001), with no significant differences across different invasive layers (P>0.05). The receiver operating characteristic (ROC) curve for CSPG4 had an area under the curve (AUC) value of 0.952, with an optimal H-score cutoff of 75, showing a sensitivity of 92.6% and a specificity of 89.1% for diagnosing EBSCC. For SFRP1, the ROC curve had an AUC value of 0.880, with an optimal H-score cutoff of 1.5, showing a sensitivity of 81.5% and a specificity of 94.5%. When combined, CSPG4 and SFRP1 achieved a sensitivity of 80.2% and a specificity of 100% for diagnosing EBSCC. Among the 79 EBSCC cases with follow-up data, 17.7% showed high expression of both CSPG4 and SFRP1, 17.7% showed high CSPG4 but low SFRP1 expression, 13.9% showed low CSPG4 but high SFRP1 expression, and 50.6% showed low expression of both molecules. Compared to patients with low expression of both CSPG4 and SFRP1, those with high CSPG4 and low SFRP1 expression had the worst prognosis (disease-free survival: P=0.190; overall survival: P=0.031), particularly in stage Ⅰ-Ⅱ patients (disease-free survival: P=0.031; overall survival: P=0.013). Conclusions: CSPG4 and SFRP1 are primarily expressed in EBSCC. The combined application of immunohistochemical staining for these two markers can serve as a molecular indicator for the differential diagnosis and prognostic prediction of EBSCC.

Objective: To assess the utility of histopathological and immunohistochemical characteristics in identifying POLE-mutated (POLEmut) endometrial carcinoma (EC). Methods: A total of 1 541 EC cases that underwent molecular classification at Peking University Third Hospital from January 2018 to December 2024 were included. Cases were categorized into POLEmut and non-POLEmut groups (including p53-abnormal, mismatch repair-deficient, and no specific molecular profile subtypes). A comparative analysis of histopathological features, mismatch repair (MMR) protein expression, and p53 immunostaining patterns was performed. A multivariable logistic regression-derived prediction model for POLEmut status was developed and internally validated. Results: POLEmut tumors showed significantly higher frequencies of prominent peritumoral lymphocytes (PTLs) and tumor-infiltrating lymphocytes (TILs), high-grade nuclei, bizarre nuclei, clear cytoplasm, and ambiguous morphology compared with non-POLEmut tumors (all P<0.05). Multivariable analysis identified severe PTLs/TILs infiltration, high-grade nuclei, ambiguous morphology, and clear cytoplasm as independent positive correlates for POLE mutation status, while aberrant p53 expression and MMR protein loss were negative correlates. The scoring system showed robust discrimination, with an area under the curve (AUC) of 0.867 in the training set (n=1 319) and 0.873 in the test set (n=222). At the ≥3- point cutoff, it provided a sensitivity of 80.8%, specificity of 66.3%, and negative predictive value (NPV) of 96.3% in the test set. Calibration analysis indicated good overall performance (Brier score=0.045), though local miscalibration was observed in intermediate-and low-risk subgroups. Conclusions: This POLEmut scoring system achieves high sensitivity and high NPV for initial screening of POLEmut EC. Despite a relatively low positive predictive value requiring confirmatory sequencing, it effectively enriches candidates needing POLE gene sequencing in resource-limited settings. Future multicenter validation is warranted to assess its clinical utility.

Objective: To study the clinicopathological features and key differential diagnosis of clear cell adenocarcinoma (CCA) of the urinary tract. Methods: A retrospective analysis was performed on the clinicopathological data, immunophenotypes, and molecular test results of patients with pathologically confirmed primary CCA of the urinary tract at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China from December 2015 to September 2024. This study was supplemented by a review of the relevant literature. Results: Nine patients were included (1 male and 8 females), age 57.0 (44.5, 61.0) years old. The main symptoms were urinary tract irritation and hematuria. Th lesions were in the urethra of 5 patients and in the bladder in 4 patients. Macroscopically, the tumors were cauliflower-like, with edema and firm consistency. Microscopically, they showed mostly papillary/tubular-cystic structures, with solid sheet-like arrangements. The tumor cells showed clear or eosinophilic cytoplasm, moderate to high nuclear grade, prominent nucleoli, and frequent mitotic figures. The tumor cells also exhibited strong expression of PAX8, CK7, and HNF1-β, various positivity of Napsin A and P504s, and partial expression of SOX17, CK20, and GATA3. The Ki-67 index ranged from 30% to 70%, and p53 showed a heterogeneous expression pattern. The cells were negative for p63 and the renal cell carcinoma marker (RCC). Among the 7 cases subject to urine fluorescence in situ hybridization (FISH) testing, 5 cases showed abnormal centromeric signals. One case underwent next-generation sequencing (DNA-seq) and harbored a nonsense ARID1A mutation. Two patients underwent radical surgery, 3 total urethrectomy, and 4 palliative surgery. Four patients received postoperative chemotherapy. The follow-up ranged from 9 to 58 months: 3 patients had tumor recurrence while 2 died. Conclusions: CCA of the urinary tract is a rare and aggressive malignancy. Its histological morphology resembles that of ovarian CCA. The diagnosis should be based on a combination of morphological features and immunophenotype. It is recommended to use PAX8, CK7, HNF1-β, and Napsin A as a core immunohistochemical panel, while testing SOX17 can also help.