Search Results (441)

Background: Prognosis in vulvar squamous cell carcinoma (VSCC) is strongly influenced by lymph node involvement and adverse clinicopathological features. Systemic inflammatory indices derived from blood counts may reflect tumor–host interactions associated with adverse pathological phenotypes. Objective: To assess associations of preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) with nodal metastasis, lymphovascular space invasion (LVSI), and tumor size. Methods: This retrospective single-center study included 93 surgically treated patients between March 2017 and February 2026. Results: NLR was associated with nodal metastasis (unadjusted p = 0.015; false discovery rate [FDR]-adjusted q = 0.047) and LVSI (unadjusted p < 0.001; FDR-adjusted q = 0.006). NLR showed modest discrimination for nodal metastasis (area under the receiver operating characteristic curve [AUC] = 0.647). For LVSI, NLR had the highest AUC among the evaluated markers (AUC = 0.789; 95% confidence interval [CI]: 0.683–0.894), but 16 cases were positive and the positive predictive value (PPV) was low (0.378). Nominal MLR findings for LVSI and large tumor size did not remain significant after FDR correction (both q = 0.308), while PLR showed no consistent associations. Elevated NLR was associated with nodal metastasis in univariable analysis (odds ratio [OR] = 3.291; p = 0.012) but not in multivariable models including LVSI (adjusted OR = 1.296; p = 0.654) or excluding LVSI (adjusted OR = 1.823; p = 0.261). Conclusions: NLR was associated with adverse pathological features but was not independently associated with nodal metastasis and should not be used as a standalone predictive or clinical decision-making tool. Full article

Background/Objectives: Evaluation of renal tumour masses relies on conventional imaging, which cannot reliably characterise the histopathological type, and no validated blood-based diagnostic marker is available for renal cell carcinoma. The cfDNA integrity index, the ratio of long to short circulating cell-free DNA (cfDNA) fragments, may reflect the necrotic origin of tumour-derived DNA and is a candidate qualitative marker of malignancy. This exploratory, single-centre case–control study assessed the preoperative plasma cfDNA integrity index in patients with clear cell renal cell carcinoma (ccRCC). Methods: Plasma concentrations of 90 bp and 222 bp cfDNA fragments were measured by quantitative real-time PCR (qPCR) in 46 patients with histopathologically confirmed ccRCC (before surgery) and 17 healthy volunteers; the two groups were a convenience sample, were not matched, and differed in age and body-mass index. The cfDNA integrity index was defined as the ratio of the 222 bp to the 90 bp fragment concentration. Results: The cfDNA integrity index was higher in patients with ccRCC than in controls (median 0.28 vs. 0.15; p < 0.001, Mann–Whitney test) and rose progressively across healthy, non-metastatic (M0) and metastatic (M1) groups (p < 0.001, Kruskal–Wallis test; M0 vs. M1 p = 0.004). In unadjusted ROC analysis, both the integrity index (AUC 0.83, 95% CI 0.72–0.94) and its long 222 bp fragment component (AUC 0.93) discriminated patients with ccRCC from healthy volunteers, and the index separated metastatic from non-metastatic disease with an AUC of 0.79 (95% CI 0.64–0.88). The index was higher in high-grade (Fuhrman G3 + G4) tumours (p = 0.04) and in tumours with lymphovascular invasion (p < 0.001), and correlated with primary-tumour diameter. Conclusions: In this exploratory cohort, the preoperative plasma cfDNA integrity index was higher in patients with ccRCC than in healthy volunteers and was associated with several adverse pathological features; these findings require confirmation in larger, matched studies that include benign renal masses before any diagnostic role can be claimed. Full article

Mismatch repair deficiency (MMRd) is a critical biomarker in endometrial cancer (EC) for prognostication, Lynch syndrome screening, and immunotherapy eligibility. This study aimed to determine the prevalence of MMRd and its correlation with clinicopathological characteristics in EC. This prospective observational cohort included 93 patients with EC undergoing primary surgical treatment, managed as per the European Society of Gynaecological Oncology (ESGO) guidelines. MLH1, PMS2, MSH2, and MSH6 expression was assessed through immunohistochemistry (IHC) on formalin-fixed, paraffin-embedded hysterectomy specimens. Associations between mismatch repair (MMR) status and histology, grade, lymphovascular space invasion (LVSI), myometrial invasion, FIGO 2023 stage, nodal status, recurrence, and survival were analyzed. The median age was 66 years. Most tumors were endometrioid (86%), 29% were grade 3, 45.2% showed deep myometrial invasion, and 23.7% had substantial LVSI. MMRd was identified in 41.9% of cases, with MLH1 and PMS2 loss being most frequent, and was significantly associated with endometrioid histology (p = 0.027) and deep myometrial invasion (p = 0.011). No significant correlations were found with grade, LVSI, FIGO stage, nodal involvement, recurrence, or overall survival. Routine MMR assessment may refine risk stratification and guide individualized treatment decisions. Full article

Purpose: This study aimed to determine the optimal temporal threshold for distinguishing “early” from “late” liver metastasis in patients who developed liver metastasis after colorectal cancer (CRC) surgery, and to evaluate whether KRAS and BRAF^V600E mutations, along with other clinicopathological factors, are associated with the timing of liver metastasis. Methods: This retrospective study utilized clinical and pathological data from patients who developed liver metastasis after radical CRC surgery at two centers from 2019 to 2023. X-tile software was used to identify the optimal temporal threshold. Logistic regression analysis was applied to determine if KRAS/BRAF^V600E mutations and other potential factors are independently associated with the time to onset of liver metastasis. Results: X-tile analysis identified 11 months post-surgery as the optimal cutoff for distinguishing early metachronous liver metastasis (EMLM) from late metachronous liver metastasis (LMLM), classifying 114 cases into the EMLM group and 72 into the LMLM group. Comparative analysis indicated statistically significant differences between the two groups in lymphovascular tumor emboli, perineural invasion, and postoperative adjuvant therapy (p < 0.05). Logistic regression analysis revealed that neither KRAS mutation (OR, 1.185; 95% CI: 0.641–2.190; p = 0.587) nor BRAF^V600E mutation (OR, 2.836; 95% CI: 0.302–26.642; p = 0.363) was independently associated with the timing of liver metastasis. In contrast, postoperative adjuvant therapy showed a statistical association with a likelihood of LMLM (OR, 0.253; 95% CI: 0.105–0.611; p = 0.002). Conclusions: This study identified 11 months post-CRC surgery as the optimal cutoff for differentiating EMLM versus LMLM. In this cohort, no statistically significant association was observed between KRAS/BRAF^V600E mutations and the timing of liver metastasis, whereas postoperative adjuvant therapy was statistically correlated with the likelihood of LMLM. This stratification may guide personalized surveillance strategies and provide valuable insights for future mechanistic investigations into the temporal heterogeneity of post-surgical liver metastasis. However, the interpretation and generalization of the findings require external validation in prospective cohorts. Full article

The prediction of the therapeutic response and of the patient outcome following neoadjuvant chemoradiotherapy (nCRT) in rectal cancer (RC) is still a challenging issue. The role of Annexin 1 (ANXA1) in the modulation of the tumor cells’ growth and metastasis has been recently demonstrated, being associated with aggressive pathological features and poor outcome in specific malignancies. The present study aimed to evaluate the association between ANXA1 expression, survival, and clinicopathological parameters of a group of patients diagnosed with ypT3 locally advanced rectal cancer (LARC) following nCRT. The study group consisted of 60 LARC patients with ypT3 tumor stage showing a tumor fragmentation pattern following nCRT. The clinicopathological characteristics and survival parameters in relation to ANXA1 immunohistochemistry characteristics and its scoring were evaluated. ANXA1 expression in tumor cells showed variable intense luminal membrane or combined luminal membrane and cytoplasmic location, excepting three negative cases. The statistical analysis demonstrated a significant association between high ANXA1 expression and ypN category (p < 0.001), perineural invasion (PnI) (p = 0.002), and lymphovascular invasion (LVI) (p = 0.021). Survival analysis showed that high ANXA1 expression is associated with a reduced overall survival (OS) (p = 0.001), while univariate Cox regression confirmed ANXA1 value as an independent predictor of prognosis (H = 5.922, p = 0.004). Our results support ANXA1 value as a potential biomarker of aggressive tumor behavior and poor prognosis in ypT3 LARC patients, with potential implications in diagnosis stratification, opening the prospective to apply precision oncology strategies. However, further studies are required to certify ANXA1 diagnostic and therapeutic relevance in RC patients. Full article

Objectives: Assessment of the impact on survival of endometrial carcinoma according to the 2009 FIGO (International Federation of Gynecology and Obstetrics) classification and the new FIGO 2023 classification highlighting the worse prognosis of the aggressive subtypes. Methods: This multicenter retrospective study included 1181 patients with endometrial cancer. Comprehensive clinical, pathological and treatment-related variables were collected. Primary outcomes included overall survival assessed through five-year follow-ups. Statistical analysis included comparative tests, Kaplan–Meier survival estimation, Cox proportional hazards models and ROC curves analysis to review prognostic accuracy. Results: Aggressive endometrial carcinoma (n = 353) showed significant worse overall survival compared with non-aggressive cases (35.7 versus 60 months). A novel classification based on FIGO 2023 was developed, integrating histological aggressiveness into a different stage and combining early non-aggressive stages in only one stage. While FIGO 2009 and 2023 classifications showed prognostic value, the new model improved risk stratification, clearly distinguishing high-risk groups. Multivariate analysis identified aggressive subtype, stage, age, diabetes, myometrial invasion and lymphovascular invasion as independent predictors. Conclusions: Aggressive histological subtype in endometrial cancer should carry greater prognostic weight in terms of survival and clinical management. Our findings support a potential shift in the current paradigm for these relatively rare but high-risk cases. Full article

Peripheral facial palsy is often attributed to idiopathic Bell’s palsy, but secondary structural causes should be considered when local red flags are present. A 61-year-old man with a 40-pack-year smoking history and former betel quid chewing presented with a verrucous-appearing mass involving the left oral commissure and buccal mucosa, intermittent purulent discharge from the lesion, progressive left facial swelling, and ipsilateral lower-motor-neuron facial palsy with lagophthalmos. Magnetic resonance imaging demonstrated a left buccal/oral-cavity lesion with ipsilateral parotid duct obstruction. He underwent tracheostomy, wide excision, left supraomohyoid neck dissection, and radial forearm free-flap reconstruction. Pathology confirmed squamous cell carcinoma, pT2N0, cM0 (stage II), with perineural invasion; surgical margins were negative, and lymphovascular invasion was not identified. At follow-up, wound healing was satisfactory and purulent discharge had resolved, but lower-motor-neuron facial palsy persisted; adjuvant radiotherapy was recommended. This case emphasizes that lower-motor-neuron facial palsy with an oral mass, purulent discharge, facial swelling, or salivary-duct obstruction should prompt careful oral examination and head-and-neck imaging. Full article

Small intestinal adenocarcinoma (SIAC) is a rare malignancy with a rising incidence and poor prognosis. Although exportin-7 (XPO7) is typically characterized as a tumor suppressor, recent evidence suggests context-dependent oncogenic functions, yet its role in SIAC remains unexplored. This study evaluated the clinicopathological significance of XPO7 expression and its association with KRAS status, autophagy, and cancer stemness in 191 surgically resected primary SIAC cases using immunohistochemistry and automated digital quantification. XPO7 was significantly upregulated in SIAC compared to normal mucosa (p < 0.001). High XPO7 expression, observed in 27.2% of cases, correlated with higher histological grade (p = 0.023) and was identified as an independent predictor of poor overall survival (hazard ratio = 1.703; p = 0.008). Subgroup analysis revealed that high XPO7 levels were associated with significantly shorter median overall survival specifically in cases featuring lymphovascular invasion, nodal metastasis, and KRAS mutations. Furthermore, XPO7 expression demonstrated a significant positive correlation with autophagy markers (LC3B and p62) but not with stemness markers (Sox2, Oct4, and Nanog). In conclusion, XPO7 serves as a significant independent prognostic biomarker for SIAC, and its correlation with autophagy markers in aggressive subgroups highlights its potential as a promising therapeutic target. Full article

Lymphovascular space invasion (LVSI) is a well-established prognostic factor in endometrial cancer; however, its independent contribution to para-aortic nodal metastasis remains incompletely defined. Identifying factors associated with nodal dissemination is important for surgical staging and postoperative management. This retrospective, single-center cohort study included 121 patients with endometrial cancer who underwent laparoscopic pelvic and para-aortic lymphadenectomy. The cohort was predominantly obese (median BMI: 32 kg/m²). Clinicopathological variables were analyzed using univariable and multivariable logistic regression models to identify associations with lymph node metastasis and para-aortic lymph node metastasis. Lymph node metastasis was observed in 16.5% of patients, including para-aortic involvement in 9.9%. In univariable analysis, the LVSI category was significantly associated with lymph node metastasis (p = 0.002), with substantial LVSI being present in 50.0% of patients with nodal metastasis compared with 14.9% of those without. LVSI was categorized as negative, focal, or substantial. In multivariable logistic regression analyses using negative LVSI as the reference category, substantial LVSI remained independently associated with both overall nodal metastasis (OR 5.44, 95% CI 1.67–17.65, p = 0.005) and para-aortic nodal metastasis (OR 6.98, 95% CI 1.81–26.78, p = 0.005), whereas focal LVSI was not significantly associated with either outcome. These findings suggest that the extent of LVSI may be relevant to nodal metastasis, with substantial LVSI showing a stronger association than focal LVSI. Full article

Breast cancer is a leading global diagnosis where lymphovascular invasion (LVI) serves as a critical indicator of metastatic potential. Conventional assessment is often hindered by its reliance on postoperative findings, sampling errors, and subjective interobserver variability. This review evaluates how artificial intelligence (AI), digital pathology, and MRI radiomics provide earlier, quantitative estimations of LVI-related risk. The strongest direct evidence currently comes from MRI-based studies, where validation performance often reaches area under the receiver operating characteristic curve (AUC) values of 0.84–0.90. By contrast, digital pathology is especially mature for LVI-adjacent tasks such as lymph node metastasis detection and slide-based relapse-risk modelling, which together provide an important translational foundation for future LVI-specific tools. This review also addresses issues that remain underdeveloped in the literature, including the distinction between lymphatic and vascular invasion, AI-specific risk-of-bias and reporting frameworks, the emerging regulatory landscape for adjacent breast AI tools, and the gap between resection-based development datasets and biopsy-level preoperative use. Although most modern computational models are developed using extensive surgical resection specimens, their true clinical utility hinges on successful validation and performance within the highly restricted, fragmented tissue context of preoperative core needle biopsies. Overall, the field appears most promising when LVI prediction is framed not as an isolated binary task, but as one component of a broader metastatic-risk workflow that supports calibrated, multidisciplinary breast cancer decision-making. Full article

Background/Objectives: Perineural invasion (PNI) and lymphovascular invasion (LVI) are adverse histopathological features in head and neck squamous cell carcinoma (HNSCC). Their relationship with clinical and pathological T categories remains clinically relevant, particularly in surgically treated cohorts. This exploratory retrospective study evaluated the frequency of PNI and LVI according to clinical and pathological T stage in primary HNSCC staged according to the AJCC/UICC 8th edition. Methods: We analyzed 170 consecutive surgically treated patients with primary HNSCC. PNI and LVI were recorded from histopathology reports of resection specimens. Results: PNI status was available in 124 cases and was positive in 61 (49.2%); LVI status was available in 126 cases and was positive in 62 (49.2%). PNI frequency increased with advancing clinical T stage (12.5% in cT1, 54.3% in cT2, 70.0% in cT3, and 69.2% in cT4) and pathological T stage (14.3% in pT1, 51.5% in pT2, 71.9% in pT3, and 66.7% in pT4). LVI also increased with higher clinical T stage (28.1%, 53.2%, 57.1%, and 61.5%) and pathological T stage (25.7%, 50.0%, 54.6%, and 75.0%). Tongue tumors showed descriptively high crude proportions of PNI and LVI, but these subgroup findings were based on small numbers and were not adjusted for T stage, depth of invasion, or other confounders. Conclusions: In this single-center cohort, PNI and LVI were more frequent in higher T categories. These findings should be interpreted as descriptive and hypothesis-generating, because no recurrence, survival, or treatment-outcome analyses were available and the adjusted models were exploratory. Full article

Background/Objectives: Following the LACC trial, the role of minimally invasive radical surgery for early-stage cervical cancer remains controversial. Robotic-assisted approaches have been proposed as a potential strategy to preserve the benefits of minimally invasive surgery while incorporating contemporary oncologic precautions. This study compared perioperative, pathological, and early oncologic outcomes between robotic and open radical surgical management in patients with FIGO 2018 stage IA2–IIA1 cervical cancer. Methods: Patients underwent robotic surgery (n = 20; da Vinci Xi), including robotic radical hysterectomy, compartment-based procedures, and fertility-sparing surgery when clinically indicated, or open abdominal radical hysterectomy (n = 22). Perioperative outcomes, histopathological parameters (including lymphovascular space invasion [LVSI], lymph node status, and margin status), and early oncologic outcomes were evaluated. Exploratory multivariable regression analyses were performed to adjust for baseline differences, including age and tumor size. Results: Patients in the open-surgery cohort were older (56.23 ± 15.87 vs. 45.67 ± 9.31 years; p = 0.012) and had significantly larger tumors (3.07 ± 1.10 vs. 1.4 ± 0.7 cm; p = 0.003). Robotic surgery was associated with longer operative time (178 ± 42 vs. 150 ± 38 min; p = 0.028), lower blood loss (112 ± 61 vs. 518 ± 98 mL; p < 0.001), and shorter hospital stay (4.2 ± 1.6 vs. 6.2 ± 1.4 days; p < 0.001). The robotic cohort also demonstrated a higher lymph node yield (median 18 vs. 9; p < 0.001). No statistically significant differences were observed between groups in lymph node metastasis (20.0% vs. 22.7%; p = 1.000), LVSI (33.3% vs. 63.6%; p = 0.121), or R0 resection rate (100% vs. 95.5%; p = 1.000). In exploratory adjusted analyses, surgical approach was not associated with adverse pathological features, whereas tumor size emerged as an independent predictor of both lymph node metastasis and LVSI. No recurrences were observed in the robotic cohort during the available follow-up period. Conclusions: In this exploratory comparative cohort study, robotic radical surgical management in carefully selected patients with predominantly small-volume disease was associated with favorable perioperative outcomes and no statistically significant differences in pathological parameters compared with open surgery. Tumor size, rather than surgical approach, emerged as the principal predictor of adverse pathological features. Given the limited sample size, baseline imbalances between cohorts, heterogeneous robotic procedures, and absence of mature survival data, these findings should not be interpreted as evidence of oncologic equivalence and require confirmation in larger prospective studies. Full article

Apocrine sweat gland adenocarcinoma is an uncommon feline adnexal neoplasm, and lower-lip involvement is rarely documented. A 14-year-old spayed female Siamese cat was evaluated for a firm 1.3 cm right lower-lip mass at a documented hemorrhagic lesion site. Approximately 1 year earlier, the lesion was fluctuant and superficially erosive to ulcerative; fine-needle aspiration yielded bloody fluid with cytologically nondiagnostic material. The lesion reportedly subsided after empirical treatment, but reassessment, tissue diagnosis, and objective confirmation of resolution were not performed. Cytology of the later same-site mass supported malignant epithelial neoplasia. Contrast-enhanced computed tomography (CT) identified a 12.5 × 13.2 × 16.6 mm rim-enhancing mass without mandibular invasion or distant metastasis; the ipsilateral mandibular lymph node was mildly thickened. Histopathology supported a diagnosis of lower-lip apocrine sweat gland adenocarcinoma with lymphovascular tumor emboli, lymphatic invasion, and nodal metastasis. The diagnosis was supported by superficial dermal/subcutaneous location, adjacent adnexal structures, skeletal-muscle separation from nearby minor salivary glands, epithelial immunoreactivity, periodic acid-chiff (PAS) and Alcian blue findings without distinct intratumoral mucin/mucopolysaccharide-rich material. The cat died without necropsy on postoperative day 87. This case supports tissue-based diagnosis and regional lymph node assessment for suspicious feline lower-lip glandular epithelial lesions. Full article

Early detection of hepatocellular carcinoma (HCC) is crucial for curative treatment, yet current screening strategies for high-risk liver cirrhosis (LC) patients lack sufficient sensitivity. This study evaluates plasma cell-free DNA(cfDNA) concentration and fragmentomics as biomarkers to improve HCC diagnosis and prognosis. Plasma samples from 39 HCC and 46 LC patients were analyzed for cfDNA concentration and fragment patterns. A multivariate logistic regression model (CMAC), integrating cfDNA concentration, mononucleosome proportion (%MN), alpha-fetoprotein (AFP), and c-reactive protein (CRP), was developed and validated using Leave-One-Out Cross-Validation and bootstrapping. HCC patients exhibited significantly higher cfDNA concentrations (p < 0.0001) and longer fragment lengths (p < 0.05) compared to LC patients. The CMAC model demonstrated superior diagnostic performance (AUROC = 0.946) compared to AFP alone (AUROC = 0.777, p < 0.001). Notably, in early-stage HCC, the CMAC model remained highly accurate (AUROC = 0.941), whereas AFP failed to reach statistical significance. Higher CMAC scores were significantly associated with advanced BCLC stages (p = 0.009), lymphovascular invasion (p = 0.0063) and reduced overall survival (p = 0.0037). Integration of cfDNA analysis with established clinical markers in the CMAC model shows promise as a complementary tool for the early detection of HCC in LC patients. Validation in larger, multicenter cohorts will be necessary to confirm these findings and their clinical applicability. Full article

Background and Objectives: The relationship between preoperative inflammatory markers and lymphovascular space invasion (LVSI) in endometrioid-type endometrial cancer (EC) remains incompletely defined and warrants evaluation using robust statistical methods. This study aimed to evaluate the independent association of preoperative inflammatory markers, analyzed strictly as continuous variables, with the presence of LVSI, and to develop a refined predictive nomogram adjusted for established clinical confounders. Materials and Methods: Data from 156 patients who underwent standard staging surgery for endometrioid-type EC were retrospectively analysed. To preserve statistical power and avoid structural artifacts from data forcing, preoperative glucose-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were modeled on their original continuous scale. Multivariable logistic regression analysis was performed to identify independent risk factors for LVSI, adjusting for patient age and maximum tumor diameter. Internal validation was conducted using bootstrap resampling (1000 iterations). Results: In the multivariable logistic regression model, continuous PLR emerged as a significant independent risk factor for the presence of LVSI (adjusted OR: 1.013 per 1-unit increase, 95% CI: 1.001–1.024; p = 0.033). Among clinical parameters, maximum tumor diameter demonstrated the strongest independent association with LVSI (adjusted OR: 1.595 per 1 cm increase, 95% CI: 1.211–2.099; p = 0.001). Continuous NLR (p = 0.513) and GLR (p = 0.545) did not retain statistical significance due to overlapping explanatory variance and shared hematological components. The optimized 3-variable nomogram (PLR, tumor size, and age) demonstrated an apparent C-index of 0.816 (95% bootstrap CI: 0.719–0.920) and a robust optimism-corrected C-index of 0.794. The bootstrap-corrected calibration slope was 0.909, and Decision Curve Analysis (DCA) demonstrated a positive net clinical benefit across clinically relevant threshold probabilities. Conclusions: Preoperative PLR, evaluated as a continuous parameter, provides a statistically stable framework for preoperative risk stratification in endometrioid EC. When integrated with tumor size and age, the proposed nomogram demonstrates promising discriminative performance and potential clinical utility pending external validation for predicting LVSI. However, given the limited number of LVSI-positive events (n = 17), these findings should be regarded as exploratory and hypothesis-generating and require external validation before clinical use. Full article