Adela Saco

Objectives: To improve the differentiation of borderline ovarian-adnexal tumours (BOTs) from malignant ovarian-adnexal masses, most of which fall into the indeterminate O-RADS MRI 4 category, by developing a multimodal predictive model that integrates clinical, analytic, and MRI parameters. Methods: This retrospective, single-centre study included 248 women who underwent standardised MRI for ovarian-adnexal mass characterisation between 2019 and 2024. Of these, 201 had true ovarian-adnexal masses (114 benign, 22 borderline, and 65 malignant), confirmed by histopathology or stability after ≥12-month follow-up. Forty-one clinical, laboratory, and imaging variables were initially assessed, and after a bivariate evaluation, 18 final predictors with clinical relevance were selected for model construction with thresholds learned from the data. A classification and regression tree (CART) model (“Full Model”) was applied as a second-stage tool after O-RADS MRI scoring, using 10-fold cross-validation to prevent overfitting. A pruned “Simplified Model” was also derived to enhance interpretability. Results: O-RADS MRI performed well at the extremes (scores 2–3 and 5) but showed limited discrimination between BOTs and malignancies within category 4 (PPV for borderline = 0.50). The decision-tree models significantly improved diagnostic performance, increasing overall accuracy from 0.856 with O-RADS MRI alone to 0.905 (Simplified Model) and 0.955 (Full Model). The PPV for BOTs within the intermediate O-RADS MRI 4 category increased from 0.49 with O-RADS MRI alone to 0.77 and 0.90 with the simplified and full models, respectively, while maintaining high accuracy for benign and malignant lesions. Conclusions: In this retrospective single-centre cohort, the addition of an interpretable rule-based predictive model as a second-line tool within O-RADS MRI category 4 was associated with improved discrimination between borderline and invasive malignant ovarian-adnexal tumours. These findings suggest that multimodal integration of clinical, laboratory, and MRI features may help refine risk stratification in indeterminate cases; however, external validation in prospective multicentre cohorts is required before clinical implementation.

Objective: To evaluate the oncologic and survival outcomes in patients diagnosed with early-stage cervical cancer who underwent both sentinel lymph node (SLN) and pelvic lymphadenectomy (PLD) compared with those who underwent SLN alone at primary surgery. Methods: From 2001 to 2022, women who underwent SLN biopsy for nodal staging were recruited. The group of women who underwent SLN biopsy and PLD (SLN + PLD group) was compared with the group who underwent SLN mapping alone (SLN group). Results: 210 patients were evaluated (98 and 112 in each group). The overall SLN detection rate was 97.6%. Lymph node involvement was detected in 23 patients (11%), and the rate of positive SLN increased from 6.2 to 11% after final pathological examination. At a median follow-up of 80 months, the recurrence and mortality rates were 6.2 and 2.4%, respectively. The 3-year progression-free survival (PFS) rate was 93.7 and 97.2%, and the overall survival (OS) rate was 98.9 and 99.0% in the SLN + PLD and SLN group, respectively. There were no significant differences in the Kaplan–Meier PFS (p = 0.471; HR 0.66; 95% CI 0.22–2.04) and OS (p = 0.228; HR 0.28; 95% CI 0.03–2.53) curves between the groups. Conclusion: Pending further confirmation from prospective trials, SLN biopsy appears to be an effective method of nodal assessment in early-stage cervical cancer. This technique does not appear to increase the risk of recurrence compared with complete PLD in selected patients and may offer a viable, less invasive alternative for accurate nodal staging.

Background: Assessment of the peritoneal cancer burden is crucial for determining the optimal treatment in advanced ovarian cancer (AOC). Effective non-invasive methods to predict tumour load remain limited. This study aimed to assess the applicability of 2-[¹⁸F]FDG PET/CT volumetric parameters, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for predicting the surgical peritoneal cancer index (PCI) in AOC before primary treatment. Methods: Patients with high-grade serous or undifferentiated AOC who underwent surgical PCI evaluation and 2-[¹⁸F]FDG PET/CT between 01/2013 and 12/2018 were included. MTV and TLG were calculated using thresholds of 40% and 50% (MTV40, MTV50, TLG40, and TLG50). Correlations between the peritoneal carcinomatosis MTV (car_MTV) and TLG (car_TLG) were analysed. The capacity of volumetric parameters to estimate PCIs above or below 14 and 20 was assessed for the whole abdominal cavity and in per-quadrant analysis, specifically for upper-abdomen areas 1, 2, and 3 (MTV40_1, 2, 3 and TLG40_1, 2, 3). Results: MTV40, MTV50, TLG40, and TLG50 significantly correlated with the PCI in the final study population (n = 45). MTV40 showed a Pearson coefficient of 0.41 (p = 0.003). MTV3_40 (AUC 0.79) and TLG3_40 (AUC 0.81) presented the highest AUCs for predicting a PCI above or below 14. The volumetric parameters allowed the prediction of a PCI greater or less than 20, with an AUC of 0.77 for MTV40_1 and 0.78 for TLG40_1. Conclusions: 2-[¹⁸F]FDG PET/CT MTV and TLG correlate significantly with the surgical PCI when assessing peritoneal carcinomatosis or quadrant-specific disease. This approach offers a reliable non-invasive method for evaluating tumour burden in AOC.

Vulvar squamous cell carcinoma (VSCC) can be classified according to human papillomavirus (HPV) status as HPV-associated (HPV-A) and HPV-independent (HPV-I). However, a small subset of tumors may show overlapping features and become a serious diagnostic challenge for pathologists. We report an unusual case of VSCC arising in a 21-year-old patient with type 1 diabetes mellitus. The tumor had keratinizing histologic features, was associated with a premalignant lesion with features of a high-grade squamous intraepithelial lesion (HSIL), and showed consistent p53 immunohistochemical (IHC) overexpression, but variable results in the HPV testing and p16 IHC staining. Molecular analysis revealed mutation of TP53 and overexpression of cell cycle-regulating genes (including CCND1) and collagen-coding genes (such as COL6A1). These molecular findings in genes, previously reported as upregulated in HPV-I VSCC, supported an etiological origin independent of HPV for the tumor. In conclusion, molecular analysis may help to correctly classify challenging VSCC, showing puzzling clinical, morphologic, and IHC characteristics.

Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)–associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

Background: Penile squamous cell carcinoma (PSCC) is classified into two prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. Conversely, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with prognosis in a large series of PSCC patients. p53 was analysed according to a recently described immunohistochemical (IHC) pattern-based framework that includes two normal (scattered, mid-epithelial) and four abnormal patterns (diffuse, basal overexpression, cytoplasmic and null) and closely correlates with TP53 mutational status. Methods: A total of 122 patients with surgically treated PSCC in three hospitals in Barcelona, Spain, were included. Based on HPV in situ hybridization and p16 and p53 IHC expression, the tumors were classified into three molecular types: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed for at least 22 months (median 56.9 months), and disease-specific survival (DSS) was analysed. Results: Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively (p<0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 patterns not recognized in the classical p53 IHC interpretation (basal, null, cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired DSS (hazard ratio=23.4, 95% confidence interval [CI]= 2.7-3095.3; p=0.001 and 16.3, 95% CI=1.8-2151.5; p=0.008, respectively). CONCLUSION: Compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define two prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.

P53 immunohistochemistry (IHC) has been proposed as a surrogate for TP53 mutations in penile squamous cell carcinomas (PSCC). We aimed to evaluate the performance of a pattern-based evaluation of p53 IHC in PSCC. Human papilloma virus (HPV) DNA testing, p16 and p53 IHC, and whole exome sequencing were performed in a series of 40 PSCC. p53 IHC was evaluated following a pattern-based framework and conventional p53 IHC evaluation. Out of 40 PSCC, 12 (30.0%) were HPV-associated, and 28 (70.0%) were HPV-independent. The agreement between the p53 IHC pattern-based evaluation and TP53 mutational status was almost perfect (k = 0.85). The sensitivity and accuracy of the pattern-based framework for identifying TP53 mutations were 95.5% and 92.5%, respectively, which were higher than the values of conventional p53 IHC interpretation (54.5% and 70.0%, respectively), whereas the specificity was the same (88.9%). In conclusions, the pattern-based framework improves the accuracy of detecting TP53 mutations in PSCC compared to the classical p53 IHC evaluation.

Women with high-grade squamous intraepithelial lesions/cervical intraepithelial neoplasia (HSIL/CIN) are at high risk of anal human papillomavirus HPV infection, and it has also been suggested that self-inoculation of the virus from the anal canal to the cervix could explain HPV recurrence in the cervix after treatment of HSIL/CIN. We aimed to evaluate the bidirectional interactions of HPV infection between these two anatomical sites. We evaluated 68 immunocompetent women undergoing excisional treatment for HSIL/CIN. Immediately before treatment, samples from the anus and the cervix were obtained (baseline anal and cervical HPV status). Cervical HPV clearance after treatment was defined as treatment success. The first follow-up control was scheduled 4–6 months after treatment for cervical and anal samples. High resolution anoscopy (HRA) was performed on patients with persistent anal HPV infections or abnormal anal cytology in the first control. Baseline anal HPV was positive in 42/68 (61.8%) of the women. Anal HPV infection persisted after treatment in 29/68 (42.6%) of the women. One-third of these women (10/29; 34.5%) had HSIL/anal intraepithelial neoplasia (AIN). Among women achieving treatment success, cervical HPV in the first control was positive in 34.6% and 17.6% of the patients with positive and negative baseline anal HPV infection, respectively (p = 0.306). In conclusion, patients with persisting anal HPV after HSIL/CIN treatment are at high risk of HSIL/AIN, suggesting that these women would benefit from anal exploration. The study also suggests that women with anal HPV infection treated for HSIL/CIN might be at higher risk of recurrent cervical HPV even after successful treatment.