Search Results (472)

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Partial cystectomy is a surgical bladder-sparing option for selected patients with muscle-invasive bladder cancer (MIBC), urachal adenocarcinoma and diverticular bladder tumors. Partial cystectomy hold several advantages. It allows for definite pathology and accurate staging while avoiding side effects from radiation therapy and preserves the option for salvage radical therapy (radical cystectomy or radical radiotherapy). Patients should have a CT urogram, prostatic urethral biopsy and mapping biopsies or blue light cystoscopy to rule out multifocal disease or CIS. Small solitary MIBC patients without carcinoma in situ in an area of the bladder where resection can be performed with negative margin would be the ideal candidates for partial cystectomy. Neoadjuvant systemic therapy is recommended for patients undergoing partial cystectomy. Partial cystectomy can be performed either by open or robotic approaches. When compared to radical cystectomy, partial cystectomy affords a lower complication rate and length of stay and better quality of life. Recurrence-free survival, cancer-specific survival and overall survival at 5 years is 39–67%, 62–84% and 45–70%, respectively. Following partial cystectomy, patients should have three monthly cystoscopy and urinary cytology for the first 24 months followed by 6-monthly cystoscopy for year 3 and 4 and then yearly for life. Cross-sectional imaging should be performed every 3–6 months for the first 2–3 years and then annually for 5 years. Full article

Mammary Paget disease (MPD) is a rare cutaneous malignancy associated with underlying ductal carcinoma in situ (DCIS) or invasive ductal carcinoma (IDC). Clinically, it appears as eczematous changes in the nipple and areola complex (NAC), which may include itching, redness, crusting, and ulceration; these symptoms can sometimes mimic benign dermatologic conditions such as nipple eczema, making early diagnosis challenging. A 56-year-old woman presented with persistent erythema and scaling of the left nipple, which did not respond to conventional dermatologic treatments: a high degree of suspicion prompted further investigation. Reflectance confocal microscopy (RCM) revealed atypical, enlarged epidermal cells with irregular boundaries, while line-field confocal–optical coherence tomography (LC-OCT) demonstrated thickening of the epidermis, hypo-reflective vacuous spaces and abnormally large round cells (Paget cells). These non-invasive imaging findings were consistent with an aggressive case of Paget disease despite the absence of clear mammographic evidence of underlying carcinoma: in fact, several biopsies were needed, and at the end, massive surgery was necessary. Non-invasive imaging techniques, such as dermoscopy, RCM, and LC-OCT, offer a valuable diagnostic tool in detecting Paget disease, especially in early stages and atypical forms. Full article

Purpose: This study aimed to develop a predictive nomogram integrating AI-based BI-RADS lexicons and lesion-to-nipple distance (LND) ultrasound features to differentiate mass-type ductal carcinoma in situ (DCIS) from invasive ductal carcinoma (IDC) visible on ultrasound. Methods: The final study cohort consisted of 170 women with 175 pathologically confirmed malignant breast lesions, including 26 cases of DCIS and 149 cases of IDC. LND and AI-based features from the S-Detect system (BI-RADS lexicons) were analyzed. Rare features were consolidated into broader categories to enhance model stability. Data were split into training (70%) and validation (30%) sets. Logistic regression identified key predictors for an LND nomogram. Model performance was evaluated using receiver operating characteristic (ROC) curves, 1000 bootstrap resamples, and calibration curves to assess discrimination and calibration. Results: Multivariate logistic regression identified smaller lesion size, irregular shape, LND ≤ 3 cm, and non-hypoechoic echogenicity as independent predictors of DCIS. These variables were integrated into the LND nomogram, which demonstrated strong discriminative performance (AUC = 0.851 training; AUC = 0.842 validation). Calibration was excellent, with non-significant Hosmer-Lemeshow tests (p = 0.127 training, p = 0.972 validation) and low mean absolute errors (MAE = 0.016 and 0.034, respectively), supporting the model’s accuracy and reliability. Conclusions: The AI-based comprehensive nomogram demonstrates strong reliability in distinguishing mass-type DCIS from IDC, offering a practical tool to enhance non-invasive breast cancer diagnosis and inform preoperative planning. Full article

Vulvar carcinoma is the fourth most common gynecological cancer, with squamous cell carcinoma being the most frequent type. Vulvar intraepithelial neoplasia (VIN) is a precursor lesion and is strongly associated with human papillomavirus (HPV) infection. This paper presents two patients in their sixth decade of life, the first diagnosed with VIN 3 (carcinoma in situ) and the second with stage IA keratinizing squamous cell carcinoma. Both patients had HPV infection; immunohistochemistry confirmed HPV-dependent VIN3 in the first case, while the second patient had a pre-existing HPV high-risk 53 infection. Both patients underwent partial vulvectomy, with the second also having bilateral inguinal–femoral lymph node dissection, which showed no lymph node invasion. The first patient had a histopathological result of VIN 3 with clear margins. The second patient underwent adjuvant radiotherapy following restaging pathology. Both are showing favorable postoperative progress. Conclusions. The early diagnosis of vulvar neoplasms enables less radical but effective surgeries, balancing oncologic control with quality of life. A multidisciplinary approach is essential for adjusting treatments, improving both clinical outcomes and patient well-being. Full article

Background/Objectives: In non-muscle-invasive bladder cancer (NMIBC), the decision for immediate postoperative single-dose intravesical chemotherapy (SI) is based on clinical and presumed pathological features, as a definitive pathology is unknown at the time of surgery. This study aims to assess how accurately urologists can predict the pathological features of bladder tumors based solely on cystoscopic appearance and evaluate their ability to identify patients eligible for SI. Methods: A total of 104 patients with bladder masses were included. Seven senior urologists and four residents participated. Before transurethral resection, both groups predicted tumor stage, grade, and the presence of carcinoma in situ (CIS). Resident predictions were collected for all 104 patients, while senior predictions were collected for 72 patients. Based on these predictions, patient eligibility for SI was determined according to the EAU NMIBC guidelines. After final pathology reports, risk scores were recalculated and compared with the surgeons’ predictions. Cohen’s Kappa (κ) coefficient was used to assess agreement between predictions and pathology. Positive and negative predictive values were also calculated for both groups. Results: Strong agreement with final pathology could not be demonstrated for stage, grade, or CIS for either group. Urology residents’ predictions were slightly more accurate than those of senior urologists. Overall, 19.4% (14/72) (based on senior urologists’ predictions) and 18.2% (19/104) (based on resident predictions) of patients were misclassified and either overtreated or undertreated. Conclusions: Cystoscopic visual prediction alone is insufficient for determining eligibility for immediate postoperative intravesical chemotherapy, regardless of the urologist’s experience. More objective criteria are needed to improve the selection of appropriate patients for SI. Full article

Background/Objectives: Thirty to fifty percent of ductal carcinoma in situ (DCIS) cases are high-grade and at risk of progressing to invasive carcinoma. The most important treatment-related risk factor for recurrence is the presence of residual DCIS. The aim of our study was to evaluate the relationship between size and imaging features on preoperative mammography and magnetic resonance imaging (MRI) and histopathological size and nuclear grade in patients with pure DCIS. Methods: Between 2015 and 2023, 90 patients who underwent surgery for DCIS, had no microinvasive/invasive component, and underwent a preoperative mammography and MRI were included in this study. Results: DCIS was detected in 91.1% of patients using mammography and 95.5% using MRI. Microcalcifications (MCs) were most common in mammography (85.4%). Thin pleomorphic and thin linear branching MCs were detected in 42% of high-grade DCIS, while amorphous (42%) MCs were most common in low-grade DCIS. In low-grade DCIS cases, a grouped distribution of MCs was observed most commonly (69%). There was a statistically significant difference between DCIS groups in terms of MC morphology and distribution (p = 0.043, p = 0.005, respectively). Diffusion restriction on MRI was associated with high-grade DCIS (p = 0.043). The tumor size was greater than the pathological size and correlated poorly with mammography and moderately with MRI. Conclusions: Compared to mammography, MRI is more effective in detecting and estimating the size of DCIS. Both methods overestimate tumor size compared to histopathological size. The nuclear grade is associated with a poor prognosis and local recurrence in DCIS. Full article

Breast cancer invasion and subsequent metastasis to distant tissues occur when cancer cells lose cell–cell contact, develop a migrating phenotype, and invade the basement membrane (BM) and the extracellular matrix (ECM) to penetrate blood and lymphatic vessels. The identification of the mechanisms which induce the development from a ductal carcinoma in situ (DCIS) to a minimally invasive breast carcinoma (MIBC) is an emerging area of research in understanding tumor invasion and metastatic potential. To investigate the progression from DCIS to MIBC, we analyzed peritumoral collagen architecture using correlative scanning electron microscopy (SEM) on histological sections from human biopsies. In DCIS, the peritumoral collagen organizes into concentric lamellae (‘circular fibers’) parallel to the ducts. Within each lamella, type I collagen fibrils align in parallel, while neighboring lamellae show orthogonal fiber orientation. The concentric lamellar arrangement of collagen may physically constrain cancer cell migration, explaining the lack of visible tumor cell invasion into the peritumoral ECM in DCIS. A lamellar dissociation or the development of small inter fiber gaps allowed isolated breast cancer cell invasion and exosomes infiltration in the DCIS microenvironment. The radially arranged fibers observed in the peri-tumoral microenvironment of MIBC biopsies develop from a bending of the circular fibers of DCIS and drive a collective cancer cell invasion associated with an intense immune cell infiltrate. Type I collagen fibrils represent the peri-tumoral nano-environment which can play a mechanical role in regulating the development from DCIS to MIBC. Collectively, it is plausible to suggest that the ECM effectors implicated in breast cancer progression released by the interplay between cancer, stromal, and/or immune cells, and degrading inter fiber/fibril hydrophilic ECM components of the peritumoral ECM, may serve as key players in promoting the dissociation of the concentric collagen lamellae. Full article

In postmenopausal women with high-grade cervical intraepithelial neoplasia (CIN3), hysterectomy is frequently performed after loop electrosurgical excision procedure (LEEP) due to the concern for residual disease or occult carcinoma. However, the decision to proceed with hysterectomy is often made without validated predictive criteria, increasing the risk of overtreatment or underdiagnosis. The aim of this study is to identify independent predictors of residual CIN2+ (CIN2, CIN3, adenocarcinoma in situ, invasive carcinoma) or invasive disease in hysterectomy specimens following LEEP in this high-risk population. Methods: We conducted a multicenter retrospective study including 154 postmenopausal women (aged 50–75) who underwent total hysterectomy within 12 months after LEEP for histologically confirmed CIN3. Data collected included human papillomavirus (HPV) genotyping (pre- and post-LEEP), endocervical curettage (ECC), cone margin status, transformation zone type, and histopathological outcomes of the hysterectomy specimen. Logistic regression and ROC curve analysis were used to assess predictive factors. Results: Residual disease (CIN2+, AIS, or carcinoma) was found in 38 patients (24.7%), including 7 cases (4.5%) of occult carcinoma. Persistent high-risk HPV post-LEEP was the strongest independent predictor (adjusted OR for HPV 16/18: 74.0; p < 0.001), followed by positive ECC (OR: 3.64; p = 0.028). Cone margin status was not independently associated. The multivariate model showed good discriminative performance (AUC = 0.860; sensitivity 67.2%, specificity 72.8%). Conclusions: Our findings suggest that persistent high-risk HPV infection and positive ECC are reliable predictors of residual or occult disease. These markers should be integrated into post-LEEP follow-up protocols to better identify candidates for hysterectomy and minimize unnecessary surgeries. Full article

Background/Objectives: Accurately correlating mammographic findings with corresponding histopathologic features is considered one of the essential aspects of mammographic evaluation, guiding the next steps in cancer management and preventing overdiagnosis. The objective of this study was to evaluate patterns of mammographic microcalcifications and their association with histopathological findings related to various breast tumors. Methods: 110 out of 3603 women had microcalcification of BIRADS 3 or higher and were subjected to stereotactic/ultrasound (USG) guided biopsies, and hook-wire localization excision procedures. Ultrasound and mammography images were reviewed by experienced radiologists using the standard American College of Radiology Breast-Imaging Reporting and Data System (ACR BI-RADS). Results: Our study showed that features with a high positive predictive value (PPV) of breast malignancy were heterogeneous (75%), fine linear/branching pleomorphic microcalcifications (66.7%), linear (100%), and segmental distributions (57.1%). Features that showed a higher risk of association with ductal carcinoma in situ (DCIS) were fine linear/branching pleomorphic (odds ratio (OR): 3.952), heterogeneous microcalcifications (OR: 3.818), segmental (OR: 5.533), linear (OR: 3.696), and regional (OR: 2.929) distributions. Furthermore, the features with higher risks associated with invasive carcinoma had heterogeneous (OR: 2.022), fine linear/branching pleomorphic (OR: 1.187) microcalcifications, linear (OR: 6.2), and regional (OR: 2.543) distributions. The features of associated masses in mammograms that showed a high PPV of malignancy had high density (75%), microlobulation (100%), and spiculated margins (75%). Conclusions: We concluded that specific patterns and distributions of microcalcifications were indeed associated with a higher risk of malignancy. Those with fine linear or branching pleomorphic and segmental distribution were at a higher risk of DCIS, whereas those with heterogeneous morphology with a linear distribution were at a higher risk of invasive carcinoma. Full article

Background/Objectives: Given the increasing interest in the predictive role of inflammation in oncology, we aimed to assess the association between inflammatory factors (IFs) and the histopathological characteristics of bladder cancer (BC). Our objective was to correlate some of these IFs with BC progression and recurrence, identifying possible new diagnostic tools. Methods: We retrospectively analyzed 285 patients (79.8% male, 20.4% female; median age 73) who underwent transurethral resection of the bladder (TURB) between January 2016 and January 2022. The preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), systemic inflammation response index (SIRI), and standard clinical variables were collected one month before TURB and evaluated as predictors of recurrence and progression. Patients were stratified using the Youden Index and ROC analysis. Cox regression models were applied to identify independent predictors. Results: High-grade tumors were present in 74.6% of cases, and 34% were recurrent. Carcinoma in situ was found in 5%. After 72 months, 53% underwent radical cystectomy, and 13.7% died within 5 years. The optimal cutoffs were PLR 139, SIRI 1.12, PIV 248.49, NLR 2, SII 327. Smoking, primary MIBC, age, and lymph node status were significantly associated with recurrence. Elevated PLR correlated with recurrence and T2 progression (p = 0.004). Higher SIRI, PIV, and PLR levels were significantly associated with lymphovascular invasion and nodal metastasis (p < 0.05). PLR was linked to recurrence in tumors ≥ 3 cm post-BCG (p = 0.004); high SIRI predicted recurrence within 48 months (p = 0.05). Conclusions: High PLR and SIRI levels were associated with recurrence. Our findings support the emerging role of IFs in predicting BC outcomes and suggest their potential inclusion in future prognostic models. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is the most common oral cancer, progressing from hyperplasia to dysplasia, carcinoma in situ (CIS), and finally invasive squamous cell carcinoma (ISCC). Developing an animal model that mimics both early and advanced OSCC stages has been challenging. The 4-Nitroquinoline 1-oxide (4NQO) model is considered one of the most suitable, as it represents all stages of OSCC. Nevertheless, thoroughly understanding the properties of the 4NQO model is essential for preclinical testing of novel therapeutics. Methods: We aimed to characterize the 4NQO rat model using two application methods—drinking water and topical application—over eight months. Monthly sacrifices allowed histopathological analysis and ex vivo magnetic resonance imaging (MRI) to track tumor progression. Results: CIS was observed at three months in the drinking water group, evolving into ISCC by six months, while topical application induced CIS at eight months without ISCC formation. The tongue was divided into three regions and histological properties, lesion size, and invasion depth were analyzed. In the drinking water group, particularly in the body of the tongue, we saw earlier CIS development, larger lesions, and deeper invasion. Additionally, assessment of proliferative properties showed an increased cell division in dysplastic lesions that reduced upon invasion. MRI was able to show macroscopic tumoral lesions, in concordance with histology. Conclusions: Overall, the drinking water method closely mimics human OSCC, validating the 4NQO model for translational OSCC research. Full article

Background and Objectives: The assessment of HER2 status in invasive breast carcinomas (IBCs) is critical for determining treatment strategies. The aim of this study was to evaluate the FICTION technique as a potential method for assessing HER2 status and to compare it with the standard sequential immunohistochemistry (IHC)–in situ hybridization (ISH) assays. Materials and Methods: This study included 49 patients diagnosed with invasive breast carcinomas. HER2 status was assessed using both IHC+FISH and FICTION techniques, and the results were compared. Results: Comparative analysis demonstrated an 83.67% categorical agreement between IHC and IF using the ASCO/CAP system. The percentage of cells showing any degree of HER2 protein expression was higher with IF (73.77%) than with IHC (60.71%) (p = 0.00026). The in situ hybridization assays showed an excellent agreement, with a 90% or higher concordance. The concordance of the ASCO/CAP group classification of cases using both ISH assays (FICTION and standard FISH) was high (85, 7%). Agreement was 100% for the final classification of cases (Her2 positive/negative). Conclusions: We compared standard tests for Her2 protein expression and the gene copy number with a modified FICTION protocol. The study showed moderate agreement between IHC and IF for Her2 protein and excellent agreement between FISH and FICTION ISH for the gene copy number. Final Her2 status was unaffected by low IF IHC concordance. Optimizing the FICTION protocol could improve results. Combining protein and gene assays may enhance IBC patient stratification. Full article

Ductal carcinoma in situ (DCIS) is the most common form of non-invasive breast cancer and a recognized precursor to invasive ductal carcinoma (IDC). Although DCIS itself is confined to the milk duct and not immediately life-threatening, its potential for progression to invasive disease necessitates careful clinical management. The increased detection of DCIS due to advancements in imaging and widespread screening programs has raised critical questions regarding its classification, prognosis, and optimal treatment strategies. While most cases exhibit indolent behavior, others harbor molecular characteristics that drive malignant transformation. A key challenge lies in distinguishing low-risk DCIS, which may never progress, from aggressive cases requiring intervention. Tumor microenvironment dynamics, immune cell infiltration, and molecular alterations, including hormone receptor (HR) status, human epidermal growth factor 2 (HER2) expression, and genetic mutations, play crucial roles in determining disease trajectory. This review explores the biological and molecular mechanisms underlying DCIS progression, with an emphasis on myoepithelial cells, tumor-infiltrating lymphocytes, and microenvironmental factors. By integrating recent findings, this article aims to refine risk stratification approaches and guide future strategies for personalized DCIS management. Improved prognostic biomarkers and targeted therapeutic interventions could help optimize treatment decisions, balancing the need for effective cancer prevention while minimizing overtreatment in low-risk patients. Full article

Background/Objectives: Actinic keratosis (AK) is considered to be the most common form of in situ carcinoma and typically arises on skin that has been chronically exposed to ultraviolet radiation. The need for early diagnosis, using non-invasive methods, has allowed for a non-surgical approach to these conditions with a significant impact on the quality of life of patients. Methods: A retrospective study was conducted on 58 patients diagnosed with AK who underwent surgical excision at a tertiary center in Bucharest, Romania between 2018 and 2023. Clinical parameters (age, sex, lesion size, anatomical location, comorbidities) and histopathological variables (AK subtype, KIN grade, pleomorphism, solar elastosis, inflammatory infiltrate) were analyzed. Statistical associations between histological findings and clinical features were assessed using Fisher’s exact test. Conclusions: The study confirmed a predominance of AK among elderly patients, with hypertrophic lesions and moderate dysplasia (KIN II) being most common. Higher KIN grades correlated significantly with more severe pleomorphism, solar elastosis, and inflammatory response, suggesting progressive UV-induced skin damage. The findings underscore the importance of clinicopathological correlation for risk stratification and support the integration of non-invasive diagnostic tools to improve early detection and management of AK. Full article