Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positivity, low-to-intermediate proliferation, and atypical metastatic spread to bone and gastrointestinal/peritoneal sites. Diagnostic assessment is often challenging owing to diffuse infiltration, frequently yielding non-measurable disease per response evaluation criteria in solid tumors (RECIST). Molecularly, ILC is enriched for phosphoinositide 3-kinase (PI3K) activation and harbors emerging vulnerabilities-such as ROS1 synthetic lethality in CDH1-deficient tumors and fibroblast growth factor receptor 1 (FGFR1)/bromodomain and extra-terminal (BET) dependencies-now under study. Because metastatic ILC remains underrepresented in trials, systemic therapy often mirrors invasive ductal carcinoma (IDC). This short communication synthesizes current evidence to distinguish shared from plausibly lobular-specific signals; highlights near-term opportunities-including antibody-drug conjugates (ADCs), oral selective ER degraders (SERDs), and selective use of immunotherapy in an immune-enriched subset with higher tumor-infiltrating lymphocytes (TILs) and PD-L1; and outlines trial-design adaptations-such as incorporating 18F-fluoroestradiol PET (FES-PET)-to improve representation and interpretability in metastatic ILC research.

Differentiating large-duct pancreatic ductal adenocarcinoma from malignant intraductal papillary mucinous neoplasm: MRI characteristics and diagnostic implications.

Venous invasion in upper tract urothelial carcinoma: Diagnostic features and oncologic outcomes.

Intraoperative Image of Modified Radical Mastectomy with Axillary Lymph Node Dissection of Left Invasive Breast Carcinoma

Mucin-producing breast lesions encompass a diverse range of entities with varied morphologies, distinct molecular genetics and different outcomes. Mucocele-like lesions (MLLs) are being increasingly recognised and sampled due to advancements in imaging techniques. These lesions can present with or without epithelial proliferation and atypia, which hold prognostic significance. Diagnosing MLLs on limited core needle biopsy (CNB) samples can be challenging. Mucinous breast carcinoma (MuBC) generally has an excellent prognosis in its pure form. Recent studies indicate that mucin-producing invasive cancers with micropapillary growth pattern, high nuclear grade or HER2 overexpression/amplification may not fare as well as their pure counterparts, suggesting that they should be distinguished from pure MuBCs. Invasive lobular carcinoma with extracellular mucin (ILCEM) is an emerging subtype of ILC characterised by neoplastic cells in cords, nests and trabeculae, often with signet ring morphology, floating in extracellular mucin. This can lead to misdiagnosis as a ductal phenotype due to varied architectural patterns or a MuBC due to the presence of extracellular mucin. This review highlights the spectrum of mucin-producing breast lesions, focusing on the above-mentioned entities along with recent molecular updates, potential mimics and diagnostic pitfalls on CNB specimens. Awareness of these entities, a practical approach to their diagnosis, combined with judicious use of immunohistochemistry, are crucial for accurate diagnosis by pathologists, which is in turn essential for guiding clinical decision making for optimal patient outcomes.

Urinary arsenic levels and risk of breast cancer among women in the Canadian health measures survey: a population-based prospective study.

Radiation-induced angiosarcomas of the breast are rare malignancies that carry a poor prognosis. Expected immunohistochemical profiles reflect vascular differentiation: CD31 and ERG positivity, with variable CD34 positivity. GATA-3 is a transcription factor important for mammary gland development, playing a role in ductal epithelial cell differentiation. It serves as an important immunohistochemical marker of breast-origin carcinomas and is not associated with angiosarcomas. We report a case of an 83-year-old woman with breast radiation-induced angiosarcoma, which displayed diffuse GATA-3 positivity, which has not been previously reported in the literature. The patient had a history of inflammatory carcinoma of the left breast (histologically a high-grade invasive ductal carcinoma of no special type) treated with lumpectomy and radiation therapy. Ten years later, she presented with skin thickening and 3 tender nodules (ranging from 0.6 to 2 cm) confined to the left breast skin. Biopsy showed a high-grade, epithelioid dermal neoplasm with abundant hemorrhage. The tumor was diffusely positive for GATA-3, CD31, and ERG, with focal CD34 positivity. Strong and diffuse MYC positivity with an increased Ki-67 proliferative index was also demonstrated. CK5/6, AE1/AE3, MOC-31, CK5/6, CK7, ER, PR, S100, Melan A, and synaptophysin were all negative. The histopathologic features and immunohistochemical profile were consistent with radiation-induced angiosarcoma. With this case, we highlight a diffusely positive GATA-3 staining pattern in radiation-induced angiosarcoma of the breast, which has not been previously documented. Awareness of this potential staining pitfall is essential for arriving at the correct diagnosis particularly when recurrent or metastatic high-grade carcinoma is a diagnostic consideration.

Recent trials suggest omission of sentinel lymph node biopsy (SLNB) for selected early-stage breast cancer patients. However, invasive lobular carcinoma (ILC) is underrepresented, and retrospective data indicate higher rates of nodal metastases, raising concerns about axillary understaging. This study aimed to evaluate the prevalence and predictors of nodal metastases in early-stage, clinically node-negative ILC. This study retrospectively analyzed 491 patients with estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, clinical T1, clinically node-negative ILC who underwent breast-conserving surgery at our institution between 2004 and 2024. The exclusion criteria ruled out neoadjuvant therapy, tumor larger than 2 cm, and metastatic disease at diagnosis or prior breast cancer. Among 491 patients, 392 (79.8 %) were pN0, whereas 99 (20.2 %) had nodal metastases (pN1mi-pN3). Pathologic tumor size was significantly associated with axillary nodal involvement (p = 0.004). In contrast, histologic subtype was not significantly associated with nodal status (p = 0.15), although pleomorphic tumors demonstrated numerically higher rates of nodal involvement than classic invasive lobular carcinoma. Menopausal status was not predictive of nodal positivity (p = 0.96). Approximately one (20.2 %) in five patients with early-stage, clinically node-negative ILC harbors occult axillary nodal metastases. Pathologic tumor size emerged as the primary determinant of nodal involvement. Pleomorphic variants showed a tendency toward higher nodal burden. These findings indicate that omission of SLNB in ILC may carry a risk of axillary understaging with potential therapeutic implications. Pending evidence from prospective studies specifically designed for lobular histology, SLNB should continue to be considered an essential component of axillary evaluation in this subgroup.

Thyroid carcinoma is the most prevalent endocrine malignancy, with a worldwide increasing incidence. Capsular invasion and neural invasion (NI) are pivotal prognostic factors for recurrence and survival; however, their preoperative noninvasive assessment remains challenging. We aimed to identify computed tomography (CT) radiomic biomarkers associated with capsular invasion in thyroid carcinoma, construct machine learning models integrating radiomic and clinical data, and evaluate their utility for NI risk stratification. In this retrospective cohort, 111 patients with thyroid carcinoma were divided into capsular invasion-positive (n=63) and capsular invasion-negative (n=48) groups, with 37 (33.3%) cases presenting concurrent NI. Radiomic features were extracted from arterial and venous phase CT images at original resolution, including 111 gray-level co-occurrence matrix features. Nine key radiomic features (A1-A9) were selected via least absolute shrinkage and selection operator regression (λ=0.017). To preserve the physical meaning of texture features (eg, spatial correlation and contrast reflecting tumor microstructural heterogeneity), no resampling or scaling was performed on the regions of interest during radiomic feature extraction. Nomogram models and random forest (RF) models were constructed based on clinical indicators (galectin-3, etc) and radiomic features, respectively. Additionally, a neural network (NN) model integrating multimodal data was developed. Model stability was verified using 5-fold cross-validation and 1000-time bootstrap resampling, while performance was evaluated via receiver operating characteristic curves, calibration curves, and decision curve analysis. Model performance analysis revealed that among the nomogram models, the clinical indicator-based nomogram achieved an internally estimated area under the curve (AUC) of 0.9418 (95% CI 0.892-0.976) in the capsular invasion prediction task. The radiomic-based nomogram had an internally estimated AUC of 0.9334 (95% CI 0.881-0.968) in the capsular invasion prediction task and 0.8001 (95% CI 0.663-0.898) in the cross-label association analysis task. In RF models, clinical indicator-based and radiomic-based RFs exhibited an AUC of 0.7646 (95% CI 0.651-0.857) and 0.8102 (95% CI 0.703-0.892) in the cross-label association analysis task, respectively. The NN model performed promisingly, with an AUC of 0.775 (95% CI 0.621-0.903) in the cross-label association analysis task and a mean absolute error of <0.05 on the calibration curve. Capsular invasion is a strong predictor of NI risk in thyroid carcinoma. Radiomic models based solely on preoperative CT images show potential for preoperative NI risk stratification. Models incorporating clinical parameters (obtained from postoperative tissue), including the integrated multimodal model, are more accurately characterized as postoperative risk stratification tools. The NN model, which integrated raw CT images with clinical data, achieved an AUC of 0.775 (95% CI 0.621-0.903), underscoring the potential of such multimodal analysis to capture complex relationships between imaging phenotypes and tissue-level biomarkers for enhanced postoperative assessment. This framework's radiomic component points toward purely image-based, preoperative evaluation tools' development.

Signet-ring cells (SRCs) or SRC-like cells are a characteristic cytological feature observed in several malignancies. However, the diagnostic significance of SRC-like cells, including SRCs, in intraductal papillary mucinous neoplasms (IPMN) remains unclear. Therefore, this study aimed to evaluate the diagnostic significance of SRC-like cells in pancreatic juice cytology (PJC) of patients with IPMN. We retrospectively analyzed the prevalence, quantity, and mucus coloration of SRC-like cells in PJC specimens from 63 patients with IPMN, categorized by the histological grade and subtype. SRC-like cells were observed in 5.0% (1/20) of low-grade dysplasia (LGD), 26.9% (7/26) of high-grade dysplasia (HGD), and 47.1% (8/17) of invasive carcinoma (IC) cases. Based on receiver operating characteristic curve analysis, the presence of ≥ 30 SRC-like cells (termed the "SRC pattern") was identified as the optimal threshold for diagnosing HGD/IC, demonstrating 100% specificity and positive predictive value. Among the 16 patients with SRC-like cells, the histological subtypes were gastric (n = 4) and intestinal (n = 12). Gastric-type IPMN cases showed < 30 SRC-like cells with yellow to orange mucus, whereas intestinal-type IPMN cases showed ≥ 30 SRC-like cells with clear to pink mucus. SRC pattern, defined as the presence of ≥ 30 SRC-like cells in PJC, may be a supportive cytological finding for diagnosing IPMN with HGD/IC, particularly the intestinal subtype. Furthermore, the mucus coloration of SRC-like cells might reflect subtype‑related morphological tendencies.

Association of genetic variation in TLR4 and TLR9 genes with susceptibility to invasive ductal breast carcinoma.

Invasive micropapillary carcinoma (IMPC) of the breast is a rare and aggressive histologic subtype characterized by frequent lymph node metastasis and poor prognosis. The conventional American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system does not account for treatment modalities or advanced nodal metrics such as the log odds of positive lymph nodes (LODDS), which may limit prognostic accuracy. This study aimed to develop and internally validate a nomogram integrating clinicopathologic characteristics, treatment variables, and LODDS to predict overall survival (OS) in breast IMPC. Clinicopathologic and survival data from 1,105 patients diagnosed between 2010 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The entire cohort was used for model development, with bootstrap resampling for internal validation. Least absolute shrinkage and selection operator (LASSO) regression and multivariable Cox analysis were used for variable selection and nomogram construction. Model performance was assessed using the optimism-corrected concordance index (C-index), calibration plots, time-dependent area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), and clinical impact curves (CICs), while incremental value over the AJCC TNM system was evaluated by net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Ten prognostic factors were retained in the nomogram: age, tumor size, LODDS, marital status, tumor grade, M stage, rural/urban residence, molecular subtype, radiotherapy, and chemotherapy. The nomogram showed superior discrimination to TNM staging, with better optimism-corrected C-index and 3-, 5-, and 10-year AUCs (all p< 0.05), significant improvements in NRI and IDI (all p< 0.001), excellent calibration, and greater net clinical benefit on DCA and CICs. Exploratory risk stratification identified high- and low-risk groups with significantly different survival outcomes (log-rank p< 0.001). This nomogram may improve prognostic assessment in breast IMPC, although the risk stratification remains exploratory and requires external validation before clinical application.

Endoscopic breast-conserving surgery (EBCS) aims to offer improved cosmetic outcomes while maintaining oncologic safety. Although well established in East Asian programs¹⁻³, its use remains uncommon in India⁴. This pilot feasibility series describes early Indian experience with EBCS and sentinel lymph node biopsy (SLNB) performed entirely through a single concealed axillary incision. Three consecutive women with biopsy-proven, clinically node-negative early invasive carcinoma underwent single-incision EBCS with SLNB between January and March 2025. The technique used CO₂ insufflation, a glove-port system, and ultrasonic dissection. Primary outcomes included operative parameters, margin status, sentinel node retrieval, and perioperative complications. Secondary outcomes were seroma, drain duration, pain scores, recovery milestones, and cosmetic satisfaction using a 5-point Likert scale. Follow-up was recorded individually for each patient. All cases were completed endoscopically without conversion. Mean operative time was 145min (range 130-160), and blood loss averaged 60ml. Margins were negative in all three patients. One minor seroma resolved with conservative management. No wound infections, skin necrosis, dimpling, or lymphedema occurred. At a median follow-up of nine months, all patients remained disease-free. Cosmetic satisfaction was high (average Likert 4.6/5), with preserved breast contour and no visible deformity. Single-incision EBCS with SLNB is feasible, safe, and cosmetically favourable in selected Indian patients offering oncologic adequacy. While early outcomes are reassuring, larger series, longer follow-up, and validated PROMs such as BREAST-Q are required to better define the technique's role in routine oncologic practice.

Development and validation of a SHAP-explainable preoperative predictive model for microvascular invasion in hepatocellular carcinoma.

Lymphovascular space invasion (LVSI) is associated with increased nodal involvement and disease recurrence in cervical squamous cell carcinoma (SCC). While LVSI is currently included in some clinical risk assessment algorithms, the reproducibility of diagnosing LVSI remains understudied in cervical SCC. We aimed to assess the inter-observer agreement for LVSI diagnosis using digital whole slide images (WSIs) of haematoxylin and eosin-stained (H&E) slides with presumed true LVSI (n = 20) and LVSI mimics (n = 20) from early-stage cervical SCC identified in an international cohort. The reference diagnosis for LVSI status was established by 2 pathologists through consensus review. Ten independent pathologists from North and South America, Europe, Asia and South Africa were included for blinded scoring of true LVSI versus LVSI mimics. Complete concordance was seen in 57% of cases. Overall percent agreement was 88% with the κ value being 0.76, reflecting substantial agreement on LVSI diagnosis based on H&E WSIs. Our findings support the diagnostic feasibility and reliability of including LVSI as a parameter in routine histologic evaluation for risk stratification of cervical SCC. While the inter-observer agreement in our study is acceptable, there remains a need for standardised diagnostic criteria and guidance on the use of immunohistochemical studies for the detection or confirmation of LVSI in daily practice.

Rare but distinct: A systematic review of primary neuroendocrine tumors of the breast according to WHO 2019 guidelines.

Papillary thyroid carcinoma (PTC) poses a risk of recurrence, and the efficacy of existing treatments is limited. Consequently, there is an urgent need to identify new prognostic markers and potential therapeutic targets. N6-methyladenosine (m6A) mRNA methylation is involved in tumorigenesis and progression, yet the role of m6A RNA methylation regulators in PTC remains unclear. The Cancer Genome Atlas database was utilized to analyze 17 m6A regulators in PTC. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) was markedly down-regulated in PTC, yet higher IGF2BP1 expression predicts better 5-year survival, acting as an independent prognostic marker with high accuracy. Elevated IGF2BP1 also indicated greater sensitivity to doxorubicin and sunitinib. Clinically, low IGF2BP1 correlated with central lymph-node metastasis and BRAFV600E mutation. Additionally, IGF2BP1 overexpression suppresses thyroid carcinoma cell proliferation, invasion, and migration. In conclusion, High expression of IGF2BP1 was associated with a favorable prognosis in PTC, and it served as an independent prognostic factor and a potential therapeutic target for PTC.

Accurate assessment of muscularis propria invasion is critical for therapeutic decision-making in bladder cancer. The application of Contrast-Enhanced Ultrasound (CEUS) in bladder cancer requires further validation. Using histopathology as the reference standard, we compared the diagnostic performance of CEUS and enhanced magnetic resonance imaging (E-MRI) in 190 patients who underwent transurethral resection of bladder tumor (TURBT). The accuracy, sensitivity, and specificity of both modalities in determining malignancy and muscular invasion were analyzed. For diagnosing malignant tumors, the accuracy of CEUS and E-MRI was 83.87% and 80.64%, respectively. No significant differences were observed in sensitivity (85.71% vs. 84.28%) or specificity (78.26% vs. 69.56%) (P > 0.05). In assessing muscular invasion, CEUS demonstrated significantly higher specificity than E-MRI (95% vs. 77.5%, P = 0.039), while no significant difference was found in sensitivity (77.33% vs. 74.66%). CEUS exhibits superior specificity for evaluating muscular invasion in bladder urothelial carcinoma and can serve as a valuable complement to E-MRI for clinical staging.

In breast pathology, tumor protein 63 (p63) is a highly sensitive and specific immunohistochemical marker for myoepithelial cells. It plays a crucial role in distinguishing benign from malignant diseases and in differentiating in situ carcinoma from invasive carcinoma. Aberrant p63 expression has also been increasingly recognized as a subject of clinical and diagnostic interest. A comprehensive understanding of the biological characteristics of p63, appropriate selection of antibodies, and its variable expression patterns across different breast diseases is essential for the accurate application and interpretation of p63 immunohistochemistry, enabling the avoidance of diagnostic pitfalls, minimizing misinterpretations, and ultimately supporting more precise pathological diagnosis.

5-year results of hypofractionated locoregional radiotherapy in early breast cancer HypoG-01 (UNICANCER): a French multicentre, randomised, non-inferiority, phase 3, open-label, controlled trial.