Nuclear Grade Research Articles

Creep deformation and constitutive modelling of 316LN SS with varying nitrogen content

In this investigation, two different constitutive models were employed to examine the creep deformation and damage behaviour of nuclear grade austenitic 316LN SS with four different nitrogen contents (0.07–0.22 wt%) at 923 K. Creep deformation resistance of the alloys investigated by “internal-stress based kinetic creep law” for primary and secondary creep stages revealed an increase in internal stress and decrease in obstacle spacing accompanied with lower dynamic recovery with increasing nitrogen. The aforementioned outcomes substantiated the experimentally observed beneficial role of nitrogen on lowering of creep strain rate with increasing nitrogen level. In contrast to the above observations, the analysis of coupled creep deformation and damage using the Kachanov-Rabotnov model and the subsequent development of iso-damage contours indicated evolution of higher creep damage at lower strains with increasing nitrogen content. With increasing % nitrogen, damage rate dominated over the strain rate thus justifying the observed significant intergranular damage at and above 0.14% N. Based on the above results and in-house studies on low cycle fatigue and creep–fatigue interaction, optimum nitrogen content is suggested between 0.07 and 0.14% N in 316LN SS that combines the benefits of low nitrogen content and strengthening effects of high nitrogen content.

Potential role of vacuum-assisted procedures in resecting breast cancers and highlighting selection criteria to support future trials.

The purpose of this study was to evaluate the role of vacuum-assisted biopsy (VAB) in resecting breast cancers. Retrospective database analysis of 116 cancers [both invasive breast cancers (IC) and ductal carcinoma in situ (DCIS)] diagnosed by VAB submitted to standard surgical treatment with complete histological data from VAB and surgery. Excision following VAB was defined as complete resection (CR) if there was no residual tumor in the surgical specimen, minimal residual disease (MRD) if residual tumor ≤ 3mm, gross residual disease (GRD) if residual tumor > 3mm, and upgrade from DCIS on VAB to IC. CR and MRD were combined as potentially resected percutaneously (PRP). GRD and those with upgrade to IC were determined not eligible for percutaneous resection (NPR). Factors predictive of PRP were evaluated. Mean age was 55.6 years (20-91; SD: 12,27). CR was seen in 29 of 116 cases (25%), MRD in 18 of 116 cases (15.5%), GRD in 64 of 116 cases (55.2%), and five of 116 cases (4.3%) were upgraded from DCIS to IC, and those groups combined represented 47 cases of PRP (40.5%) and 69 (59,5%) of NPR. For 77 tumors ≤ 10mm, 45 (58.5%) were PRP. Multivariate analysis reveals significance for enlarged VAB (EVAB) (p = 0.008, OR: 4.4, 95% CI), low/intermediate nuclear grade (p < 0.001, OR: 12.5, 95% CI) and final tumor size (T) ≤ 10mm (p = 0.001, OR: 50.1, 95% CI) for PRP. This study showed that lesions completely excised with VAB that were cancer could have been treated with VAB rather than surgery but tumor selection in terms of subtype and size is important.

Detailed fine needle aspiration cytopathology findings of noninvasive follicular thyroid neoplasm with papillary-like nuclear features with nuclear grading correlated to that of biopsy and Bethesda category and systematic review.

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses diagnostic challenge in fine needle aspiration cytopathology (FNAC). We aimed first to document our FNAC Bethesda categories (BCs) for all of our NIFTPs and compare our findings with those in the literature with series containing at least 14 cases each. Cases with final histopathological diagnoses of NIFTP and their preoperative FNAC were retrieved from 2006 to 2022 and our cytopathological BCs were documented. Then the slides were re-reviewed in a blinded manner for detailed classification and the results of both the BCs and blinded reclassification were compared with series in the literature for both BCs and detailed cytopathological review of the cases. Thyroid FNACs of 43 out of 86 patients with final NIFTP diagnoses were obtained. Females composed 72.1% (F/M: 31/12); mean age and mean tumor diameter was 47.6 (19-72 years) and 23.4 mm (7-60 mm), respectively. Totally 81.4% (35/43) were classified in the "indeterminate" diagnostic categories; namely 44.2% (19/43) were reported as atypia of undetermined significance (AUS; BC III), 20.9% (9/43) were follicular neoplasm (FN; BC IV), and 16.3% (7/43) were suspicious for malignancy (SM; BC V). No patient was diagnosed as positive for malignancy (BC VI), preoperatively. Detailed cytomorphologic reevaluation revealed heterogeneous cytopathologic findings and nuclear grade (especially nuclear enlargement, membrane irregularity and elongation) significantly increased with respect to BCs. Systematic review confirmed extremely heterogeneous cytomorphologic nature of NIFTP. NIFTPs were categorized most frequently as AUS, followed by FN and SM on FNAC. Our re-review were not able to specify features solely unique to NIFTP alone but may distinguish these cases from classic papillary thyroid carcinoma.

Encapsulated papillary carcinoma of the breast: A single institution experience.

Encapsulated papillary carcinoma (EPC) is a relatively rare form of breast cancer. To date, no evidence-based guidelines for the treatment of EPC have been established. Between January 2015 and December 2021, patients with histologically confirmed EPC of the breast were recorded in a database by The Third Hospital of Nanchang City (Nanchang, China). A total of 46 patients with EPC were retrieved from the database. Age at diagnosis ranged from 41-88 years (median age, 62 years). A total of 21 of these patients had pure EPC, 6 patients had EPC associated with ductal carcinoma in situ and 19 patients had EPC associated with invasive carcinoma. The majority of EPC cases were low nuclear grade, hormone receptor-positive and human epidermal growth factor receptor-2-negative. Additionally, myoepithelial cells were always absent in the papillae of the EPC. All patients underwent lumpectomy or mastectomy with sentinel lymph node biopsy, and almost all of the patients received adjuvant hormonal therapy. Adjuvant chemotherapy was only suggested to 4 patients who were diagnosed with axillary lymph node involvement. Subsequently, the clinicopathological features of non-invasive EPC were compared with invasive EPC. The results indicated that larger tumor sizes and axillary lymph node metastases were more common in invasive tumors. During the follow-up, only 2 patients with invasive EPC experienced recurrence or metastasis. In conclusion, a substantial proportion of invasive EPC cases display aggressive characteristics and metastatic potential, despite it being considered a subtype of carcinoma in situ with excellent prognosis, and local surgical resection is the initial method of treatment. Therefore, adjuvant endocrine therapy, radiotherapy and chemotherapy should be considered in select patients, especially in those diagnosed with invasive EPC tumors.

Prediction of Fuhrman nuclear grade for clear cell renal carcinoma by a multi-information fusion model that incorporates CT-based features of tumor and serum tumor associated material.

Prediction of Fuhrman nuclear grade is crucial for making informed herapeutic decisions in clear cell renal cell carcinoma (ccRCC). The current study aimed to develop a multi-information fusion model utilizing computed tomography (CT)-based features of tumors and preoperative biochemical parameters to predict the Fuhrman nuclear grade of ccRCC in a non-invasive manner. 218 ccRCC patients confirmed by histopathology were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify independent predictors and establish a model for predicting the Fuhrman grade in ccRCC. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves, calibration, the 10-fold cross-validation method, bootstrapping, the Hosmer-Lemeshow test, and decision curve analysis (DCA). R.E.N.A.L. Nephrometry Score (RNS) and serum tumor associated material (TAM) were identified as independent predictors for Fuhrman grade of ccRCC through multivariate logistic regression. The areas under the ROC curve (AUC) for the multi-information fusion model composed of the above two factors was 0.810, higher than that of the RNS (AUC 0.694) or TAM (AUC 0.764) alone. The calibration curve and Hosmer-Lemeshow test showed the integrated model had a good fitting degree. The 10-fold cross-validation method (AUC 0.806) and bootstrap test (AUC 0.811) showed the good stability of the model. DCA demonstrated that the model had superior clinical utility. A multi-information fusion model based on CT features of tumor and routine biochemical indicators, can predict the Fuhrman grade of ccRCC using a non-invasive approach. This model holds promise for assisting clinicians in devising personalized management strategies.

Positive GPNMB Immunostaining Differentiates Renal Cell Carcinoma With Fibromyomatous Stroma Associated With TSC1/2/MTOR Alterations From Others.

Renal cell carcinoma with fibromyomatous stroma (RCCFMS) include ELOC/TCEB1 -mutated renal cell carcinoma (RCC) and those with TSC1/2 / MTOR alterations. Besides morphologic similarity, most of these tumors is known to be diffusely positive for carbonic anhydrase IX and cytokeratin 7 by immunohistochemistry. We previously showed strong and diffuse expression of GPNMB (glycoprotein nonmetastatic B) in translocation RCC and eosinophilic renal neoplasms with known TSC1/2/MTOR alterations. We retrospectively identified molecularly confirmed cases of TCEB1/ELOC -mutated RCC (7 tumors from 7 patients), and RCCFMS with alterations in TSC1/2/MTOR (6 tumors from 5 patients, 1 patient with tuberous sclerosis syndrome). In addition, we included 7 clear cell papillary renal cell tumors (CCPRCTs) and 8 clear cell RCC, as they can also present morphologic overlap with RCCFMS. Morphologically, RCCs with TSC1/2/MTOR alterations and those with TCEB1/ELOC mutations were indistinguishable and characterized by papillary, nested, or tubular architecture, with tumor cells with clear cytoplasm and low nuclear grade. By immunohistochemistry, cytokeratin 7 was positive in 5/7 (71%) of TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/mTOR alterations, and 7/7 (100%) of CCPRCTs ( P =not significant). Carbonic anhydrase IX was positive in 7/7 TCEB1/ELOC -mutated RCCs, 6/6 (100%) of RCCs with TSC1/2/MTOR alterations, and 7/7 (100%) of CCPRCTs ( P =NS). GPNMB was strongly and diffusely positive in all tumors with TSC1/2/MTOR alterations (6/6), while negative in all TCEB1/ELOC -mutated RCCs (0/6), or CCPRCTs (0/7) ( P =0.002). Two of 8 clear cell RCC showed focal weak staining, while 6/8 were negative. In conclusion, the results support the use of GPNMB to distinguish RCCFMS with TSC1/2/MTOR alterations from others with similar morphology.

Feasibility analysis of magnetic resonance imaging-based radiomics features for preoperative prediction of nuclear grading of ductal carcinoma in situ.

The nuclear grading of ductal carcinoma in situ (DCIS) affects its clinical risk. The aim of this study was to investigate the possibility of predicting the nuclear grading of DCIS, by magnetic resonance imaging (MRI)-based radiomics features. And to develop a nomogram combining radiomics features and MRI semantic features to explore the potential role of MRI radiomic features in the assessment of DCIS nuclear grading. A total of 156 patients (159 lesions) with DCIS and DCIS with microinvasive (DCIS-MI) were enrolled in this retrospective study, with 112 lesions included in the training cohort and 47 lesions included in the validation cohort. Radiomics features were extracted from Dynamic contrast-enhanced MRI (DCE-MRI) phases 1st and 5th. After feature selection, radiomics signature was constructed and radiomics score (Rad-score) was calculated. Multivariate analysis was used to identify MRI semantic features that were significantly associated with DCIS nuclear grading and combined with Rad-score to construct a Nomogram. Receiver operating characteristic curves were used to evaluate the predictive performance of Rad-score and Nomogram, and decision curve analysis (DCA) was used to evaluate the clinical utility. In multivariate analyses of MRI semantic features, larger tumor size and heterogeneous enhancement pattern were significantly associated with high-nuclear grade DCIS (HNG DCIS). In the training cohort, Nomogram had an area under curve (AUC) of 0.879 and Rad-score had an AUC of 0.828. Similarly, in the independent validation cohort, Nomogram had an AUC value of 0.828 and Rad-score had an AUC of 0.772. In both the training and validation cohorts, Nomogram had a significantly higher AUC value than Rad-score (P<0.05). DCA confirmed that Nomogram had a higher net clinical benefit. MRI-based radiomic features can be used as potential biomarkers for assessing nuclear grading of DCIS. The nomogram constructed by radiomic features combined with semantic features is feasible in discriminating non-HNG and HNG DCIS.

Evaluation of A New Approach to Enhance Visualization Performance in Cataract Surgery: 3D Visualization System with Coaxial Illumination.

To evaluate the visualization performance of different approaches, including the 3D Visualization system with coaxial illumination and the 3D system or microscope with standard illumination. Fuzhou Ophthalmic Hospital, Fuzhou City, China. Cross-sectional study. This two-part performance assessment for visualization comprised of an objective analysis utilizing surgical video images and a subjective survey collecting feedback from surgeons. Data of each eye were obtained with 3 approaches: standard surgical microscope with standard illumination (SOM-S), 3D Visualization system with standard illumination (3D-S) and 3D Visualization system with coaxial illumination (3D-C). Totally 112 eyes (107 cases) and 6 cataract surgeons were involved. Red reflex value was markedly greater in the 3D-C approach compared with other 2 approaches (P<0.001). Compared with the SOM-S approach, red reflex increased by 55%, 57%, and 53% in the 3D-C approach corresponding to nuclear grades of II, III, and IV, respectively. In the questionnaire survey, red reflex scores were consistently significantly higher in the 3D-C approach than in the others (P<0.001). Depth of field was enhanced in both 3D approaches compared with the SOM-S approach (P<0.05). The only minor advantage of the SOM system over the 3D-C approach was in the surrounding field clarity score, and the difference was not statistically significant (P=1.000). The 3D-C approach significantly increased the red reflex in both objective and subjective assessments. Surgeons' responses also showed a superior performance for the 3D-C approach.

T1a Renal Cell Carcinoma With Metastasis: Japanese Society of Renal Cancer Retrospective Multi-institute Results.

Small renal cell carcinomas (sRCC) have drastically increased in recent years. Considering that sRCC have heterogeneous biology, it would be clinically relevant if specific clinical or pathological parameters could predict sRCC metastasis. In the present study, we aimed to assess the clinicopathological factors of pathologic T1a RCC (pT1a RCC) with or without metastasis to explore factors predicting metastasis. The present study included 198 patients with pT1a RCC who underwent radical or partial nephrectomy at fifteen institutions belonging to the Japanese Society of Renal Cancer, between1985 and 2017. Clinicopathological parameters, including age, sex, tumour size, tumour side, histological subtype, histological nuclear grade, lymphovascular invasion, and histological growth patterns, were analysed. Fuhrman grade 3 or 4 tumours and infiltrative tumour growth patterns were significantly higher in patients with metastasis than in those without. The most common site of synchronous metastasis was the bone in patients with pT1a RCC (65.4%), whereas for patients with post-surgery metachronous metastasis (46.2%), it was the lungs. Histological growth pattern and nuclear grade are vital for predicting metastasis in pT1a RCC, suggesting careful long-term follow-up for such patients.

Clinical Utility of Pre-Therapeutic [18F]FDG PET/CT Imaging for Predicting Outcomes in Breast Cancer.

[18F]FDG PET/CT is used for staging and could also provide information associated with clinical outcomes. The objective of this study was to determine the clinical utility of biomarkers measured using [18F]FDG PET/CT to predict the absence of pathological complete response (no-pCR) and recurrence. In this retrospective study, we included patients with non-special-type breast carcinoma who underwent [18F]FDG PET/CT before neoadjuvant chemotherapy between 2011 and 2019. Clinicopathological data were collected. Tumor SUVmax and total metabolic tumor volume (TMTV) were measured from PET images. The association between biomarkers and no-pCR was studied using logistic regression. The cut-off value was determined using the area under the ROC Curve. To predict 3-year recurrence-free survival (RFS), we used a multivariable Cox model, and the cut-off value was determined using time-dependent ROC and predictiveness curves. Two hundred and eighty-six patients were included in the analysis. One hundred and twelve patients had a pCR (39.2%). The pCR rate was significantly higher in patients with a high nuclear grade (p < 0.01), HER2+ and TNBC subtypes (p < 0.01), high Ki67 (p < 0.01), and low TMTV (p < 0.01). A high TMTV value (>9.0 cm3) was significantly associated with no-pCR in the whole cohort (OR = 2.4, 95% CI: 1.3-4.2, p < 0.01). After a median follow-up of 4.5 years, 65 patients experienced recurrence and 39 patients died. High TMTV (>13.5 cm3) was associated with shorter RFS (HR = 4.0, 95% CI: 1.9-8.4, p < 0.01). High TMTV in pre-therapeutic imaging is associated with no-pCR and recurrence. It can help in identifying high-risk patients and be considered as an intensified or alternative adjuvant therapy for closely monitoring patients.

Assessment of nuclear grade-based recurrence risk classification in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, node-positive high-risk early breast cancer

BackgroundHistological grade (HG) has been used in the MonrachE trial to select patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive high-risk early breast cancer (EBC). Although nuclear grade (NG) is widely used in Japan, it is still unclear whether replacing HG with NG can appropriately select high-risk patients.MethodsWe retrospectively reviewed 647 patients with HR-positive, HER2-negative, node-positive EBC and classified them into the following four groups: group 1: ≥ 4 positive axillary lymph nodes (pALNs) or 1–3 pALNs and either grade 3 of both grading systems or tumors ≥ 5 cm; group 2: 1–3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 ≥ 20%; group 3: 1–3 pALNs, grade < 3, tumor < 5 cm, and Ki-67 < 20%; and group 4: group 2 or 3 by HG classification but group 1 by NG classification. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) among the four groups using the Kaplan–Meier method with the log-rank test.ResultsGroup 1 had a significantly worse 5-year IDFS and DRFS than groups 2 and 3 (IDFS 80.8% vs. 89.5%, P = 0.0319, 80.8% vs. 95.5%, P = 0.002; DRFS 85.2% vs. 95.3%, P = 0.0025, 85.2% vs. 98.4%, P < 0.001, respectively). Group 4 also had a significantly worse 5-year IDFS (78.0%) and DRFS (83.6%) than groups 2 and 3.ConclusionsNG was useful for stratifying the risk of recurrence in patients with HR-positive, HER2-negative, node-positive EBC and was the appropriate risk assessment for patient groups not considered high-risk by HG classification.

Establishment and validation of a novel nomogram to predict overall survival after radical nephrectomy

Objective: To establish a nomogram prognostic model for predicting the 5-, 10-, and 15-year overall survival (OS) of non-metastatic renal cell carcinoma patients managed with radical nephrectomy (RN), compare the modelled results with the results of pure pathologic staging, the Karakiewicz nomogram and the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score commonly used in foreign countries, and stratify the patients into different prognostic risk subgroups. Methods: A total of 1 246 non-metastatic renal cell carcinoma patients managed with RN in Sun Yat-sen University Cancer Center (SYSUCC) from 1999 to 2020 were retrospectively analyzed. Multivariate Cox regression analysis was used to screen the variables that influence the prognosis for nomogram establishment, and the bootstrap random sampling was used for internal validation. The time-receiver operating characteristic curve (ROC), the calibration curve and the clinical decision curve analysis (DCA) were applied to evaluate the nomogram. The prediction efficacy of the nomogram and that of the pure pathologic staging, the Karakiewicz nomogram and the SSIGN score was compared through the area under the curve (AUC). Finally, patients were stratified into different risk subgroups according to our nomogram scores. Results: A total of 1 246 patients managed with RN were enrolled in this study. Multivariate Cox regression analysis showed that age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological T and N stages were independent prognostic factors for RN patients (all P<0.05). A nomogram model named SYSUCC based on these factors was built to predict the 5-, 10-, and 15-year survival rate of the participating patients. In the bootstrap random sampling with 1 000 iterations, all these factors occurred for more than 800 times as independent predictors. The Harrell's concordance index (C-index) of SYSUCC was higher compared with pure pathological staging [0.770 (95% CI: 0.716-0.823) vs 0.674 (95% CI: 0.621-0.728)]. The calibration curve showed that the survival rate as predicted by the SYSUCC model simulated the actual rate, while the clinical DCA showed that the SYSUCC nomogram has a benefit in certain probability ranges. In the ROC analysis that included 857 patients with detailed pathological nuclear stages, the nomogram had a larger AUC (5-/10-year AUC: 0.823/0.804) and better discriminating ability than pure pathological staging (5-/10-year AUC: 0.701/0.658), Karakiewicz nomogram (5-/10-year AUC: 0.772/0.734) and SSIGN score (5-/10-year AUC: 0.792/0.750) in predicting the 5-/10-year OS of RN patients (all P<0.05). In addition, the AUC of the SYSUCC nomogram for predicting the 15-year OS (0.820) was larger than that of the SSIGN score (0.709), and there was no statistical difference (P<0.05) between the SYSUCC nomogram, pure pathological staging (0.773) and the Karakiewicz nomogram (0.826). The calibration curve was close to the standard curve, which indicated that the model has good predictive performance. Finally, patients were stratified into low-, intermediate-, and high-risk subgroups (738, 379 and 129, respectively) according to the SYSUCC nomogram scores, among whom patients in intermediate- and high-risk subgroups had a worse OS than patients in the low-risk subgroup (intermediate-risk group vs. low-risk group: HR=4.33, 95% CI: 3.22-5.81, P<0.001; high-risk group vs low-risk group: HR=11.95, 95% CI: 8.29-17.24, P<0.001), and the high-risk subgroup had a worse OS than the intermediate-risk group (HR=2.63, 95% CI: 1.88-3.68, P<0.001). Conclusions: Age, smoking history, pathological nuclear grade, sarcomatoid differentiation, tumor necrosis and pathological stage were independent prognostic factors for non-metastasis renal cell carcinoma patients after RN. The SYSUCC nomogram based on these independent prognostic factors can better predict the 5-, 10-, and 15-year OS than pure pathological staging, the Karakiewicz nomogram and the SSIGN score of patients after RN. In addition, the SYSUCC nomogram has good discrimination, agreement, risk stratification and clinical application potential.

Evaluation of a retinal oximetry image quality indicator in patients with cataract.

To evaluate a new automated retinal oximetry image quality indicator with cataract as a clinical model. Sixty-one eyes in 61 patients were imaged by the Oxymap T1 Retinal Oximeter at baseline and 25 eyes were also examined 3 weeks after cataract surgery. Image quality (0-10 on a continuous scale) was compared with standardized AREDS cataract grading and Pentacam lens densitometry. Associations with retinal oximetry measurements and visual acuity were examined. Image quality correlated with total, nuclear and posterior subcapsular cataract grades (ANOVA, p < 0.05), tended to be associated with lens densitometry and it improved from 4.3 ± 1.4 to 5.7 ± 1.0 (p < 0.05) after cataract surgery. Very low image quality, below 3, led to vessel detection failure in retinal oximetry images. Higher image qualities were linearly associated with higher measured retinal oxygen saturations (r = 0.52 in arteries and r = 0.46 in veins; p < 0.001). Retinal oximetry image quality deteriorated with increasing cataract density and improved after cataract surgery, supporting its use as a measure of optical clarity. The numerical quality indicator demonstrated a threshold below which images of poor optical quality should be discarded. Image quality affects the estimates of retinal oximetry parameters and should therefore be included in future analyses.

Multinucleated tumor cells in clear cell renal cell carcinoma.

Multinucleated tumor cells (MTCs) in clear cell renal cell carcinoma (ccRCC) are not well understood. Our study included ccRCC cases in a single institution between 2010 and 2019. We classified MTC as MTC with degenerative atypia (MTCD), MTC with no anaplasia (MTCNA), and MTC with anaplasia (MTCA). Clinicopathologic characteristics and outcomes were compared between MTC groups. In all, 92 of 256 people (36%) with ccRCC had MTC. People with ccRCC with MTCD and those with ccRCC but no MTC had similar clinicopathologic characteristics and outcomes. Also, MTCNA and MTCA were associated with larger tumor size, advanced pathologic tumor stage, higher World Health Organization/International Society of Urologic Pathologists nuclear grade, and higher metastatic potential (P < .001 for each parameter). Overall, MTCA was associated with an increased rate of recurrence (P = .004), higher metastatic potential (P < .001), and shorter time to metastasis (P = .033), regardless of tumor stage. Univariate Cox regression revealed MTCNA as a significant predictor of metastasis at 5 years (hazard ratio [HR], 4.171; 95% CI, 1.934-8.998); moreover, MTCA was a significant predictor of recurrence (HR, 5.723; 95% CI, 2.495-13.124), metastasis (HR, 12.024; 5.966-24.232), and death (HR, 5.661; 95% CI, 2.688-11.924) at 5 years. Although MTCD may not be relevant in tumor grading, MTCNA and MTCA are associated with adverse outcomes.

Computer tomography-based shape of tumor contour and texture of tumor heterogeneity are independent prognostic indicators for clinical T1b-T2 renal cell carcinoma.

To evaluate association between computer tomography (CT)-based features of renal cell carcinoma (RCC) and survival outcomes. Data of 958 patients with clinical T1b-T2 RCC who underwent partial/radical nephrectomy from June 2003 to March 2022 were retrospectively evaluated. CT images of patients were reviewed by two radiologists for texture analysis of tumor heterogeneity and shape analysis of tumor contour. Patients were divided into three groups according to patterns of CT-based features: (1) favorable feature group (n = 117); (2) intermediate feature group (n = 606); and (3) unfavorable feature group (n = 235). Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed to evaluate overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS). RCCs with unfavorable CT-based feature showed larger size on CT, higher nuclear grade, higher rate of histologic necrosis, and higher rate of capsular invasion than those in the other two groups (all p < 0.001). Unfavorable feature was associated with poorer OS (p = 0.001), CSS (p < 0.001), and RFS (p < 0.001) on Kaplan-Meier analysis. In multivariate analysis, intermediate and unfavorable features were independent predictors for recurrence (hazard ratio [HR] 2.51, 95% confidence interval [CI] 1.09-5.79, p = 0.031 and HR 3.71, 95% CI 1.58-8.73, p = 0.003, respectively), but not for overall death or RCC-specific death. A combination of irregular tumor contour feature with heterogeneous tumor texture feature on CT is associated with poor RFS in clinical T1b-T2 RCC preoperatively.

Prognostic role of the immunohistochemical expression of proteins related to the renin-angiotensin system pathway in nonmetastatic clear cell renal cell carcinoma.

Stage migration has been observed in renal cell carcinoma (RCC) in recent decades; however, mortality rates have continuously increased in some countries. Tumoral factors have been characterized as major predictors of RCC. Nonetheless, this concept can be improved by combining these tumoral factors with other variables, including biomolecular factors. This study aimed to assess the immunohistochemical (IHC) expression and prognostic value of renin (REN), erythropoietin (EPO), and cathepsin D (CTSD), and to evaluate whether the concomitant expression of these markers can influence the prognostic outcomes in patients without metastasis. In total, 729 patients with clear cell RCC (ccRCC) who underwent surgical treatment between 1985 and 2016 were evaluated. All the cases in the tumor bank were reviewed by dedicated uropathologists. The IHC expression patterns of the markers were assessed using a tissue microarray. REN and EPO were classified as "positive" or "negative" expression. CTSD was grouped into "absent or weak expression" or "strong expression." Associations between clinical and pathological variables and the studied markers, in addition to 10-year overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival rates, were described. REN and EPO expressions were positive in 70.6% and 86.6% of patients, respectively. Absent or weak and strong expressions of CTSD were observed in 58.2% and 41.3% of the patients, respectively. EPO expression had no impact on survival rates even when assessed concomitantly with REN. Negative REN expression was associated with advanced age, preoperative anemia, larger tumors, perirenal fat, hilum or renal sinus infiltration, microvascular invasion, necrosis, high nuclear grade, and clinical stages III to IV. In contrast, strong CTSD expression was associated with poor prognostic variables. The expression patterns of REN and CTSD were unfavorable predictors of the 10-year OS and CSS. In particular, the combination of negative REN and strong CTSD expression had a negative impact on these rates, including a higher risk of recurrence. Loss of REN expression and strong CTSD expression were independent prognostic factors in nonmetastatic ccRCC, particularly when the concomitant expression pattern of both markers was present. EPO expression did not influence survival rates in this study.

SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival.

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan-Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.

DUCTAL CARCINOMA IN SITU ARISING WITHIN BREAST FIBROADENOMA: A CASE REPORT AND REVIEW OF THE LITERATURE

Fibroadenoma is the most common benign breast tumor in women under 30. However, carcinoma arising in a fibroadenoma is unusual and very rare, with over 100 cases reported in the literature. Histological diagnosis is usually incidental. We report the case of a 51-year-old perimenopausal patient with a family history of a mother who died of breast cancer. She was admitted with a hard elastic mass in the upper outer quadrant of her left breast. Imaging revealed a heterogeneous nodule with ductal dilatation. A core needle biopsy with four specimens showed a fibroepithelial tumor with atypical ductal hyperplasia. Left breast-conserving surgery was performed for radical treatment. The diagnosis on the specimen was carcinoma in situ of intermediate nuclear grade and massive compact and cribriform type developed on a fibroadenoma. We present this case to raise awareness of this entity and highlight the need for histological evaluation of specific breast masses.

Comparison of clinicopathologic characteristics of Invasive Papillary Carcinoma with Invasive Ductal Carcinoma and their survival outcome

Background: Invasive Papillary Carcinoma (IPC) of the breast is a rare breast cancer subtype. This study aimed to evaluate the clinicopathologic characteristics of IPC of the breast, its differences from Invasive Ductal Carcinoma (IDC), and their survival outcomes.Materials and Methods: The medical records of 6599 patients were retrospectively reviewed at the Breast Disease Research Center from December 1993 to December 2021. The patients were divided into two groups: IPC and IDC. The tumor size, lymph node metastasis, pathologic stage, nuclear and histological grade, hormonal receptor status, and survival were reviewed and compared between the IPC and IDC groups.Results: Of the 6599 patients, 27 had IPC, and 6572 had IDC. The mean age of patients with IPC and IDC was 58.5 and 49 years, respectively (P=0.02). Patients with IPC were more likely to have a positive node status and had a significantly higher incidence of lymphovascular invasion (14.9% for IPCs and 53.3% for IDCs, P&lt;0.001). ER status was positive in 66.6% of IPCs and 78.1% of IDCs (P=0.23). Additionally, 62.5% of patients with IPC and 94.9% of those with IDC received adjuvant chemotherapy (P&lt;0.001). Disease-free survival (DFS) and overall survival (OS) were better in IPC patients for stage I (5-year DFS: 69% vs. 81%, P=0.008; 5-year OS: 75% vs. 85%, P=0.001).Conclusion: IPC is a rare tumor type that presents unique clinicopathological characteristics and is associated with a higher rate of breast-conserving surgery and a favorable prognosis than IDC

Loss of aquaporin-1 expression is associated with worse clinical outcomes in clear cell renal cell carcinoma: an immunohistochemical study.

Aquaporin (AQP) expression has been investigated in various malignant neoplasms, and the overexpression of AQP is related to poor prognosis in some malignancies. However, the expression of AQP protein in clear cell renal cell carcinoma (ccRCC) has not been extensively investigated by immunohistochemistry with large sample size. We evaluated the AQP expression in 827 ccRCC with immunohistochemical staining in tissue microarray blocks and classified the cases into two categories, high and low expression. High expression of aquaporin-1 (AQP1) was found in 320 cases (38.7%), but aquaporin-3 was not expressed in ccRCC. High AQP1 expression was significantly related to younger age, low TNM stage, low World Health Organization/International Society of Urologic Pathology nuclear grade, and absence of distant metastasis. Furthermore, high AQP1 expression was also significantly associated with longer overall survival (OS; p<.001) and progression-specific survival (PFS; p<.001) and was an independent predictor of OS and PFS in ccRCC. Our study revealed the prognostic significance of AQP1 protein expression in ccRCC. These findings could be applied to predict the prognosis of ccRCC.