Context-aware heterogeneous graph neural network for multi-level description and invasiveness prediction in renal cell carcinoma.

The renal sinus is the fatty compartment located within the confines of the kidney not delineated from the renal cortex by a fibrous capsule. Because it contains numerous veins and lymphatics, invasion into this compartment may permit dissemination of a tumor otherwise regarded as renal-limited. Thirty-one consecutive renal carcinomas were studied: 22 clear cell renal cell carcinomas (3 multilocular cystic renal cell carcinomas), 4 chromophobe renal carcinomas, and 5 papillary renal carcinomas. The entire interface between the neoplasm and the sinus was embedded. Seventeen carcinomas did not invade the renal sinus and 16 were pT1 or pT2 tumors. Fourteen carcinomas, 13 clear cell renal cell carcinoma and one chromophobe renal carcinoma, invaded the renal sinus fat, and 9 of 14 invaded the lumen of renal sinus veins (all clear cell renal carcinomas). Although 14 of 22 clear cell renal carcinomas appeared to be renal limited pT1 and pT2 cancers, 6 of 14 carcinomas invaded sinus fat and 4 invaded into the lumen of renal sinus veins. Compared with the nine sinus-negative clear cell renal cell carcinomas, the 13 sinus-positive cancers were larger, exhibited more frequent renal capsule and renal vein involvement, and had higher nuclear grades. Renal sinus invasion was most common in clear cell renal cell carcinomas but was uncommon (one in 12) in 3 more indolent renal cell carcinomas: multilocular cystic renal cell carcinoma, chromophobe renal carcinoma, and papillary renal carcinoma. The follow-up period was short (1-17 months), but metastases developed in four of 31 cases. In three cases with metastases, carcinoma had involved the lumen of sinus veins but not the main renal vein, although two of three had also invaded through the renal capsule. This study shows that in carcinomas which appear to be renal limited (pT1/pT2), seven of 23 (30.4%) had invaded sinus fat and four of 23 (17.4%) had invaded sinus veins. We conclude that renal sinus invasion, especially sinus vein invasion, could identify a patient at risk for metastases even in a putative renal limited tumor, and suggest that all cases be examined for this feature. Renal sinus invasion merits further investigation to establish its prognostic importance and possible incorporation into future revisions of the TNM staging system for renal cell carcinomas.

Introduction and objectives: Sarcomatoid morphology (SM) in renal cell carcinoma (RCC) is associated with poor outcomes. The objective was to evaluate the prevalence of sarcomatoid morphology in different types of RCC and determine its association with other adverse prognostic factors.Methodology: Data was retrieved and analysed from the departmental database from January 2018 to December 2021. Presence or absence of sarcomatoid morphology in different tumours and its association with tumour size, WHO/ISUP grade, necrosis, renal sinus invasion, extracapsular invasion, renal vein invasion and tumour stage were documented. SPSS was used for data analysis.Results: Of the 94 RCCs clear cell RCC was the commonest 75/94(79.8%), followed by papillary RCC 16/94(17%) and chromophobe RCC 3/94(3.2%). SM was present in 23/94 (24.5%.) RCCs and the highest prevalence was in clear cell RCC 19/75(25.3%) followed by papillary RCC 4/16(25%). SM was not seen in chromophobe RCC. Of the RCC with SM, 11/23(47.8%) had tumour size>7 cm, 23/23(100%) were WHO/ISUP grade 4, 19/23(82.6%) had tumour necrosis, 13/23 (56.5%) showed renal sinus invasion and 11/23(42.8%) had lymphovascular invasion. Of the RCC without SM, 22/71(31%) had tumour size>7 cm, 1/71(1.4%) was WHO/ISUP grade 4, 28/71(39.4%) had tumour necrosis, 14/71 (19.7%) had renal sinus invasion and 23/71(32.4%) had lymphovascular invasion. Chi square test showed a significant difference between the tumours with and without SM in relation to WHO/ISUP grade (p<0.001), renal sinus invasion (p=0.003) and tumour necrosis (p=0.001). A significant difference was not seen in relation to tumour size (p=0.303), renal vein invasion (p=0.179), TNM stage (p=0.150) and lymphovascular invasion(p=0.181).Discussion and conclusion: SM is more prevalent in clear cell RCC compared to other renal tumours which indicates that extensive sampling is warranted for clear cell RCC. Renal tumours with SM show a significant association with several poor prognostic factors.

Renal cell carcinoma (RCC) is unusual among cancers in that it often grows as a spherical, well-circumscribed mass. Increasing tumour size influences the pathological pT stage category within pT1 and pT2, with cutoffs of 40, 70 and 100mm; however, with increasing size also comes a sharp increase in the likelihood of renal sinus or renal vein tributary invasion, such that clear cell RCC rarely reaches 70mm without invading one of these. To clarify some previous challenges in assigning tumour stage, the American Joint Committee on Cancer 2016 tumor-node-metastasis classification has removed the requirements than vein invasion be recognised grossly and that vein walls contain muscle for the diagnosis of vein invasion. Renal pelvis invasion has also been added as an additional route to pT3a. Multinodularity or finger-like extensions from a renal mass should be viewed with great suspicion for the possibility of vein or renal sinus invasion, and, as tumour size increases to over 40-50mm, thorough sampling of the renal sinus interface should always be undertaken. With increasing interest in adjuvant therapy in renal cancer, the pathologist's role in RCC staging will continue to be an important prognostic parameter and a tool for selection of patients for enrolment in clinical trials.

PurposeRenal sinus invasion is an attributive factor affecting the prognosis of renal cell carcinoma (RCC). This study aimed to construct a risk prediction model that could stratify patients with RCC and predict renal sinus invasion with the help of a machine learning (ML) algorithm.Patients and MethodsWe retrospectively recruited 1229 patients diagnosed with T1 stage RCC at the Baotou Cancer Hospital between November 2013 and August 2021. Iterative analysis was used to screen out predictors related to renal sinus invasion, after which ML-based models were developed to predict renal sinus invasion in patients with T1 stage RCC. The receiver operating characteristic curve (ROC), decision curve analysis (DCA), and clinical impact curve (CIC) were performed to evaluate the robustness and clinical practicability of each model.ResultsA total of 21 candidate variables were shortlisted for model building. Iterative analysis screened that neutrophil to albumin ratio (NAR), hemoglobin level * albumin level * lymphocyte count/platelet count ratio (HALP), prognostic nutrition index (PNI), body mass index*serum albumin/neutrophil-lymphocyte ratio (AKI), NAR, and fibrinogen (FIB) concentration (NARFIB), platelet to lymphocyte ratio (PLR), and R.E.N.A.L score was related to renal sinus invasion and contributed significantly to ML-based algorithm. The areas under the ROC curve (AUCs) of the random forest classifier (RFC) model, support vector machine (SVM), eXtreme gradient boosting (XGBoost), artificial neural network (ANN), and decision tree (DT) ranged from 0.797 to 0.924. The optimal risk probability of renal sinus invasion predicted was RFC (AUC = 0.924, 95% confidence interval [CI]: 0.414–1.434), which showed robust discrimination for identifying high-risk patients.ConclusionWe successfully develop practical models for renal sinus invasion prediction, particularly the RFC, which could contribute to early detection via integrating systemic inflammatory factors and nutritional parameters.

BackgroundPapillary renal cell carcinoma (pRCC) is characterized by pronounced molecular and phenotypic heterogeneity. The traditional dichotomous classification was discontinued in the 2022 World Health Organization (WHO) Fifth Edition Classification, leading to the introduction of new renal cancer categories, including fumarate hydratase (FH)-deficient renal cell carcinoma (RCC). But there remains a significant risk of misdiagnosis between FH-deficient RCC and high-grade pRCC. Furthermore, existing studies rarely provide comprehensive comparative analyses of these types of renal cancer. This study aims to investigate the clinical and pathological characteristics, as well as the prognosis, of FH-deficient RCC and high-grade pRCC, thereby providing a basis for precise diagnosis.MethodsWe retrospectively analyzed the clinical and pathological data of patients diagnosed with high-grade pRCC (n=40) or FH-deficient RCC (n=20) between May 2012 and May 2023.ResultsCompared to high-grade pRCC, FH-deficient RCC exhibited significant differences in several parameters: age (P<0.001), presence of necrosis (P=0.007), sarcomatoid differentiation (P=0.03), vascular cancer thrombus formation (P=0.02), lymph node metastasis (P=0.001) renal sinus invasion (P=0.042), perirenal fat invasion (P=0.01), adrenal gland invasion (P=0.003), and pathological tumor (pT) stage (P=0.009). Patients with FH-deficient tumors tended to be younger and were more likely to exhibit features such as necrosis, sarcomatoid differentiation, renal sinus and perinephric fat invasion, adrenal gland involvement, lymph node metastasis, and more advanced pathological stages compared with those with high-grade pRCC. However, FH-deficient RCC demonstrated a significantly lower incidence of lymphovascular invasion when compared to high-grade pRCC. The 3-year progression-free survival (PFS) rates were 16.9% for FH-deficient RCC and 76.2% for high-grade pRCC. Patients with FH-deficient RCC had significantly worse outcomes than those with high-grade pRCC (P<0.001).ConclusionsPatients who are younger, have advanced pathological stages, or exhibit sarcomatoid differentiation should undergo mandatory immunohistochemical staining for FH and molecular testing to prevent misdiagnosis as conventional pRCC. Despite its aggressive local behavior and poorer clinical outcomes, FH-deficient RCC shows a significantly lower frequency of vascular invasion relative to high-grade pRCC. Further investigation into the mechanisms underlying the metastasis of these tumors is warranted to identify potential therapeutic targets.

A total of 100 renal cell carcinomas were prospectively examined for renal sinus invasion, 74 clear cell renal cell carcinomas (CC), 3 renal cell carcinomas, unclassified (RUC), 16 papillary renal cell carcinomas (PapC), and 7 chromophobe renal cell carcinomas (ChC). Using the 2002 TNM staging formulation, 49 tumors were T1, 5 were T2, and 46 were T3 or T4. Renal sinus invasion occurred more often than renal capsule invasion. No tumor invaded the capsule that did not also invade the sinus. Renal sinus invasion correlated with Fuhrman grade; 17% of grades 1/2 tumors invaded the sinus, while 71% of grade 3/4 tumor invaded the sinus (P < 0.001). Sinus invasion correlated with tumor type; 2 of 23 PapC and ChC invaded the sinus compared with 44 of 77 CC and RUC. Sinus invasion occurred in approximately 16% of tumors 1 to 4 cm in size, then abruptly increased for larger tumors (P < 0.001). When tumors are staged by the 1997 and 2002 TNM formulation, renal sinus invasion upstaged 28% of cases stage T1 or T2 by the 1997 formulation, to T3 using the 2002 criteria. In conclusion, renal sinus invasion is the most common site of extrarenal extension of renal carcinoma and correlates with tumor type, grade and size. Appropriate evaluation for sinus invasion reduces the incidence of T1b and T2 CC tumors, limiting prognostic utility and suggesting reassessment of the T1 and T2 stage designations.

T2 CLEAR CELL RENAL CELL CARCINOMA IS A RARE ENTITY: A STUDY OF 120 CLEAR CELL RENAL CELL CARCINOMAS

Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†.

ObjectiveTo identify the association between renal tumor complexity and pathologic renal sinus invasion (RSI) and evaluate the usefulness of computed tomography tumor features for predicting RSI in patients with renal cell carcinoma (RCC).Materials and MethodsThis retrospective study included 276 consecutive patients who underwent radical nephrectomy for RCC with a size of ≤ 7 cm between January 2014 and October 2017. Tumor complexity and anatomical renal sinus involvement were evaluated using two standardized scoring systems: the radius (R), exophytic or endophytic (E), nearness to collecting system or sinus (N), anterior or posterior (A), and location relative to polar lines (RENAL) nephrometry and preoperative aspects and dimensions used for anatomical classification (PADUA) system. CT-based tumor features, including shape, enhancement pattern, margin at the interface of the renal sinus (smooth vs. non-smooth), and finger-like projection of the mass, were also assessed by two independent radiologists. Univariable and multivariable logistic regression analyses were performed to identify significant predictors of RSI. The positive predictive value, negative predictive value (NPV), accuracy of anatomical renal sinus involvement, and tumor features were evaluated.ResultsEighty-one of 276 patients (29.3%) demonstrated RSI. Among highly complex tumors (RENAL or PADUA score ≥ 10), the frequencies of RSI were 42.4% (39/92) and 38.0% (71/187) using RENAL and PADUA scores, respectively. Multivariable analysis showed that a non-smooth margin and the presence of a finger-like projection were significant predictors of RSI. Anatomical renal sinus involvement showed high NPVs (91.7% and 95.2%) but low accuracy (40.2% and 43.1%) for RSI, whereas the presence of a non-smooth margin or finger-like projection demonstrated comparably high NPVs (90.0% and 91.3% for both readers) and improved accuracy (67.0% and 73.9%, respectively).ConclusionA non-smooth margin or the presence of a finger-like projection can be used as a preoperative CT-based tumor feature for predicting RSI in patients with RCC.

The International Society of Urological Pathology Consensus Conference regarding the classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors

ASSESSMENT OF TUMOR INVASION OF THE VENA CAVAL WALL IN RENAL CELL CARCINOMA CASES BY MAGNETIC RESONANCE IMAGING

Advances in Renal Neoplasia: Recommendations From the 2012 International Society of Urological Pathology Consensus Conference

Renal sinus fat invasion was incorporated as one of the parameters for pT stage definition of renal cell carcinoma (RCC) only in the latest 2002 American Joint Committee on Cancer/tumor-node-metastasis staging protocol. The current pT3a subcategory (in addition to adrenal gland involvement) groups 2 modes of extrarenal extension by RCC, either by peripheral perinephric fat extension or by renal sinus fat invasion. Recent prospective studies have shown that with more directed gross sampling and histologic evaluation, renal sinus invasion is actually more commonly diagnosed than previously reported, or when compared with retrospectively sampled RCC nephrectomy specimens. These studies have demonstrated that renal sinus invasion is the principal pathway for extrarenal extension for clear cell RCC; the incidence of which is related to size (tumors greater than 4 cm more frequently involve the renal sinus). More significantly, a recent retrospective study of pT3a clear cell RCC nephrectomy specimens showed that tumors invading the renal sinus fat portend a more aggressive outcome than tumors invading only the peripheral perinephric fat. Clear cell RCCs invading the renal sinus are more likely to have higher nuclear grade, regional lymph node involvement and sarcomatoid transformation than tumors invading only the perinephric fat. Given the importance of renal sinus invasion, sampling strategies for nephrectomy specimens should be modified to focus in this region as appropriate and pathologists should be familiar with the histologic criteria for staging renal sinus invasion.

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35). Most questions included 1 to 4 images, focusing on: vascular and renal sinus invasion (n=24), perinephric invasion (n=9), and gross pathology/specimen handling (n=17). Responses were collapsed for analysis into positive and negative/equivocal for upstaging. Consensus was regarded as an agreement of 67% (2/3) of participants, which was reached in 20/33 (61%) evaluable scenarios regarding renal sinus, perinephric, or vein invasion, of which 13/33 (39%) had ≥80% consensus. Lack of agreement was especially encountered regarding small tumor protrusions into a possible vascular lumen, close to the tumor leading edge. For gross photographs, most were interpreted as suspicious but requiring histologic confirmation. Most participants (61%) rarely used special stains to evaluate vascular invasion, usually endothelial markers (81%). Most agreed that a spherical mass bulging well beyond the kidney parenchyma into the renal sinus (71%) or perinephric fat (90%) did not necessarily indicate invasion. Interobserver agreement in pathologic staging of renal cancer is relatively good among urologic pathologists interested in kidney tumors, even when selecting cases that test the earliest and borderline thresholds for extrarenal extension. Disagreements remain, however, particularly for tumors with small, finger-like protrusions, closely juxtaposed to the main mass.

Renal cancer is a serious public health problem which may be under reported and registered in our setup, since the Karachi cancer registry documented only 43 cases out of 4,268 incident cancer cases over 3 year duration. Therefore we aimed to determine the clinicopathologic characteristics of adult renal tumors in our setup. The study was conducted in histopathology department, Liaquat National Hospital and included total of 68 cases of adult renal tumors over 4 years. Detailed histopathologic characteristics of tumors were analyzed. Mean age of patients was 56.4 (18-84) years. Renal cell carcinoma (RCC) was the most common cell type (78%) cases; followed by transitional/urothelial carcinoma (12.5%), leiomyosarcoma (4.7%), oncocytoma (1.6%), squamous cell carcinoma (1.6%) and high grade pleomorphic undifferentiated sarcoma (1.6%). Among 50 RCC cases; 62% were conventional/clear cell RCC (CCRCC) type followed by papillary RCC(PRCC), 24%; chromophobe RCC(CRCC), 6% and sarcomatoid RCC(SRCC), 8%. Mean tumor size for RCC was 7.2 cm. Most RCCs were intermediate to high grade (60% and 40% respectively). Capsular invasion, renal sinus invasion, adrenal gland involvement and renal vein invasion was seen in 40%, 18%, 2% and 10% of cases respectively. We found that RCC presents at an earlier age in our setup compared to Western populations. Tumor size was significantly larger and most of the tumors were of intermediate to high grade. This reflects late presentation of patients after disease progression which necessitates effective measures to be taken in primary care setup to diagnose this disease at an early stage.