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 100 mm; 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 70 mm 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 40–50 mm, 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.
Background: Pan-cancer studies of somatic copy number alterations (SCNAs) have demonstrated common SCNA patterns across cancer types, but despite demonstrable differences in aggressiveness of some cancers by race, pancancer SCNA variation by race has not been explored. This study investigated a) racial differences in SCNAs in both breast and prostate cancer, b) the degree to which they are shared across cancers, and c) the impact of these shared, race-differentiated SCNAs on cancer survival. Methods: Utilizing data from The Cancer Genome Atlas (TCGA), SCNAs were identified using GISTIC 2.0, and in each tumor type, differences in SCNA magnitude between African Americans (AA) and European Americans (EA) were tested using linear regression. Unsupervised hierarchical clustering of the copy number of genes residing in race-differentiated SCNAs shared between tumor types was used to identify SCNA-defined patient groups, and Cox proportional hazards regression was used to test for association between those groups and overall/progression-free survival (PFS). Results: We identified SCNAs that differed by race in breast (n = 58 SCNAs; permutation p < 10 − 4) and prostate tumors (n = 78 SCNAs; permutation p = 0.006). Six race-differentiated SCNAs common to breast and prostate found at chromosomes 5q11.2-q14.1, 5q15-q21.1, 8q21.11-q21.13, 8q21.3-q24.3, 11q22.3, and 13q12.3-q21.3 had consistent differences by race across both tumor types, and all six were of higher magnitude in AAs, with the chromosome 8q regions being the only amplifications. Higher magnitude copy number differences in AAs were also identified at two of these race-differentiated SCNAs in two additional hormonally-driven tumor types: endometrial (8q21.3-q24.3 and 13q12.3-q21.3) and ovarian (13q12.3-q21.3) cancers. Race differentiated SCNA-defined patient groups were significantly associated with survival differences in both cancer types, and these groups also differentiated within triple negative breast cancers based on PFS. While the frequency of the SCNA-defined patient groups differed by race, their effects on survival did not.
Our findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non-clear cell histology (particularly papillary or chromophobe RCC).
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