Contemporary Clinical Definitions, Differential Diagnosis, and Novel Predictive Tools for Renal Cell Carcinoma

Abstract

Despite significant progress regarding clinical detection/imaging evaluation modalities and genetic/molecular characterization of pathogenesis, advanced renal cell carcinoma (RCC) remains an incurable disease and overall RCC mortality has been steadily rising for decades. Concomitantly, clinical definitions have been greatly nuanced and refined. RCCs are currently viewed as a heterogeneous series of cancers, with the same anatomical origin, but fundamentally different metabolisms and clinical behaviors. Thus, RCC pathological diagnosis/subtyping guidelines have become increasingly intricate and cumbersome, routinely requiring ancillary studies, mainly immunohistochemistry. Meanwhile, RCC-associated-antigen targeted systemic therapy has been greatly diversified and emerging, novel clinical applications for RCC immunotherapy have already reported significant survival benefits, at least in the adjuvant setting. Even so, systemically disseminated RCCs still associate very poor clinical outcomes, with currently available therapeutic modalities only being able to prolong survival. In lack of a definitive cure for advanced RCCs, integration of the amounting scientific knowledge regarding RCC pathogenesis into RCC clinical management has been paramount for improving patient outcomes. The current review aims to offer an integrative perspective regarding contemporary RCC clinical definitions, proper RCC clinical work-up at initial diagnosis (semiology and multimodal imaging), RCC pathological evaluation, differential diagnosis/subtyping protocols, and novel clinical tools for RCC screening, risk stratification and therapeutic response prediction.

Qualitative and quantitative characteristics of CEUS for renal cell carcinoma and angiomyolipoma: a narrative review

“…These features are attributed to tumor growth, causing compression, ischemia, and subsequent necrosis of adjacent parenchyma, followed by the deposition of fibrous tissue. Additionally, heterogeneous enhancement and early-stage hyperenhancement on CEUS are often linked to the likelihood of rapidly growing RCCs, characterized by thin-walled immature blood vessels and many arterial-venous fistulas [ 22 , 23 ]. On the other hand, AMLs often demonstrated iso-enhancement on CEUS, with slow contrast accumulation and gradual wash-out [ 16 , 17 ].…”

Immunotherapy Applications for Thymine Dimers and WT1 Antigen in Renal Cancers: A Comparative Statistical Analysis

“…The World Health Organization's (WHO’s) 2022 Classification of Kidney Tumors now includes twenty-one distinct subtypes of malignant kidney tumors [ 5 ]. Yet, these refined classifications have not significantly improved patient outcomes, particularly for advanced RCCs, which remain incurable [ 8 ].…”

“…Immunohistochemistry (IHC) is a vital part of the routine pathological evaluation of kidney tumors [ 9 , 10 , 11 , 12 ], and RCCs in particular. Recent developments have provided a wide variety of potentially relevant RCC-associated proteomic targets [ 8 , 13 , 14 , 15 ]. However, herein there are substantial limitations, i.e., retrospective designs, limited samples, inconsistent clinical data, and an overall lack of standardization, with implicit extensive data heterogeneity [ 16 ].…”

Rats, Neuregulins and Radical Prostatectomy: A Conceptual Overview

“…Currently accounting for ~3.8% of all deaths caused by cancer in men, prostate cancer represents the fifth leading cause of death worldwide [ 1 ]. Important developments for urological malignancies in general [ 2 , 3 , 4 ], and PC in particular, include improved diagnostic technologies and fundamental scientific understanding of pathogenesis, as well as steadily evolving clinical tools for screening/early detection and risk stratification/therapeutic decision-making. In addition, superior and highly specific clinical methods are available for PC diagnosis, which include Prostate Specific Antigen (PSA) screening, multi-parametric magnetic resonance imaging (mpMRI), PSA isoforms, and micro ribonucleic acid (microRNA).…”