Differential Diagnosis of Renal Tumors With Clear Cytoplasm: Clinical Relevance of Renal Tumor Subclassification in the Era of Targeted Therapies and Personalized Medicine

Abstract

Context.—The World Health Organization classification of renal tumors synthesizes morphologic, immunohistochemical, and molecular findings to define more than 40 tumor types. Of these, clear cell (conventional) renal cell carcinoma is the most common malignant tumor in adults and—with the exception of some rare tumors—the most deadly. The diagnosis of clear cell renal cell carcinoma on morphologic grounds alone is generally straightforward, but challenging cases are not infrequent. A misdiagnosis of clear cell renal cell carcinoma has clinical consequences, particularly in the current era of targeted therapies. Objective.—To highlight morphologic mimics of clear cell renal cell carcinoma and provide strategies to help differentiate clear cell renal cell carcinoma from other renal tumors and lesions. The role of the pathologist in guiding treatment for renal malignancies will be emphasized to stress the importance of proper tumor classification in patient management. Data Sources.—Published literature and personal experience. Conclusions.—In challenging cases, submission of additional tissue is often an inexpensive and effective way to facilitate a correct diagnosis. If immunohistochemical stains are to be used, it is best to use a panel of markers, as no one marker is specific for a given renal tumor subtype. Selection of limited markers, based on a specific differential diagnosis, can be as useful as a large panel in reaching a definitive diagnosis. For renal tumors, both the presence and absence of immunoreactivity and the pattern of labeling (membranous, cytoplasmic, diffuse, focal) are important when interpreting the results of immunohistochemical stains.

Multidetector CT imaging features of invasive renal parenchyma urothelial carcinoma

“…22 In common with IRPUCs, collecting duct carcinomas, chromophobe renal cell carcinomas 23 and renal lymphomas are hypovascular compared with renal parenchyma on enhanced CT imaging. The majority of collecting duct carcinomas 24 show mild enhancement on all enhanced scan phases. However, the latter are reported to be more common in the medulla, which is dissimilar to IRPUC.…”

The Application of Immunohistochemical Biomarkers in Urologic Surgical Pathology

“…Numerous renal epithelial tumor-associated immunomarkers have been reported in the literature in differentiating subtypes of renal epithelial neoplasms. [4][5][6][7] Most of these markers, such as cluster of differentiation (CD) 10, renal cell carcinoma marker (RCCma), a-methylacyl-CoA racemase (P504S), epithelial membrane antigen (EMA), paired box gene (PAX) 8, PAX2, S100A1, and kidney-specific cadherin (ksp-cad), are also expressed in proximal and/or distal renal tubules as well. Therefore, most of these markers have little value in the distinction of a benign process from a renal epithelial tumor.…”

“…6,7,55,58 Based on a study of 443 consecutive nephrectomies from a single institution, the incidence of TRCC in adults has been reported as 1.6%. 57 The typical morphologic features include papillary and nested structures lined by clear to granular cells with voluminous cytoplasm, hyaline material, and psammoma bodies.…”

voomDDA: discovery of diagnostic biomarkers and classification of RNA-seq data

“…This RNA-Seq data has 606, 323 and 91 specimens from the kidney renal papillary cell (KIRP), kidney renal clear cell (KIRC) and kidney chromophobe carcinomas (KICH), respectively. These three classes are referred as the most common subtypes of RCC (account for nearly 90%–95% of the total malignant kidney tumors in adults) and treated as three separate classes in our analysis (Goyal et al, 2013). …”