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Adverse Histopathologic Characteristics in Small Clear Cell Renal Cell Carcinomas Have Negative Impact on Prognosis

A Study of 631 Cases With Clinical Follow-up

Yang, Chen MD*; Shuch, Brian MD; Serrano, Maria MD; Kibel, Adam S. MD§; Nawaf, Cayce MD; Vollmer, Robin MD; Humphrey, Peter A. MD, PhD*; Adeniran, Adebowale J. MD*

The American Journal of Surgical Pathology: October 2019 - Volume 43 - Issue 10 - p 1413–1420
doi: 10.1097/PAS.0000000000001333
Original Articles

Tumor size has been used for decision making in the management of patients with renal masses. Active surveillance in selected patients is now increasingly common in tumors ≤4 cm in size. Clear cell renal cell carcinoma (CCRCC) is the most common type of renal malignancy. Adverse histopathologic characteristics that correlate with worse prognosis have been described in CCRCCs. The aim of our study was to determine the frequency and extent of adverse histopathologic characteristics in CCRCCs ≤4 cm and their association with patient outcome. A search of a single institution for nephrectomies performed for CCRCC identified 631 consecutive cases. Cases were reviewed for the following morphologic features: high nuclear grade, necrosis, lymphovascular invasion, and rhabdoid or sarcomatoid histology. Relationships between the variables were examined by Kruskal-Wallis test, Wilcoxon test, χ2 test, and logistic regression. We found adverse tumor histopathologic characteristics were significantly related to size: In CCRCCs >4 versus ≤4 cm, there were more high nuclear grade (45% vs. 15%, P<0.01), necrosis (46% vs. 21%, P<0.01), and lymphovascular invasion (17% vs. 3%, P<0.01). Although adverse histologic features are less commonly seen in CCRCCs ≤4 cm, their presence was associated with lower disease-free survival (P<0.01). Adverse histopathologic characteristics in CCRCCs ≤4 cm correlated with worse prognosis and identification of these features through needle core biopsy examination may guide clinical management, especially in patients for whom active surveillance is considered.

Departments of *Pathology

Urology, Yale School of Medicine, New Haven, CT

Department of Urology, University of California Los Angeles, Los Angeles

Kaiser Permanente, San Francisco, CA

§Department of Urology, Brigham & Women’s Hospital, Boston, MA

Department of Pathology, Duke University, Durham, NC

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Adebowale J. Adeniran, MD, Department of Pathology, Yale School of Medicine, 310 Cedar Street, CB 510A, New Haven, CT 06510 (e-mail:

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