Clinicopathological and Molecular Characteristics of Macroscopically Yellowish-Colored Chromophobe Renal Cell Carcinoma Compared to Non-Yellowish-Colored Chromophobe Renal Cell Carcinoma

Abstract

Each histological variant of renal cell tumors has a unique color. The yellowish color of clear cell renal cell carcinoma (CCRCC) is explained by the presence of intracytoplasmic lipid and glycogen accumulation. Color changes in CCRCC are correlated with clinicopathological and metabolic changes, as well as biological behavior. We analyzed and compared the clinical, histopathological, and immunohistochemical features and gene expression profiles, in lipid metabolism of yellowish-colored ChRCC (ChRCC-Y), non-yellowish-colored ChRCC (ChRCC-N), and CCRCC. Of 14 ChRCCs, we retrieved 6 ChRCC-Ys. Patients with ChRCC-Y are younger than those with ChRCC-N, and the tumor is not predominant in males. ChRCC-Ys are smaller than ChRRC-Ns. Three ChRCC-Ys exhibited individual discrete tubule formation. No ChRCC-Ns exhibited individual discrete tubule formation. Two of 6 ChRCC-Ys showed relatively diffuse adipophilin positivity. No ChRCC-Ns demonstrated diffuse positivity for adipophilin. The expression of SCD, FDFT1, and E2F1 showed a tendency to be lower in ChRCC-Y than in ChRCC-N. The expression of PDGFB showed a tendency to be higher in ChRCC-Y than in ChRCC-N. This study demonstrated ChRCC-Y did not indicate an increase in lipid and cholesterol metabolism and that ChRCC-Y did not have the common molecular alteration of CCRCC. The absence of such metabolic acceleration in ChRCC-Y might support the biological indolent behavior. Furthermore, we revealed that macroscopic color changes might be correlated with various clinicopathological features and immunohistochemical and molecular changes from different perspectives. We believe further characterization of RCC, including tumor heterogeneity, is needed to improve the management of patients with RCC.

Recurrent Tuberous Sclerosis Complex/Mammalian Target of Rapamycin Mutations Define Primary Renal Hemangioblastoma as a Unique Entity Distinct From Its Central Nervous System Counterpart

“…We also noticed that a few cases of RCCs with HBlike features have been reported in the literature, exhibiting both CCRCC-like areas and HB-like areas. 33,34 A common characteristic among the majority of these RCCs with HBlike features was the presence of a thick fibromuscular capsule, which often extended from the outer capsule into the tumor's periphery. 34 Upon molecular examination, 2 of these RCCs were found to harbor a recurrent mutation in mTOR, 34 and another harbored a mutation in TSC2.…”

“…33,34 A common characteristic among the majority of these RCCs with HBlike features was the presence of a thick fibromuscular capsule, which often extended from the outer capsule into the tumor's periphery. 34 Upon molecular examination, 2 of these RCCs were found to harbor a recurrent mutation in mTOR, 34 and another harbored a mutation in TSC2. 35 As proposed by Kojima et al, 34,36 the histologic, IHC, and molecular profiles of RCC with HB-like features shared similarities with RCC with fibromyomatous stroma (RCC FMS), 16 suggesting that RCC with HB-like features may be on the same spectrum as RCC FMS with TSC/mTOR mutations.…”

“…34 Upon molecular examination, 2 of these RCCs were found to harbor a recurrent mutation in mTOR, 34 and another harbored a mutation in TSC2. 35 As proposed by Kojima et al, 34,36 the histologic, IHC, and molecular profiles of RCC with HB-like features shared similarities with RCC with fibromyomatous stroma (RCC FMS), 16 suggesting that RCC with HB-like features may be on the same spectrum as RCC FMS with TSC/mTOR mutations. In our study, renal HBs also exhibited a thick encapsulation that extended into the tumor periphery and occasionally penetrated inside the tumor, and were characterized by recurrent mutations in the TSC/mTOR genes.…”