A novel tumor grading scheme for chromophobe renal cell carcinoma: Prognostic utility and comparison with fuhrman nuclear grade

Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
The American journal of surgical pathology (Impact Factor: 5.15). 09/2010; 34(9):1233-40. DOI: 10.1097/PAS.0b013e3181e96f2a
Source: PubMed


Chromophobe renal cell carcinoma (RCC) is a histologic subtype of RCC that portends a favorable prognosis. It is controversial whether the Fuhrman nuclear grade of chromophobe RCC has prognostic utility. Irregular nuclei, prominent nucleoli, and nuclear pleomorphism are inherently present in chromophobe RCC. Hence, the Fuhrman nuclear grade is higher even though the majority of these tumors have a favorable outcome. In this study, the prognostic utility of a novel 3-tiered tumor grading system in which the innate nuclear atypia of chromophobe RCC was discounted, herein referred to as chromophobe tumor grade from a series of 124 chromophobe RCC, was compared with Fuhrman nuclear grade. Chromophobe tumor grade is based on the assessment of geographic nuclear crowding and anaplasia. The Fuhrman nuclear grade distribution between the tumors was grade 1 (1%), grade 2 (19%), grade 3 (74%), and grade 4 (6%), whereas the chromophobe tumor grade distribution was grade 1 (74%), grade 2 (16%), and grade 3 (10%). Neither Fuhrman nuclear grade nor chromophobe tumor grade was significantly associated with patient's age or sex and chromophobe RCC cell types, but both showed a significant association with tumor size. Both Fuhrman nuclear grade and chromophobe tumor grade showed statistically significant positive associations with broad alveolar growth, necrosis, vascular invasion, and with pathologic stage; however, all these associations tended to be dictated by tumors with sarcomatoid change. When tumors with sarcomatoid change were excluded, a strong positive association persisted between chromophobe tumor grade and pathologic stage. In contrast, there was no such association between Fuhrman nuclear grade and stage in nonsarcomatoid chromophobe RCCs. Characterizing aggressive chromophobe RCC with aggressive behavior with the time from surgery to first occurrence of metastasis, local recurrence, or death owing to disease, we found that both Fuhrman nuclear grade and chromophobe tumor grade were highly associated with adverse outcome. However, as with the pathologic stage, only a significant association between chromophobe tumor grade and outcome was retained among nonsarcomatoid chromophobe RCCs. Multivariable Cox regression analysis also tended to support chromophobe tumor grade rather than Fuhrman nuclear grade as an independent predictor of adverse outcome, controlling for other univariably significant risk factors [estimated relative hazard=3.68 (P=0.026) vs. 1.86 (P=0.42)]. In conclusion, the novel chromophobe tumor grading system proposed herewith provides superior prognostic value to that of the Fuhrman nuclear grade in chromophobe RCC and will potentially help stratify patients of chromophobe RCC who are at a greater risk of disease progression.

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    • "Recently, however, it has been recognized that this grading system is not useful for chRCC, since its nuclei are essentially Fuhrman grade 3 by definition [16]. To address this controversial grading issue, Paner et al. [17] recently developed a three-tiered CTG system which downplays the expected nuclear atypia of chRCC. This new grading system, but not traditional Fuhrman grading, demonstrated a strong positive association with pathologic stage and outcome in their series of 124 chRCCs. "
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    ABSTRACT: The chromophobe subtype of renal cell carcinoma (chRCC) has generally been associated with a better prognosis than the clear cell type; however, debate continues as to absolute prognosis as well as the significance of certain prognostic variables. We investigated the significance of pathologic stage and a recently proposed chromophobe tumor grading (CTG) scheme in predicting chRCC outcomes. All available chRCCs were identified from our surgical pathology archives from 1987-2010. Original slides were reviewed to verify diagnoses and stage, and each case was graded following a novel chromophobe tumor grade system criteria. Disease status was obtained from a clinical outcome database, and cancer specific deaths and recurrences were recorded. Eighty-one cases of chRCC were identified, and 73 had adequate follow-up information available. There were only 3 instances of cancer related recurrence or mortality, which included 1 disease specific mortality and 2 disease recurrences. Pathologic stage and CTG 3 were found to be significantly associated with the recurrences or death from chRCC, but there was no association with CTG 1 and CTG 2. chRCC is associated with a very low rate of cancer specific events (4.1%) even at a tertiary referral center. In our study, pathologic stage and CTG 3, but not CTG 1 or 2, were significantly associated with the development of these events.
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  • The American journal of surgical pathology 02/2011; 35(4):620; author reply 620-1. DOI:10.1097/PAS.0b013e31820f14d7 · 5.15 Impact Factor

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