Multiphasic contrast-enhanced MRI: single-slice versus volumetric quantification of tumor enhancement for the assessment of renal clear-cell carcinoma fuhrman grade.

Renal cortical tumors represent a biologically and genetically heterogeneous group of neoplasms with variable clinical behavior. Clear-cell carcinoma is the most common histological type of malignant renal cortical tumors, accounting for ~75% (1,2). It is often characterized by hypoxic microenvironments due to local imbalance between oxygen supply and consumption, which results in compensatory hyperactivation of angiogenesis (3,4). However, as tumors outgrow their blood supply, coagulative necrosis ensues, reflecting aggressive tumor biology, rapid proliferation, and progression (5). Necrosis accounts for the commonly encountered heterogeneous appearance of clear-cell carcinomas on computed tomography (CT) and magnetic resonance imaging (MRI), and is associated with larger tumor size, stage, and grade (5–7). These prognostic features have all been found to be independent predictors of survival (8). They are most reliably established from the surgical pathology specimen following partial or total nephrectomy. To establish the tumor grade the Fuhrman classification system is widely used, and is based on the characteristics of nuclei and nucleoli within tumor cells. Grade 1 tumors are the least aggressive, and demonstrate round and uniform nuclei that measure ~10 µm and inconspicuous or absent nucleoli, while grade 4 tumors are the most aggressive, demonstrating bizarre nuclei greater than 20 µm with clumped chromatin, prominent nucleoli, and often spindled cells (9). Although surgery remains the mainstay of treatment, in recent years there has been a paradigm shift in the approach to renal cortical tumors, with increasing management options including simple observation or focal therapy (eg, radiofrequency ablation and cryotherapy) for indolent or inoperable tumors and systemic antiangiogenic chemotherapy for extensive metastatic disease. This has in turn resulted in a pressing need for accurate methods that allow risk stratification and assessment of prognostic features (including tumor grade) prior to surgery. One possible means to achieve this is through sampling of renal lesions using image-guided biopsies and fine-needle aspiration (FNA). However, widespread use of these techniques has been controversial in this setting, particularly as the correlation between the Fuhrman grade at biopsy or FNA and the Fuhrman grade in the complete surgical specimen is variable, as renal cortical tumors can be extremely heterogeneous and the findings depend on the portion of the tumor that is sampled. The wide variability in the reported grading accuracy of biopsy (46%–76%) and FNA (28%–72%) is therefore not surprising (10–14). Furthermore, the rate of nondiagnostic biopsies has been reported to be between 5% and 40% (15), and despite the low complication rates reported in the literature, it is still an invasive procedure with potentially serious risks. Contrast-enhanced imaging techniques such as MRI are ideally positioned to be used as noninvasive tools that could serve as in vivo surrogate markers of tumor angiogenesis and necrosis. However, subjective evaluation of MRI tumor enhancement has been shown to be suboptimal for predicting tumor grade at surgery (16,17). Thus, more robust methods to quantify tumor enhancement are needed. Although this is technically feasible using the currently available clinical MRI systems, other methodological issues still need to be addressed. One of the most relevant ones is establishing which portion of the tumors ought to be measured to quantify enhancement. For example, given the aforementioned tumor heterogeneity due to variable amounts of necrosis, different enhancement patterns would be obtained if measurements are taken from enhancing or necrotic areas within the same tumor. Furthermore, earlier approaches to determining enhancement patterns with imaging have focused on measurements performed on a single representative slice (18), further disregarding the potential variability in enhancement in different portions of the tumor. Thus, the purpose of this study was to assess the correlation between pathology grade on the nephrectomy specimens and MRI tumor enhancement as measured using two different approaches: 1) the most enhancing portion of the tumor on a single slice and 2) volumetric analysis of enhancement in the entire tumor.