Initial experience with arterial spin-labeling MR imaging to assess histology of renal masses

Each year over 60,000 cases of renal malignancies are diagnosed, representing 3.8% of all newly diagnosed cancers. Renal malignancies result in over 13,000 deaths each year, which account for 2.3% of all cancer deaths (1). Since the 1970s, the incidence of renal tumors has been increasing by approximately 3% each year. This trend is in part explained by the widespread increase in use of ultrasounds and CT scans, resulting in the incidental detection of early renal cell carcinoma (RCC). However, the mortality rate for RCC has also increased, which suggests that other unidentified factors account for this trend. Approximately one third of patients will have metastatic disease at the time of diagnosis, and after treatment for localized RCC, 25-50% of patients will suffer recurrence (2-5). The prognosis associated with recurrent and metastatic RCC is poor; historical 3-year survival is less than 5% and virtually all patients eventually die of their disease (6). Of all urologic malignancies, RCC has the highest ratio of disease-related deaths to incidence.

The standard-of-care for the management of solid renal tumors is surgical intervention such as radical nephrectomy, partial nephrectomy or ablative therapy. Unlike most other solid tumors where biopsy is an important part of the workup and management, renal tumors are often treated without a biopsy and presumed to be malignant. There are several reasons why biopsy is not routinely performed. (I) 10-15% of biopsies are indeterminate (7) and renal tumors are often treated despite lack of proof of malignancy on biopsy; (II) Although the risk of tumor spillage is not clinically significant for solid renal tumors, concern remains that renal lesions with cystic components can rupture and spill tumor cells into the retroperitoneum. The consequence of definitively managing solid renal lesions without a confirmed histologic diagnosis is that 10-20% of patients with benign lesions undergo surgery simply because we lack more effective diagnostic strategies.

A percutaneous biopsy is minimally invasive and it can identify the histologic subtype in approximately 90% of cases (8). However, it is less reliable for determining tumor grade and has been shown to underestimate grade in the majority of cases. Therefore, many expert pathologists simply choose not to report grade from a biopsy sample. Improved imaging technology holds out the promising of noninvasively delivering information traditionally obtained used a microscope. Lanzman and colleagues explore the use of arterial spin-labeling magnetic resonance imaging (ASL MRI) to assess renal histology and tumor grade. ASL MRI is a completely noninvasive imaging technique for assessing perfusion without the need for injection of contrast agent (9). To accomplish this, water in endogenous blood is magnetized to “label” the blood. The difference in images acquired with and without labeling allows tissue perfusion to be quantified (10).

Lanzman and collegues performed ASL MRI as well as standard dynamic contrast enhanced (DCE) MRI on 42 patients and asked whether differences in the perfusion of renal tumors can provide information on histologic subtype and grade (9). Their final analysis included 34 patients for whom histopathologic data was available for use as the reference standard. The study included patients with low grade clear cell RCC (n=8), high grade clear cell RCC (n=7), chromophobe RCC (n=4), papillary RCC (n=5), unclassified RCC (n=4), and oncocytoma (n=4); one patient with urothelial carcinoma and one patient with tubulocystic RCC were excluded due to the low frequency of the histologic subtypes in their series. Renal tumor perfusion as measured by ASL or DCE produced statistically significant differences between histologic subtypes. Papillary renal tumors had the lowest perfusion, and oncocytomas had the highest perfusion. ASL-MRI was not useful for differentiating between low and high-grade clear cell RCC or between pT1 and pT3 tumors. However, there was a statistically significant correlation between peak tumor perfusion and size of clear cell RCC.

Based on these results the authors suggested that ASL MRI may be useful for identifying oncocytomas, which is a benign lesion. If oncocytomas can be identified with complete confidence, surgery can be avoided. However, as the authors point out, this is a small study that needs to be confirmed. Importantly, even in this small study that only contained 4 oncocytomas, there was overlap in the mean and peak ASL perfusion levels between oncocytomas and the other malignant RCC subtypes. Therefore, a larger study may provide clinicians with a measurement of sensitivity and specificity for diagnosing oncocytomas; however, it is unlikely that ASL MRI in its current form will provide the diagnostic accuracy available after nephrectomy. However, it is possible to envision a combination of ASL MRI and percutaneous biopsy to increase diagnostic accuracy. Additional diagnostic information may be available by characterizing small renal tumors with serial ASL MRI studies to provide information about tumor changes over time.

Acknowledgements

Disclosure: The authors declare no conflict of interest.

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