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Thoughtful consideration of the risks and benefits of pre-treatment biopsy for the small renal cortical neoplasm will often lead the reasonable clinician towards the routine application of biopsy in this setting.
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The current urologic reticence in using pre-treatment biopsy of renal cortical neoplasms clearly stems from the historically common presentation of renal tumors. The classic triad including pain, a flank mass, and hematuria almost always resulted in the discovery of a large renal tumor. These tumors were mostly malignant, and, by definition, symptomatic. As such, the use of renal biopsy in this setting was not warranted.1
In the past, the presence of small incidental renal cortical neoplasms was quite rare, and biopsy even rarer. Indeed, biopsies were typically being performed only when the origin of the tumor was in question, as may be the case in patients with a known extra-renal primary tumor or when the tumor has the atypical appearance of an infiltrating process, which might suggest a lymphoma or infectious etiology.
For these reasons, the urologic community developed a culture of renal cortical mass treatment without biopsy. This culture must be re-evaluated in the era of the incidental small renal cortical neoplasm. Not only will biopsy help avoid surgery for some patients with benign renal tumors, but identification of more indolent renal cell carcinoma (RCC) subtypes will help the urologist select appropriate minimally invasive treatment options for less aggressive cancers.
Biology and epidemiology of the small renal cortical neoplasm
The increased use of imaging has dramatically increased the number of renal cortical neoplasms identified. Additionally, advances in imaging, specifically multi-detector computerized tomography (CT) and magnetic resonance imaging (MRI) technology, which have less partial volume averaging effects, have allowed radiologists to identify progressively smaller renal masses. In fact, in contemporary practice, up to 90% of kidney tumors are discovered before symptoms arise.2
In current practice, the majority of tumors are treated. As such, the mean size of tumors that undergo active treatment has progressively decreased over the course of the last decade.3 Despite the vastly increased number of incidental small renal cortical neoplasms, the age-adjusted U.S. mortality for renal carcinoma has remained fairly steady.4 (Figure 1). The increased incidence and stable mortality is strong evidence of over-treatment using our current management algorithm. Additionally, surgical treatment for renal masses carries a morbidity ranging from approximately 15% in the general population to 38.8% in octogenarians.5,6
Furthermore, both nephron-sparing surgery and radical nephrectomy can diminish renal function, although postoperative creatinine is lower after partial as compared with radical nephrectomy, and radical nephrectomy carries a higher risk of chronic renal insufficiency. A recent multicenter prospective phase 2 clinical trial was conducted examining the treatment algorithm of active surveillance of 209 small renal masses in 178 elderly and/or infirm patients with treatment delayed until progression.7 Tumor diameters increased by an average of 0.13 cm/year and local progression occurred in 25 patients (12%). Needle core biopsy in 101 of these masses demonstrated that the presence of RCC did not significantly change growth rate.
RCC is the most common malignant primary renal mass in adults. There are distinct subtypes, and the biological aggressiveness and the prognosis of these subtypes has been documented. Clear-cell RCC is the most common RCC subtype followed by papillary RCC, chromophobe RCC, and unclassified RCC. Collecting duct carcinoma is a rare and highly malignant type of RCC. Although most enhancing renal masses in adults are RCC, a significant percentage are benign, commonly oncocytoma, and these benign tumors cannot be distinguished from malignant tumors based on imaging alone.
Benign primary renal masses include simple renal cyst, psuedotumors, angiomyolipoma, oncocytoma, juxtaglomerular tumor, multilocular cystic nephroma, mesoblastic nephroma, and papillary adenoma. In a recent surgical series of 482 patients who underwent partial or radical nephrectomy, of the 228 lesions ≤4 cm, 26.3% were benign.8 The relatively high fraction of benign renal cortical neoplasms that undergo surgery highlights the importance of biopsy to avoid over-treatment.
Even among malignancies, biopsy findings can aid in making decisions about the management of these masses, whether extirpative (partial or radical nephrectomy), ablative, or non-surgical (surveillance). More indolent malignancies, such as chromophobe RCC, may be well served with renal sparing options or even surveillance in the appropriate patient.
A recent review of the SEER database found histology to be significantly associated with disease-specific and overall survival.9
Sarcomatoid elements may be associated with any subtype of RCC and portend a worse prognosis, even when presenting with low-stage disease. The same is true of collecting duct carcinoma. In a recent review of nonmetastatic renal cortical tumors treated with partial or radical nephrectomy, controlling for size and stage, chromophobe RCC, as compared to papillary, was a significant variable for disease progression.10 Still, chromophobe RCC is very indolent and may often be managed conservatively. Much recent focus has been placed on differentiation between chromophobe RCC and oncocytoma, as both may contain oncocytic cells.
However, this differentiation may be causeless as even the diagnosis of an “oncocytic neoplasm” can be very helpful in the management of many patients. In considering biopsy, the urologist is no longer looking only for a binary answer: malignant or benign. Rather, consideration of RCC subtype is important, as indolent RCC histopathology may lead the decision-making process towards a less invasive modality even in younger and healthier patients.
