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An incidental low-density renal mass on non-contrast computed tomography (CT) could actually be an aggressive subtype of papillary renal cell carcinoma (pRCC) but diagnosed as a benign cyst using current guidelines, investigators warned.

Results from a review of 61 patients with type-1 or type-2 pRCC subtypes who had undergone either partial or radical nephrectomy from 2003 to 2017 showed that 49% of tumors exhibited very low pre-contrast attenuation (less than 20 Hounsfield Units [HU]). Of these, 80% were type 2 with "significant biological potential," reported Robert G. Uzzo, MD, of Fox Chase Cancer Center in Philadelphia, and colleagues.

After adjustment, lower pre-contrast HU was an independent predictor of pRCC subtype and associated with a 5.5-fold increase of being type-2 (odds ratio [OR] 5.47; 95% confidence interval [CI] 1.67-17.92 P< 0.01), the researchers reported online in the .

They noted that some studies have reported significant differences in cancer-specific between the two types of pRCC, with type-2 carrying a much less favorable .

"Importantly, we demonstrate that not only were these low attenuation lesions not benign but they were associated with the more aggressive type 2 subtype. These data contradict the opinion that low attenuation renal lesions require no further evaluation, and suggest that attenuation on non-contrast CT imaging is insufficient as a single parameter to rule out malignancy," Uzzo and co-authors wrote.

Historically, lesions with have been thought to have negligible malignant potential. For this reason, the true incidence of RCC harboring less than 20 HU unenhanced attenuation remains unknown, the researchers explained.

In a recent , the American College of Radiology (ACR) recommended that homogeneous renal masses smaller than 20 HU incidentally detected on non-contrast CT require no further work-up. However, the current study findings demonstrated that each unit decrease in HU was associated with an 8% increase in the odds of the lesion being type-2 pRCC (OR 1.08; 95% CI 1.02-1.14 p=0.006), Uzzo and colleagues said.

The ability to accurately differentiate preoperatively between a benign cyst and a pRCC subtype would make the difference between offering a patient simple reassurance or potentially curative surgery for localized RCC, the investigators emphasized.

"Clinicians must recognize that low attenuation lesions on CT scan are not all cysts," Uzzo told MedPage Today. "We hope clinicians will be more cognizant that some low density lesions on non-contrast CT are papillary RCCs, and they should be more discerning in their evaluation of these lesions, particularly in the appropriate demographic for RCC."

He explained that in a common clinical scenario, the patient presents to the emergency department with unrelated abdominal symptoms suggestive of a kidney stone. After non-contrast low-dose screening CT reveals a low attenuation lesion, "the radiologist calls it a probable cyst based on low density, and it is never worked up. By our data it could be a renal cancer."

In the study, low unenhanced median attenuation was defined as 20 or fewer HU. Type-2 pRCC was identified by institutional uropathologists in 37 patients. These lesions demonstrated a lower pre-contrast attenuation than type-1 tumors, which were identified in 24 patients.

Review of preoperative non-contrast CT images, conducted by an experienced genitourinary radiologist, showed that the median HU of type-2 pRCC was 19.8 vs 29.6 for type-1 pRCC (P< 0.01). The maximum HU was 25.3 vs 36.5, respectively.

"Application of the traditional 20 HU cutoff to our data risks misclassifying 23% (using max HU) to 49% (using average HU) of pRCC in this series as benign cysts despite their solid and potentially biological aggressive nature," the researchers wrote. "It follows that the current ACR guidelines regarding incidental renal masses on non-contrast CT must be interpreted with caution."

At Fox Chase, where the database contains more than 4,000 renal cancer cases, the protocol for managing incidental renal masses is to first measure the HU of the lesion on non-contrast CT. If the HU is less than 10, then the likelihood of a cyst is very high and no further work-up is needed, Uzzo said.

However, if the lesion is 10 to 20 HU, other characteristics such as size and homogeneity are taken into consideration, he continued. "If the lesion is more than 3 cm and we think it is heterogeneous even though it has non-con HU of less than 20, we obtain pre- and post-contrast CT or [magnetic resonance imaging] to be sure it is not a papillary RCC."

When asked if current guidelines need to change, Uzzo replied: "We believe the guidelines should specifically address this issue more clearly."

As a member of the American Urological Association (AUA) guidelines committee, Uzzo contributed to recommendations for the management of localized renal masses. He was also a member of the American Association for Cancer Research (AACR) guidelines committee that produced recommendations for the evaluation of incidental renal tumors.

Although both the AUA and AACR guidelines address the need for appropriate pre- and post-contrast images, the AUA guidelines do not comment on the evaluation of low-density renal lesions on non-contrast scans (less than 20 HU), he noted. The AACR guidelines refer to the likelihood that homogeneous lesions less than 20 HU are cysts but do not state specifically that heterogeneous lesions less than 20 HU on non-contrast CT could represent cancer.

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