Rhabdoid Differentiation Is Associated With Aggressive Behavior in Renal Cell Carcinoma

Abstract

Rhabdoid differentiation has been associated with aggressive behavior in carcinomas from different organ systems. A recent consensus statement of the International Society of Urological Pathology (ISUP), in addition to proposing a nucleolar grading system (ISUP grade) for renal cell carcinoma (RCC) to replace the Fuhrman system, recommended reporting the presence of rhabdoid differentiation in RCC and considering tumors with rhabdoid differentiation to be ISUP grade 4. Although it has been shown that rhabdoid differentiation is associated with increased grade and stage of RCC, it has not been fully demonstrated whether it has an adverse effect independent of this association with increased grade and stage. We provide the largest clinicopathologic analysis of RCC with rhabdoid differentiation to date (76 cases), including characterization of metastatic disease. In addition, by constructing a multivariable model including tumor grade, stage, necrosis, and distant metastasis to compare a series of 49 clear cell RCC with rhabdoid differentiation with a cohort of 41 clear cell RCCs without rhabdoid differentiation, we demonstrate that the presence of rhabdoid differentiation in clear cell RCC confers an increased risk of death (hazard ratio=5.25; 95% confidence interval, 2.1-14.3) independent of these other adverse prognostic factors. These findings underscore the significance of rhabdoid differentiation in RCC as an adverse prognostic factor and support the recent reporting and grading recommendations of the ISUP.

Review of renal cell carcinoma with rhabdoid features with focus on clinical and pathobiological aspects

“…The underlying types of carcinoma include clear cell RCC, papillary RCC, chromophobe RCC, collecting duct carcinoma, renal medullary carcinoma, acquired cystic disease-associated RCC, ALK-positive renal cancer and unclassified RCC . The most common histological type of RCC with rhabdoid change is clear cell RCC and up to 35% of Fuhrman grade 4 clear cell RCCs displays rhabdoid features [2][3][4][5][6][7]. Rhabdoid morphology can be seen in 9.8% of cases with clear cell RCC consisting of all grades [24].…”

“…1A, B) [1][2][3][4][5][6][7]. The architectural patterns include solid, organoid or sheet-like, and neoplastic cells exhibit a variable degree of discohesion [6,7]. Renal cell carcinoma with rhabdoid features also demonstrate sarcomatoid change in up to 22% of cases [2,4,6,7].…”

“…Metastasis occurs in up to 70% of cases, and distant metastasis can occur in lung, bone, soft tissue, liver, skin, adrenal gland and diaphragm [4-10, 13, 14, 16-18, 25, 31]. Metastases to lymph nodes occur in approximately 20% of cases [7,10,16,18,25].…”

“…1A, B) [1][2][3][4][5][6][7]. The architectural patterns include solid, organoid or sheet-like, and neoplastic cells exhibit a variable degree of discohesion [6,7].…”

Percutaneous biopsy for risk stratification of renal masses

“…Despite the development of multiple new therapies, patients with mRCC continue to have a poor prognosis [Heng et al 2009]. Aggressive features such as sarcomatoid dedifferentiation are associated with short overall survival and may not benefit from cytoreductive surgery [Mian et al 2002;Molina et al 2011;Przybycin et al 2014]. An analysis of 417 patients undergoing cytoreductive nephrectomy for mRCC compared those with sarcomatoid histology with conventional RCC [Shuch et al 2009].…”