1906P - Metastasized non-clear cell renal cell carcinoma: Which entities are dangerous? Results learned from reference pathology of the SuniForecast study

Background

In the 2022 WHO classification more than 20 entities of renal cell carcinomas (RCC) were defined. Several molecularly defined RCC were separated. There is urgent need for studies investigating well defined patients with these specific entities. One prerequisite is an exact classification of non-clear cell RCC (nccRCC) including histopathological and molecular diagnostics.

Methods

The SUNNIFORECAST study (NCT03075423) is a phase 2 randomised investigator-initiated trial of nivolumab with ipilimumab vs. standard of care in patients with previously untreated and advanced nccRCC. For study inclusion a reference pathology to confirm diagnosis of nccRCC was mandatory.

Results

350 cases were submitted for reference pathology as paraffin blocks or unstained slides. Diagnoses was done by HE staining, immunohistochemistry and molecular testing. Reference pathology confirmed the diagnoses of nccRCC in 334 of 350 cases. Only few cases were diagnosed in reevaluation as ccRCC, liposarcoma or epithelioid angiomyolipoma. Histopathological diagnoses included papillary RCC (n=138-41%), chromophobe RCC (n=58-17%), RCC, NOS, mostly with sarcomatoid pattern (n=46-14%) TFE3 or TFEB altered RCC (n=25 and n=1,8%), FH-deficient RCC (n=33-10%), SDHB-deficient RCC (n=4-1%), SMARCB1-deficient renal medullary carcinoma (n=9-3%), collecting duct carcinoma (n=14-4%) and tubulocystic RCC (n=1). Interestingly no tumors out of the group of other oncocytic tumous or clear cell papillary renal cell tumors were detected. Compared to primary pathology diagnosis changed in 116/350 cases. There was no correct primary diagnosis in 28/33 cases of FH-deficient RCC, 3/4 cases of SDHB deficient RCC and 17/26 cases of translocation RCC. All chromophobe RCC showed sarcomatoid dedifferentiation or coagulative tumor necrosis. In papillary renal cell carcinoma, micropapillary and microcystic architecture was very frequently detected in G1/G2 tumors.

Conclusions

Reference pathology is a prerequisite for clinical studies investigating ncc RCC. The diagnosis of molecular defined RCC is still problematic in daily diagnosis. The study was supported by a grant of BMS (BMS).

Clinical trial identification

NCT03075423.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

BMS.

Disclosure

A. Hartmann, L. Vorfelder, M. Ahrens, J.B.A.G. Haanen, B. Escudier, A. Ravaud, E. Boleti, G. Gravis, A. Flechon, M. Grimm, J. Bedke, B. Mellado Gonzalez, P. Ivanyi, F. Lange, A. Agaimy, L. Bergmann, C.G. Stöhr: Financial Interests, Institutional, Funding: BMS.I. Polifka: Financial Interests, Institutional, Invited Speaker: BMS.