gms | German Medical Science

Introduction: Renal cell carcinoma is the third most common urogenital malignancy. While most often sporadic, at least 5% of cases appear to be due to monogenic causes, e.g. the MET-associated hereditary papillary renal cell carcinoma, or they are part of the spectrum of more pleiotropic hereditary tumor predispositions (e.g. Von Hippel-Lindau disease (VHL), Birt-Hogg-Dube´-Syndrome (BHD)).

Methods: Based on a validated questionnaire developed by us and regularly used by the German Cancer Society, we performed a retrospective analysis of 172 patients who were treated for non-metastatic and metastatic renal cancer between June 2019 and 2022. 172/340 (50.59%) patients answered the questionnaire completely and could be evaluated in this study. The questionnaire was designed to identify patients at increased risk of a monogenic renal tumor predisposition. Clinically abnormal parameters used to stratify the risk of a hereditary predisposition include bilateral and/or multifocal tumors, tumors with striking histopathologic features such as HOCT, SDHB-deficient RCC, HLRCC-associated renal cell carcinomas, extrarenal abnormalities (e.g. the presence of leiomyomas, angiofibromas, pheochromocytomas, lung cysts or spontaneous pneumothoraces in the history, hemangioblastomas of the CNS or retina, GIST) or a positive family history (renal tumors in at least one 1st or 2nd degree relative, known renal tumors associated tumor syndromes).

Results: A total of 30/172 (17.44%) patients had the suspicion of hereditary renal cancer and were recommended to undergo human genetic counselling. In 16/30 (53.33%) patients, young age below 47 years was the only predisposing parameter. In 10/30 (33.33%) patients, age and an additional parameter for hereditary RCC such as tumor localisation (bilateral tumor and/or multifocal tumors with more than three tumor foci) positive family history, were decisive. 17/30 (56.67%) patients underwent molecular genetic testing for the presence of pathogenic variants in BAP1, BUB1B, CDKN1B, DICER1, DIS3L2, FH, FLCN, HRAS, MAX, MET, NF1, NF2, PIK3CA, SDHB, TRIP13, TSC1, TSC2 and VHL. 13/30 (43.33%) patients declined molecular workup. 5/30 patients are still under diagnostic investigation of the above-mentioned RCC panel. Of the so far tested 12 patients, we found a monogenic cause of the renal tumors in 3 patients (25%). One patient each was diagnosed with BHD, VHL, and tuberous sclerosis, respectively.

Conclusion: Our questionnaire was used to identify patients at increased risk of hereditary kidney cancer. In 10% of these patients, and in 25% of those who underwent molecular genetic testing, a hereditary cause was confirmed and the patients and their relatives were counselled accordingly. In the future, the widespread use of this questionnaire could lead to better care for kidney cancer patients and a reduction of the diagnostic gap regarding hereditary cases.