Type 1 papillary RCC is often multifocal, and characterized by papillae and tubular structures with small cells containing basophilic cytoplasm and small, uniform oval nuclei. Patients with hereditary papillary RCC have an increased risk of developing Type 1 papillary RCC. It is characterized by activating germline mutations of the MET gene. Dr. Linehan emphasized that surgical management of patients with hereditary papillary RCC should follow the “3-centimeter rule” such that surgery should be delayed until the diameter of the largest renal tumor is at least 3 centimeters in size. Furthermore, he stated that patients with hereditary papillary RCC should generally be offered nephron sparing surgery given the propensity for tumor recurrences. Alternatively, patients with hereditary papillary RCC may be managed with foretinib, an oral multi-kinase inhibitor targeting MET, VEGF, RON, AXL, and TIE-2 receptors.
Type 2 papillary RCC is more heterogenous, and contains papillae covered by large cells with eosinophilic cytoplasm and large spherical nuclei with prominent nucleoli. It is characterized by SETD2 mutations and increased expression of NRF2-antioxidant pathway. There are two distinct subgroups of type 2 papillary RCC: TFE3 RCC and FH-deficient RCC. Although TFE3 RCC only accounts for 2% of all renal tumors, it accounts for 42% of RCC in children and young adults. Given the relatively aggressive nature of TFE3 RCC, Dr. Linehan emphasized the importance of not delaying surgical management in this patient cohort. Furthermore, he recommended resecting the tumor with wide surgical margins and urged consideration of open surgical modality. FH-deficiency causes hereditary leiomyomatosis RCC (HLRCC), which is characterized by cutaneous leiomyomas, uterine leiomyomas, and aggressive type 2 papillary RCC. Similar to TFE3 RCC, renal malignancies associated with HLRCC are aggressive. As such, Dr. Linehan emphasized the importance of not delaying surgical management in this patient cohort. Furthermore, he recommended resecting the tumor with wide surgical margins and urged consideration of open surgical modality. In the setting of metastatic renal lesions associated with HLRCC, the combination of bevacizumab and erlotinib has been shown to have promising activity and is currently considered to be first-line treatment in this setting.
Presented by: W. Marston Linehan, MD, Center for Cancer Research, National Cancer Institute
Written by: Ziho Lee, MD, Fellow in Advanced Robotic Oncology and Reconstruction, Temple University, Philadelphia, PA, Twitter: @ZLeeGU at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California