Table 2:

Clinical course and molecular profile of cases.

Case number/location	NGS/IHC results	Clinical course
Case 1 Adrenal	PBRM1 exon 21 KDM5C Exon 4 TUBB3 40% ERCC10%	Received IL-2 for RCC with bone mets with CR Relapsed with bilateral adrenal metastases, 11 and 12.5 years after IL-2 therapy. Treated with local therapy, cryo therapy on one lesion and surgery on the other.
Case 2 KidneyAdrenal	PBRM1 exon 18 SETD2 exon 10 VHL exon 1 PBRM1 exon 18 SETD2 exon 10 VHL exon 1	Clear cell RCC post-nephrectomy Relapsed with adrenal metastasis, treated with local therapy. No systemic therapy.
Case 4 KidneyMediastinal	VHL exon 1 CDKN1B exon 1 VHL exon 1 CDKN2A exon 2	Clear cell RCC post-nephrectomy Relapsed with lung metastases 46 months after and treated with ICI.Response seen in lung, but adrenal metastases appeared 67 months after nephrectomy as sites of PD during ICI therapy. Responding well currently to TKI therapy.
Case 6 Kidney	SETD2 exon 3 ATM VUS exon 26 VHL exon 2	Synchronous presentation with kidney mass and metastases to lung and bone. Received ICI therapy and had response at other sites but PD with new adrenal metastases. Responding well currently to TKI therapy.
Case 7 AdrenalLung	PBRM1 exon 26 SETD2 exon 16 VHL exon 2 ERCC 100% IHC	Post-nephrectomy presented with lung metastases. Received IL-2 and progressed. Treated with ICI and had a response in lung but adrenal metastasis emerged. Treated with local therapy.

NGS, next-generation sequencing; IHC, immunohistochemistry; PD-L1, programmed death ligand-1; Int, intermediate; VUS, variant of uncertain significance; IL-2, interleukin-2; ICI, immune checkpoint inhibitor; RCC, reviewed renal cancer.