Clinicopathological and molecular characterization of seven rare cases of renal cell carcinoma with hemangioblastoma-like features: Expanding the morphological spectrum of renal tumours with tuberous sclerosis complex/mammalian target of rapamycin mutations.

Abstract

Aims: Renal cell carcinoma with hemangioblastoma-like features (RCC-HB) is a rare renal cell carcinoma (RCC) subtype. It consists of renal cell carcinoma with fibromyomatous stroma (RCC FMS)-like and hemangioblastoma (HB)-like components. However, its molecular characteristics and whether it is a subtype of clear cell renal cell carcinoma (CCRCC), a part of the morphologic spectrum of RCC FMS, or a distinct entity remain unclear.

Methods and results: We conducted clinicopathological evaluation, immunohistochemistry testing, and next-generation sequencing (NGS) on seven RCC-HB cases of tumour tissue, non-tumour tissue, and blood samples. The cohort included five female and two male patients, aged 33-68 years, with no personal or family history of syndromic disease. Six cases were unifocal, and one was multifocal. Tumours measured 1.2-6.0 cm and were well-circumscribed by a thick fibrous capsule, with fibromuscular bundles extending into and dividing the lesions. RCC FMS-like regions resembled CCRCC, RCC FMS, or clear cell papillary renal cell tumour (CCPRCT) and showed CK7 positivity. HB-like regions featured polygonal or short spindle-shaped neoplastic stromal cells interspersed with rich capillary networks and were highlighted by S100, α-inhibin, and GPNMB. DNA sequencing revealed pathogenic variants in MTOR, TSC1, and TSC2 in six cases, while one case did not detect these gene mutations. All patients were alive without recurrence or metastasis after surgery, with a mean follow-up of 47.7 months (range: 4-111 months) and a median of 46 months.

Conclusion: This is the largest clinicopathological study to date on RCC-HB. Our findings support that the vast majority of RCC-HB harboured TSC/MTOR mutations, different from CCRCC, expanding the morphological spectrum of TSC/MTOR-mutated renal tumours.