Clinicopathological features and molecular genetic changes of primary renal hemangioblastoma, a TSC-associated tumor.

Background: Renal hemangioblastoma (HB) is a rare extra-central nervous system (CNS) tumor, typically not linked to Von Hippel-Lindau (VHL) Syndrome, and its underlying genetic drivers and molecular mechanisms remain elusive. The objective of this study is to investigate the clinicopathological features and molecular genetic changes of primary renal hemangioblastomas.

Methods: Herein, the clinical, imaging, clinicopathological features, and immunophenotype in 3 cases of renal HB were retrospectively analyzed. Next generation sequencing (NGS) was employed to detect 116 gene loci, including VHL gene.

Results: Three patients (two males and one female) aged between 39 and 61 presented with renal masses detected by physical examination or imaging. Macroscopically, the tumors were well-demarcated, with a fibrous capsule and a grayish-yellow to brown, solid, medium-texture cut surface. Microscopically, the tumor cells were polygonal to oval and were separated by thin-walled branching capillaries into sheets and nests. The cells exhibited abundant, translucent, or pale pink cytoplas. Immunohistochemical (IHC) staining showed diffuse positivity for S-100 protein (3/3), Vimentin (3/3), α-Inhibin (3/3), and NSE (3/3) in all cases, with focal positivity for AE1/AE3, EMA, CD10, and PAX-8. Staining for SMA, CgA, Syn, HMB-45, and Melan-A was negative. CD31 and CD34 highlighted an abundant vascular network. NGS revealed TSC1 gene alterations in all 3 cases, with no VHL gene mutation detected.

Conclusions: Primary renal HB is a rare mesenchymal tumor that requires differentiation from clear cell renal cell carcinoma (CCRCC) using morphological, IHC markers, and genetic testing when necessary. TSC1 could be a specific molecular hallmark of renal HB. Additional case data is required to better understand the molecular genetic alterations of the disease.