Clinicopathological and molecular features of renal cell carcinomas with haemangioblastoma‐like features distinct from clear cell renal cell carcinoma

Aims Haemangioblastomas arise in the central nervous system. Rarely, haemangioblastomas may develop in extra‐neural sites, such as the kidneys. A few reported cases of renal cell carcinomas (RCCs) with haemangioblastoma‐like features have exhibited both clear cell renal cell carcinoma (CCRCC)‐ and haemangioblastoma‐like components. The clinicopathological and molecular characteristics of RCCs with haemangioblastoma‐like features were analysed, focusing on VHL alterations, in comparison with CCRCCs partially resembling haemangioblastoma. Methods and Results Four RCCs with haemangioblastoma‐like features and five CCRCCs partially resembling haemangioblastoma were included. The RCCs with haemangioblastoma‐like features were indolent and lacked adverse prognostic factors. All RCCs with haemangioblastoma‐like features had a well‐circumscribed appearance and a thick fibromuscular capsule, with fibromuscular bundles extending into the tumour to varying degrees in the three tumours. Each RCC with haemangioblastoma‐like features exhibited CCRCC‐like areas with indistinct tubular structures and foci of haemangioblastoma‐like areas, in which vessels and short spindle cells overwhelmed tumour cells. Whereas haemangioblastoma‐like areas in the CCRCCs partially resembling haemangioblastoma exhibited sparse vessels and spindle cells and distinct clear cells. The RCCs with haemangioblastoma‐like features exhibited a unique immunohistochemical profile, with positive staining for inhibin‐α, S100, carbonic‐anhydrase‐9, keratin7, and high molecular weight keratin and negative staining for (alpha‐methylacyl‐CoA racemase) AMACR. RCC with haemangioblastoma‐like features did not display any VHL alterations, including VHL mutation, 3p LOH, and methylation of the VHL promoter region, and the two tumours harboured a likely oncogenic missense variant of MTOR (c.7280T>G). Conclusion The histopathological, immunohistochemical, and molecular findings suggest that RCC with haemangioblastoma‐like features is a distinct entity from CCRCC. Renal cell carcinomas (RCCs) with haemangioblastoma‐like features were composed of clear cell renal cell carcinoma‐like and haemangioblastoma‐like area. RCCs with haemangioblastoma‐like features had unique histological and immunohistochemical features. Additionally, RCCs with haemangioblastoma‐like features did not have any VHL alterations. This study suggests that RCC with haemangioblastoma‐like features is a distinct entity from CCRCC.