Tao Xuan, Wang Xiao-Tong, Wang Peng-Cheng, Chen Yu-Peng, Wu Yi-Juan, Xia Qiu-Yuan, Rao Qiu, Qiu Xiao-Ming, Chen Ni, Chen Hong
Department of Pathology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Department of Pathology, National Regional Medical Center, Binhai Campus of The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Histopathology. 2025 Sep 23. doi: 10.1111/his.70003.
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.
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.
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.
具有成血管细胞瘤样特征的肾细胞癌（RCC-HB）是一种罕见的肾细胞癌（RCC）亚型。它由具有纤维肌瘤样基质的肾细胞癌（RCC FMS）样和成血管细胞瘤（HB）样成分组成。然而，其分子特征以及它是透明细胞肾细胞癌（CCRCC）的一种亚型、RCC FMS形态学谱的一部分还是一个独立的实体仍不清楚。
我们对7例RCC-HB病例的肿瘤组织、非肿瘤组织和血液样本进行了临床病理评估、免疫组织化学检测和二代测序（NGS）。该队列包括5名女性和2名男性患者，年龄在33-68岁之间，无综合征性疾病的个人或家族史。6例为单灶性，1例为多灶性。肿瘤大小为1.2-6.0 cm，被厚纤维包膜完整包绕，有纤维肌束延伸至病变内并将其分隔。RCC FMS样区域类似于CCRCC、RCC FMS或透明细胞乳头状肾细胞肿瘤（CCPRCT），并显示CK7阳性。HB样区域的特征是多边形或短梭形肿瘤性基质细胞散布于丰富的毛细血管网中，S100、α-抑制素和GPNMB染色呈阳性。DNA测序显示6例患者的MTOR、TSC1和TSC2存在致病性变异，而1例未检测到这些基因突变。所有患者术后均存活，无复发或转移，平均随访47.7个月（范围：4-111个月），中位数为46个月。
这是迄今为止关于RCC-HB的最大规模临床病理研究。我们的研究结果支持绝大多数RCC-HB存在TSC/MTOR突变，与CCRCC不同，扩展了TSC/MTOR突变型肾肿瘤的形态学谱。
