伴有髓质特征的SMARCB1缺失型肾细胞癌病例报告并文献复习

SMARCB1-deficient renal cell carcinoma with medullary features: a case report and literature review

摘要

目的 探讨伴有髓质特征的SMARCB1缺失型肾细胞癌的命名、临床病理学特征、分子特征及生物学行为，以期为该疾病的病理诊断及临床诊治提供指导。方法 分析1例伴有髓质特征的SMARCB1缺失型肾细胞癌的临床资料，本例采用了免疫组化EnVision二步法和高通量二代测序进行染色和测序，并复习相关文献分析其临床病理学特点、免疫表型、分子特征、鉴别诊断及预后。结果 患者男性，74岁，体检发现肾占位4月，CTA提示左肾实质不规则占位性病变，行左肾切除术。镜下见肿瘤主要呈管状乳头状排列，细胞异型性显著，胞浆丰富嗜酸，部分呈空泡状，细胞核呈泡状，核仁明显，局部区可见横纹肌样核偏位细胞；间质纤维组织增生，可见炎细胞浸润以及渗出的正常形态的红细胞。免疫组化显示PAX8阳性，INI1失表达；二代测序检测显示SMARCB1基因丢失突变及拷贝数缺失。结合患者无镰状红细胞特征或血红蛋白病，诊断为伴有髓质特征的SMARCB1缺失型肾细胞癌。患者术后半年出现肺转移。结论 伴有髓质特征的SMARCB1缺失型肾细胞癌为一种罕见高侵袭性分子定义的肾细胞癌，病理诊断主要依靠病理学形态和免疫表型，必要时辅助荧光原位杂交（FISH）及二代测序检测，需与其他高侵袭性癌相鉴别，如高级别透明细胞肾细胞癌、FH缺陷肾细胞癌、集合管癌、尿路上皮癌等。该类型肾细胞癌预后差，分期高，常见远处转移，治疗推荐以铂类为基础的化疗和靶向治疗为主。

Abstract

Objective To investigate the nomenclature, clinicopathological characteristics, molecular features, and biological behaviors of SMARCB1-deficient renal cell carcinoma with medullary features, so as to provide guidance for its pathological diagnosis and clinical management. Methods Clinical data of a case of SMARCB1-deficient renal cell carcinoma with medullary features were retrospectively reviewed. Immunohistochemical staining was performed using the EnVision two-step method, and next-generation sequencing (NGS) was employed for comprehensive molecular profiling. A systematic literature review was conducted to analyze the clinicopathological features, immunophenotypic patterns, molecular alterations, differential diagnoses, and prognostic outcomes. Results The patient was a 74-year-old male who presented with an incidentally detected renal mass identified during a routine physical examination 4 months prior to presentation. Computed tomography angiography (CTA) revealed an irregular mass within the left renal parenchyma, leading to radical left nephrectomy. Histopathological examination demonstrated a predominantly tubular-papillary architectural pattern with marked cellular atypia. Tumor cells exhibited abundant eosinophilic cytoplasm, in some cases with vacuolated morphology. Nuclei were vesicular with prominent nucleoli. Striated muscle-like cells with nuclear displacement were seen in some parts. There was proliferation of fibrous tissue in the tumor stroma, with inflammatory cell infiltration and exudation of normal-shaped red blood cells observed. Immunohistochemistry revealed positive expression of PAX8 and complete loss of INI1. NGS analysis confirmed a pathogenic loss-of-function mutation and concurrent copy number loss in the SMARCB1 gene. Given the absence of sickle cell trait or hemoglobinopathy, a definitive diagnosis of SMARCB1-deficient renal cell carcinoma with medullary features was established. Six months after surgery, the patient developed pulmonary metastases. Conclusion SMARCB1-deficient renal cell carcinoma with medullary features is a rare and highly aggressive molecularly defined subtype of renal cell carcinoma. Diagnosis relies primarily on characteristic histomorphology and immunophenotypic profile, particularly loss of INI1 expression, with adjunctive use of fluorescence in situ hybridization (FISH) or NGS when required. Differential diagnosis should include other high-grade renal neoplasms such as high-grade clear cell renal cell carcinoma, fumarate hydratase (FH)-deficient renal cell carcinoma, collecting duct carcinoma, and urothelial carcinoma. This entity is associated with advanced disease at presentation, frequent distant metastasis, and poor overall prognosis. The treatment recommendation mainly focuses on platinum-based chemotherapy and targeted therapy.

关键词

肾细胞癌 / 髓质特征 / SMARCB1缺失 / 临床病理学特征 / 鉴别诊断

Key words

renal cell carcinoma / medullary characteristics / SMARCB1 deletion / clinicopathological features / differential diagnosis

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