A highly malignant succinate dehydrogenase-deficient renal cell carcinoma with bone metastasis misdiagnosed as hereditary leiomyomatosis and renal cell carcinoma-a case report and literature review

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is an autosomal dominant syndrome caused by heterozygous pathogenic germline variants of the SDH gene. It is associated with an increased risk of developing RCC. To date, only a few publications have described the disease, and the clinical, morphological, and molecular aspects need to be further studied. The present study reported a case of SDH-deficient RCC with high malignancy and rare bone metastasis. In addition, the patient's postoperative pathological diagnosis was uncertain, and hereditary leiomyomatosis and RCC were highly suspected. The patient was diagnosed with a right renal mass through B-ultrasound examination and was found to have carcinoma embolus in the right renal vein and inferior vena cava through kidney contrast-enhanced computed tomography. A whole-body bone scan revealed radionuclide accumulation in the upper end of the left humerus, indicating possible pathological bone destruction. As a result, surgical resection was performed. The postoperative pathology indicated a high-grade RCC, although the specific classification remained uncertain, with a strong suspicion of hereditary leiomyomatosis and RCC. Subsequently, the germline mutation of the SDH complex flavoprotein subunit A (SDHA) gene was identified through high-throughput sequencing (c.1A>G, p. Met1?) and immunohistochemistry (IHC) revealed the loss of SDHB expression. Post-operatively, the patient underwent radiotherapy and targeted therapy. After a 6-month follow-up period, there was no indication of recurrence or metastasis on imaging. Based on this report, germline screening should be encouraged in early-onset patients. Family history or pathological results may not provide accurate information for the diagnosis and differential diagnosis of SDH-deficient RCC in advance.

琥珀酸脱氢酶（Succinate dehydrogenase, SDH）缺陷型肾细胞癌（renal cell carcinoma, RCC）是一类由SDH基因杂合致病性生殖系变异引发的常染色体显性综合征，患者罹患RCC的风险显著升高。截至目前，仅有少量文献对该疾病展开描述，其临床、形态学及分子生物学特征仍有待深入研究。
本研究报道1例恶性程度较高且伴罕见骨转移的SDH缺陷型RCC病例。该患者术后病理诊断尚不明确，高度疑似遗传性平滑肌瘤病与RCC。患者经B超检查确诊右肾占位，通过肾脏增强计算机断层扫描发现其右肾静脉及下腔静脉内存在癌栓；全身骨扫描显示左肱骨上端出现放射性核素浓聚，提示存在病理性骨破坏可能，遂为其实施手术切除治疗。
术后病理提示为高级别RCC，但具体分型仍未明确，高度疑似遗传性平滑肌瘤病与RCC。后续通过高通量测序检测到SDH复合物黄素蛋白亚基A（Succinate dehydrogenase complex flavoprotein subunit A, SDHA）基因存在生殖系突变（c.1A>G, p.Met1?），免疫组化（immunohistochemistry, IHC）结果显示SDHB蛋白表达缺失。术后患者接受了放疗与靶向治疗，随访6个月后，影像学检查未发现复发或转移征象。
基于本病例报告，建议对早发患者积极开展生殖系筛查；家族史或病理结果可能无法为SDH缺陷型RCC的早期诊断及鉴别诊断提供准确依据。