- 5 例 SDHA 缺陷型 RCC：中位年龄 40 岁，男:女 4:1；初诊常为集合管癌或高级别 RCC NOS。
- 形态谱从经典型 SDHB 缺陷样到异质性高级别：乳头状/巢状结构、嗜酸/絮状胞质、胞质空泡伴包涵体常见；SDHB 均缺失，但 SDHA IHC 可在突变存在时仍保留（4/5 缺失）。
- 随访中 2/4 例在 14–34 个月内出现转移；较多数 SDHB 缺陷型 RCC 更显侵袭性，建议 SDHB 缺失时行 NGS。
摘要
琥珀酸脱氢酶（SDH）缺陷型肾细胞癌（RCC）由 SDH 亚基（A、B、C 或 D）突变所界定，部分患者可伴遗传性副神经节瘤–嗜铬细胞瘤综合征及胃肠道间质瘤（GIST）。本多中心研究以形态学、免疫组化（IHC）与二代测序（NGS）分析 5 例 SDHA 缺陷型 RCC。患者中位年龄 40 岁，男性为主（4:1）。初诊分别为 SDHA 缺陷型 RCC（1 例）、集合管癌（1 例）或高级别 RCC NOS（3 例）。随后 NGS 将其中 4 例鉴定为 SDHA 缺陷型 RCC。
常见组织学特征包括乳头状（100%）与巢状（100%）结构、实性生长（80%）、嗜酸性/絮状胞质（100%）、伴包涵体的胞质空泡（80%）及核沟（20%）。5 例中 4 例为高级别（ISUP/WHO 3 级），伴促结缔组织增生性间质，偶见炎症。全部肿瘤 SDHB 表达缺失（5/5），而 SDHA 表达缺失见于 4/5，说明即便存在 SDHA 突变，SDHA IHC 仍可保留。NGS 在 4 例肿瘤中检出 SDHA 突变。随访期间，4 例中 2 例在 14–34 个月内出现转移，其余 2 例在 11–19 个月无播散。
SDHA 缺陷型 RCC 的谱系涵盖经典型 SDHB 缺陷型 RCC 形态至异质性高级别肿瘤。对于高级别 RCC——尤其是具有乳头状或集合管癌样形态、肿瘤细胞空泡变的 RCC NOS——应予以考虑。推荐行 NGS，特别是在检出 SDHB 缺失时，因为 SDHA IHC 可能仍保留。与多数 SDHB 缺陷型 RCC 不同，SDHA 缺陷型 RCC 似更侵袭，转移风险更高、预后更差。
Abstract
Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is defined by mutations in SDH subunits (A, B, C, or D) and is associated with hereditary paraganglioma-pheochromocytoma syndrome and gastrointestinal stromal tumors (GISTs) in some patients. This multi-institutional study analyzed 5 SDHA-deficient RCCs using morphology, immunohistochemistry (IHC), and next-generation sequencing (NGS). Patients had a median age of 40 years with male predominance (4:1). Initially, tumors were diagnosed as SDHA-deficient RCC (1), collecting duct carcinoma (1), or high-grade RCC, NOS (3). NGS subsequently identified 4 tumors as SDHA-deficient RCC. Common histologic features included papillary (100%) and nested (100%) architecture, solid growth (80%), eosinophilic/flocculent cytoplasm (100%), cytoplasmic vacuoles with inclusions (80%), and nuclear grooves (20%). Four of 5 tumors were high-grade (ISUP/WHO grade 3) with desmoplastic stroma and occasional inflammation. All tumors showed loss of SDHB expression (5/5), while SDHA expression was lost in 4/5, demonstrating that SDHA IHC may be preserved despite SDHA mutation. NGS identified SDHA mutations in four tumors. During follow-up, 2 of 4 patients developed metastases within 14 to 34 months, whereas the remaining 2 had no spread after 11 to 19 months. SDHA-deficient RCC displays a spectrum from classic SDHB-deficient RCC morphology to heterogeneous high-grade tumors. It should be considered in high-grade RCCs, particularly RCC NOS with papillary or collecting duct carcinoma-like morphology and vacuolated tumor cells. NGS is recommended, especially when SDHB loss is detected, as SDHA IHC may be retained. Unlike most SDHB-deficient RCCs, SDHA-deficient RCC appears more aggressive, with increased metastatic risk and poorer prognosis.