Objective: To investigate the clinicopathological, molecular pathological features, and family genetic pedigree of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Methods: A total of 16 cases of SCCOHT diagnosed in Obstetrics and Gynecology Hospital of Fudan University from January 2013 to January 2023 were collected. The clinicopathologic features, SMARCA4/2/B1 protein expression, outcomes and SMARCA4 gene detection were reported. A follow-up study was also carried out. Results: The average age at diagnosis was 28.7 years (range 17-38 years). The preoperative calcium level was evaluated in 3 of 6 patients. The tumor was unilateral in all 16 cases, ranged from 8 to 26 cm (average 15.8 cm) in the greatest dimension. Extraovarian spread was present in 7 cases. In 10 cases, the tumors were initially misinterpreted as other ovarian neoplasms. BRG1 and BRM expression by immunohistochemistry were all lost in detected cases, while INI1 exhibited retained nuclear expression. All BRM-negative SCCOHTs also lacked BRG1 protein,but retained INI1 expression. SCCOHTs were only focally positive for EMA, CKpan, Calretinin, SALL4, and diffusely positive for WT1. Two of nine cases exhibited mutation-type p53 immunoreactivity. Ki-67 index was 58% on an average. ER, PR, FOXL2, α-inhibin, chromogranin A and LCA were negative in all the cases. SMARCA4 sequencing was available in 8 cases of SCCOHT, which revealed a germline SMARCA4 mutation in one patient, and others carried somatic mutation. Furthermore, two daughters, mother and an aunt of a patient with germline mutation were reported to be SMARCA4 mutation carriers. Follow-up was available for 15 patients, and the 6-month, 1-year and 2-year survival rate was 65.8%, 45.1%, and 22.6%, respectively. For patients in FIGO stages Ⅱ+Ⅲ, 6-month, 1-year survival rate was 53.6% and 35.7% respectively, compared to 80% (6-month) and 60% (1-year) in patients of staged I (P=0.358). Conclusions: With dismal prognosis of SCCOHT, accurate diagnosis is necessary. The typical age distribution, a panel of various staining results, especially concomitant loss of BRG1 and BRM may be of diagnostic aid and can be used to distinguish SCCOHT from its histological mimics. After the diagnosis of SCCOHT, genetic testing and genetic counseling are recommended.
目的： 探讨卵巢高钙血症型小细胞癌（SCCOHT）的临床病理特征、分子病理及家族遗传谱系。 方法： 收集复旦大学附属妇产科医院2013年1月至2023年1月诊断的SCCOHT共16例，通过电子病史系统、外院病历收集患者相关临床病理检查资料，加做免疫组织化学和基因检测，对患者进行随访。 结果： 16例SCCOHT患者平均年龄28.7岁（17~38岁），主要症状为腹胀、腹部肿块。6例患者术前有血钙检查，3例（50%）升高。肿瘤均单侧发生，平均直径15.8 cm（8.0~26.0 cm），切面实性为主，可见出血、坏死。7/16例患者手术时肿瘤已发生卵巢外播散。10/16例初始诊断为卵巢的其他肿瘤类型。BRG1和BRM均缺失表达，而INI1均无缺失；肿瘤局灶表达上皮细胞膜抗原（EMA）、广谱细胞角蛋白（CKpan）、Calretinin、SALL4，弥漫表达WT-1；p53偶为突变表型；Ki-67阳性指数平均58%。肿瘤不表达雌激素受体（ER）、孕激素受体（PR）、FOXL2、α-抑制素、嗜铬粒素A和白细胞共同抗原（LCA）。8例行分子病理检测，1例检出SMARCA4胚系突变，余7例为体系突变，胚系突变患者家族内亲属亦检出突变携带者。15例获得随访，6个月、1年、2年患者总体生存率分别是65.9%、45.1%、22.6%。国际妇产科联盟（FIGO）Ⅰ期患者6个月、1年生存率分别是80%、60%，而>Ⅰ期患者6个月、1年生存率分别是53.6%、35.7%。 结论： SCCOHT预后极差，准确诊断非常关键，对于年轻患者的单侧卵巢肿块，体积大，快速生长，甚至广泛播散，伴有高钙血症，应考虑到该罕见肿瘤，形态学基础上辅以BRG1和BRM缺失表达可明确诊断，确诊后患者需行SMARCA4基因检测，若为胚系突变，建议其家族成员进行基因检测和遗传咨询。.