PDF(Pubmed)
Abstract：
Small-cell carcinoma of the ovary, the hypercalcemic type (SCCOHT) is a rare, aggressive tumor that primarily affects young females. It is a monogenic disorder caused by germline and/or somatic SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations. Here, we report a case of SCCOHT harboring multiple previously unreported somatic mutations in SMARCA4 (c.2866_2867delC>T; c.3543del). A 28-year-old breastfeeding Japanese female presented to a previous hospital with nausea and vomiting. She had no family history of relevant malignancies, including ovarian cancer. Based on an evaluation performed at another institution, she was referred to a gynecologist for suspected ovarian cancer. Imaging studies revealed a 16×15 cm heterogenous enhancing mass within the right ovary without lymph node or distant metastasis. She had mild ascites without peritoneal dissemination, but there was an elevation in the serum calcium level (15.1 mg/dL). The patient underwent cytoreductive surgery and was pathologically diagnosed with SCCOHT. Auxiliary immunohistochemical staining confirmed the loss of SMARCA4 protein expression. The patient was diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2014 stage IA (pT1a pN0 M0). The serum calcium levels returned to normal post-surgery. Matched-pair analysis using tumor tissue and peripheral blood revealed multiple somatic mutations in SMARCA4, but no deleterious germline mutations were present. Microsatellite instability was not significant, and the patients had a heterozygous mutation of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6. She underwent six cycles of irinotecan hydrochloride plus cisplatin chemotherapy and achieved complete remission. The patient was finally examined and evaluated 45 months postoperatively; there was no evidence of the disease. Overall, the genetic findings will not aid in the SCCOHT diagnosis and relevant genetic counseling; however, they may have implications for the treatment of this disease in the future.
摘要：
卵巢小细胞癌,高血钙型（SCCOHT）是一种罕见的，主要影响年轻女性的侵袭性肿瘤。它是由种系和/或体细胞SWI/SNF相关引起的单基因疾病，矩阵关联，肌动蛋白依赖性染色质调节因子，亚族a,成员4（SMARCA4）突变。这里,我们报告了一例SCCOHT在SMARCA4中具有多个以前未报告的体细胞突变（c.2866_2867delC>T;c.3543del）。一名28岁的日本母乳喂养女性因恶心和呕吐出现在前一家医院。她没有相关恶性肿瘤的家族史，包括卵巢癌.根据在另一家机构进行的评估，她因怀疑患有卵巢癌而被转介给妇科医生。影像学检查显示，右卵巢内有16×15cm异质增强肿块，无淋巴结或远处转移。她有轻度腹水，没有腹膜播散，但血清钙水平升高（15.1mg/dL）。患者接受了细胞减灭术，经病理诊断为SCCOHT。辅助免疫组织化学染色证实SMARCA4蛋白表达缺失。患者被诊断为国际妇产科联合会（FIGO）2014年IA期（pT1apN0M0）。术后血清钙水平恢复正常。使用肿瘤组织和外周血的配对分析显示SMARCA4中存在多个体细胞突变，但不存在有害的种系突变。微卫星不稳定性不显著，并且患者具有尿苷二磷酸葡萄糖醛酸转移酶1A1（UGT1A1）*6的杂合突变。她接受了六个周期的盐酸伊立替康加顺铂化疗，并获得了完全缓解。最终在术后45个月对患者进行检查和评估；没有疾病的证据。总的来说,遗传发现将无助于SCCOHT诊断和相关的遗传咨询;然而，它们可能对未来这种疾病的治疗有影响。
