Fan Frank S, Yang Chung-Fan
Section of Hematology and Oncology, Department of Medicine, Ministry of Health and Welfare Changhua Hospital, Chang-Hua County, Taiwan, Republic of China.
Department of Administration, Ministry of Health and Welfare Changhua Hospital, 80, Sec. 2, Chung-Jeng Rd, Pu-Shin Township, Chang-Hua County, Taiwan, Republic of China.
J Med Case Rep. 2018 May 6;12(1):122. doi: 10.1186/s13256-018-1674-3.
Definite diagnosis of metastasis from unknown primary depends on a comprehensive immunohistochemical investigation of tumor specimen. Accurate identification of the origin site usually helps a lot in choosing the most appropriate treatment. Molecular characterization provides more chance of a cure. Echoing modern medical development, BRCA1/2 mutations have been correlated with high efficiency of poly(adenosine diphosphate-ribose) polymerase inhibitors in ovarian cancer. While a previous case report demonstrated a surprising cure of platinum-resistant ovarian cancer with BRCA2 mutation by orally administered melphalan.
A 53-year-old Taiwanese woman's malignant pleural effusion was diagnosed to be a metastasis from an occult cancer in female genital organ by diligent pathological study despite absence of image evidence. She resolutely refused intravenously administered chemotherapy. After failure of anti-estrogen tamoxifen, orally administered melphalan achieved excellent complete remission. Pathogenic homozygous BRCA1 and BRCA2 mutations were later detected in tumor cells by next-generation sequencing. The same BRCA2 mutation exists in a heterozygous status in the germline deoxyribonucleic acid.
This is so far the second report of long-term remission of advanced female genital organ cancer with BRCA mutations achieved by orally administered melphalan. BRCA1/2 mutations and even all "BRCAness" of malignancy, at least ovarian cancer and ovarian-related cancers, probably not only correlate with high efficacy of poly(adenosine diphosphate-ribose) polymerase inhibitors but also lead to a high-potential cure by orally administered melphalan. We recommend that clinical trials that test this assumption be carefully designed and sophisticatedly performed.
原发灶不明转移瘤的明确诊断依赖于对肿瘤标本进行全面的免疫组化检查。准确识别原发部位通常对选择最合适的治疗方法有很大帮助。分子特征分析提供了更多治愈的机会。与现代医学发展相呼应，BRCAI/2突变与卵巢癌中聚（腺苷二磷酸核糖）聚合酶抑制剂的高效性相关。此前有一例病例报告显示，一名携带BRCA2突变的铂耐药卵巢癌患者通过口服美法仑获得了惊人的治愈效果。
一名53岁的台湾女性，尽管缺乏影像学证据，但通过细致的病理研究，其恶性胸腔积液被诊断为女性生殖器官隐匿性癌症的转移。她坚决拒绝静脉化疗。抗雌激素他莫昔芬治疗失败后，口服美法仑实现了出色的完全缓解。随后通过二代测序在肿瘤细胞中检测到致病性纯合BRCA1和BRCA2突变。相同的BRCA2突变以杂合状态存在于生殖系脱氧核糖核酸中。
这是迄今为止第二例关于口服美法仑使携带BRCA突变的晚期女性生殖器官癌症长期缓解的报告。BRCA1/2突变乃至所有恶性肿瘤的“BRCA特征”，至少在卵巢癌和卵巢相关癌症中，可能不仅与聚（腺苷二磷酸核糖）聚合酶抑制剂的高效性相关，还可通过口服美法仑实现高治愈潜力。我们建议仔细设计并精心开展验证这一假设的临床试验。
