Tokunaga Mayumi, Takahashi Hiroyuki, Hirose Natsuki, Hibino Yuto, Teranaka Hiroshi, Washimi Kota, Okubo Yoichiro, Hiroshima Yukihiko, Tanaka Masatsugu, Sakai Rika
Department of Hematology and Medical Oncology, Kanagawa Cancer Center, 2-3-2, Nakao, Asahi, Yokohama, Kanagawa 2418515 Japan.
Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan.
Int Cancer Conf J. 2024 Oct 17;14(1):1-6. doi: 10.1007/s13691-024-00701-6. eCollection 2025 Jan.
A 50-year-old man presented with a bulky mass in the left thigh and was referred to our department. He showed an impaired Eastern Cooperative Oncology Group performance status of 3 due to swelling of the left thigh and pain. Imaging analysis revealed a large mass measuring 16 cm in the left thigh and right forearm, along with the bilateral adrenal gland, right lung, right axillary lymph nodes, liver, and left femur. Despite additional tests, including pathological examination, the primary origin of the tumors could not be identified. Because of the rapid tumor progression, he was placed on nivolumab (NIVO; 240 mg/body, every 2 weeks) monotherapy based on the diagnosis of cancer of unknown primary, unfavorable type. Simultaneous comprehensive genomic profiling (CGP) test revealed a high tumor mutation burden (15.69 Muts/Mb) and a truncating mutation of , along with loss of BRG1 expression detected by additional immunohistochemical (IHC) analysis. Based on the predominance of soft tissue in the lesion, histological and IHC findings, and genomic phenotype, the patient was finally re-diagnosed with SMARCA4-deficient, SMARCB1/INI-1-preserved epithelioid sarcoma (ES). He showed a dramatic improvement in physical and laboratory findings at 5 weeks after the initial NIVO dose. Although he experienced immune-related adverse events, such as liver dysfunction, colitis and relative adrenal failure, and severe sepsis due to pulmonary cyst infection, he was able to overcome these complications. By the 12th dose of NIVO (13 months after the initial treatment), he has exhibited a positive response to NIVO without any additional complications. Among SMARCA4-deficient tumors, there have been multiple reports on the sensitivity of SMARCA4-deficient thoracic tumors to immune checkpoint inhibitors (ICIs), including PD-1 blockade agents. This case indicates that SMARCA4-deficient SMARCB1/INI-1-preserved ES may share molecular pathological characteristics with SMARCA4-deficient thoracic tumors, given their similar sensitivity to ICIs. In addition, CGP may play an important role in hypothesizing the primary site of tumors and guiding treatment selection for rare cancers, as in the present case, which lacks established treatment options. Further data accumulation is essential to validate this approach.
一名50岁男性因左大腿出现巨大肿块前来就诊，并被转诊至我科。由于左大腿肿胀和疼痛，他的东部肿瘤协作组（ECOG）体能状态评分为3分，提示功能受损。影像学分析显示，左大腿和右前臂有一个直径达16厘米的巨大肿块，同时累及双侧肾上腺、右肺、右腋窝淋巴结、肝脏和左股骨。尽管进行了包括病理检查在内的多项检查，但仍无法确定肿瘤的原发部位。由于肿瘤进展迅速，基于未知原发灶、不良类型癌症的诊断，他开始接受纳武单抗（NIVO；240毫克/体，每2周一次）单药治疗。同时进行的综合基因组分析（CGP）检测显示肿瘤突变负荷较高（15.69个突变/兆碱基），存在一种截短突变，额外的免疫组织化学（IHC）分析检测到BRG1表达缺失。基于病变中软组织的优势、组织学和IHC结果以及基因组表型，该患者最终被重新诊断为SMARCA4缺陷、SMARCB1/INI-1保留的上皮样肉瘤（ES）。在首次使用NIVO剂量后的5周，他的身体状况和实验室检查结果有了显著改善。尽管他经历了免疫相关不良事件，如肝功能障碍、结肠炎和相对性肾上腺功能衰竭，以及因肺囊肿感染导致的严重脓毒症，但他能够克服这些并发症。到第12次使用NIVO剂量时（初始治疗后13个月），他对NIVO表现出阳性反应，且无任何其他并发症。在SMARCA4缺陷型肿瘤中，已有多篇报道称SMARCA4缺陷型胸部肿瘤对免疫检查点抑制剂（ICIs）敏感，包括PD-1阻断剂。本病例表明，SMARCA4缺陷、SMARCB1/INI-1保留的ES可能与SMARCA4缺陷型胸部肿瘤具有相似的分子病理特征，因为它们对ICIs的敏感性相似。此外，CGP可能在推测肿瘤原发部位和指导罕见癌症的治疗选择方面发挥重要作用，就像本例中缺乏既定治疗方案的情况一样。进一步的数据积累对于验证这种方法至关重要。
