Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare autosomal dominant disorder that results from a germline mutation in the fumarate hydratase gene (FH). Individuals with FH mutations are at risk of developing renal cell carcinoma (RCC). Patients with HLRCC-associated RCC (HLRCC-RCC) have aggressive clinical courses, but there is as yet no standardized therapy for advanced HLRCC-RCC. We report an aggressive RCC case in a 49-year-old man. Nine weeks after undergoing a total nephroureterectomy of the right kidney, he had a metastasectomy at port site. Within 14 weeks of the initial surgery, multiple recurrent tumors developed in the right retroperitoneal space. The pathological diagnosis was FH-deficient RCC. Genetic testing identified a heterozygous germline mutation of FH (c.641_642delTA), which confirmed the diagnosis of HLRCC-RCC. He received combination therapy with the immune checkpoint inhibitors (ICIs) nivolumab and ipilimumab as the first-line therapy. After 31 weeks of ICI treatment, a complete response was achieved. The disease-free condition has been prolonged for 24 months since the initial surgical treatment. This is the first case report of successful treatment of HLRCC-RCC with nivolumab plus ipilimumab. This combination immunotherapy is expected to be an effective approach to treat patients with advanced-stage HLRCC-RCC.
Familial cancer. 2020 Jul 15 [Epub ahead of print]
Yasuhiro Iribe, Mitsuko Furuya, Yousuke Shibata, Masato Yasui, Makoto Funahashi, Junichi Ota, Hiromichi Iwashita, Yoji Nagashima, Hisashi Hasumi, Narihiko Hayashi, Kazuhide Makiyama, Keiichi Kondo, Reiko Tanaka, Masahiro Yao, Noboru Nakaigawa
Department of Urology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan., Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan. ., Department of Urology, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan., Department of Pathology, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan., Department of Surgical Pathology, Tokyo Women's Medical University, Tokyo, Japan., Medical Mycology Research Center, Chiba University, Chiba, Japan.