Miura Yuji, Motoshima Takanobu, Anami Toshiki, Takemura Kohji, Kinowaki Keiichi, Oka Suguru, Urakami Shinji, Kamba Tomomi, Komohara Yoshihiro
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
Department of Medical Oncology, Toranomon Hospital, Tokyo, Japan.
Cancer Diagn Progn. 2023 Jul 3;3(4):522-527. doi: 10.21873/cdp.10249. eCollection 2023 Jul-Aug.
Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare RCC subtype, and FH-deficient RCC may be misdiagnosed as another type of RCC, such as type 2 papillary RCC or collecting duct carcinoma. FH and 2-succinocysteine (2SC) are useful diagnostic markers for FH-deficient RCC and can be measured using immunohistochemistry (IHC).
A 30-year-old female with 3-month history of fatigue and left-flank mass was diagnosed with a 20×13×10 cm left-side renal mass with massive inferior vena cava (IVC) tumor thrombus that extended into the right atrium. She underwent nephrectomy and IVC thrombectomy, and a pathological diagnosis of type 2 papillary RCC was made. Four months after the surgery, computed tomography scan showed multiple liver metastases not observed immediately after surgery. Systemic treatment with sorafenib was initiated; however, she did not respond and died 3 months after treatment. Subsequent re-review of hematoxylin and eosin-stained sections indicated morphologic characteristics consistent with FH-deficient RCC, and IHC staining was negative for FH but positive for 2SC, indicating a diagnosis of FH-deficient RCC. Further immunological analyses revealed the loss of HLA-class I, b2 microglobulin, and HLA-DR antigens in cancer cells. In addition, a few CD8-positive cytotoxic T cells and CD163-positive tumor-associated macrophages were noted.
An immunosuppressive tumor microenvironment that facilitates cancer immune evasion might be associated with the rapid progression and poor prognosis in our patient. Further investigation of the tumor immune microenvironment in patients with FH-deficient RCC is warranted.
富马酸水合酶（FH）缺陷型肾细胞癌（RCC）是一种罕见的RCC亚型，FH缺陷型RCC可能被误诊为其他类型的RCC，如2型乳头状RCC或集合管癌。FH和2-琥珀酰半胱氨酸（2SC）是FH缺陷型RCC的有用诊断标志物，可通过免疫组织化学（IHC）进行检测。
一名30岁女性，有3个月疲劳和左腰部肿块病史，被诊断为左侧肾脏有一个20×13×10 cm的肿块，并伴有巨大的下腔静脉（IVC）肿瘤血栓，血栓延伸至右心房。她接受了肾切除术和IVC血栓切除术，病理诊断为2型乳头状RCC。术后4个月，计算机断层扫描显示出现了多个肝转移灶，术后即刻未观察到。开始使用索拉非尼进行全身治疗；然而，她没有反应，治疗3个月后死亡。随后对苏木精和伊红染色切片的再次复查显示形态学特征与FH缺陷型RCC一致，IHC染色显示FH阴性但2SC阳性，表明诊断为FH缺陷型RCC。进一步的免疫学分析显示癌细胞中HLA-I类、β2微球蛋白和HLA-DR抗原缺失。此外，还发现了一些CD8阳性细胞毒性T细胞和CD163阳性肿瘤相关巨噬细胞。
促进癌症免疫逃逸的免疫抑制性肿瘤微环境可能与我们患者的快速进展和不良预后有关。有必要对FH缺陷型RCC患者的肿瘤免疫微环境进行进一步研究。
