title: Radical nephrectomy and regional lymph node dissection for locally advanced type 2 papillary renal cell carcinoma in an at-risk individual from a family with hereditary leiomyomatosis and renal cell cancer: a case report.
abstract: BACKGROUND
  Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant tumor susceptibility syndrome, and the disease-related gene has been identified as fumarate hydratase (fumarase, FH). HLRCC-associated kidney cancer is an aggressive tumor characterized by early metastasis to regional lymph nodes and distant organs. Since early diagnosis and provision of definitive therapy is thought to be the best way to reduce the tumor burden, it is widely accepted that germline testing and active surveillance for an at-risk individual from a family with HLRCC is very important. However, it still remains controversial how we should treat HLRCC-associated kidney cancer. We successfully treated the patient with locally advanced HLRCC-associated kidney cancer, who has received active surveillance because of at-risk individual, by radical nephrectomy and extended retroperitoneal lymph node dissection, and examined surgically resected samples from a molecular point of view.
  
  
  METHODS
  We recommended that 13 at-risk individuals from a family with HLRCC should receive active surveillance for early detection of renal cancer. A 48-year-old woman with a left renal tumor and involvement of multiple regional lymph nodes with high accumulation of fluorine-18-deoxyglucose on positron emission tomography was treated with axitinib as a neoadjuvant therapy. Preoperative axitinib induced the shrinkage of the tumor with decreased fluorine-18-deoxyglucose accumulation. Resected samples showed two thirds tumor tissue necrosis as well as high expression of serine/threonine kinase Akt and low expression of nuclear factor E2-related factor 2 (Nrf2) which activates anti-oxidant response and protects against oxidative stress in viable cancer cells. Targeted next-generation sequencing revealed that FH mutation and loss of the second allele were completely identical between blood and tumor samples, suggesting that FH mutation plays a direct role in FH-deficient RCC. She has remained well after radical operation for over 33 months.
  
  
  CONCLUSIONS
  FH mutation plays a role in tumorigenic feature, a metabolic shift to aerobic glycolysis, and increased an anti-oxidant response phenotype in HLRCC-associated kidney cancer.
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi Mibu, Tochigi, 321-0293, Japan. kamait@dokkyomed.ac.jp.
authors.forename: Takao
authors.initials: T
authors.lastname: Kamai
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi Mibu, Tochigi, 321-0293, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Abe
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi Mibu, Tochigi, 321-0293, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Arai
authors.affiliation: Division of Field Application, Life Technologies, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Murakami
authors.affiliation: PET Center, Dokkyo Medical University Hospital, Tochigi, Japan.
authors.forename: Setsu
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Department of Radiology, Dokkyo Medical University, Tochigi, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kaji
authors.affiliation: Department of Urology, Dokkyo Medical University, 880 Kitakobayashi Mibu, Tochigi, 321-0293, Japan.
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Yoshida
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D018231:Leiomyomatosis / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000473:pathology / Q000601:surgery*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D009386:Neoplastic Syndromes, Hereditary; D009392:Nephrectomy; D012878:Skin Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D014594:Uterine Neoplasms / Q000235:genetics / Q000473:pathology / Q000601:surgery*
chemical_list: D005649:Fumarate Hydratase
keywords: Axitinib; Fumarate hydratase (FH); Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC); Targeted next-generation sequencing; Type 2 papillary renal cell carcinoma