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Fumaratehydratase-deficient renal cell carcinoma: a clinicopathological and molecular study of 13 cases
  1. Xiuyi Pan1,
  2. Mengni Zhang1,
  3. Jin Yao2,
  4. Hao Zeng3,
  5. Ling Nie1,
  6. Jing Gong1,
  7. Xueqin Chen1,
  8. Miao Xu1,
  9. Qiao Zhou1,
  10. Ni Chen1
  1. 1 Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
  2. 2 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China
  3. 3 Department of Urology, West China Hospital, Sichuan University, Chengdu, China
  1. Correspondence to Dr Ni Chen, Pathology, West China Hospital, Sichuan University, Chengdu 610041, China; chenni1{at}; Dr Qiao Zhou, Department of Pathology, West China Hospital, Sichuan University, Chengdu, China; 64548122{at}


Aims Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a newly recognised entity in the WHO 2016 classification defined as the germline mutation of FH gene. Fumaratehydratase-deficient renal cell carcinoma (FH-deficient RCC) is recommended for tumours with FH deficiency but lacking of genetic evidences of FH germline mutation. In this study, we described the clinicopathological and molecular changes of 13 FH-deficient RCCs.

Methods and results Histology features, clinicopathological data, radiology performance and outcomes were collected for each patient. Next-generation sequencing and DNA sequencing of FH gene were performed to examine FH mutations. The patient group included five females and eight males. Different morphological patterns of papillary, nested, adenoid, foam adenoid, cribriform, tubular, tubulocystic, cystic and loose oedema stroma were observed. Except typical big nuclei with or without eosinophilic nucleoli and perinucleolar halos, raisin-like, hobnail-like and even low-grade nuclei were also observed in these tumours. Eleven cases with high-grade nuclei showed disease progression or death, but no disease progression was detected in two cases with low-grade nuclei and eosinophilic cytoplasm. FH expression was absent in tumour cells except for case 11. Next-generation sequencing and DNA sequencing verified seven FH germline mutations and four somatic mutations out of 13 cases.

Conclusions FH-deficient RCC is a rare renal tumour and has a wide morphological spectrum. Most of the tumours had high-grade nuclei and were aggressive. However, we observed a morphological subtype of FH-deficient RCC with low-grade nuclei and eosinophilic cytoplasm, which might mainly occur in young women and show a relatively good prognosis.

  • fumaratehydratase-deficient renal cell carcinoma
  • NGS
  • PCR-based direct sequencing
  • outcomes

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  • Handling editor Runjan Chetty.

  • Contributors XP and MZ collected the patients, did DNA sequencing and write the paper; JY supplied the radiology image; HZ, LN and JG organised the clinical data; XC and MX did the immunohistochemistry. QZ and NC organised and modified the paper.

  • Funding Supported by grants from the Natural Science Foundation of China (NSFC 81872107, 81872108, 81572540 and 81572541).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval In accordance with the institutional ethics guidelines, under permission from Ethics Committee of West China Hospital, all patients or family members provided written informed consent for genetic analysis.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.

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