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A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven

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Abstract

Hereditary leiomyomatosis and renal cell cancer (HLRCC) is caused by heterozygous germline variants in the fumarate hydratase (FH) gene and is associated with increased susceptibility to cutaneous leiomyomas, uterine leiomyomas, and renal cell carcinoma (RCC). HLRCC-associated RCC usually occurs in the middle age, with the median age being 40–44 years. This report describes a seven-year-old (84-month-old) male who developed a large right kidney tumor with multiple cystic lesions that contained enhanced solid components. There was no evidence of distant metastasis. The male patient underwent right nephrectomy and has been recovering well without metastasis or recurrence. Pathological examination revealed that tumor cells with relatively prominent nucleoli and surrounded by halos, were located in a limited area. Immunohistochemical staining was negative for FH. Whole-exome sequencing identified his germline variant in the FH gene and its loss of heterozygosity in the tumor. At nine years (114 months) of age, the male patient showed no recurrence of the tumor. This was the youngest-onset case of HLRCC-associated RCC to date. This report may affect the starting age for future RCC-surveillance programs for patients with HLRCC.

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Fig. 1

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Data is available upon request.

References

  1. Menko FH, Maher ER, Schmidt LS, Middelton LA, Aittomäki K, Tomlinson I, Richard S, Linehan WM (2014) Hereditary leiomyomatosis and renal cell cancer (HLRCC): renal cancer risk, surveillance and treatment. Fam Cancer 13:637–644

    Article  CAS  Google Scholar 

  2. Muller M, Ferlicot S, Guillaud-Bataille M, Le Teuff G, Genestie C, Deveaux S, Slama A, Poulalhon N, Escudier B, Albiges L, Soufir N, Avril MF, Gardie B, Saldana C, Allory Y, Gimenez-Roqueplo AP, Bressac-de Paillerets B, Richard S, Benusiglio PR (2017) Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers. Clin Genet 92:606–615

    Article  CAS  Google Scholar 

  3. Forde C, Lim DHK, Alwan Y, Burghel G, Butland L, Cleaver R, Dixit A, Evans DG, Hanson H, Lalloo F, Oliveira P, Vialard L, Wallis Y, Maher ER, Woodward ER (2019) Hereditary leiomyomatosis and renal cell cancer: clinical, molecular, and screening features in a cohort of 185 affected individuals. Eur Urol Oncol 3:764–772

    Article  Google Scholar 

  4. Chayed Z, Kristensen LK, Ousager LB, Rønlund K, Bygum A (2021) Hereditary leiomyomatosis and renal cell carcinoma: a case series and literature review. Orphanet J Rare Dis 16:34

    Article  Google Scholar 

  5. Moch H, Cubilla AL, Humphrey PA, Reuter VE, Ulbright TM (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-Part A: renal, penile, and testicular tumours. Eur Urol 70:93–105

    Article  Google Scholar 

  6. Nix J, Shuch B, Chen V, Middleton L, Peterson J, Gautam R, Merino M, Metwalli A, Bratslavsky G, Pinto P, Srinivasan R, Linehan M (2012) Clinical features and management of hereditary leiomyomatosis and renal cell cancer (HLRCC). J Urol 187:e810

    Article  Google Scholar 

  7. Taniguchi R, Muramatsu H, Okuno Y, Suzuki K, Obu S, Nakatochi M, Shimamura T, Takahashi Y, Horikoshi Y, Watanabe K, Kojima S (2018) Comprehensive genetic analysis of donor cell derived leukemia with KMT2A rearrangement. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.26823

    Article  PubMed  Google Scholar 

  8. Park I, Shim YS, Go H, Hong BS, Lee JL (2019) Long-term response of metastatic hereditary leiomyomatosis and renal cell carcinoma syndrome associated renal cell carcinoma to bevacizumab plus erlotinib after temsirolimus and axitinib treatment failures. BMC Urol 19:51

    Article  Google Scholar 

  9. Pollard PJ, Spencer-Dene B, Shukla D, Howarth K, Nye E, El-Bahrawy M, Deheragoda M, Joannou M, McDonald S, Martin A, Igarashi P, Varsani-Brown S, Rosewell I, Poulsom R, Maxwell P, Stamp GW, Tomlinson IP (2007) Targeted inactivation of FH1 causes proliferative renal cyst development and activation of the hypoxia pathway. Cancer Cell 11:311–319

    Article  CAS  Google Scholar 

  10. Terada N, Ichioka K, Matsuta Y, Okubo K, Yoshimura K, Arai Y (2002) The natural history of simple renal cysts. J Urol 167:21–23

    Article  Google Scholar 

  11. Lehtonen HJ, Kiuru M, Ylisaukko-Oja SK, Salovaara R, Herva R, Koivisto PA, Vierimaa O, Aittomäki K, Pukkala E, Launonen V, Aaltonen LA (2006) Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet 43:523–526

    Article  CAS  Google Scholar 

  12. Sánchez-Heras AB, Castillejo A, García-Díaz JD, Robledo M, Teulé A, Sánchez R, Zúñiga Á, Lastra E, Durán M, Llort G, Yagüe C, Ramon Y, Cajal T, López S, Martin C, López-Fernández A, Balmaña J, Robles L, Mesa-Latorre JM, Chirivella I, Fonfria M, Perea Ibañez R, Castillejo MI, Escandell I, Gomez L, Berbel P, Soto JL (2020) Hereditary leiomyomatosis and renal cell cancer syndrome in Spain: clinical and genetic characterization. Cancers (Basel) 12:3277

    Article  Google Scholar 

  13. Ristau BT, Kamat SN, Tarin TV (2015) Abnormal cystic tumor in a patient with hereditary leiomyomatosis and renal cell cancer syndrome: evidence of a precursor lesion? Case Rep Urol 2015:303872

    PubMed  PubMed Central  Google Scholar 

  14. Hol JA, Jongmans MCJ, Littooij AS, de Krijger RR, Kuiper RP, van Harssel JJT, Mensenkamp A, Simons M, Tytgat GAM, van den Heuvel-Eibrink MM, van Grotel M (2020) Renal cell carcinoma in young FH mutation carriers: case series and review of the literature. Fam Cancer 19:55–63

    Article  CAS  Google Scholar 

  15. Alam NA, Olpin S, Leigh IM (2005) Fumarate hydratase mutations and predisposition to cutaneous leiomyomas, uterine leiomyomas and renal cancer. Br J Dermatol 153:11–17

    Article  CAS  Google Scholar 

  16. Gardie B, Remenieras A, Kattygnarath D et al (2011) Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. J Med Genet 48:226–234

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to thank all of the clinicians and the family who made this study possible by providing samples. The authors would also like to thank Mr. Akitaka Sugishita, Ms. Yoshie Miura, Ms. Hiroko Ono, and Ms. Chie Amahori for their valuable assistance. The authors acknowledge the help of the Division for Medical Research Engineering, Nagoya University Graduate School of Medicine, for the technical support with next-generation sequencing. The authors also acknowledge the help of the Human Genome Center, University of Tokyo, for providing super-computing resources (http://sc.hgc.jp/shirokane.html).

Funding

This study was supported by Nagoya Pediatric Cancer Fund.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Rieko Taniguchi, Hideki Muramatsu, Taro Yoshida, Manabu Wakamatsu, Motoharu Hamada, Seiji Kojima & Yoshiyuki Takahashi

  2. Medical Genomics Center, Nagoya University Hospital, Nagoya, Japan

    Yusuke Okuno

  3. Department of Pediatric Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Chiyoe Shirota, Wataru Sumida, Takahisa Tainaka & Hiroo Uchida

  4. Department of Rare/ Intractable Cancer Analysis Research, Nagoya University Graduate School of Medicine, Nagoya, Japan

    Akinari Hinoki

  5. Department of Pediatric Nephrology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan

    Yoshimitsu Gotoh

  6. Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan

    Toyonori Tsuzuki

  7. Department of Pathology, Kanagawa Children’s Medical Center, Kanagawa, Japan

    Yukichi Tanaka

Authors
  1. Rieko Taniguchi
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  2. Hideki Muramatsu
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  3. Yusuke Okuno
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  4. Taro Yoshida
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  5. Manabu Wakamatsu
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  6. Motoharu Hamada
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  8. Wataru Sumida
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  9. Akinari Hinoki
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  10. Takahisa Tainaka
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  11. Yoshimitsu Gotoh
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  12. Toyonori Tsuzuki
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  13. Yukichi Tanaka
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  14. Seiji Kojima
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  15. Hiroo Uchida
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  16. Yoshiyuki Takahashi
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Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by RT, CS, WS, AH, TT, YG, TT, and YT. Data analysis was performed by RT, YO, TY, MW, and HM. The first draft of the manuscript was written by RT and HM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hideki Muramatsu or Yoshiyuki Takahashi.

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Conflict of interest

The authors report no potential conflicts of interest.

Ethical approval

This research was approved by the Ethics Committee of Nagoya University Graduate School of Medicine (No. 2016-0025).

Informed consent

Informed consent was obtained from the patient’s parents. The patient’s parents consented to publication of deidentified information.

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Taniguchi, R., Muramatsu, H., Okuno, Y. et al. A patient with very early onset FH-deficient renal cell carcinoma diagnosed at age seven. Familial Cancer 21, 337–341 (2022). https://doi.org/10.1007/s10689-021-00268-8

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  • DOI: https://doi.org/10.1007/s10689-021-00268-8

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