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.
Data availability
Data is available upon request.
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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).
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This study was supported by Nagoya Pediatric Cancer Fund.
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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.
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This research was approved by the Ethics Committee of Nagoya University Graduate School of Medicine (No. 2016-0025).
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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