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  • Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome

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Cancer genetics
Short report
Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumours: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome
  1. Peter Igaz1,2,3,
  2. Geza Toth4,
  3. Peter Nagy5,
  4. Katalin Dezső5,
  5. Peter Istvan Turai1,2,3,
  6. Marta Medvecz6,
  7. Norbert Wikonkal6,
  8. Gergely Huszty7,
  9. László Piros7,
  10. Erika Toth8,
  11. Aniko Bozsik9,10,
  12. István Likó9,
  13. Attila Patócs9,10,11,
  14. Henriett Butz9,10,11
  1. 1 Department of Endocrinology, Semmelweis University Faculty of Medicine, Budapest, Hungary
  2. 2 MTA-SE Molecular Medicine Research Group, Eötvös Loránd Research Network, Budapest, Hungary
  3. 3 Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
  4. 4 Szt. Lazar Hospital, Salgotarjan, Hungary
  5. 5 1st Department of Pathology and Experimental Cancer Research, Semmelweis University Faculty of Medicine, Budapest, Hungary
  6. 6 Department of Dermatology, Venereology and Dermatooncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
  7. 7 Department of Transplantation and Surgery, Semmelweis University Faculty of Medicine, Budapest, Hungary
  8. 8 Department of Surgical and Molecular Pathology, National Institute of Oncology, Budapest, Hungary
  9. 9 MTA-SE Hereditary Tumors Research Group, Eötvös Loránd Research Network, Budapest, Hungary
  10. 10 Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary
  11. 11 Department of Laboratory Medicine, Semmelweis University Faculty of Medicine, Budapest, Hungary
  1. Correspondence to Professor Peter Igaz, Department of Endocrinology, Semmelweis University Faculty of Medicine, Budapest, Hungary; igaz.peter{at}med.semmelweis-univ.hu

Abstract

Gorlin-Goltz syndrome (GGS) or nevoid basal cell carcinoma syndrome is a rare tumour-overgrowth syndrome associated with multiple developmental anomalies and a wide variety of tumours. Here, we describe a case of a man aged 23 years with GGS with bilateral giant tumours adjacent to both adrenals that raised the suspicion of malignancy on imaging. Histological analysis of both surgically resected tumours revealed perivascular epitheloid cell tumours (PEComas) that were independent of the adrenals. Exome sequencing of the patient’s blood sample revealed a novel germline heterozygous frameshift mutation in the PTCH1 gene. As a second hit, a somatic five nucleotide long deletion in the PTCH1 gene was demonstrated in the tumour DNA of both PEComas. To the best of our knowledge, this is the first report on PEComa in GGS, and this finding also raises the potential relevance of PTCH1 mutations and altered sonic hedgehog signalling in PEComa pathogenesis. The presence of the same somatic mutation in the bilateral tumours might indicate the possibility of a postzygotic somatic mutation that along with the germline mutation of the same gene could represent an intriguing genetic phenomenon (type 2 segmental mosaicism).

  • genetics
  • medical
  • medical oncology

https://doi.org/10.1136/jmedgenet-2021-108082

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    Footnotes

    • Contributors Research conception (PI), manuscript writing (PI, HB), molecular studies (HB, AP, AB, ET, PIT), bioinformatics (IL), pathology/immunohistochemistry (PN, KD), clinical management (PI, GT, MM, NW, GH, LP).

    • Funding Hungarian National Research, Development and Innovation Office (NKFIH) grants K134215 to PI and K125231 to AP. The study was also financed by the Higher Education Institutional Excellence Program—of the Ministry of Human Capacities in Hungary, within the framework of the molecular biology thematic programme of the Semmelweis University. HB is a recipient of Bolyai Research Fellowship of the Hungarian Academy of Sciences. AP and HB acknowledge financial support from the National Laboratories Excellence programme (under the National Tumorbiology Laboratory project (NLP-17)).

    • Competing interests None declared.

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

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.