Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK

Abstract

Introduction

Desmoid-type fibromatosis (DF) are locally infiltrative, non-metastasizing tumours associated with significant morbidity and mortality if located intra-abdominally, retroperitoneally or in head and neck localisation. They are mostly sporadic, due to somatic CTNNB1 mutations. Alternatively, they can be associated with germline pathogenic variants in APC causing Familial Adenomatous Polyposis (FAP). Germline APC variants and somatic CTNNB1 mutations are mutually exclusive.

Aims and methods

We conducted a retrospective descriptive analysis of patients with DF seen at the Royal Marsden NHS Foundation Trust Sarcoma Unit in London. We aimed to describe the methods of screening for FAP in patients with DF from a specialist unit. Patients diagnosed between 1992 and 2020 were selected from the prospectively maintained Sarcoma Unit database.

Results

226 patients were identified and 67% (n = 152) were female. Median age at diagnosis was 37.5 (range 2–81) years. Tumour localisation was limbs/pelvis in 30.9% (N = 70), intra-abdominal 16.8% (N = 38), abdominal wall 23.5% (N = 53), thorax 18.6% (N = 42), head and neck 3.1% (N = 7) and vertebral/paravertebral 7.1% (N = 16). Colonoscopy was requested in 65 patients (28.8% of all cases) and was completed in forty-six (20.4%). Molecular testing of CTNNB1 testing was requested in 35 cases (15.5%). APC germline test was requested in 12 cases. Four patients in our cohort had an FAP-associated DF.

Conclusions

CTNNB1 ± APC testing and colonoscopy are useful tools for the screening of patients with DF. CTNNB1 molecular testing should be performed in all cases of newly diagnosed DF. Negative CTNNB1 results, alongside clinical assessment, should prompt APC testing and/or colonoscopy.

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Acknowledgements

R L Jones: Receipt of grants/research support: MSD, GSK. Receipt of consultation fees: Adaptimmune, Athenex, Blueprint, Boehringer- Ingelheim, Clinigen, Eisai, Epizyme, Daichii, Deciphera, Immunedesign, Lilly, Merck, Pharmamar, UptoDate. T P McVeigh: Receipt of grants and honoraria from Roche, Novartis, Astra Zeneca/MSD, Blackrock Clinic, Hermitage Medical Clinic and Galway Clinic.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors

Contributions

Conceptualization: EC, TMcV. Data curation: EC, SG, TMcV. Supervision: TMcV, RJ, CB, MS, AH, DS. Writing—original draft: EC, TMcV. Writing—review & editing: all authors

Corresponding author

Correspondence to T. P. McVeigh.

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The authors have no conflicts of interest to declare.

Ethics approval

Institutional approval for use of the data was sought through the service evaluation that was approved (SE964, date 24/05/2020) by the Royal Marsden Institutional Review Board.

Informed consent

Because this was a retrospective study, written informed consent was not obtained from the subjects. At Royal Marsden Hospital, for retrospective clinical studies such as case reports and treatment effects, we confirm with patients the consent for comprehensive clinical studies. All participants in this study agree on its comprehensive research participation.

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Cojocaru, E., Gennatas, S., Thway, K. et al. Approach to screening for Familial Adenomatous Polyposis (FAP) in a cohort of 226 patients with Desmoid-type Fibromatosis (DF): experience of a specialist center in the UK. Familial Cancer (2021). https://doi.org/10.1007/s10689-021-00230-8

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Keywords

  • Desmoid fibromatosis
  • CTNNB1
  • Beta-catenin
  • Familial Adenomatous Polyposis (FAP)