Familial adenomatous polyposis-associated desmoid disease: comprehensive review.
Familial adenomatous polyposis (FAP)-associated desmoid disease is a rare but important manifestation of FAP and remains a major cause of morbidity and mortality. In contrast to sporadic desmoids, which most commonly occur in the abdominal wall or extra-abdominal sites, approximately 70% of FAP-associated desmoids arise intra-abdominally, usually within the small bowel mesentery. These lesions can cause bowel and ureteric obstruction, sepsis, intestinal failure, and death. This review summarizes current evidence regarding the pathogenesis, risk factors, diagnosis, surveillance, and management of FAP-associated desmoid disease, and identifies key evidence gaps.
A literature search was performed in accordance with PRISMA methodology using Medline, Embase, PROSPERO, Cochrane, Campbell, and Joanna Briggs Institute databases. Original research studies, reviews, and guidelines relating to desmoid disease, FAP-associated desmoid disease, and FAP published up to August 2025 were eligible. Data were extracted and synthesized narratively by topic.
Aberrant Wnt/β-catenin signalling resulting from a germline APC pathogenic variant and a somatic second hit underpin the development of FAP-associated desmoid disease. Established risk factors include a distal APC pathogenic variant, positive family history, and previous abdominal surgery. Diagnosis in patients with established FAP is usually clinicoradiological, and routine biopsy is generally unnecessary, except in select circumstances. Active surveillance is now recommended as first-line management for most patients because many lesions remain stable or regress spontaneously. Surgery is primarily reserved for complications, particularly in small bowel mesenteric disease, owing to substantial operative morbidity and a lack of demonstrated survival benefit from complete resection. Systemic therapy is indicated for progressive or symptomatic disease. Tyrosine kinase inhibitors and the γ-secretase inhibitor nirogacestat have demonstrated efficacy in randomized trials, although patients with FAP-associated disease comprise only a small proportion of enrolled patients. Evidence supporting the use of non-steroidal anti-inflammatory drugs and anti-oestrogens remains limited.
Important evidence gaps remain regarding optimal imaging strategies, predictors of aggressive disease, clinically meaningful trial endpoints, and FAP-specific treatment algorithms. Dedicated studies in genetically defined FAP cohorts are required to improve risk stratification and management.
A literature search was performed in accordance with PRISMA methodology using Medline, Embase, PROSPERO, Cochrane, Campbell, and Joanna Briggs Institute databases. Original research studies, reviews, and guidelines relating to desmoid disease, FAP-associated desmoid disease, and FAP published up to August 2025 were eligible. Data were extracted and synthesized narratively by topic.
Aberrant Wnt/β-catenin signalling resulting from a germline APC pathogenic variant and a somatic second hit underpin the development of FAP-associated desmoid disease. Established risk factors include a distal APC pathogenic variant, positive family history, and previous abdominal surgery. Diagnosis in patients with established FAP is usually clinicoradiological, and routine biopsy is generally unnecessary, except in select circumstances. Active surveillance is now recommended as first-line management for most patients because many lesions remain stable or regress spontaneously. Surgery is primarily reserved for complications, particularly in small bowel mesenteric disease, owing to substantial operative morbidity and a lack of demonstrated survival benefit from complete resection. Systemic therapy is indicated for progressive or symptomatic disease. Tyrosine kinase inhibitors and the γ-secretase inhibitor nirogacestat have demonstrated efficacy in randomized trials, although patients with FAP-associated disease comprise only a small proportion of enrolled patients. Evidence supporting the use of non-steroidal anti-inflammatory drugs and anti-oestrogens remains limited.
Important evidence gaps remain regarding optimal imaging strategies, predictors of aggressive disease, clinically meaningful trial endpoints, and FAP-specific treatment algorithms. Dedicated studies in genetically defined FAP cohorts are required to improve risk stratification and management.