Definition

Autosomal dominant, inherited familial colorectal cancer syndrome due to mutation in APC gene on chromosome 5q.
- ~75% is inherited; which means 25% arise without family history, as first mutation
Risk of colorectal cancer is nearly 100%
Gardner syndrome is a sub-type
- Polyps + desmoid/osteomas etc

Characterised by:

Hundreds of colorectal adenomatous polyps at young age
Duodenal adenomatous polyps
Multiple extraintestinal manifestations
- Ectoderm: epidermoid cyst, pilomatrixoma, CNS tumours, congenital hypertrophy of retinal pigment epithelium (CHRPE)
- Mesoderm: connective tissue – (desmoid tumour, excessive adhesions), bone – (osteoma, exostosis, sclerosis), dental – dentigerous cyst, odontoma, supernumerary teeth, unerupted teeth)
- Endoderm: adenomas and carcinomas of duodenum, stomach, small intestine, biliary tract, thyroid, adrenal cortex, fundic gland polyps, hepatoblastoma

Clinical/endoscopic – over 100 colorectal adenomas.
- Chromoendoscopy with dye spray, and random biopsies to look for microadenomas (hallmark of FAP and MAP, not in Lynch)
- Gastroscopy may show fundic gland polyps or duodenal adenomas
Genetic – mutation of APC gene (only 80% of polyps affected)
Family history. However, 20% will be new mutations with no family history.
Ddx: MAP (MUTYH-associated polyposis)

Affected family member tested first. Once mutation identified, at risk family offered simple blood test.
Genotype-phenotype correlation:
- Different levels of expression, due to different site of mutation in APC gene, along with modifier genes and environment

Colonoscopy - from age 10-12 (AFAP 18-20) until colectomy at which point the rectal cuff/J pouch requires annual flexible sigmoidoscopy
Gastroscopy (including side viewing scope) - from age 25 and then as per the Spigelman stage
Thyroid USS - age 18 then eery 2-5 years

Surgery

Should be done as early as possible. Depends on social and educational factors.
Options:
- Colectomy + ileorectal anastomosis (IRA)
  - Slightly better functional outcome
Restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis
- Benefit of no rectum
- Good option of high polyp burden in rectum
- Small cuff of rectal mucosa retained at anastomosis – small risk of cancer here
- Risk of infertility in women and sexual dysfunction in men
Total proctocolectomy and end ileostomy

Surveillance

Fundic gland polyps
Duodenal adenomas occur in nearly all patients with FAP, but malignant only in 5%

Total points	Spigelman stage	Recommended follow-up interval
0	0	5 years
1–4	I	5 years
5–6	II	3 years
7–8	III	1 year and consider endoscopic therapy
9–12	IV	Consider prophylactic duodenectomy

Treatment

Fibromatous lesions consisting of clonal proliferations of myofibroblasts
15% of FAP, mostly intraabdominal or abdominal wall, can be on extremities or trunk.
Histologically benign (lack nuclear atypia & features of malignancy), however can cause SBO, ureteric obstruction, intestinal ischaemia or perforation, which could be fatal.
Aetiology: multifactorial. Trauma e.g. operative, oestrogens, specific APC mutations
- FAP related due to inactivation of APC and subsequent accumulation of beta-catenin in cells.
- Sporadic desmoid usually mutation in gene for beta-catenin (uncommon for APC mutation).
Investigations: CT is best. MRI may be useful. USS to monitor ureters.

Treatment:

Observation usually preferred for asymptomatic, stable desmoids.
Surgical – excision (1st line for abdominal wall and extra-abdominal)
- High recurrence rates
- Avoided for intra-abdominal desmoids due to significant morbidity/mortality unless desmoid-related complications develop
Medical – NSAIDS, antioestrogens (tamoxifen), cytotoxic chemotherapy, non-cytotoxic approach – tyrosine kinase inhibitors (sorafenib, sunitinib)
Radiotherapy may be used.