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Surgical Pathology Criteria

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Familial Adenomatous Polyposis


  • Autosomal dominant syndrome characterized by germ line mutation of APC resulting in intestinal adenomatous polyposis and a very high incidence of colorectal adenocarcinoma

Alternate/Historical Names

  • Familial polyposis coli
  • Gardner syndrome (if extra-GI lesions present)
  • Turcot syndrome (if CNS neoplasms present; some cases are associated with mismatch repair deficiency instead)

Covered Separately

Diagnostic Criteria

  • Current definition of familial adenomatous polyposis (FAP) requires evidence of any one of below
    • Germline mutation in APC gene
      • Identifiable in about 60-80% of cases
      • APC mutations also seen in many sporadic carcinomas
        • Must be germline for diagnosis of FAP
    • Or, ≥100 colorectal adenomatous polyps (classical definition)
    • Or, any colorectal adenomas under age 30 in a patient with a family history of FAP
    • Or, intra-abdominal desmoid fibromatosis, osteoma of the mandible, or multiple epidermoid cysts in a patient with a family history of FAP
  • Autosomal dominant
    • 100% penetrance
    • 25-50% of new cases are sporadic (new) mutations, lacking family history
  • Classic syndrome displays ≥100 adenomatous colorectal polyps
    • Frequently thousands of polyps
    • Tubular adenomas identical to sporadic adenomas
    • First appear at age 10-20 years
  • See Attenuated FAP below for variant with fewer polyps and later carcinoma
  • Nearly universal development of colorectal adenocarcinoma
    • Most carcinomas left sided, indistinguishable from sporadic carcinomas
    • Mean age of development/detection of carcinoma 40 years
      • 1-6% risk by age 20-25 years
  • Extra-colorectal polyps and cancers are important primarily for surveillance purposes
    • Duodenal adenomas are very common
      • 97% lifetime risk
        • 50% incidence of multiple large polyps by 70 years
        • Typically present about 10 years later than colorectal adenomas
      • Usually periampullary
      • Frequently multiple
      • May be tubular, tubulovillous or villous
      • Frequent recurrence after resection
      • High grade dysplasia may develop
        • Considered to be a precursor of invasive carcinoma
      • 3-4% lifetime risk of adenocarcinoma
        • This is the most common cause of cancer related death in FAP (if prophylactic proctocolectomy performed)
        • Markedly lower risk of malignant transformation than in the colorectum
    • Fundic gland polyps are frequent in proximal stomach
      • Focal dysplasia may be seen, but carcinoma is rare
    • Gastric adenomas (intestinal, foveolar, pyloric, oxyntic) have been described (Wood 2014)
    • Desmoid fibromatosis 9-15% prevalence
      • Mesenteric and rarely abdominal wall
        • Very rarely other sites
      • 80-95% of cases follow surgery
      • Intestinal complications are the most common cause of death due to FAP related disorders (if prophylactic proctocolectomy performed)
      • Gardner syndrome
        • Familial adenomatous polyposis
        • Osteomas, especially of mandible
        • Mesenteric, and rarely abdominal, fibromatosis
        • Cutaneous epidermoid cysts
    • Thyroid carcinoma found in 1-12%
      • Distinctive cribriform-morular variant is a mixture of three patterns
        • Papillary
          • Most nuclei hyperchromatic but some have grooves or are cleared
        • Cribriform
        • Solid with short spindled cells in short fascicles and whirling
          • Small morule-like nodules may be seen
      • Frequently multiple
      • Usually not aggressive
      • Same histologic pattern may rarely be seen in carcinomas unrelated to FAP
    • Turcot syndrome: CNS neoplasms associated with hereditary colorectal carcinoma
      • Includes two distinct syndromes
        • Familial adenomatous polyposis with various brain tumors, usually medulloblastoma
        • HNPCC with glioblastoma
    • Hepatoblastoma
      • Incidence ≤2 %
    • Rare pancreatic, biliary and endocrine neoplasms have been reported
  • A variety of characteristic non-gastrointestinal lesions may suggest the diagnosis of FAP, especially if occurring <20 years of age
    • Osteoma of mandible
    • Exostoses of long bones
    • Multiple cutaneous epidermoid cysts
    • Soft tissue Gardner-associated fibroma
    • Dental abnormalities
    • Congenital hypertrophy of retinal pigmented epithelium
  • Attenuated FAP may be especially difficult to recognize
    • Adenomas fewer and later
      • Usually <100 adenomas
        • May have only a few
        • May have >100 if first diagnosed >45 years of age
      • First appear usually in late childhood
      • Adenomas usually ≤1 cm until adulthood
    • Adenomas and carcinomas 60-75% right sided
    • Mean age of carcinoma 55 years
    • Fundic gland polyps may be frequent in the stomach
      • Usually lack other extra-colonic manifestations of classic FAP
    • 90% lack detectable APC mutations
    • 18-30% of APC mutation negative attenuated FAP may instead be due to MUTYH mutation

    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting/last update : 1/31/10, 3/26/14

Supplemental studies


  • No practical applications

Genetic testing

  • Principal test is in vitro protein synthesis
    • Detects truncated form of APC protein
      • Abnormal in 80% of FAP cases
      • Negative cases may represent mutations affecting function but not length of the protein
      • If index case is found to be abnormal, this test is virtually 100% sensitive for detecting carriers of the mutation within the same kindred

Differential Diagnosis

HNPCC / Lynch Syndrome Familial Adenomatous Polyposis
May have family history of characteristic associated neoplasms Family history of early onset of colorectal polyps
Duodenal adenoma and carcinoma rare Personal or family history of duodenal adenoma common, carcinoma may occur
Adenomas if present are only moderately increased ≥100 adenomas in classic cases
Genetic and immunohistologic evidence of mismatch repair deficiency No evidence of mismatch repair deficiency
APC mutation not present APC mutation detectable in 80%
Attenuated FAP may be very difficult to distinguish from HNPCC as it has fewer adenomas and later presentation and frequent right sided carcinoma


MUTYH Associated Polyposis Attenuated Familial Adenomatous Polyposis
Germline mutation detected in MUTYH gene No MUTYH mutation
No germline APC mutation May have detectable APC mutation (10% of cases)
Autosomal recessive Autosomal dominant
18-30% of APC mutation negative attenuated FAP may instead be due to MUTYH mutation


Juvenile Polyposis Familial Adenomatous Polyposis
Dysplasia, if present is focal Multiple adenomatous polyps, all with cytologic dysplasia
Mucous retention cysts prominent Lacks mucous retention cysts


Hereditary Mixed Polyposis Familial Adenomatous Polyposis
Mixtures of adenomatous and juvenile type polyps Colorectal polyps are all adenomatous
Polyps may have mixed adenomatous and juvenile features Colorectal polyps lack juvenile features
No extra-colorectal associated lesions May be associated with duodenal adenomas, gastric fundic gland polyps, desmoid tumors and other extra-gi disorders
No APC mutation Mutation in APC gene


  • Genetic counseling should be offered before genetic testing is performed
    • Autosomal dominant with 100% penetrance
      • Attenuated FAP may be <100%
    • 25% of cases have no family history and represent de novo germline mutations
  • Recognition of associated lesions, especially in children should lead to consideration of FAP
  • Colorectal polyps appear generally between 10-20 years of age
  • Mean age of carcinoma is 40 years
  • Mean age 55 years in attenuated FAP
  • Colectomy with constant surveillance of rectum or complete proctocolectomy removes the threat of colorectal carcinoma
    • Extra-colorectal neoplasms may still occur
  • Screening
    • If APC mutation is identified in index case, screen positive family members starting at age 10
    • If mutation not identified in the index case, screen all family members from age 10 through 40
    • Attenuated FAP families should continue screening past 40
  • All patients diagnosed with FAP require upper GI screening


  • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010
  • Hamilton SR, Liu B, Parsons RE, Papadopoulos N, Jen J, Powell SM, Krush AJ, Berk T, Cohen Z, Tetu B, et al. The molecular basis of Turcot's syndrome. N Engl J Med. 1995 Mar 30;332(13):839-47.
  • Desai TK, Barkel D. Syndromic colon cancer: lynch syndrome and familial adenomatous polyposis. Gastroenterol Clin North Am. 2008 Mar;37(1):47-72.
  • Gatalica Z, Torlakovic E. Pathology of the hereditary colorectal carcinoma. Fam Cancer. 2008;7(1):15-26.
  • Galiatsatos P, Foulkes WD. Familial adenomatous polyposis. Am J Gastroenterol. 2006 Feb;101(2):385-98.
  • Harach HR, Williams GT, Williams ED. Familial adenomatous polyposis associated thyroid carcinoma: a distinct type of follicular cell neoplasm. Histopathology. 1994 Dec;25(6):549-61.
  • Dotto J, Nosé V. Familial thyroid carcinoma: a diagnostic algorithm. Adv Anat Pathol. 2008 Nov;15(6):332-49.
  • Sturt NJ, Gallagher MC, Bassett P, Philp CR, Neale KF, Tomlinson IP, Silver AR, Phillips RK. Evidence for genetic predisposition to desmoid tumours in familial adenomatous polyposis independent of the germline APC mutation. Gut. 2004 Dec;53(12):1832-6.
  • Spigelman AD, Williams CB, Talbot IC, Domizio P, Phillips RK. Upper gastrointestinal cancer in patients with familial adenomatous polyposis. Lancet. 1989 Sep 30;2(8666):783-5.
  • Heiskanen I, Kellokumpu I, Järvinen H. Management of duodenal adenomas in 98 patients with familial adenomatous polyposis. Endoscopy. 1999 Aug;31(6):412-6.
  • Jass JR. Colorectal polyposes: from phenotype to diagnosis. Pathol Res Pract. 2008;204(7):431-47.
  • Will OC, Man RF, Phillips RK, Tomlinson IP, Clark SK. Familial adenomatous polyposis and the small bowel: a loco-regional review and current management strategies. Pathol Res Pract. 2008;204(7):449-58.
  • Goodman AJ, Dundas SA, Scholefield JH, Johnson BF. Gastric carcinoma and familial adenomatous polyposis (FAP). Int J Colorectal Dis. 1988 Nov;3(4):201-3.
  • Wood LD, Salaria SN, Cruise MW, Giardiello FM, Montgomery EA. Upper GI Tract Lesions in Familial Adenomatous Polyposis (FAP): Enrichment of Pyloric Gland Adenomas and Other Gastric and Duodenal Neoplasms. Am J Surg Pathol. 2014 Mar;38(3):389-93. PubMed PMID: 24525509.
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