What is the management approach for hereditary mixed polyposis syndrome (HMPS)?

Management of Hereditary Mixed Polyposis Syndrome

Patients with hereditary mixed polyposis syndrome require colonoscopic surveillance every 1-2 years starting at age 20 years, with all polyps >5 mm removed endoscopically, and surgical resection considered when polyp burden becomes unmanageable (typically >20 adenomas that cannot be effectively eliminated by colonoscopy). 1, 2

Diagnostic Confirmation

Before confirming HMPS, exclude other polyposis syndromes through genetic panel testing, particularly if: 1

• Patient is under 50 years of age
• Multiple affected family members are present
• Dysplasia is identified within any polyps

The diagnosis is phenotype-driven, as causative genes (GREM1 duplications) are rare and primarily described in Ashkenazi Jewish populations. 2, 3 Genetic testing should specifically evaluate for the GREM1 duplication at 15q13-14 in appropriate populations. 2, 3

Endoscopic Surveillance Protocol

Surveillance colonoscopy should begin at age 20 years and continue every 1-2 years for life. 2 This aggressive approach is warranted because:

• Polyps can develop in adolescence 3
• Rapid progression to advanced adenomas occurs 3
• Mean age of polyp detection is 28 years in screened populations 2

Technical Requirements

High-definition white light colonoscopy performed by endoscopists meeting key performance indicators for cecal intubation and adenoma detection rates is mandatory. 1 Chromoendoscopy should be considered for determining the multiple polyp phenotype. 1

All polyps >5 mm must be removed endoscopically when feasible. 1 The goal is complete clearance of all lesions >5 mm at each surveillance examination. 1

Chemoprevention Considerations

COX-2 inhibitors should be considered as pharmacologic adjunct to endoscopic surveillance for reducing polyp burden. 1 This recommendation is supported by research demonstrating that HMPS polyps express significantly elevated COX-2 levels (mean total score 11.8±4.6) compared to sporadic juvenile polyps (3.6±2.2), with COX-2 expression positively associated with degree of dysplasia. 4

Cardiovascular contraindications must be assessed before initiating COX-2 inhibitor therapy. 1

Surgical Intervention Criteria

Surgical resection is indicated when: 1

• Polyp burden becomes unmanageable endoscopically
• Typically defined as >20 adenomas that cannot be effectively eliminated by colonoscopy with polypectomy
• Dense polyposis develops despite repeated polypectomy 2

Colectomy with ileorectal anastomosis is the preferred surgical approach when rectal disease remains manageable. 1 After colectomy with ileorectal anastomosis, the retained rectum requires annual surveillance for life due to 12-29% cumulative cancer risk. 5

Family Screening Requirements

All first-degree relatives should undergo index colonoscopic screening at age 40 years or 10 years before the diagnosis of the index case, whichever comes first. 1 This is critical because HMPS demonstrates high penetrance with autosomal dominant inheritance. 2, 6

First-degree relatives require surveillance colonoscopy every 5 years unless polyp burden indicates earlier examination according to post-polypectomy surveillance guidelines. 1

Multidisciplinary Management

Patients must be managed in specialized tertiary centers with multidisciplinary teams including: 1

• Gastroenterologists
• Colorectal surgeons
• Clinical geneticists
• Genetic counselors

This ensures standardized surveillance protocols and enhances early cancer detection. 1

Lifestyle Modifications

Patients should be strongly counseled regarding: 7, 1

• Smoking cessation
• Maintaining normal body mass index
• Moderating consumption of red and processed meat
• Regular exercise

Important Clinical Pitfalls

Be aware that some HMPS families may meet diagnostic criteria for Lynch syndrome based on family history alone, leading to potential misdiagnosis. 3 The mixed histology of polyps (juvenile, hyperplastic, serrated adenomas, and tubular adenomas) is the key distinguishing feature. 4, 2

Extracolonic tumors have been reported in HMPS families, though the colorectal cancer pathway appears to progress through juvenile and hyperplastic polyps rather than the traditional adenoma-carcinoma sequence. 2, 3