Dermatologic Manifestations of Gardner Syndrome

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Background

Gardner syndrome, a variant of familial adenomatous polyposis (FAP),[1] is an autosomal dominant disease characterized by GI polyps, multiple osteomas, and skin and soft tissue tumors. Cutaneous findings[2] of Gardner syndrome include epidermoid cysts, desmoid tumors, and other benign tumors. Polyps have a 100% risk of undergoing malignant transformation (see the figure below); consequently, early identification of Gardner syndrome is critical.[3, 4]



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Adenoma-to-carcinoma sequence on a cellular level.

Pathophysiology

Gardner syndrome is genetically linked to band 5q21, the adenomatous polyposis coli locus.[5] FAP and Gardner syndrome are believed to be variants of the same condition. The wider spectrum of abnormalities found in Gardner syndrome may represent variable penetrance of a common genetic mutation.

Etiology

The cause of Gardner syndrome is genetic, with autosomal dominant inheritance.

Epidemiology

Frequency

In the United States, one person per million population is diagnosed with Gardner syndrome. The incidence of FAP is 1 case per 8000 people. The most common cutaneous finding in patients with Gardner syndrome is epidermoid cysts (50-65%).

Age

Although colonic polyps begin to form in puberty, the average age at Gardner syndrome diagnosis is 22 years. Osteoma formation precedes polyposis. Usually, progression to malignancy is observed in patients aged 30-50 years. The average age by which malignancy is diagnosed is 39.2 years.

Prognosis

With adequate screening, long-term control of colorectal tumors is possible, with desmoid tumors determining the survival and quality of life for many patients.[6]  Unless surgical transection is performed, GI polyps may progress to malignancy in almost 100% of Gardner syndrome patients (rates vary from 58-100% in studies). A genetic variant with an aggressive early childhood phenotype has been described.[7]

Patient Education

For patient education resources, see the Cancer and Tumors Center, as well as Colon Cancer.

History

Many skin findings of Gardner syndrome are evident on full body examination; however, the patient's history of the age at onset and whether lesions are present in family members is important.

Cysts in Gardner syndrome patients are usually asymptomatic, but they may be pruritic and/or inflamed.

More than half the patients with Gardner syndrome have dental anomalies.[8] Previously undiagnosed Gardner syndrome may be detected when the patient is evaluated for multiple impacted and unerupted teeth. Dentists may play a pivotal role in detecting craniomaxillofacial osteomas, a major criterion for Gardner syndrome.[9]

Physical Examination

A full body skin examination for skin tumors and epidermal inclusion cysts is necessary in Gardner syndrome.

Several factors differentiate cutaneous cysts associated with Gardner syndrome from ordinary cysts. Epidermoid cysts of Gardner syndrome occur at an earlier age (around puberty) than ordinary cysts and in less common locations, such as the face, the scalp, and the extremities. Gardner syndrome cysts tend to be multiple and are present in the multiple form in 50-65% of patients. Similar to ordinary epidermal inclusion cysts, cysts in Gardner syndrome are usually asymptomatic; however, they may be pruritic and/or inflamed, and they may rupture.

Other skin signs in Gardner syndrome include the following:

Noncutaneous features of Gardner syndrome include the following:

Other associated neoplasms in Gardner syndrome include the following:

Complications

In Gardner syndrome, polyps have a 100% risk of undergoing malignant transformation; therefore, surgical transection is indicated.

Females are at higher risk for thyroid carcinoma than males. Other neoplasms possible with Gardner syndrome include periampullary carcinoma, CNS tumors, osteosarcoma, chondrosarcoma, hepatoblastoma, and liposarcoma.

Desmoid tumors are a significant cause of the morbidity and mortality in those with Gardner syndrome; surgical procedures to excise them are complex.[11]

Laboratory Studies

Thyroid screening by physical examination and ultrasonography is recommended in Gardner syndrome. Chromosome studies from peripheral blood lymphocytes and allele-specific expression assay can be performed. Screen all first-degree relatives of patients with Gardner syndrome or FAP.

Imaging Studies

Imaging studies are essential for screening patients and family members who are affected. Panoramic radiography of the mandible can demonstrate subtle opacities at an early age. Long bone radiographs may demonstrate osteomas or hyperostosis. Ultrasonography is performed to screen for thyroid tumors. Van Epps et al reported seeing epidermal inclusion cysts on a CT scan from a patient with Gardner syndrome.[23]

Procedures

Perform an ophthalmologic examination at an early age to detect pigmented lesions of the fundus.

Fecal occult blood, sigmoidoscopy/colonoscopy, and upper GI endoscopy are required at least every 1-2 years until the patient reaches age 50 years.

Histologic Findings

Pathologic findings of the epidermoid cysts of Gardner syndrome are similar to findings in non–Gardner syndrome cysts; however, many have pilomatricomalike changes.[21] In 1 study, 63% of cysts examined from 7 patients with Gardner syndrome demonstrated 1 or more matricoma features, such as columns of shadow cells, calcification, and basophilic matrixlike cells in the cyst lining.

The Gardner fibroma, a soft tissue tumor of children and young adults, displays a bland hypocellular proliferation of haphazardly arranged coarse collagen fibers with a bland hypocellular proliferation of inconspicuous spindle cells, small blood vessels, and a sparse mast cell infiltrate. Immunohistochemically, many show nuclear reactivity for beta-catenin and most, if not all, have nuclear reactivity for both cyclin-D1 and C-myc. These fibromas may serve as an indicator for familial Gardner syndrome or similar disorder.[24, 25]

Medical Care

Treatment of the cutaneous manifestations of Gardner syndrome depends on the symptomatic or cosmetic nature and the location of the cysts. Treatment is similar to that used for ordinary cysts and involves excision[26] or use of intralesional steroids if the cysts are inflamed.

Antiestrogens and anthracycline-containing regimens may have a favorable radiological response rate against desmoid tumors and may be a viable option in some patients.[27]

Surgical Care

Colectomy[28] is recommended for Gardner syndrome patients if 30 or more polyps are detected on colonoscopy or if biopsy results reveal dysplasia or malignant degeneration. Preserving the rectum results in a 25-59% chance of rectal carcinoma occurring in Gardner syndrome patients; therefore, rectal mucosal resection is recommended. Total gastroduodenectomy with pancreatic preservation may be desirable in some settings.[29]

Generally, cutaneous findings do not require treatment. Osteomas may require excision if they are severely deforming or if they interfere with function.

Also see the General Surgery article Gardner Syndrome.

Author

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Pathology, Professor of Pediatrics, Professor of Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Specialty Editors

Michael J Wells, MD, FAAD, Dermatologic/Mohs Surgeon, The Surgery Center at Plano Dermatology

Disclosure: Nothing to disclose.

Warren R Heymann, MD, Head, Division of Dermatology, Professor, Department of Internal Medicine, Rutgers New Jersey Medical School

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD, Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD.

Additional Contributors

Sungnack Lee, MD, Vice President of Medical Affairs, Professor, Department of Dermatology, Ajou University School of Medicine, Korea

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors, Karen Allen, MD, and Raul Del Rosario, MD, to the development and writing of this article.

References

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Adenoma-to-carcinoma sequence on a cellular level.

Adenoma-to-carcinoma sequence on a cellular level.