Derm Dx: Jaw osteomas and family history of colon cancer

Gardner syndrome (GS) is an autosomal dominant syndrome characterized by the development of premalignant colonic polyps along with extraintestinal manifestations including epidermoid cysts, osteomas, lipomas, fibrosarcomas, fibromas, desmoid tumors and leiomyomas.   The coexistence of these many neoplasms may not be...

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Gardner syndrome (GS) is an autosomal dominant syndrome characterized by the development of premalignant colonic polyps along with extraintestinal manifestations including epidermoid cysts, osteomas, lipomas, fibrosarcomas, fibromas, desmoid tumors and leiomyomas.  

The coexistence of these many neoplasms may not be noticed until the surgical removal of an intestinal malignancy, at which time the presence of the syndrome may be suggested. Moreover, cutaneous and bony abnormalities frequently appear during childhood, before the onset of intestinal polyposis.

Osteomas are typically found on the membranous bones of the face and head, specifically the mandible and maxilla. However, they can be found elsewhere on the skull and on long bones. These neoplasms are painless. They may form large exostoses or may be only detectable by radiographic studies.

Dental anomalies are seen in a fraction of patients with GS. These anomalies include odontomas, supernumerary teeth, unerupted teeth and multiple caries.

Desmoid tumors are locally aggressive benign tumors. They are non-encapsulated, non-metastasizing and can occur spontaneously or at incision sights. Commonly developing after colectomy, intra-abdominal involvement of desmoid tumors may obstruct the small bowel or ureters, causing much morbidity. They can be invasive and may recur.

Epidermal inclusion cysts on GS patients usually occur on the face and scalp. Most have pilomatrical differentiation. They may be present at birth and will increase in size and number before stabilizing.

Additionally, fibromas may arise in the skin, subcutaneous tissues, mesentery or retroperitoneum. These have a predilection for the back and paraspinal region and may be a precursor to desmoid tumors.

One of the earliest signs of GS is congenital hypertrophy of the retinal pigment epithelium (CHRPE), which is present in two-thirds of patients at birth. Ophthalmologic examination easily detects CHRPE. Multiple and bilateral lesions of CHRPE serve as sensitive and specific signs of GS.

In addition to colon cancer, patients with GS have an increased risk for developing other neoplasms such as papillary carcinoma of the thyroid, hepatoblastoma (in children), pancreatic and biliary tract cancers, adrenal adenomas and carcinomas and various sarcomas.

GS is due to mutations in the adenomatous polyposis coli (APC) gene. The APC gene downregulates the Wnt/b-Catenin signaling pathway, which helps regulate cell proliferation and differentiation. It is inherited in an autosomal dominant fashion.

Muir-Torre syndrome (MTS), an autosomal dominant disorder, is also associated with colonic adenocarcinoma. MTS is also characterized by genitourinary carcinomas. Cutaneous manifestations of MTS include sebaceous neoplasms and multiple keratoacanthomas. It is caused by mutations in DNA mismatch repair genes (e.g. MSH2, MLH1, MSH6).

Nevoid basal cell carcinoma syndrome (NBCC), also known as Gorlin syndrome, is an autosomal dominant disorder characterized by multiple basal cell carcinomas, mandibular odontogenic keratocysts, palmoplantar pits, calcification of the falx cerebri and skeletal anomalies (e.g. bifid ribs, fusion of vertebral bodies). Patients may also develop meningiomas, ovarian or cardiac fibromas and medulloblastomas. Mutations in the PTCH gene cause NBCC.

Brooke-Spiegler syndrome, another autosomal dominant disorder, is characterized by multiple spiradenomas, cylindromas, and trichoblastomas/trichoepitheliomas, all of which are benign skin adnexal neoplasms. Mutations in the CYLD gene cause this syndrome.

Diagnosis

GS may first present in adults as gastrointestinal bleeding due to adenomatous polyps. Anemia, abdominal pain, diarrhea, constipation or weight loss may accompany bleeding.

Polyps are commonly found in the colon but may be found in the small intestine and stomach. Half of GS patients have colonic polyps by age 20 years. Progression to colorectal cancer usually develops before age 40 years.

As described above, early screening for multiple and bilateral lesions of congenital hypertrophy of the retinal pigment epithelium (CHRPE) is sensitive and specific for GS.

Treatment

Total colectomy, usually between ages 15 and 25 years, is advised due to the very high probability of progression to colorectal carcinomas once polyps are clinically evident. 

Prior to this, children with GS are advised to have a yearly monitoring sigmoidoscopy beginning at 10 to 12 years of age. If polyps are detected, patients are advised to have colonoscopies annually until a total colectomy is performed. 

Periodic upper gastrointestinal endoscopies can screen for pancreatic-biliary tract malignancies, and both barium studies and capsule endoscopies can screen for malignancies in the small bowel.

As hepatoblastomas typically occur early in childhood, some patients may opt for annual abdominal ultrasounds or measurement of serum a-fetoprotein levels. Family members should be evaluated for GS signs and genetic testing is very important.

Although there is a risk for recurrence, epidermal cysts and desmoid tumors can be treated with surgical excision. Radiotherapy, hormonal therapy or chemotherapy are other treatment options for desmoid tumors. However, osteomas are not easily surgically excised.

Michael Montuno, BS, is a senior medical student at University of Florida College of Medicine.

Adam Rees, MD, is a graduate of the University of California Los Angeles School of Medicine and a resident in the Department of Dermatology at Baylor College of Medicine also in Houston.