Hereditary Desmoid Disease (HDD)

Variant of familial adenomatous polyposis (FAP) characterized by benign growths of fibrous tissue (hyperproliferation of epithelial mesenchymal tissues) that form either spontaneously or after surgery. These tumors can become large and aggressive, compressing abdominal organs.

Aggressive Fibromatosis; Familial Infiltrative Fibromatosis (FIF).

Up to 13% of patients with FAP have associated desmoid disease (FAP affects 1:8000 individuals). The incidence of HDD occurring alone remains to be determined.

Autosomal dominant with 100% penetrance. The majority of mutations affect the adenomatous polyposis coli (APC) gene (a tumor suppressor) on chromosome 5 distal to the beta-catenin-binding domain (5q15-22). New mutations account for 20 to 30% of families affected with this condition (direct mutation testing is required to establish diagnosis).

The APC gene is a tumor suppressor. The APC protein seems to act like a cell-signaling protein. Mutations in the APC gene are responsible for generating slowly growing fibrous masses consisting of bundles of spindle cells with variable amounts of collagen. Hereditary desmoid disease occurs with or without colonic polyposis and consists of infiltrative fibromatosis of connective tissues invading multiple parts of the body. Desmoid tumors may also present as extracolonic manifestations in some patients with FAP.

Based on clinical aspect, familial history, genetic studies, and tissue biopsy.

HDD patients develop multifocal fibromatosis: arms, breast, paraspinal muscles, occiput, lower ribs, abdominal wall, and mesentery. Desmoid tumors may proliferate in various areas: arms, ribs, breasts, occiput, mesentery, abdominal wall, and paraspinal muscles. Epidermal cysts and osteomata of the skull and mandible, as well as scoliosis caused by desmoid disease, have been described. Desmoid tumors are not considered malignant per se, but their local aggressiveness and recurrence after surgical removal are frequent. Although some families with HDD are predisposed to colonic carcinoma, colonic polyposis is rare. Up to 90% of FAP patients have congenital hypertrophy of the retinal pigment epithelium (<40% of control patients).

Inquire about associated familial colonic polyposis (anemia). Inquire about the location of the lesions to be excised (some locally invasive desmoid tumors may be close to major blood vessels). Obtain hemoglobin level and blood cell count.

Careful positioning and padding are required to avoid trauma to superficial lesions. Although very rare, mandibular osteomata have not been known to make tracheal intubation difficult. Should mandibular lesions become such that they interfere with laryngoscopy, fiberoptic intubation should be considered by either oral or nasal route. Depending on the location and degree of invasion of the tumor, significant blood loss is possible.

No known specific implications with this condition.

Other mutations within the APC gene, including the following:

Familial Adenomatous Polyposis (FAP): Most severe autosomal dominant variant of mutation in the APC gene (tumor suppressor gene). FAP is characterized clinically by the development of a considerable number of adenomatous polyps within the colon that become cancerous if they are not treated.

Gardner Syndrome: Another autosomal dominant variant of FAP characterized by congenital hypertrophy of the retinal pigment epithelium, gastrointestinal polyps, multiple osteomas, and skin and soft tissue tumors.

Peutz-Jeghers Syndrome: Autosomal dominant inherited disorder characterized by intestinal hamartomatous polyps in association with mucocutaneous melanocytic macules. In most cases, it is caused by a germline mutation of the STK11 (serine threonine kinase 11) gene (gene map locus is 19p13.3).

Turcot Syndrome: Autosomal recessive syndrome characterized by the association of a primary brain tumor and multiple colorectal adenomas (could be a variant of Gardner syndrome).