Interpretation of Test Results

Approximately 80% of Turcot syndrome families with polyposis will have a detectable APC mutation, similar to that of FAP. Turcot syndrome families associated with tumors with replication errors or HNPCC have a lower mutation detection rate in the DNA mismatch repair genes.

PEUTZ-JEGHERS SYNDROME

Peutz-Jeghers syndrome is a rare autosomal dominant disorder characterized by mucocutaneous melanin pigmentation, gastrointestinal hamartomatous polyposis, and benign and malignant tumors of the gastrointestinal tract, breast, ovary, cervix, and testis. The incidence of Peutz-Jeghers syndrome is unknown, but estimates range from 1 in 8,300 to 200,000 live births.16,17 An estimated 25% of Peutz-Jeghers cases are not familial.

Hamartomas with a smooth muscle core are the pathognomonic feature of Peutz-Jeghers (Figure 18-2a and b). Peutz-Jeghers polyps exhibit a central branching smooth muscle cell structure that extends to the lamina

Figure 18-2. (a) The harmatomatous polyp of a Peutz-Jeghers patient is distinguished by its smooth branching muscle core and normal-appearing epithelium that covers its surface. (b) Magnified view of a harmatomatous Peutz-Jegher polyp. (Courtesy of Dr. Catherine Sewell.)

propria and is covered with epithelial cells of normal appearance.17 Polyposis usually becomes symptomatic early in adolescence, though intestinal obstruction has been reported in infancy.16 Hamartomatous polyps may be present throughout the entire gastrointestinal tract, but are commonly present in the small intestine (90%) or the colon and rectum (33%). Polyps may be of mixed histologic types (hyperplastic, adenomatous) but are mostly hamartomatous and may number from one to dozens.

Melanin pigmentation may develop in Peutz-Jeghers patients under the age of 5 years as dark blue to dark brown macules around the mouth, eyes, nostrils, perianal area, buccal mucosa, hands, feet, or axillary areas. Pigmentation may vary greatly between affected individuals of a family and between families. If pigmentation does develop, it may fade or disappear with age. The presence of pigmentation is helpful in the diagnosis of Peutz-Jeghers but may not be used as a sole clinical indication, as similar pigmentation may be found in up to 15% of the general population.17

The clinical presentation of Peutz-Jeghers is variable. The most common presentations of Peutz-Jeghers are small bowel intussusception, colon obstruction, and gastrointestinal bleeding. Severe digestive obstruction may be identified in affected individuals throughout life, but the average age of onset is 29 years.18 Affected individuals also may exhibit intermittent abdominal pain or rectal prolapse. For an individual to be clinically diagnosed with Peutz-Jeghers, one of the following criteria must be met: (a) three or more histologically confirmed Peutz-Jeghers polyps, (b) any number of Peutz-Jeghers polyps with a family history of Peutz-Jeghers, (c) characteristic mucocu-taneous pigmentation with a family history of Peutz-Jeghers, or (d) any number of Peutz-Jeghers polyps and characteristic mucocutaneous pigmentation.15

The estimated incidence of cancer among Peutz-Jeghers patients is 18-fold higher than in the general population.19 No correlation has been found with the incidence of cancer and the severity of polyposis or the presence of pigmentation.17 Cancer is most frequently identified in the colon (40%), small intestine (13%), stomach (29%), pancreas (36%), lung (15%), breast (54%), ovary (21%), and uterus (9%).19 A rare form of cervical cancer that is seen more frequently in women with Peutz-Jeghers is adenoma malignum. This is an aggressive form of cervical cancer that originates from glandular cells of the cervix.16

Benign ovarian sex-cord tumors with annular tubules and estrogen-producing ovarian tumors resulting in precocious puberty are found more commonly in females affected with Peutz-Jeghers.16 Two cases of Sertoli cell tumor of the ovary were reported in sisters with the syndrome. In young males with Peutz-Jeghers, estrogen-producing testicular Sertoli cell tumors can occur and may lead to precocious puberty and gynecomastia.

Figure 18-2. (a) The harmatomatous polyp of a Peutz-Jeghers patient is distinguished by its smooth branching muscle core and normal-appearing epithelium that covers its surface. (b) Magnified view of a harmatomatous Peutz-Jegher polyp. (Courtesy of Dr. Catherine Sewell.)

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