|PART 1:||SMALL INTESTINE, JEJUNUM, JEJUNAL INTUSSUSCEPTION RESECTION:
||PART 2:||POLYP, ILEUM, POLYPECTOMY : HAMARTOMATOUS POLYP (3.5 CM.)
||PART 3:||APPENDIX, APPENDECTOMY: APPENDIX WITH NO SPECIFIC PATHOLOGICAL CHANGES.|
Peutz-Jeghers Syndrome (PJS) is an autosomal dominant heritable polyposis syndrome characterized by a triad of findings, including multiple large hamartomatous polyps of the gastrointestinal tract, mucocutaneous melanocytic macules, and an increased incidence of neoplastic disease, both within and outside the gastrointestinal tract.
In 1998, the PJS gene was localized to chromosome 19p13.3 by linkage analysis performed by Jenne, et al. Recently, the PJS gene at this locus was identified by Mehenni, et al, as LKB1, a ubiquitously-expressed serine-threonine kinase. The latter research group identified more than seven novel mutations in the LKB1 gene that caused loss of kinase function. It is likely that this kinase defect underlies the increased incidence of benign and malignant neoplasms seen in PJS patients.
Hamartomatous polyps of PJS range from 0.3 to 6 centimeters in size, and usually number less than 100. They are frequently found most commonly in the small intestine, and less commonly in the stomach and large intestine.
PJS polyps have a classical histological appearance. The muscularis mucosa shows an arborization (or angular networking) throughout the body of the polyp, with normal bowel mucosa resting upon and between the muscularis mucosal branches. Frequently one sees mucosal glands and mucin completely surrounded by interlocking muscularis mucosal branches. This "pseudo-invasion" may give the unwary the false impression of muscularis invasion by a well-differentiated adenocarcinoma; the absence of cellular atypia, however, should allow exclusion of the latter diagnosis.
PJS polyps begin in the 1st decade of life, and tend to grow slowly, commonly causing intestinal obstruction during the 2nd or 3rd decade of life by providing a lead point for a bowel intussusception. Patients may alternatively present with gastrointestinal bleeding, or prolapse of a rectal polyp. In this case, the patient had a unusual presentation of a simultaneous double-intussusception of the small bowel, each with the classic finding of a large polyp as the intussusception nidus. Histology confirmed these polyps as classic PJS hamartomatous polyps.
Mucocutaneous melanocytic spots:
The brown to black, freckle-like hyperpigmented macules of PJS are commonly found on the buccal mucosa, nose, lips, and skin of the perioral and perianal regions. Less commonly they are seen on the palms of the hands and soles of the feet. Histologically, these macules demonstrate an excess of melanocytes.
Although the presence of mucocutaneous melanocytic macules is considered an important diagnostic criterion for PJS, a number of studies suggest that they are unreliable indicators, being present in only 80-90% of patients (Brigg, et al). To illustrate this important caveat, the patient in this presented case not only failed to have pigmented macules on careful physical exam, but also denied ever having had perioral, labial, or nasal pigmentation.
Further, by puberty, these macules tend to disappear from all but the buccal mucosa. The absence of these macules in post-pubertal patients may mislead clinicians who rely upon a simple visual inspection of the skin to confirm a suspicion of PJS (Erbe).
Increased incidence of neoplasms:
Peutz-Jeghers syndrome is associated with an increased incidence of neoplastic disease, both benign and malignant, with an estimated lifetime incidence of malignancy of 50% (Giardiello, et al). Women have an increased incidence of bilateral breast carcinoma and ovarian tumors, whereas men have increased incidence of testicular tumors. Incidence of gastrointestinal malignancy is estimated to be 2-13%, occasionally arising from the hamartomatous polyps, which themselves have an incidence of adenomatous change of 3-6% (Spigelman et al).
Management of PJS: Management of PJS involves surveillance of the gastrointestinal tract via repeated endoscopy and fecal occult blood testing. Endoscopic removal of all polyps (especially those over 1 cm in size) helps eliminate their malignant and intussusceptive potential.
Contributed by James Davie, MD PhD