This month’s selected commentary

Peutz-Jeghers syndrome
Warren R. Heymann, MD
Based on the dialogue ‘‘Lip dermatoses’’
between Drs Margaret E. Parsons and Stuart Brown

Dialogues in Dermatology, a monthly audio program from the American Academy of Dermatology,
contains discussions between dermatologists on timely topics. Commentaries from Dialogues Editor-in-
Chief Warren R. Heymann, MD, are provided after each discussion as a topic summary and are provided
here as a special service to readers of the Journal of the American Academy of Dermatology. ( J Am Acad
Dermatol 2007;57:513-4.)

O suffering, sad humanity! puberty; those on the buccal mucosa, palate, and
O ye afflicted ones, who lie tongue, however, persist.’’ Laser and intense pulsed
Steeped to the lips in misery, light treatments may be successful in treating these
Longing, yet afraid to die, lesions on the lips and face.3
Patient, though sorely tried!
McGarrity and Amos4 state that gastrointestinal
Henry Wadsworth Longfellow polyposis may occur anywhere throughout the gas-
A verse from ‘‘The Goblet of Life’’ trointestinal tract, but tends to arise predominantly in
the small intestine. Symptoms due to these hamar-

D ermatoses of the lip may bring misery to

our patients. In this dialogue Dr Parsons
discusses a host of lip disorders including
irritant and allergic contact dermatitides, perlèche
(angular cheilitis), and actinic cheilitis. Abnormalities
of the lips may also reflect internal disease, examples
being acanthosis nigricans, hereditary hemorrhagic
telangiectasia (Osler-Weber-Rendu syndrome), and
the Peutz-Jeghers syndrome (PJS). This commentary
reviews new perspectives on PJS.
PJS (MIM 175200) is a rare, autosomal dominant,
multiple-organ cancer syndrome involving primarily
the gastrointestinal tract, pancreas, lungs, and the
reproductive organs.1 According to Paller and
Mancini,2 ‘‘Characteristic bluish brown to black
spots, often apparent at birth or in early childhood,
represent the cutaneous marker of this syndrome.
These discrete, flat pigmented lesions are irregularly
oval and usually measure less than 5 mm in diameter.
They are most commonly seen on the lips and buccal
mucosa, nasal and periorbital regions, elbows, dor-
sal aspects of the fingers and toes, palms, soles, and
periumbilical, perianal, or labial regions; occasion-
ally the gums and hard palate and, on rare occasions,
even the tongue may be involved. The pigmented
lesions on the skin and lips frequently fade after
The statements and opinions expressed in this commentary are
those of the Editor-in-Chief of Dialogues in Dermatology.
tomatous polyps occur early in life, with more than
one third of patients presenting with symptoms in
the first decade, and 60% by age 20 years. Clinical
manifestations may include abdominal pain, anemia
secondary to bleeding, and intestinal obstruction
due to intussusception. Routine endoscopic surveil-
lance of the small and large intestines, with polypec-
tomy, are standard recommendations.4 Terauchi,
Snowberger, and Demarco5 note that since 2000,
capsule endoscopy has revealed images previously
only available by radiological imaging or by biopsy
specimens. Polypectomies may be performed con-
currently with double-balloon endoscopy, a proce-
dure utilizing sequentially inflated and deflated
balloons, allowing the endoscope to advance deep
into the small bowel.5
According to McGarrity and Amos,4 with advanc-
ing age, the risk of intestinal cancer increases in
patients with PJS. Indeed, the malignant transforma-
tion of previously benign polyps has been referred to
as the ‘‘hamartoma-adenoma-carcinoma sequence.’’
Patients with PJS are also at risk for extraintestinal
malignancies, including cancers of the breast, lung,
ovary, uterus, cervix, testicle, and pancreas.
According to Song et al,6 ‘‘Genital tract neoplasms
in the female patient with PJS include ovarian neo-
plasms from the epithelium and stromal cells, ade-
noma malignum of the cervix and adenocarcinoma
of the endometrium. The most common ovarian

513
514 Dialogues in Dermatology
neoplasm found in patients with PJS is the sex cord
tumor with annular tubules (SCTAT), followed by
Sertoli cell tumor of the ovary, mucinous epithelial
ovarian tumor, serous tumor and ovarian mature
hamartoma.’’ Breast cancer in female patients with
PJS is usually ductal, but may also be lobular.6
Lefevre et al7 state that endocrine manifestations
in PJS include gynecomastia due to calcified Sertoli
cell testicular tumors usually referred to as large-cell
calcifying Sertoli cell tumors. The authors report
two siblings with PJS with biochemical evidence
of Sertoli cell dysfunction based on elevated levels of
inhibin-a. One sibling had gynecomastia. Although a
mastectomy was ultimately required, the gynecoma-
stia improved while the patient received the aroma-
tase inhibitor anostrozole (Arimidex), presumably
due to decreased estrogen production. The authors
propose the use of aromatase inhibitors as a potential
alternative to a bilateral orchiectomy.7
The gene for PJS has been mapped to chromo-
some 19p13.13. Thakur et al1 assert that more than
140 different mutations in the STK11 gene have been
reported, with mutations affecting the serine/threo-
nine protein kinase, LKB1. McGarrity and Amos4
note that LKB1 regulates p53-mediated apoptotic
pathways. LKB1 regulates cell proliferation via G1
cell-cycle arrest and WAF1 signaling. LKB1 mutations
alter cell polarity, presumptively playing a patho-
genic role in tumor development in patients with PJS.
By further understanding of the molecular complex-
ities of the signaling pathways involved in PJS,
perhaps specifically designed targeted therapies
could be developed, thereby rendering our current
screening methodology and surgical approaches
obsolete.
REFERENCES
1. Thakur N, Reddy DN, Rao GV, Mohankrishna P, Singh L,
Chandak GR. A novel mutation in the STK11 gene is associated
J AM ACAD DERMATOL
SEPTEMBER 2007
with Peutz-Jeghers syndrome in Indian patients. BMC Med
Genet 2006;7:73.
2. Paller AS, Mancini AJ. Disorders of Pigmentation. In: Hurwitz.
Clinical pediatric dermatology. London (UK): Elsevier; 2006. pp.
265-305.
3. Remington BK, Remington TK. Treatment of facial lentigines in
Peutz-Jeghers syndrome with an intense pulsed light source.
Dermatol Surg 2002;28:1079-81.
4. McGarrity TJ, Amos C. Peutz-Jeghers syndrome: clinicopathol-
ogy and molecular alterations. Cell Mol Life Sci 2006;63:
2135-44.
5. Terauchi S, Snowberger N, Demarco D. Double-balloon endos-
copy and Peutz-Jeghers syndrome: a new look at an old
disease. Proc (Bayl Univ Med Cent) 2006;19:335-7.
6. Song SH, Lee JK, Saw HS, Choi SY, Koo BH, Kim A, et al.
Peutz-Jeghers syndrome with multiple genital tract tumors and
breast cancer: a case report and review of the literatures.
J Korean Med Sci 2006;21:752-7.
7. Lefevre H, Bouvattier C, Lahlou N, Adamsbaum C, Bougneres
P, Carel JC. Prepubertal gynecomastia in Peutz-Jeghers syn-
drome: incomplete penetrance in a familial case and man-
agement with an aromatase inhibitor. Eur J Endocrinol 2006;
154:221-7.
Additional topics from the August 2007 issue
of the Dialogues in Dermatology:
1. Dermatology in the Civil War
With Thomas G. Cropley, MD, interviewed
by Gary Brauner, MD
2. Assessment of management of postacne scarring
With Greg J. Goodman, FACD, interviewed
by Naomi Lawrence, MD
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