Discussion:
Peutz-Jeghers syndrome (PJS) was first defined by Peutz in 1921 and
Jeghers in 1944, as a familial autosomal dominant disorder,
characterized by hamartomatous polyps of the gastrointestinal tract, and
specific mucocutaneous hyperpigmentations (3-6). It is an extremely rare
disease, with an incidence of 1 in 12-30,000 live births (2,7,8), and
whose pathogenesis has been related to a germline mutation on the
serine/threonine kinase 11 (STK11/LKB1) tumor suppressor gene on
chromosome 19p13.3(9).
Despite its rarity, PJS has become a well-known entity with specific
diagnostic criteria (1,10,11), which are both clinical and histological.
Recently, Beggs et al proposed to consider the diagnosis in presence of:
1) Two or more histologically confirmed PJS polyps or 2). Any number of
PJS polyps in an individual who has a family history of PJS in close
relative(s), or 3) Characteristic mucocutaneous pigmentation in an
individual who has a family history of PJS in close relative(s) or, 4)
Any number of PJS polyps in an individual who also has characteristic
mucocutaneous pigmentation (12).
Diagnosis of PJS was attributed to our patient according to the fourth
Beggs’ criteria, as she had multiple gastrointestinal PJ polyps
associated to dark pigmented macula at the lip mucosa. PJ polyps are
very characteristic due to their histologic features, looking like an
unusual type of hamartomatous polyp. Microscopic aspect is characterized
by a tree-like branching of smooth muscle fibers, with a core of smooth
muscle arising from the muscularis mucosa and extending into the polyp,
covered by mucosal tissue with near-normal appearance (9).
Muco-cutaneous pigmentations appearing with PJ affected patients have
also characterized aspect and location. They correspond to small, oval
or circular and dark brown lentigines (1) and their most common
locations are lip and buccal mucosae.
Our patient presented to the emergency department with recurrent
abdominal pain and vomiting which suddenly worsened, likely due to
intermittent small bowel intussusceptions. According to literature data,
such symptoms are mostly caused by polyp-related complications and often
represent the discovery circumstance of PJS in children (10,13-15). This
is certainly due to anatomical characteristics of these polyps. In a
large multicenter study, Van Lier et al reported a cumulative
intussusception risk in PJS of 15% by age 10 years and 50% by age 20
(16,17). They also concluded that PJ polyps depend on small bowel in
more than 95% of cases, the jejunum being the preferential location,
which may act as leading point for the intussusceptions. Moreover,
polyp-size was probably an important risk factor for small-bowel
intussusception, as they were generally caused by hamartomas larger than
or equal to 15 mm in diameter (17). In our case, the recurrent aspect of
intussusceptions, their jejuna location on US, as well as presence of
dark macula at the lip mucosa, led us to suspect the presence of
underlying lead point, in particular PJ polyps. That is why we
investigated further using abdominal CT scan and upper gastrointestinal
series permitting the identification of polypoid lesions inside the
jejuna lumen. Referring to the literature, PJ polyps are often detected
in US, barium studies, CT enterography, and MR enterography which has
the advantage of a lack of ionizing radiation. The sensitivity of video
capsule endoscopy (VCE) has also been demonstrated even for detection of
small polyps, but it cannot be used in the presence of intestinal
obstruction (18,19).
For our patient, all intussusceptions depended on small bowel and were
successfully reduced through open surgical approach. For polyps’
identification, we checked and palpated the whole intestine wall. They
then were entirely removed by small elective enterotomies without need
of resection. In a large series, C.Fallon et al demonstrated that
children with a lead point such as polyps have increased risk of
requiring surgery (20). According to the latest European Hereditary
Tumor Group (EHTG) guidelines, laparotomy is the safest option for the
surgical treatment of intussusception secondary to PJS. Then, the
preferred strategy is the manual reduction, if possible, followed by
resection of the polyp that acts as a hypomochlion at its base by
enterotomy, without bowel resection. Moreover, entire small bowel should
be critically checked by palpation or intraoperative enteroscopy through
enterotomy is recommended to find and remove over 15 mm size polyps
(10). Laparoscopic approach was also showed to be feasible and efficient
in these cases, but should better be combined with upper/lower endoscopy
to avoid multiple surgical interventions (10,13,21).
In general, the gravity of PJS is related to two major complications:
small bowel intussusception, with its urgent and even life-threatening
character especially in children, and the increased risk of malignancy
at adulthood. Several meta-analysis and cohort studies have demonstrated
that this risk varies between 55 and 85% (10). That’s why patients with
confirmed PJS must have regular and periodic surveillance (1,10).
Based on the reviewed literature, recommendations and statements were
formulated on clinical genetic, gastrointestinal, surgical, pancreatic,
breast, and gynecological management (10).
As PJS is inherited in an autosomal dominant pattern, genetic germline
screening of the STK11gene is recommended for asymptomatic at risk
children, before onset of symptoms, and for symptomatic patients meeting
the clinical PJS criteria, and this regardless age. However, diagnosis
of PJS should be considered in presence of clinical criteria, even if an
underlying causative germline variant is not identified, because of the
important genetic heterogeneity (1,10).
Based on recent recommendations of the European Society of
Gastrointestinal Endoscopy, gastro intestinal surveillance should be
initiated no later than 8 years in an asymptomatic individual with PJS,
and earlier if symptomatic. These investigations include
oeso-gastro-duodenoscopy, colonoscopy and MRI studies or video capsule
enteroscopy for the small bowel, and should generally be repeated at
least every 3 years. Then, elective polypectomy should be performed for
small-bowel polyps up to 15–20 mm of diameter, to prevent
intussusception (1,10,12). Similarly, we have begun a gastro-intestinal
surveillance program for our patient. She undertook an initial
esophago-gastroduodenoscopy and a colonoscopy revealing one colonic and
two gastric polyps which were safely removed by endoscopy.
Moreover, according to the American College of Gastroenterology and the
EHTG guidelines, adults with PJS should undergo an annual complete blood
cell count with physical examination including evaluation of the
abdomen, pelvis, breasts and testes. Lifelong cancer surveillance is
recommended, in order to early detect pancreatic, testes, breast and
gynecological tumors (3,10).