Intestinal obstruction with oral pigmentation: a clue to Peutz-Jeghers syndrome

Abstract

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder, which manifests as mucocutaneous hyperpigmentation and, intestinal and extraintestinal polyps. The classic triad of abdominal pain, mass and jam-like stools are not found commonly. On clinical examination, a strong suspicion of PJS should be made if patients below 18 years, present with mucocutaneous hyperpigmentation and intestinal obstruction. We report a case of a 16-year-old woman who presented to the surgical emergency with a 1-day history of acute pain in abdomen, in right iliac fossa and features of intestinal obstruction. A thorough history and clinical examination supported by diagnostic imaging should be done in suspicious cases for prompt diagnosis and appropriate treatment.

Background

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder, which manifests as mucocutaneous hyperpigmentation and gastrointestinal (GI) polyp. GI polyps have a wide spectrum of presentation. They are mostly found in the small intestine but may be present at any location from the stomach to rectum. They may be asymptomatic or present as intestinal obstruction secondary to intussusception. The intussusception may occasionally undergo spontaneous recanalisation, otherwise it requires resection of the affected intestinal loop. Individuals with PJS have increased risk of GI as well as non-GI malignancies, hence long-term follow-up is warranted.

Case presentation

A young girl aged 16 years, with no prior comorbidities, presented to the emergency room with reports of colicky abdominal pain and bilious vomiting for 1 day. She had not passed stools or flatus since the onset of symptoms. There was no associated history of fever, GI bleed, reduced appetite or similar episodes in the past. At presentation, pulse rate was 86 bpm and blood pressure was 114/86 mm Hg. Her abdominal examination revealed tenderness in right iliac fossa and exaggerated bowel sounds. A clinical diagnosis of acute intestinal obstruction was made, keeping acute appendicitis and ovarian pathology as the differentials. Systemic examination revealed hyperpigmented lesions over the oral mucosa, neck, forearm and the digits.

Investigations

Plain X-ray of the abdomen revealed dilated small bowel loops with multiple air-fluid levels confirming the diagnosis of obstruction. Ultrasonography of the abdomen revealed long segment bowel mass having concentric rings and ‘bowel within bowel’ appearance, extending from right iliac fossa to right hypochondrium with some amount of fluid between concentric rings.

Treatment

After adequate resuscitation, the patient was wheeled in for emergency surgery. Intraoperatively, a 30 cm long segment of intussusception was present, at a distance of 100 cm from the duodenojejunal flexure (figure 1). The segment lying proximal to it was dilated. Intussusception was reduced by constant pushing force from proximal to distal direction over intussuscipiens. Toxic fluid was drained out after reduction of the segment and gangrenous changes noted over the bowel segment (figure 2). Approximately 60 cm of the jejunal loop was resected with viable margins and a double-layered end-to-end anastomosis was performed. A polypoidal growth was seen 8 cm from the proximal resection margin after the specimen was bivalved (figure 3). The rest of the bowel was palpated on-table, but no evidence of concurrent polyps were found elsewhere. The postoperative period was uneventful. Histopathological analysis of the resected specimen came as a surprise with a diagnosis of a hamartomatous polyp. Retrospective examination revealed hyperpigmented lesions which were present since childhood. These lesions were mostly seen over the oral mucosa (figure 4), although skin lesions were also noteworthy (figure 5). Family members did not bear any similar lesions. Clinicopathological correlation led to the diagnosis of PJS. Postoperatively the patient was planned for upper GI endoscopy and colonoscopy along with a CT scan of the abdomen. However, no lesions elsewhere were picked up from the tests.

Figure 1.

Intussusception with proximal dilated loops (arrowhead points to the site of obstruction).

Figure 2.

Gangrenous bowel loops after reduction.

Figure 3.

Polyp as the lead point of the intussusception.

Figure 4.

Mucosal hyperpigmentation on lips and oral cavity.

Figure 5.

Cutaneous hyperpigmentation on neck and digit (marked by arrows).

Outcome and follow-up

Individuals with PJS have a high risk of GI as well as non-GI malignancies. They should be periodically screened to ascertain early detection. There is no consensus regarding the periodicity of surveillance, however, a protocol should be laid out on an individual basis and based on the availability of screening equipment. Fraser et al have proposed 2 yearly upper GI endoscopy, barium enema, endoscopic ultrasound and 3 yearly colonoscopy at the emergence of symptoms. They have also proposed annual breast examination and pelvic imaging.¹ The patient described in the above case is on regular follow-up. She has not developed any further episodes of pain in abdomen and symptoms of GI bleed until 12 months from the initial hospital admission. Although genetic analysis of the patient should ideally be performed with screening of family members, the same could not be done due to constraint of resources for the same at our facility and the poor economic background of the patient. However, the parents have been counselled regarding the nature of the disease and been made aware regarding the possibility of similar symptoms in any of the family members. Strict follow-up has been advised for the patient as well as her family members to avoid complications

Discussion

Incidence of PJS ranges from 1/50 000 to 1/200 000 live births.² It was first described by Dr Jan Peutz in 1921, and later Dr Harold Jeghers in 1949, and hence named as PJS.³ PJS is an autosomal dominant inherited condition involving the mutation of gene STK-11/LKB-1. It equally affects men and women. It is characterised by hyperpigmented macules on lips, hands and feet, along with the mucous membrane of the oral cavity. It is also characterised by hamartomatous polyps in the GI tract. The hyperpigmented lesions usually appear in early childhood and disappear during adolescence except for the oral mucosa lesions. These lesions do not have malignant potential. The GI polyps are hamartomatous in origin and have a low malignant potential. The polyp is usually located in jejunum or ileum and rarely found in duodenum and colon.⁴

The hamartomatous polyps present as bleeding (either upper or lower GI bleed) or pain in abdomen secondary to intussusception, obstruction, infarction. They mostly present as small bowel intussusception, but colocolic intussusception have been reported.⁵ Pedunculated nature of the polyp renders them prone to become a lead point and lead to intussusception. In this case the patient presented with acute abdominal pain which was localised to right iliac fossa. Further examination revealed tenderness over the same region which led to suspicion of acute appendicitis or any ovarian pathology as differentials, but further radiological investigations revealed bowel in bowel appearance which was suggestive of intussusception of the bowel loops.

Histopathological analysis of typical PJS polyp has an arborising type of smooth muscle proliferation. There is also evidence of hamartomatous-adenomatous-carcinomatous sequence in patients with PJS and, of the direct transformation of a hamartoma into malignancy.⁶ Rarely polyps may be seen in the ureter, bladder, lungs, bronchi and gall bladder.³

Individuals with PJS are at increased risk of gastrointestinal and other cancers including breast, cervix, uterine, pancreas and lung. The lifetime risk of developing cancer in affected individuals can be as high as 93%.⁷ Individuals develop cancer mostly in the fifth decade. Women have an increased risk of sex cord tumours.

Radiological investigations should be performed in symptomatic individuals. In the Ultrasonography (USG) of the abdomen, ‘doughnut’ or ‘target’ sign is seen in transverse view and ‘pseudo kidney’ sign is seen in the longitudinal view. CT scan is the most sensitive method to confirm the diagnosis. The characteristic feature in CT is inhomogeneous ‘target’ or ‘sausage’ shaped soft tissue mass with a layering effect.⁷

The diagnosis of PJS is established by WHO criteria, which are the presence of two or more histologically confirmed PJ polyps, or any number of PJ polyps with a family history of PJS, or characteristic prominent mucocutaneous pigmentation with a family history of PJS, or any number of PJ polyps and characteristic mucocutaneous pigmentation.⁸ Any patient who fulfils any of the criteria should undergo genetic testing and family members should undergo genetic counselling. An individual with PJS should undergo screening with upper GI endoscopy and colonoscopy to rule out concurrent GI polyps. In this case, the patient was retrospectively diagnosed as PJS, when the clinicopathological correlation was established. Also, the patient did not have any history of similar disease in her family. Therefore it could be a sporadic case and genetic counselling must be undertaken.

Surgical management is warranted in most of the cases with intussusception. Resection and anastomosis of the affected bowel loop is the definitive treatment. Although there is no specific guideline regarding the resection margins, 5 cm of healthy bowel proximal and distal to the involved bowel loop was resected. Asymptomatic polyps can be tackled in two ways, intraoperative endoscopy (IOE) or double balloon enteroscopy (DBE). Polyp can be removed by endoscopic snaring which minimises the need for laparotomy. DBE is a new enteroscopy method that allows examination and treatment of jejunum and ileum.^{4 9} It is useful for obtaining a diagnosis and performing a therapeutic polypectomy. IOE used to be the procedure of choice before the advent of DBE. IOE is still in use in cases of failed DBE, adhesions, multiple small transmural lesions.

Relatively low incidence of the disease and dearth of data on effective protocols makes the surveillance guidelines mostly consensus-based. Further studies on molecular genetics and potential biomarkers can add to the existing knowledge.

Learning points.

• Peutz-Jeghers syndrome (PJS) is a rare entity and commonly manifests as mucocutaneous hyperpigmentation in the first decade of life.

• In the second decade of life, it presents as a complication of gastrointestinal (GI) polyp either with intussusception or GI bleed.

• Any young age patient presenting with intestinal obstruction with features of hyperpigmentation gives an important clue to suspect PJS.

• It is not only useful to proceed for genetic analysis but also crucial for the evaluation of the whole GI tract for presence of polyp and carrying out the necessary treatment.

• These patients are also at risk of GI and non-GI malignancies later in their life, and hence, must be subjected to regular follow-up.