Peutz–Jeghers Syndrome: Lessons to be Learned in the Clinical Diagnosis

Abstract

Introduction:

Peutz–Jeghers Syndrome (PJS) is an autosomal dominant disease presenting with hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on lips and oral mucosa. The incidence of this syndrome is approximately 1 in 1,20,000 births.

Materials and Methods:

In this article, we are presenting 11 cases of PJS which were misdiagnosed and patients were compelled to visit hospital repeatedly. All these cases were diagnosed based on clinical suspicion, family history, and histopathological examination of specimens. Most of the cases presented with intussusception and required emergency surgical management.

Results:

PJS can be diagnosed by the presence of microscopically confirmed hamartomatous polyps and a minimum of two of the following clinical criteria: Family history, mucocutaneous melanotic spots, and small bowel polyps with bleeding per rectally. The diagnosis can be missed if the melanotic spots on the face are missed. Routine investigations, imaging, and endoscopy were done in all cases. PJS patients need regular follow-up due to chance of recurrence of symptoms and susceptibility to cancer.

Conclusion:

PJS needs a high index of suspicion for diagnosis in cases of recurrent abdominal pain with bleeding per rectum. Proper family history and meticulous clinical examination for melanosis are very important to prevent the misdiagnosis of these cases.

INTRODUCTION

Peutz–Jeghers Syndrome (PJS) is an autosomal dominant disease identified by melanotic pigmentation of the oral mucosa, with numerous hamartomatous polyps in the small and large intestine.[1] Its incidence is 1 in 120,000 births.[2]

The gene STK11 (LKB1) on chromosome 19p13.3 has been found in a proportion of patients with this condition.[3] The long-term follow-up of the family described by Peutz had shown decreased survival as a result of complications of intestinal obstruction and the occurrence of different types of neoplasms. Upper and lower gastrointestinal (GI) endoscopy should be done in all patients. Females need regular surveillance for the possible occurrence of breast and cervical cancer. Malignant changes are rare, so polyps should be excised only when they cause symptoms such as heavy per rectal (PR) bleeding and intussusception.[1]

PJS can present in an emergency with features of intestinal obstruction due to intussusception, bleeding per rectum, and recurrent colicky pain in the abdomen. Management of acute surgical crisis, regular follow-up, family screening, and repeated endoscopies are needed for the treatment of these patients. We present this series of 11 patients who presented at our institution with a diagnostic dilemma and were managed successfully. To the best of our knowledge, this is one of the largest series in the English literature of this syndrome in children from India.

MATERIALS AND METHODS

This is a retrospective study of 11 cases of PJS including their affected elderly sibling and parents who presented to department of pediatric surgery between January 2013 and May 2021.

Methodology

All the patients who presented with abdominal complaints and had hyperpigmentation over lips and oral cavity were suspected to have PJS and were included in the study. All the patients were found to have multiple intestinal polyps on laparotomy which were hamartomatous on histology so confirming diagnosis of PJS. Four more patients of PJS were found on family screening of index patients which were included in study. Surgical management of intussusception was done in the form of resection and anastomosis or stoma and multiple polyps were excised with enterotomies and later via endoscopy. Histopathological evaluation of polyps was done which was hamartomatous in all the cases. These children were diagnosed with PJS and later their family members were screened.

Details of the patients in our study are shown in Table 1.

Table 1.

Demographic profile, clinical presentation, family history, operative intervention and follow up of patients of Peutz Jegher’s syndrome

Case number	Age (years)/sex	Presentation
		Obstruction	Intussusception	Bleeding PR	Melanosis	Family history	Surgery	Follow up
1	12/female	Present, previously misdiagnosed as malrotation and Koch’s abdomen	Ileocolocolic	Present	Present [Figure 2]	Present, mother and 3 siblings [Figure 1]	Ileostomy with biopsy, followed by endoscopic polypectomy then multiple enterotomies with removal of polyp [Figure 3]	Doing well
2	21/female	Present	Ileocolocolic	Present	Present	Present	Ileotransverse anastomosis 3 years back	Doing well
3	17/female	present	Ileocolocolic	Present	Present	Present	Ileotransverse anastomosis 7 years back	Doing well
4	10/female	Absent	Absent	Present	Present	Present	Not operated	Doing well
5	55/female	Absent	Absent	present	present	Present	Coloscopy showed polyposis	Doing well
6	8/male	Present, misdiagnosed as malrotation previously	Ileocolocolic	Present	Present, being treated with dermatologist for 2 years	Present, father	Ileoascending anastomosis	Doing well
7	38/male	Absent	Absent	Present	Present	Present	Colonoscopy and upper GI endoscopy showed polyposis	Doing well
8	8/male	Present	Jejunojejunal [Figure 4]	Present	Present	Lost to follow up	Jejunojejunal anastomosis	Doing well
9	8/male	Present	Ileocolocolic	Present	Present	Lost to follow up	Ileoascending anastomosis	Doing well
10	9/male	Present	Ileocolocolic	Present	Present	Present	Ileoascending anastomosis	Doing well
11	7/male	Present	Jejunojejunal	Present	Present	Present	Jejunojejunal anastomosis	Doing well

PR: Per rectal, GI: Gastrointestinal

Figure 1.

Melanotic spots over the lips

Figure 2.

Pedigree chart of 1st family with Peutz–Jegher's Syndrome

Figure 3.

(a) Showing a large 6 cm × 4 cm benign hamartomatous polyp. (b) Histopathology of the hamartomatous polyp

Figure 4.

Showing jejunojejunal intussusception due to polyp in the jejunum acting as lead point

RESULTS

A total of 11 cases of PJS were included in this study, of which eight (73%) patients presented with abdominal pain and acute intestinal obstruction and all 11 had bleeding per rectum. Two patients were misdiagnosed as malrotation of the gut and one was misdiagnosed as Koch's abdomen. Two (18%) patients presented with small bowel intussusception and six (54%) with both small and large bowel intussusception. None of the patients had gastric outlet obstruction but one had gastric polyps. Seven patients underwent resection and anastomosis, one required ileostomy and the same patient needed multiple enterotomies for removal of the polyps. All patients had melanosis periorally and on lips which were missed initially by other physicians. All patient's specimens were evaluated histopathologically and were confirmed to be hamartomatous. The family screening was done in all except two cases which were lost to follow up.

In the first family, the mother was found to be affected along with her four daughters. Only one out of her five daughters was normal. In the second family, the father was having the disease which affected his son while his daughter was normal. In the other 2 families mentioned in the table, the father along with the son were affected. Two of our patients who had positive family history were lost to follow up and so their family members could not be screened.

DISCUSSION

The hamartomatous polyposis syndromes are characterized by an overgrowth of cells native to the area in which they normally occur. Polyps seen in PJS can be distinguished from sporadic hamartomatous polyps and hamartomatous polyps of different syndromes by a unique core of smooth muscle that branches throughout the polyp. Benign hamartomatous polyps in PJS lack specific endoscopic features and can be differentiated from other polyps by histopathology. The unique PJS polyp pathology is best seen in PJS small bowel polyps.[4] Foci of adenomatous tissue have been found in large hamartomas which may have malignant potential.[5]

Hyperpigmentation is present as mucocutaneous macules on the lips and around the mouth, eyes, nostrils, and on the buccal mucosa; and sparsely on the fingers, soles of the feet, palms, anal area and intestinal mucosa. In the first family in our study, the mother was found to be affected along with her four daughters. All of them had many melanotic spots on the lips and buccal mucosa. The index case of this family also had melanosis over the palms, soles and face. Majority (95%) of the patients have classical flat, blue-gray to brown pigmentations as were seen in our series also. In the 2^nd family few pigmentations were seen over the lip and buccal mucosa in the boy who was operated but his father had a single melanotic spot over the right buccal mucosa. Malignant degeneration of these lesions is extremely rare. PJS can be diagnosed by the presence of microscopically confirmed hamartomatous polyps and a minimum of two of the following clinical criteria: Family history, mucocutaneous melanotic spots, and small bowel polyps with bleeding per rectally.[6] In our series, we established the diagnosis using above-mentioned criteria.

The average time for the first presentation with polyps is about 11–13 years of age, but in the present study, it is 8 years. In the first three decades; anemia, bleeding per rectum, colicky pain, obstruction, and/or intussusception are the common presentations in patients with PJS. Around 50% of the patients suffer from small bowel intussusception during their lifetime.[7] But in our study, most patients had both large and small bowel intussusception. A giant gastric polyp can lead to mechanical gastric outlet obstruction.[8,9,10] In our study, there was a case of multiple gastric polyps but without any features of gastric outlet obstruction. Extra-intestinal polyps are also reported in PJS. Nasal polyposis which is an uncommon complication was not seen in any of our patients.[11]

The most common cancers reported in literature were of GI origin and in non-GI tumors, the breast cancer was the most common.[12,13] Screening recommendations for PJS patients include not only for multiple GI polyps but also regular cancer screening. Earlier, enteroclysis was the only method of screening but now, wireless capsule endoscopy has been found to detect more polyps. Capsule enteroscopy is a feasible, safe, and sensitive test for the small bowel surveillance in patients with PJS, even in children.[14,15] However, it was not possible in our patients due to lack of such facilities. Regular screening for possible malignancies in patients with PJS should be done via upper GI endoscopy, colonoscopy, computed tomography, magnetic resonance imaging or ultrasonography (USG) of the pancreas, chest X-ray, mammography, CA 125 and USG of pelvis in females, examination of testis in males and so on.

CONCLUSION

Melanotic spots, which are commonly misdiagnosed by clinicians as seen in our study should be examined carefully and the diagnosis of PJS should be kept in mind. Inspite of the fact that PJS is an uncommon disease, it is essential for clinicians to diagnose these disorders early to reduce the associated morbidity due to delay in treatment and mortality due to misdiagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.