Overview
A rare autosomal disorder characterized by mucosal macules and multiple polyps in the gastrointestinal tract, mainly associated with mutations in the STKll/LKB1 gene, including general, endoscopic, and surgical treatments.
Definition
Melanotic polyp syndrome is an autosomal dominant disorder characterized by multiple polyps of the gastrointestinal tract accompanied by mucocutaneous melanosis. It is also known as familial mucocutaneous melanotic polyposis of the gastrointestinal tract, hyperpigmented polyp syndrome, and Peutz-Jeghers syndrome.
The syndrome was first reported by Peutz in 1921, and then described in detail and systematically by Jeghers in 1944 and 1949, so it is called Peutz-Jeghers syndrome (Peutz-Jeghers syndrome, PJS).
Dark spot polyp syndrome is characterized by hyperpigmentation of the face, lips, and periocular area, and bilateral fingers, feet, and palms, with multiple misshapen polyps in the gastrointestinal tract.
The polyps can be located anywhere in the GI tract, with polyps of the small intestine (duodenum, jejunum, and ileum) being the most common.
Pathogenesis
Melanoma polyp syndrome is a rare autosomal disorder with a prevalence of approximately 1 in 200,000 [1], with approximately equal incidence in both sexes [2].
It can occur at any age, mostly in children and adolescents, with a cancer rate of 2% to 3%.
About 50% of patients have no obvious family history, which may be related to gene mutation [2].
Etiology
Causes
The etiology of melanotic polyp syndrome is currently not fully understood. The proven causative gene is serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1), which is located on chromosome 19p13.3 [3-5].
The positivity rate of STK11 pathogenic mutations in our patients with melanotic polyp syndrome ranges from 50% to 90%, with an average of about 70%.
However, the specific mechanism of STK11 gene pathogenicity is not clear, and may involve multiple cell signaling pathways, leading to the development of misshapen polyps and related tumors.
Risk factors
Patients with a family history of melanotic polyp syndrome are predisposed.
Symptoms
Main Symptoms
Abdominal pain
Patients with dark spot polyp syndrome have intermittent abdominal cramps, often around the umbilicus, of variable duration, relieved by expectoration, which may be due to temporary intussusception and may recur over several years.
Episodes of abdominal pain may be accompanied by vomiting and hyperactive bowel sounds.
Mucosal pigmentation
Mucosal hyperpigmentation is the most typical clinical manifestation of dark spot polyposis, which is more common, and the areas of hyperpigmentation are found on the lips, fingers, toes, and dorsal and palmar sides of the hands and feet, and in some cases can even be found in the perianal region and near the genital region [6].
The dark spots usually appear in infancy and some patients are even born with such manifestations. They are usually flat, grayish-blue to brownish spots with an average size of 1-5 mm [6].
The earliest appearance of hyperpigmentation can be pinpoint or grain size, with the growth and development of children, the color of hyperpigmentation deepens, and some patients in adulthood, the color gradually faded or even disappeared, but buccal mucosal pigmentation can be accompanied by lifelong.
The location, size and color of mucosal pigmentation are not necessarily related to the number and location of gastrointestinal polyps and the severity of the disease.
Polyps
Most polyps in macular polyp syndrome are misshapen polyps that are widely distributed in the gastrointestinal tract, mostly in the small and large intestine, and may be isolated or in clusters.
Polyps can also be found outside the gastrointestinal tract, such as in the gallbladder, nasal cavity, respiratory tract, and urinary system.
Polyps tend to occur in clusters rather than covering the intestinal tract. Polyps are usually of different shapes and sizes, may be tipped or sessile, and larger lesions may be lobulated proliferations.
Symptoms usually arise from larger polyps, which may cause infarction, ulceration, bleeding, and lead to intestinal obstruction and intussusception, which are most common in the small intestine.
Other symptoms
May also manifest as abdominal distension and perianal prolapse.
Complications
Carcinoma
Black spot polyps have a tendency to become cancerous and are capable of progressing to colorectal cancer. The probability of polyps becoming cancerous is related to the size of the polyp and the duration of the disease, but there is no necessary connection with the number of polyps.
Not only gastrointestinal tumors, but also tumors outside the gastrointestinal tract such as gynecological tumors, pancreatic cancer, lung cancer, and male reproductive tract tumors are at increased risk [7].
Extra-intestinal malignant tumors are most common in breast and pancreatic cancer.
Intussusception.
Polyp size is closely related to the occurrence of intestinal volvulus, which may be single or multiple, and some volvulus may resolve on its own.
According to the literature, polyps >15 mm in diameter can cause intussusception, and the polyps that cause intussusception are mostly located at the head of the intussusception [8-9].
Intestinal obstruction
Intestinal polyps and intussusception itself can lead to intestinal obstruction, which is often recurrent and can occur in multiple places at the same time. A mass may be palpated in the abdomen during an attack, but disappears spontaneously on remission.
Anemia
It may be associated with polyp surface breakdown, which repeatedly causes gastrointestinal hemorrhagic anemia.
Consultation
Department of Medicine
Gastroenterology
Gastroenterology may be consulted when symptoms such as abdominal pain, hyperpigmentation of the skin and mucous membranes, or blood in the stool occur.
Emergency Medicine
If you have severe and persistent abdominal pain accompanied by nausea, vomiting, or severe bloody stools, it is recommended that you consult the Emergency Department.
General Surgery
General Surgery is recommended for people with persistent abdominal pain, a history of polyposis, or a family history of other tumors.
Preparation
Consultation: registration, preparation of documents, FAQs
Tips
If you have blood in your stool, take a picture of it and provide it to the doctor.
Wear loose-fitting clothes to facilitate medical checkups and examinations.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
Is there any pigmentation of the skin and mucous membranes? How long has it been there? Is there any change in quantity, color, etc.?
Are there symptoms such as abdominal pain, nausea, black stools, blood in the stool?
Has there been a cessation of gas and bowel movements?
Where is the abdominal pain located? Is it paroxysmal or persistent? Any aggravating or relieving factors?
What is the color, character, amount and frequency of black stools?
Are there any symptoms such as dizziness, fatigue, panic, fainting, etc.?
Any loss of appetite, weight loss, emaciation, etc.?
List of medical history
Is there a family history of gastrointestinal polyps, etc.?
Any autoimmune disease?
Is there any family history of related tumors in the family or close relatives?
Checklist
Test results of the past 6 months, which can be brought to the doctor’s office
Laboratory tests: blood test, stool routine + occult blood, tumor markers.
Imaging: abdominal ultrasound, abdominal CT, etc.
Endoscopy: including gastroscopy, colonoscopy and small enteroscopy, capsule endoscopy, etc.
Endoscopic mucosal pathology examination.
List of medications used
Medication used in the last 3 months, if available in boxes or packages, carry with you to the doctor’s office
Acid suppressants: e.g. omeprazole, rabeprazole, cimetidine, etc.
Glucocorticoids: e.g. prednisone, dexamethasone, etc.
Non-steroidal anti-inflammatory drugs: e.g. aspirin, clopidogrel, etc.
Antispasmodics: e.g. atropine, belladonna, probenecid, etc.
Diagnosis
Diagnostic basis
Dark spot polyp syndrome is diagnosed primarily by family history, skin pigmentation, and multiple polyps in the gastrointestinal tract. In patients with no family history or typical clinical symptoms, histopathologic confirmation of a misshapen polyp is required for a definitive diagnosis.
Medical history.
There may be a family history of melanotic polyp syndrome.
There may be a history of gastrointestinal polyps.
There may be a history of intestinal malignancy in the immediate family.
Clinical manifestations
Symptoms
Gastrointestinal symptoms such as abdominal pain, bloating, blood in the stool, and intestinal obstruction are present in most patients.
Physical signs
Physical examination may reveal characteristic skin and mucosal pigmentation.
There may be varying degrees of subxiphoid tenderness or no tenderness.
An abdominal mass may be palpable in patients with intestinal obstruction.
Patients with abdominal pain may have hyperactive bowel sounds.
Laboratory tests
Blood tests
Significantly decreased hemoglobin suggests anemia and allows assessment of the degree of anemia.
Increased leukocytes suggest inflammatory infection.
Blood biochemistry
Blood biochemistry, including electrolytes, liver and kidney function, can indicate the presence of liver and kidney impairment, electrolyte disorders and malnutrition.
Stool routine + Occult blood test
Stool routine and fecal occult blood test can help to identify the presence of blood in stool and intestinal infection.
Tumor Markers
Abnormal elevation of tumor markers suggests the possibility of cancer or complication of cancer.
Imaging
X-ray imaging of the digestive tract
Barium X-ray contrast helps to detect organomegaly, etc.
Abdominal CT
Abdominal CT provides a better understanding of the location, size, number, morphology, and relationship of small bowel lesions to the surrounding tissues, facilitating the development of a treatment plan [9].
Endoscopy
It mainly includes gastroscopy, colonoscopy, capsule endoscopy and balloon-assisted small enteroscopy.
Balloon-assisted small colonoscopy is divided into double-balloon small colonoscopy and single-balloon small colonoscopy, which is a reliable method for diagnosis and treatment of small bowel diseases, and polypectomy is also feasible.
Capsule endoscopy is also a feasible, safe and highly sensitive monitoring method to detect polyps throughout the GI tract.
Endoscopy can help in early diagnosis and early treatment to alter the progression of the disease.
Pathologic examination
According to Yamada typing, all types of polyps are present in melanotic polyp syndrome, with most gastric polyps being type II and type III, and most colon and small bowel polyps being type III and type IV [10].
The pathological characteristics of polyps are mainly misshapen tumor-like polyps, but proliferative polyps, adenomatous polyps and other pathological types can also be present at the same time.
Genetic testing
In most patients, genetic testing reveals mutations in the STK11 gene.
Diagnostic criteria
According to the World Health Organization’s diagnostic criteria, a diagnosis of macular polyp syndrome is made when any of the following are met
≥3 pathologically confirmed macular polyps;
Any number of macular polyps in combination with a close family history of macular polyp syndrome;
Characteristic cutaneous mucosal hyperpigmentation with a combined close family history;
Any number of macular polyps combined with characteristic cutaneous mucosal hyperpigmentation.
Patients who meet the clinical criteria may undergo STK11 (LKB1) gene testing for definitive diagnosis, which mostly reveals STK11 gene mutations.
Differential diagnosis
Juvenile polyp syndrome
Similarities: Both are autosomal dominant disorders, and most are misshapen polyps.
Differences: Juvenile polyp syndrome is mainly found in children, the most common age is 5-10 years old, and it can be characterized by growth retardation, sometimes accompanied by cleft lip and palate, congenital heart disease, and cranial developmental abnormality; whereas melanotic polyp syndrome is mostly found in adults, and it is mainly characterized by abnormal pigmentation, and intussusception.
Carney syndrome
Similarities: Both syndromes are characterized by hyperpigmentation of the skin and mucous membranes.
Differences: carney syndrome is a special type of multiple endocrine gland tumor syndrome, which is mainly characterized by primary pigmentation, nodular adrenal hyperplasia, cardiac mucocele, and may be accompanied by mucous edema, etc., while melanotic polyp syndrome usually does not have manifestations of mucous edema, and is not combined with endocrine adenomas.
Treatment
Aim of treatment: symptomatic treatment, symptomatic relief, early detection, early treatment, prevention and reduction of complications, and improvement of prognosis.
Treatment principle: endoscopic treatment is preferred to reduce trauma and shorten recovery time, and surgical treatment is adopted when necessary.
General treatment
For patients with bleeding black spot polyp syndrome, hemostasis and rehydration can be used as treatment.
However, for uncontrollable bleeding, treatment must be carried out after further examination and clarification of the bleeding site.
If necessary, establish venous access in time to replenish blood volume.
Endoscopic treatment
The endoscopist needs to decide what kind of removal method to adopt according to the size, number, shape and location of the polyps.
For small diameter polyps, usually take the trap electric excision, for the base of the wider or non-tip small or large polyps can be taken to endoscopic mucosal resection for resection.
For the diameter ≥ 3.0 cm of non-tipped polyps, segmental resection can be taken to reduce the probability of intestinal bleeding and intestinal perforation [11].
Small bowel microscopy is clinically important for small bowel polyps that were previously more difficult to manage, and should be used as the preferred method of polyp treatment for obvious small bowel polyps.
Surgical treatment
Indications for surgical treatment
Intussusception causing obvious intestinal obstruction, ineffective conservative treatment or recurrent episodes.
Repeated episodes of gastrointestinal hemorrhage.
Individual isolated large polyps, such as >2cm small intestinal polyps or >1.5cm colorectal polyps, or multiple polyps densely packed in a certain intestinal segment, causing intussusception or bleeding.
Those who are suspected of cancer.
Surgical approach
The surgical approach generally depends on the location and extent of the intussusception, the presence of malignancy, and the degree of associated inflammation, edema, and ischemia.
They mainly include segmental resection, segmental incision polypectomy, laparoscopic combined small bowel polypectomy, and intraoperative endoscopic combined segmental resection.
For the most common intussusception, the recommended surgical approach is repositioning, bowel resection and polypectomy. Especially for cases where intestinal necrosis, perforation and malignant tendency occur, and polyps that are more numerous and dense should also undergo intestinal resection anastomosis.
Surgery is mainly aimed at relieving obstruction and removing bleeding foci, and does not necessarily lead to a radical cure of polyposis. Multiple surgeries are usually required, which may lead to complications such as short bowel syndrome and intestinal adhesions, affecting the patient’s quality of life after surgery.
Pigmentation treatment
Hyperpigmentation has no obvious cancerous tendency, if there is no cosmetic need, hyperpigmentation can be left untreated.
The treatment of freckles on the face and lips of patients with dark spot polyp syndrome is difficult, which can be treated by surgical excision, cryosurgery or argon helium knife ablation, etc. At present, laser can also be used in the treatment of pigmented spots, which has achieved considerable results.
Psychotherapy
Dark spot polyp syndrome can confuse patients in terms of their perceptions of factors such as fertility, changes in appearance, cumbersome screening and surveillance strategies, uncertain cancer risk, and lack of knowledge about PJS, which may lead to fear, anxiety, and even mild depression [10].
Understanding the patient’s psychological state and providing them with relevant genetic counseling, treatment planning, and surveillance strategies will alleviate the anxiety and discomfort to some extent.
Prognosis
Cure.
Current therapeutic strategies for melanotic polyp syndrome are mainly symptomatic and cannot achieve the goal of eradicating the disease. Prognosis is closely related to complications.
Patients with multiple polyps are prone to complications such as intestinal obstruction and intestinal bleeding, which affect the quality of life.
In the absence of cancer, the prognosis of the disease is generally good, but long-term follow-up is needed.
Patients with melanotic polyp syndrome have a significantly higher risk of cancer, especially cancers affecting the gastrointestinal tract. The increased risk of cancer, combined with the increased risk of intussusception, leads to increased mortality and affects prognosis.
Daily
Daily Management
Avoid irritating and hard foods, high fiber and coarse grains.
Stop smoking and drinking, and avoid staying up late.
Exercise moderately to enhance immunity and stabilize mood.
Discontinue aspirin, clopidogrel, warfarin and other non-steroidal anti-inflammatory drugs and anticoagulant drugs when there is gastrointestinal bleeding to avoid life-threatening active bleeding.
Follow-up
Since macular polyp syndrome runs in families, the offspring of patients should also be closely followed up with regular examinations such as gastroenteroscopy and capsule endoscopy in order to avoid missed or misdiagnosed cases.
Gastroenteroscopy is performed from the age of 8 years in asymptomatic patients with macular polyp syndrome. If polyps are found on endoscopy, gastroenteroscopy is performed at 1-3 year intervals. If the test is negative, routine endoscopy is recommended at age 18.
Patients with asymptomatic melanotic polyp syndrome undergo small bowel examination starting at 8 years of age. Magnetic resonance imaging or capsule endoscopy is recommended at intervals of l-3 years [12].
Prevention.
Black spot polyp syndrome is inherited in an autosomal dominant manner, with a 50% probability of developing the disease in children, and tends to develop in clustered families. Prenatal diagnosis or preimplantation genetic diagnosis before the birth of the fetus can effectively block the transmission of the disease in the family and prevent the birth of the next generation of affected children [13].
Prenatal diagnosis can be performed in early or mid-pregnancy, and test samples are obtained by invasive chorionic villus biopsy, amniocentesis, and umbilical cord blood puncture. However, these modalities carry some risk of miscarriage.
In recent years, non-invasive prenatal diagnosis using the mother’s free fetal DNA technology has also become more mature. Genetic diagnosis can be performed at 8-10 weeks of gestation, which is able to determine whether the fetus carries disease-causing genes at an earlier stage.
For couples who have a need to have children, genetic testing can be used to identify the causative gene. For couples who have clarified the disease-causing gene mutation, the risk of pregnancy and fertility should be further evaluated by obstetricians or reproductive medicine specialists, and finally fertility preservation, prenatal diagnosis, or pre-implantation genetic diagnosis guidance should be given according to the couple’s age and physical condition [14].
Small bowel microscopy greatly improves the quality of life and long-term prognosis of patients with melanotic polyp syndrome; endoscopic treatment does not prevent polyp recurrence, but it has a positive significance in reducing the risk of intussusception and cancer.