Clinical Management and Genetics of Gastrointestinal Polyps in Children

Polyposis syndromes have been managed in the past by geneticists and adult gastroenterologists but now increasingly fall into the remit of the pediatric gastroenterologists. Gastrointestinal polyps in children most commonly appear with rectal bleeding. Perhaps of more concern is their potential for malignant change. This article reviews the polyposis syndromes, their malignant potential, and their management algorithms. The genetics of these syndromes and future advances are also discussed. HISTOPATHOLOGIC CLASSIFICATION Gastrointestinal polyps in children fall into two major categories: hamartomas (juvenile polyps and Peutz–Jeghers polyps) and adenomas. Solitary polyps in children are most commonly hamartomas, predominantly of the juvenile type, whereas solitary adenomas are extremely rare. Of the familial syndromes, however, familial adenomatous polyposis is more common than juvenile polyposis syndrome (JPS) or Peutz–Jeghers syndrome (PJS). The pathologic features of these polyps are described in Table 1 and shown in Figure 1, A, B, and C.TABLE 1: Pathological features of GI polyps in childrenFIG. 1.: (A) Low-power photomicrograph of an ileal Peutz-Jeghers polyp. Note the arborizing strands of muscularis mucosae lined by normal small intestinal epithelium. (B) Low-power photomicrograph of several tubular adenomas in the colectomy specimen of a patient with familial adenomatous polyposis. (C) Low-power photomicrograph of a juvenile polyp of the rectum. Note the abundant lamina propria and cystically dilated glands. Stain (A–C), hematoxylin and eosin.Figure 1: ContinuedFigure 1: ContinuedCLINICAL MANAGEMENT The most common manifestation of a large bowel polyp is painless rectal bleeding. The differential diagnosis of rectal bleeding is wide and includes anal fissure, trauma, infective colitis, allergic enteropathy, Meckel's diverticulum, congenital vascular anomalies, and inflammatory bowel disease. Of 730 patients with rectal bleeding referred to a single center, 29 children were found to have colorectal polyps. Twenty-four polyps were juvenile polyps, two were Peutz–Jeghers polyps, and one was an adenomatous polyp (1). Nine of the polyps were located proximal to the sigmoid-descending junction suggesting that such children should have a full colonoscopy and not a limited flexible sigmoidoscopy. Other reviews concluded that up to 60% of juvenile polyps may be found proximal to the sigmoid colon (2), which confirms the need for full colonoscopy in the assessment of rectal bleeding. Ultrasound with saline enemas before colonoscopy has been reported to have a high specificity and sensitivity for identifying polyps (3), but published data are from small samples. This procedure does not remove the need for colonoscopy and is therefore not favored in our practice. To plan management appropriately, the pediatrician treating a child with a gastrointestinal polyp must know the histopathologic type, the number and site of polyps, and whether there is a family history of polyps or colorectal cancer. The clinician must also assess for associated extraintestinal manifestations of polyposis syndromes. HAMARTOMATOUS POLYPOSIS SYNDROMES Juvenile Polyp Children with a solitary juvenile polyp show symptoms of painless rectal bleeding or perianal polyp protrusion, at a mean age of 4 years. The risk of malignant change is almost negligible; there are only eight cases in the literature of development of neoplasia in patients with solitary juvenile polyps. The age range of these patients was 1.5 to 67 years (mean age, 24 years) (4). In addition, a review of 82 patients with solitary juvenile polyps (mean age at diagnosis, 32 years; range, 3–71 years) showed no increased risk of colorectal cancer or of dying as a result of the polyp (5). However, it is unclear which patients with a solitary juvenile polyp at diagnosis may progress to formation of more polyps and development of the phenotype of JPS. Although the risk of development of malignancy in a solitary juvenile polyp is very small, such polyps should be removed, even when discovered incidentally. If there is no relevant family history and if after full colonoscopy the polyp is found to be solitary, endoscopic polypectomy is sufficient treatment. If the patient is discharged, parents must be aware that juvenile polyps may be the first feature of JPS. If fresh symptoms arise, the child should undergo another investigation. When there is a positive family history or when multiple juvenile polyps are found, however, the possibility of JPS syndrome is raised, and a different management strategy should be used. Juvenile Polyposis Syndrome Juvenile polyposis is a rare autosomal dominant condition characterized by the occurrence of multiple juvenile polyps in the gastrointestinal tract. In children, the most common age of initial symptoms is 9 years with symptoms including rectal bleeding, anemia, or prolapse of either the polyp or rectum. Less commonly, the condition appears in infancy, with anemia and hemorrhage, diarrhea, protein-losing enteropathy, and rectal bleeding (6). The entire gastrointestinal tract is usually affected, and the prognosis is related to the severity and extent of gastrointestinal involvement. The course in such infants is fulminant, and death occurs before the age of 2 years in severe cases (7). Compared with patients with solitary juvenile polyps, patients with JPS not only have more polyps, but are also more likely to have right-side polyps, polyps with adenomatous change, and anemia (8). As the condition progresses, the number of polyps increases to 50 to 200. Polyps are found primarily in the colon but also in the stomach and small intestine (9). The number of polyps needed to make the diagnosis remains controversial. Jass et al. (10) proposed five, whereas Giardiello et al. (4) suggested that patients with as few as three juvenile polyps should undergo screening for colorectal neoplasia. This arbitrary number was based on a retrospective review of 57 patients with JPS, in which it was reported that 9 of 19 patients with three or more polyps had development of colorectal neoplasia compared with only 1 of 28 patients with only one or two polyps. A significant proportion of patients with JPS have been reported to have other morphologic abnormalities, including digital clubbing, macrocephaly, alopecia, cleft lip or palate, congenital heart disease, genitourinary abnormalities, and mental retardation (11). Infrequently, JPS occurs as part of the Bannayan–Riley–Ruvalcaba syndrome (macrocephaly, pigmentation of the genitalia, and psychomotor delay in childhood), or Cowden syndrome (multiple hamartomas of multiple organs, macrocephaly, thyroid, and breast disease). There is little doubt that JPS is a premalignant condition. There is a 15% incidence of colorectal carcinoma in patients less than 35 years of age, leading to a cumulative risk of colorectal cancer of 68% by age 60 years (10). A retrospective study of 57 patients with JPS demonstrated a mean age of onset of colonic neoplasia of 38 years (range, 6–58 years) (4). Neoplastic changes have been documented both in the polyps and in flat, apparently normal colonic mucosa. Malignancies in the stomach, duodenum, and pancreas have been described in adults. Patients with features suggestive of JPS should have surveillance colonoscopy with random biopsies of polyps and flat mucosa every 2 years. When the number of polyps is small, endoscopic polypectomy and follow-up may suffice, but it is not clear whether endoscopic surveillance is adequate to prevent malignancy. When there are numerous polyps or symptoms such as bleeding and diarrhea persist, prophylactic colectomy should be considered after adolescence. As yet, there are insufficient data to justify prophylactic colectomy solely for the risk of colorectal carcinoma. The role of cyclooxygenase (COX)-2 inhibitors in pediatric JPS is unclear at present. In three of eight families affected by JPS, polyps were identified in asymptomatic first-degree relatives (8). Thus, first-degree relatives of patients with JPS should be screened by colonoscopy beginning at age 12 years. Even when the child is asymptomatic and even if the colonoscopy is negative, some authorities continue to screen at 3-year intervals. Peutz–Jeghers Syndrome Peutz–Jeghers syndrome (PJS) is a rare autosomal dominant condition in which gastrointestinal polyps occur in association with macular melanin pigmentation. Polyps arise primarily in the small bowel and to a lesser extent in the stomach and colon. Pigmentation occurs in most, but not all, patients and is seen most frequently on the lips and buccal mucosa and occasionally on the hands, feet, and eyelids. The primary concern to the pediatrician is the risk of small bowel intussusception, causing intestinal obstruction, vomiting, and pain. In addition, intestinal bleeding leading to anemia can occur. The risk of neoplasia is well documented in young adults and includes development of unusual tumors such as Sertoli cell tumor of the ovary and testicular tumors in prepubescent boys. In most patients, PJS appears before adulthood with symptoms such as abdominal pain (and intussusception) or anemia. Of 70 cases of PJS in childhood summarized after a literature search, 50 had episodes of abdominal pain, 13 gastrointestinal bleeding, and 11 anemia (12). This study was biased, because complicated cases of PJS are more readily reported than uncomplicated cases. There is controversy about the management of midgut polyps in the young child. There is a high reoperation rate after initial laparotomy for small bowel obstruction. This rate may be reduced in skilled hands by intraoperative enteroscopy (possibly through a surgical enterotomy) to remove other polyps. More than half the patients with PJS observed at St. Mark's Hospital from 1943 through 1987 had two or more laparotomies. The average age at initial laparotomy was 15 years (range, 2–39 years;n = 23). Polyp-induced complications were responsible for 75% (23/31) of second laparotomies (13). Intraoperative small bowel endoscopy detected 38% more polyps at laparotomy (17 additional polyps) than did external palpation and small bowel transillumination. At present, it is not possible to be prescriptive about management of polyps of different sizes. The advantages and disadvantages of prophylactic polypectomy for asymptomatic patients should be discussed with the family and each case considered on its own merits. At diagnosis, treatment is according to the PJS algorithm (Fig. 2), and management is influenced by the size of the polyps and their locations. This protocol is adapted from adult practice, and therefore the size of polyps may be in young children with midgut polyps than 1.5 should be referred for laparotomy and intraoperative children are asymptomatic with small polyps than the parents should be about the risk of If symptoms the child should be referred for and for The management of children with polyps and on the number of polyps. Children with multiple midgut polyps may from prophylactic of Peutz–Jeghers syndrome in risk of both in the gastrointestinal tract and in extraintestinal is in adults with PJS than in the In the 70 cases in the literature in patients with PJS were less than years of age, patients had had one and the other (12). A of patients at St. Mark's Hospital up to found of which were gastrointestinal and The affected from years of with PJS should be aware of unusual symptoms to a testicular and have a for potential A screening for patients with PJS after is shown in Table for screening for in syndrome after POLYPOSIS In children, gastrointestinal adenomas are almost associated with adenomatous polyposis syndromes. one colorectal is found in a colonoscopy with is adenomatous polyposis is the most common of the adenomatous polyposis syndromes. is an autosomal dominant condition in which there is a in the on Patients with have multiple adenomas the large more than and more than Polyps to appear in childhood or and in number with the colorectal cancer is almost if colectomy is not patients with are also at increased risk of malignancy of the duodenum, of thyroid, and Children less than years of age may have may be to abdominal in such children, is not our practice. responsible for the of families with must be aware of the high potential for neoplasia at different There are three in which a patient with may to the of the are for screening because of a positive family some have colorectal symptoms such as bleeding or diarrhea, and a have manifestations treating a child with an unusual such as or a rare tumor such as should the possibility of if there are multiple tumors or another is manifestations of in children and young and patient should undergo screening for In families with a can whether a family has the condition. The diagnosis is by adenomas flexible sigmoidoscopy. the on of more than of the a positive if the are The of however, is of no for families with a is to screening to first-degree relatives from the age of 11 years At age the child is more to the of the result children the screening and its at a age 9 family should be considered can be follow-up the only was may to endoscopic in the on one undergo flexible from the age of years adenomas are flexible should be because there is rectal in the condition (Fig. protocol for familial adenomatous polyposis in children have had a full colonoscopy by the age of years to polyp and and of and the family and the and of the a can be the and of may be to the extent of polyposis if the to delay to the age of but and patient should be aware that surveillance is not a of colorectal malignancy is that the with the Children and should undergo colonoscopy in a pediatric to that screening are seen in a positive because are on In families in which the is not The St. Mark's is to on first-degree relatives the age of years and colonoscopy with at and even malignancy have been documented in children with are less than 12 years of to children when are to make their own may colonoscopy in children in families in which severe or have been found at a young age This is if the family has one of the associated with a severe phenotype in 11 or in of In the past has for families in the is arise when a for a condition. can for whether to undergo the but for children at the must be by the children found not to the are an sigmoidoscopy. the other of the may have result in to the or even the family arise about age is to for a that not appear or need treatment before or adult There are for not children are of an age at which can to an The should be to the possible to the child. at the age of 12 to there is a for the of children are and need not undergo In at 1 of age, the is and there is a potential for from the of In to to have their child for it is to must be the to the at or it the for polyposis syndromes should be only when there is a clear in each of patients with and their relatives and the of a or is is that the screening the of the and its possible such as and of a positive result should be discussed before and there should be a clear protocol for that undergo for and some have been is the only that the risk of colorectal cancer. In the of severe colectomy is usually in patients in the to or to and colectomy before the patient can to a colon before adolescence. case should be considered on its own merits. with are asymptomatic and in their or on The surgical must not only be but must also have and The of primary may be influenced by of the site and the likely severity of the polyposis. patients with a at 15 at may be because phenotype is characterized by a large of polyps and a risk of cancer Even a polyp a risk of malignancy it is to delay on the of polyp the of procedure may be affected colectomy with or with The is a with but the remains at risk of cancer. surveillance of the is needed after but can result in A procedure the colorectal cancer risk almost that large bowel remains with the anal and after a is not In addition, the procedure is more complicated than an a and a is associated with an as risk of and the should be have been by a number of some are by a range of such as and A study patients with had with by colectomy and showed more complications and as well as a 11 in patients with was more common after a procedure and was more affected Other have and after for is to in because the is very and the cancer risk is to an can be when the patient is Patients with a large number of rectal polyps or with may have with a procedure in the first because of the risk of malignancy and are surgical with children and their are to patients, and the and A is not considered there is which more may be anal or malignancy in the rectum. endoscopic surveillance of the stomach, duodenum, and with a is in patients after the age years by the patient has such as abdominal pain, that should be aware of the increased risk of as in Table and are but that occur with in patients with the and surgical In at St. of of were by a surgical procedure after a delay of 24 occur most commonly in the and may leading to small or vascular obstruction. may progress or may their to Patients found to have at laparotomy should be by and referred for of or surgical surgical high of and and usually of the including and have limited is as a children with extraintestinal tumors should the possibility of in the family POLYPOSIS SYNDROMES syndrome is an autosomal dominant condition gastrointestinal hamartomas and or in such as the and In addition, patients may have and and and infants should be screened by for syndrome is characterized by of a primary tumor and multiple colorectal adenomas. Patients with a polyposis syndrome and symptoms should undergo and for possible tumor The management of the colonic polyps in syndrome is the as for is a common normal of the and is with polyposis. polyps appear as of and after of severe more than 1 to be to from adenomas. Bannayan–Riley–Ruvalcaba and Cowden have been discussed skilled should polypectomy in children and can be even for an to some polyps. from for polypectomy to remove the polyp the of bleeding or Polyps may be with the if there is a risk of the on the colon may be before to the and of polyps. with of the colonic and most polyps more than 1 are readily less than 1 the diagnosis of and can be seen more by the colonic either through or the The of in pediatric is it is to the patient to the polyp change and endoscopic are also to the polyp in the before polyps less can be the This is and almost adequate must be however, to to the bowel is in the colon. Polyps more than should be by make of small polyps polyps can be by a in which the polyp is In polyps, in which may be the are in to This procedure an of the of polyp and the and of the such as and of multiple polyps but not polyp is it can be by through the into a polyp or through or a The risk of than 1 polyps is in the and more polypectomy such as of or saline to the mucosa from the bowel and polyps can also be an the the risk of and significant bleeding should be less than POLYPOSIS SYNDROMES Polyposis and adenomatous polyposis is the most common of the polyposis syndromes. The is at 1 in is as an autosomal dominant with high but with a age of The rate of is as This in the development of in the of a family The responsible for adenomatous polyposis was to in the The and of the This large 15 a of with 15 the (Fig. The appears to be a The with which in to and the have a role in cell and of cell are small or that result in the of a of the a one of the two that the to have also been found in adenomas and in colon suggesting that of is also an in colorectal cancer. are the half of the two are found at and for one of detected and are associated with a more severe Other have been observed a of colonic adenomas is found when are located in the of of the is almost if the is of A of has been described that is characterized by colonic polyps and a have been described for condition at the and of the are not and there may be which that there are other in the of the disease. of the seen in patients be by the of their and other have on and for Polyposis The for is the from usually from samples. The initial may be an or can be to identified by these of the of the that occurs with most patients have two one normal and one in to the an of normal as well as a This in two on an if both are the are of and only one is This can a in up to of the in other family and is the and the of the a is identified in an affected family a is to the is first by and for the More than different have been and the may be a should be aware that the may be detected in only 60% to of cases. is only in these cases that a can be to detected may for the of risk In small of that to or the are to the in a a diagnosis is in two family these can be in other family A of two affected is and the is therefore for relatives of with of up to the to be in a even if the of the is not of the The initial the of a patient for a At if a be found, the is and it is not possible to to asymptomatic If the case is relatives can be A result is considered in and the should be considered to an average risk for the development of adenomas and cancer. A positive result confirms the diagnosis of and patients should be screened and as has been Peutz–Jeghers Syndrome The for condition has been The a and is located on The of the is as and there potential for to However, if the is in in the it may have a role in in patients with no pigmentation even potential Juvenile Polyposis Syndrome A family history is found in to of patients, with the apparently autosomal There is for in JPS. of families have in associated with Cowden located at or in located at are needed to the for JPS and the leading to in these POLYPOSIS A polyposis was at St. Mark's Hospital in the and now on more than families with polyposis syndromes, it one of the polyposis in the The size and age of the to and family an when is families are well to to have The patients, their family their surveillance and and Children from affected families are by the to with their and to with the and have potential As well as an the also for and of including the of screening and surgical In it may the of in have suggested that may be colon cancer The through their on have shown of adenomas the of has been limited by gastrointestinal with and case of rectal cancer treatment The for Polyposis study is the of such as the of and with has two and is and responsible for whereas is in colorectal adenomas and inhibitors have reported a in the number of colorectal polyps This and also the of may to the future management of colorectal and adenomas and should have gastrointestinal may also have a role before in and as such are the of in a pediatric in are likely to in other and in the treatment of adenomas and colorectal cancer. The diagnosis of a polyposis syndrome of the and of the polyps and an of relevant family treating children with unusual tumors should the possibility of a polyposis Children and with a polyposis syndrome are not only with the complications of the polyps, such as or bleeding, but also with the extraintestinal manifestations and the risk of malignancy. should be well and families need and that is The to of these families should be a polyposis an colorectal and of must be with the and by these The Polyposis St. Mark's the polyposis and has been in of the and in St. Mark's Hospital our pediatric and on endoscopic