- Email: [email protected]
Malignant risk in juvenile polyposis coli: Increasing documentation in the pediatric age group
Malignant Risk in Juvenile Polyposis Increasing Documentation in the Pediatric By Kurt F. Heiss, Donald
Schaffner,
Coli: Age Group
Richard R. Ricketts, and Kevin Winn
Atlanta, Georgia l The presence of juvenile polyps with resulting bleeding and abdominal pain has traditionally been considered a benign, self-limiting process which would resolve with age. The dictum that these polyps were usually solitary, were found predominantly in the rectosigmoid area, and were without malignant potential has been reconsidered in recent years with the increased use of colonoscopy. Several case reports in both adults and children have documented the presence of adenomatous changes in this syndrome. We report 3 cases of children, ages 3,11, and 11 who were found to have adenomatous polyps in the midst of fields of juvenile polyps on evaluation for rectal bleeding. All three were treated definitively with endorectal pull-through. Two of these patients had atypia on histological evaluation, one of which was severe. We recommend a more aggressive approach to patients found to have multiple juvenile polyps on barium enema, including colonoscopic biopsies at several sites to determine the presence of adenomatous changes, with colectomy and endorectal pull-through should these be found. Copyright o 1993 by W.B. Saunders Company INDEX WORDS:
Juvenile polyposis.
UVENILE polyps are the most common colonic tumor in children, thought to occur in as many as 1% of all children.’ The lesion most commonly presents with painless rectal bleeding (80% to 90%), and is felt to be the most common cause of rectal bleeding in children over 1 year of age, with more than two thirds presenting before age 7.2 Most polyps tend to disappear by adolescence, with autoamputation being the most likely mechanism.3,4 The lesion is solitary and localized to the rectosigmoid area in most cases (80%), within easy reach of a rigid sigmoidoscope. However, recent clinical experience with use of flexible colonoscope reported more than 50% of patients had more than one lesion and 60% of the lesions were found, evenly distributed proximal to the sigmoid colon.5 Despite increased documentation of multiple juvenile polyps, most patients have fewer than five when they present and they are easily dealt
J
From the Department of General Surgery and Pathology, Egleston Children’s Hospital at Emory University and Scottish Rite Children S Medical Center, Atlanta, GA. Presented at the 24th Annual Meeting of the Canadian Association of Paediattic Surgeons, Ottawa, Ontario, September 10-13, 1992. Address reprint requests to Kurt F. Heiss, MD, Assistant Professor, Emory University Department of General Surgery, 1365 Clifton Rd NE, Atlanta, GA 30322. Copyright o 1993 by W. B. Saunders Company 0022-3468/93/2809-0029$03.00/O
7188
with using colonoscopy. The cystic, inflammatory, nonneoplastic histological appearance of juvenile polyps distinguishes them from adenomas and has caused most clinicians to feel that there is no risk of malignant transformation. Some have even questioned whether juvenile polyps and adenomas can even coexist in the same patient.6 In contrast to solitary juvenile polyps, the juvenile polyposis syndrome is an uncommon lesion, first described by McCall et al.’ This lesion is characterized by numerous lesions scattered throughout the colon (juvenile polyposis coli) or the entire gastrointestinal (GI) tract (multiple or diffuse juvenile polyposis), and presents with rectal bleeding, abdominal pain and nutritional problems. Several reports of the presence of adenomatous changes in juvenile polyps, adenomas, and adenocarcinomas in the presence of fields of juvenile polyps are found in the literature.8-1y This has caused increasing concern over the management of patients with the more common solitary polyps, as well.‘“J In an effort to clarify the distinction between the solitary polyp and the polyposis condition, we present three cases of juvenile polyposis coli manifesting coexisting adenomatous changes, one of which had carcinoma in situ on biopsy. Recommendations are made regarding management of a patient with these entities. CASE REPORTS
Case 1 An 11-year-old black girl presented with a history of painless bright red blood per rectum resulting in anemia. There was no family history of polyposis or GI problems. The physical examination was noncontributory. An air-contrast enema showed polyps spread diffusely from the rectum to the cecum (Fig 1). She underwent a colonoscopic biopsy which produced an adenomatous polyp with no evidence of atypia. The patient underwent colectomy and ileoanal pullthrough. The histological examination of the colon showed juvenile polyposis coli with occasional polyps having adenomatous changes (Fig 2).
Case 2 A 3-year-old white girl presented with a cramping abdominal pain and a history of bright red blood in her stools for 6 months. The family history was positive for colonic adenocarcinoma in a paternal aunt and multiple forms of GI cancer in maternal relatives. An air-contrast barium enema showed diffuse colonic polyposis. A colonoscopy showed both sessile and pedunculated juvenile polyps, 3 to 15 mm in size. The biopsies were consistent with juvenile polyps with no atypia. A colectomy with endorectal pull-through was performed. The pathologic review of the colon
JournalofPediatric
Surgery, Vol28, No 9 (September),
1993: pp 1188-l 193
1189
MALIGNANT JUVENILE POLYPOSIS COLI
pull-through was performed. The rectal mucosa juvenile nature but was otherwise normal.
had a few polyps of
DISCUSSION
Juvenile polyps are relatively common lesions affecting young people and are the most common form of colonic tumor in children, accounting for > 90% of colonic polyps1 While these polyps are most common in children and young adults, these lesions have been reported in older patients as well. Roth and Helwig22 described a bimodal age distribution in their series of 158 patients with juvenile polyps. The childhood group (60%) had an average age of 4.1 years while the adult group (40%) had an average age of 25.5 years. The incidence of rectal bleeding (80%) and prolapse of an anal mass or passed tissue in the stool (10% to 30%) as the initial presentation was similar in both age groups. Juvenile polyps have been described as retention polyps and inflammatory polyps, and are routinely grouped with hamartomas in the literature. They are smooth and round, bleed easily and frequently show areas of surface ulceration. They may be sessile or
Fig 1. Photograph of a gross colectomy specimen showing pancoIonic juvenile polyposis.
showed pancolonic yps demonstrating studies are being members.
juvenile polyposis with few adenomatous polfocal mild atypia. Subsequent chromosomal investigated for both the patient and family
Case 3 An adopted 9-year-old white girl presented to an outside institution with malnutrition, diarrhea, and rectal bleeding resulting in severe anemia. After transfusion and resuscitation she underwent a contrast enema, which showed diffuse colonic polyposis. She underwent colectomy and ileoproctostomy. The histology of the colon showed juvenile polyps with occasional adenomatous areas and no atypia. Efforts to obtain information regarding the parent’s health was unsuccessful, but there was the suggestion of a possible GI malignancy in a cousin at a young age. The patient had moved to Georgia and was referred to this institution for follow-up, presenting 2 years after the initial diagnosis and treatment. Sigmoidoscopy showed two polyps in the rectum and no lesions in the ileum. The histology of the polyps were adenomas, each showing moderate to severe atypia (Fig 3). Completion endorectal
Fig 2. changes.
Histology of juvenile polyp having foci of adenomatous
1190
MISS
ET AL
tial progression of the histology toward cancer.I(-Iy The dysplasia presents in two forms: the coexistence of adenomatous changes in a juvenile polyp; and coexisting adenomas lacking features of juvenile polyps found in patients with juvenile polyposis syndrome.23 The absence of small adenomas in these latter patients is felt to negate the possibility of an independent process causing adenomas to occur, de novo. Goodman et a123has suggested that juvenile polyps represent one step in a spectrum, beginning with hyperplasia, progressing to typical juvenile polyps which then develop total adenomatous changes and progress eventually to a true adenoma. The substance for this hypothesis is a 23-year-old patient who manifested all these histological findings at the time of her colectomy to treat her adenocarcinoma of the rectum. Several groups have reported the concurrent presence of juvenile and adenomatous polyps in the same patient.8-t9 Indeed, Bussey reported adenomatous tumors in 6 of 37 patients with juvenile polyposis (16%). 24 The St Mark’s registry has reported 1032 polyps found in 87 patients diagnosed with juvenile polyposis. Sixteen percent of these
Fig 3. Adenomatous polyp from case 3 showing severe atypia consistent with carcinoma in situ.
pedunculated. Histologically, there is a continuous single layer of goblet cells, interrupted frequently by ulcerations and chronic inflammation (Fig 4). The sectioned surface show numerous cystic spaces filled with mucus. There is abundant granulation tissue and inflammatory exudate composed of plasma cells, eosinophils, polymorphonuclear cells, and histocytes. Mitoses are uncommon. This description is in contrast to the histology of adenomatous polyps which are neoplastic overgrowths of epithelium with hyperchromatic nuclei, cellular elongation, and few mature cells organized into an arborizing glandular pattern. These may form villi or papillary extensions. Their neoplastic potential has been well described. These two lesions have histologically been viewed as independent and unrelated. Indeed, a study of 50 children reported by Kottmeier and Clatworthy concluded that juvenile and adenomatous polyps did not coexist in the same patient.6 In recent years, this simple view of the benign nature of juvenile polyposis has been complicated by several factors. Several reports have documented the presence of dysplastic changes representing a poten-
Fig 4. Histology of typical juvenile polyp. Note presence of surface ulceration, inflammatory cells, and cystic spaces.
MALIGNANT
JUVENILE
POLYPOSIS
COLI
polyps had adenomatous changes, while 2% were frank adenomas. Interestingly, 18 of the 87 patients have developed large bowel cancer.25 In addition, another group has reported a colon carcinoma arising in an adolescent from a solitary juvenile p01yp.~~ While these several reports appear to lay to rest the issue of whether adenomas and malignancies can arise in the presence of juvenile polyps, this evidence has caused increased concern with regard to the management of patients found to have juvenile polyps of the solitary type, as well. This anxiety has led some authors to suggest that all pediatric patients should have any polyp removed immediately when found unless the child is less than 8 years old, or if the child becomes symptomatic, or if the polyp persists without autoamputation for more than 1 year.*” The very common nature of juvenile polyps in children, in consideration of the rarity of colorectal cancer in children raises some obvious questions as to what management scheme should be persued. The distinction between cancer risk in patients with few polyps as opposed to those with juvenile polyposis should be made. Most children have fewer than five polyps and many have solitary polyps at the time of presentation.*,*’ This is in contrast to the polyposis patient who has fields of colorectal polyps ranging from 50 to 200 in number, some of whom have polyps in the small intestine and stomach as we11.25There has been only one reported case of adenomatous change in a solitary polyp (a 21-year-old patient)** and only two cases of colorectal malignancy documented in the pediatric age group. 26~29 If these very common, solitary juvenile polyps are prone to malignant change, one might wonder why colorectal cancer is so rare in the pediatric population. It seems clear that the risk of malignant change in a solitary juvenile polyp is rare, and a distinction must be made between these lesions and juvenile polyposis, where the risk is more apparent, and there are several documented cases of malignancy.8~y~*4.16~23~25+26~29-31 In order to decrease confusion when discussing patients with juvenile polyps, Jass et a125have suggested a working definition of juvenile polyposis as: (1) more than 5 juvenile polyps of the colon/rectum; (2) juvenile polyps throughout the GI tract; or (3) any number of juvenile polyps with a family history of juvenile polyposis. There are three basic types of juvenile polyposis.3’ The infantile form presents prior to age two with severe rectal bleeding and anemia, severe diarrhea leading to hypoproteinemia, and malnutrition. Recurrent rectal prolapse and bowel obstruction from intussusception are complicating factors. Colectomy has proved curative in a few reported cases, while mortality without surgical intervention is very high.33.74
1191
Autopsy studies have shown juvenile polyps extensively involving the terminal ileum and colon, and on occasion involving the small intestine and stomach. About one third of these patients will have congenital abnormalities such as Meckel’s diverticulum, malrotation of the bowel, and heart lesions.35 Second, juvenile polyposis coli presents with abdominal pain, rectal bleeding or prolapse, and diarrhea. The colon is usually matted with polyps, but polyps elsewhere are rare. Twenty-five percent to SO% of these patients have a family history of juvenile polyp~.~~Some authors have recommended management of this lesion with colonoscopic polyp removal and surveillance, removing the colon only when dysplasia is found.36 Others have performed colectomies with ileoproctomstomy and done surveillance sigmoidoscopy to clear the rectum of p01yps.~’ This has resulted in one irreparabIe rectal cancer due to inadequate following in a 15 year old.25 Others have recommended total colectomy with mucosal proctectomy and endorectal pull-through, thus removing all coionic mucosa and the risk of colonic malignancy.‘x The third form, generalized or diffuse juvenile polyposis presents with symptoms similar to those of juvenile polyposis coli or from gastric bleeding from polyps. Polyps may be present from the stomach to the anus. Surgical therapy is indicated for bleeding, malnutrition and diarrhea. Approximately 25% of these patients may have family members with juvenile polyposis.31 The familial nature of the latter two types of juvenile polyposis has been described in several reports.R.10.‘4.15.Z3,25,32,35,39 The genetic lesion has been described as an autosomal dominant condition. The risk of gastrointestinal malignancies in affected families is greatly increased, indicating that the family, as well as the patient, must be evaluated carefully. Interestingly, the risk of malignancy is as high in the family members without polyposis as in the affected members. In addition, the malignancies have occurred in organs other than the colon. Hence, prophylactic colectomy has not been recommended in the patients with polyposis. From reports discussed above, it seems apparent that the risk of malignancy is dramatically increased in patients with juvenile polyposis coli or generalized juvenile polyposis. The incidence of 18 colorectal cancers in 87 patients on the St Marks’ registry is a dramatic increase in incidence of colon cancer in a limited population. It is noteworthy that the mean age at presentation was 34 years (range, 15 to 59) and that the clinical outcome was usually poor with a high percentage of poorly differentiated or mutinous cancers.25 In this report, Jass et al failed to identify any
1192
HEISS ET AL
markers among their 87 patients that would identify those with increased risk. Thus they conclude that the trigger causing the conversion from a juvenile polyp to a neoplasm is a random event. It is possible that the cancer risk in this group is higher than reported due to the large number of colectomies that were performed to treat unmanageable symptoms or because of confusion at the time of presentation with familial adenomatous polyposis.lo Bentley et aP1 have suggested that the incidence of carcinoma is 20% to 30% in patients with the heterogeneous mixture of both juvenile and adenomatous polyps and that patients with homogeneous juvenile polyps alone are not at risk. If the incidence of heterogeneous patients is 15% as described by Bussey et al, then the risk of carcinoma (3% to 5%) is slightly increased.35 Years of controversy over the true risk of malignancy from juvenile polyps is slowly being sorted out. Bussey et al have suggested that adenomatous changes in juvenile polyps are as common in solitary cases as they are in multiple ~01~~s.~~If true, this suggests that these solitary polyps are self amputating prior to developing atypia and becoming cancerous, since the incidence of adenocarcinoma is rare in children. The risk of cancer from solitary juvenile polyps must be vanishingly small due to its common pediatric presentation and the very small number of documented cancers arising from solitary polyps.
In conclusion, the development of colonoscopy has documented increased incidence of multiple polyps in more proximal locations than previously realized. However, the preferred status of the solitary juvenile polyp as a benign, self-limiting lesion, absent of a malignant potential should be preserved. Solitary or multiple polyps, fewer than five in number, should be removed to resolve symptoms and to establish a diagnosis in situations where concern exists regarding increased risk of familial adenomatous polyposis. Since the risk of recurrence is low, further surveillance by endoscopy is probably unwarranted. Colectomy should be performed in the presence of juvenile polyposis coli when clearing of the polyps by colonoscopy is not possible. The difficulty of screening fields of polyps with random biopsies to establish the absence of adenomatous polyps is significant. While regular colonoscopic surveillance may temporize by removing polyps, in the presence of a large number of lesions, colectomy with endorectal pullthrough could remove the affected organ and bring the risk of colon cancer to zero. This is especially true for familial cases, since these seem to be the conditions in which GI cancers are more common. Juvenile polyposis should be treated as seriously as familial adenomatous polyposis. Family members should be questioned and studied as appropriate.
REFERENCES 1. Gelb A, Minkowitz S, Tresser M: Rectal and colonic polyps occurring in young people. NY State J Med 62:513-518,1962 2. Schermeta DW, Morgan WM, Eggleston J, et al: Juvenile retention polyps. J Pediatr Surg 4:211-2151969 3. Louw JH: Polypoid lesions of the large bowel in children. S Afr Med J 46:1347-1352,1972 4. Mazier WP, MacKeigan JM, Billingham RP, et al: Juvenile polyps of the colon and rectum. Surg Gynecol Obstet 154:829-832, 1982 5. Mestre JR: The changing pattern of juvenile polyps. Am J Gastroenterol81:312-314,1986 6. Kottmeier PK, Clatworthy HW: Intestinal polyps and associated carcinoma in children. Am J Surg 110:709-716,1965 7. McCall I, Bussey HJR, Veale AMC, et al: Juvenile poloposis coli. Proc R Sot Med 57:896-897,1964 8. Smilow PC, Pryor CA, Swinton NW: Juvenile polyposis coli. A report of 3 patients in 3 generations. Dis Colon Rectum 9:248-254,1966 9. Stemper TJ, Kent TH, Summers RW: Juvenile polyposis and gastrointestinal carcinoma. Ann Intern Med 83:639-646, 1975 10. Velcek FT, Coopersmith IS, Chen CK, et al: Familial juvenile adenomatous polyposis. J Pediatr Surg 11:781-787,1976 11. Haggit RC, Pitcock JP: Familial juvenile polyposis of the colon. Cancer 26:1232-1238,197O 12. Kaschula ROC: Mixed juvenile, adenomatous and intermediate polyposis coli: Report of a case. Dis Colon Rectum 14:368374,197l
13. Reed K, Vose PC: Diffuse juvenile polyposis of the colon: A pre-malignant condition? Dis Colon Rectum 24:205-210,198l 14. O’Riordan DS, O’Dwyer PJ, Cullen AF, et al: Familial juvenile polyposis cob and colorectal cancer. Cancer 68:889-892. 1991 15. Grotsky HW, Rickert RR, Smith WD, et al: Familial juvenile polyposis coli: A clinical and pathologic study of a loarge kindred. Gastroenterology 82:494-501, 1982 16. Longo WE, Touloukian RJ, West AB, et al: Malignant potential of the juvenile polyposis coli. Report of a case and review of the literature. Dis Colon Rectum 33:980-984, 1990 17. Sandler RS, Lipper S: Multiple adenomas in juvenile polyposis. Am J Gastroenterol75:361-366,198l 18. Lipper S, Kahn LB, Sandler RS, et al: Multiple juvenile polyposis. A study of the pathogenesis of juvenile polyps and their relationship to colonic adenomas. Hum Pathol12:804-813, 1981 19. Rozen P, Baratz M: Familial juvenile colonic polyposis with associated colon cancer. Cancer 49:1500-1503,1982 20. Rolles CJ: Juvenile intestinal polyps-are they always benign? Br Med J 294:529,1987 21. Gryboski JD: All juvenile Polyps are not benign. Am J Gastroenterol81:397,1986 22. Roth Sl, Helwig EB: Juvenile polyps of the colon and rectum. Cancer 16:468-479, 1963 23. Goodman ZD, Yardley JH, Milligan FD: Pathogenesis of colonic polyps in multiple juvenile polyposis. Report of a case associated with gastric polyps and carcinoma of the rectum. Cancer 43:1906-1913,1979
MALIGNANT
JUVENILE
POLYPOSIS
1193
COLI
24. Bussey HJR: Familial Polyposis. Baltimore, MD, Johns Hopkins, 1975 25. Jass JR, Williams CB, Bussey HJR, et al: Juvenile polyposis-A pre-cancerous condition. Histopathology 13:619-630,198s 26. Liu-TH, Chen MC, Tseng HC: Malignant change of a juvenile polyp of colon: A case report. Chin Med J 4:434-439, 1978 27. Euler AR, Seibert JJ: The role of sigmoidoscopy, radiographs, and colonoscopy in the diagnostic evaluation of pediatric age patients with suspected juvenile polyps. J Pediatr Surg 16:500502,198l 28. Friedman CJ, Fechner RE: A solitary juvenile polyp with hyperplastic and adenomatous glands. Dig Dis Sci 27:946-948,1982 29. Schilla FW: Carcinoma in a rectal polyp. Am J Surg 4:434-439,1954 30. Restrepo C, Moreno J, Duque E, et al: Juvenile colonic polyposis in Columbia. Dis Colon Rectum 21:602-612, 1978 31. Bentley E, Chancrasoma P, Radi R, et al: Generalized juvenile polyposis with carcinoma. Am J Gastroenterol 84:14561459, 1989 32. Sachetallo CR, Griffen WO: Hereditary polypoid diseases of
the gastrointestinal 129:198-203,1975
tract.
A working
classification.
Am J Surg
33. Sachetallo CR, Hahn IS, Carrington CB: Juvenile gastrointestinal polyposis in a female infant: Report of a case and review of the literature of a recently recognized syndrome. Surgery 75:107114,1974 34. Soper RT, Kent Surgery 69:692-698.1971
TH:
Fatal
juvenile
polyposis
in infancy.
35. Bussey HJR, Veale AM, Morson BC: Genetics of gastrointestinal polyposis. Gastroenterology 74:1325-1330. 1978 36. Gilinsky NH, Elliot MS, Price SK, et al: The nutritional consequences and neoplastic potential of juvenile polyposis coli. Dis Colon Rectum 29:417-420,1986 37. Grosfeld J, West K: Generalized Arch Surg 121:530-534, 1986
juvenile
polyposis
cob.
38. Jaxvinen H, Fransilla KO: Familial juvenile Increased risk of colorectal cancer. Gut 25:792-800,
polyposis 1984
coli:
39. Gaithright JB, Cofer TW: Familial incidence polyposis coli. Surg Gynecol Obstet 138:185-188. 1974
of juvenile
Schaffner,
Coli: Age Group
Richard R. Ricketts, and Kevin Winn
Atlanta, Georgia l The presence of juvenile polyps with resulting bleeding and abdominal pain has traditionally been considered a benign, self-limiting process which would resolve with age. The dictum that these polyps were usually solitary, were found predominantly in the rectosigmoid area, and were without malignant potential has been reconsidered in recent years with the increased use of colonoscopy. Several case reports in both adults and children have documented the presence of adenomatous changes in this syndrome. We report 3 cases of children, ages 3,11, and 11 who were found to have adenomatous polyps in the midst of fields of juvenile polyps on evaluation for rectal bleeding. All three were treated definitively with endorectal pull-through. Two of these patients had atypia on histological evaluation, one of which was severe. We recommend a more aggressive approach to patients found to have multiple juvenile polyps on barium enema, including colonoscopic biopsies at several sites to determine the presence of adenomatous changes, with colectomy and endorectal pull-through should these be found. Copyright o 1993 by W.B. Saunders Company INDEX WORDS:
Juvenile polyposis.
UVENILE polyps are the most common colonic tumor in children, thought to occur in as many as 1% of all children.’ The lesion most commonly presents with painless rectal bleeding (80% to 90%), and is felt to be the most common cause of rectal bleeding in children over 1 year of age, with more than two thirds presenting before age 7.2 Most polyps tend to disappear by adolescence, with autoamputation being the most likely mechanism.3,4 The lesion is solitary and localized to the rectosigmoid area in most cases (80%), within easy reach of a rigid sigmoidoscope. However, recent clinical experience with use of flexible colonoscope reported more than 50% of patients had more than one lesion and 60% of the lesions were found, evenly distributed proximal to the sigmoid colon.5 Despite increased documentation of multiple juvenile polyps, most patients have fewer than five when they present and they are easily dealt
J
From the Department of General Surgery and Pathology, Egleston Children’s Hospital at Emory University and Scottish Rite Children S Medical Center, Atlanta, GA. Presented at the 24th Annual Meeting of the Canadian Association of Paediattic Surgeons, Ottawa, Ontario, September 10-13, 1992. Address reprint requests to Kurt F. Heiss, MD, Assistant Professor, Emory University Department of General Surgery, 1365 Clifton Rd NE, Atlanta, GA 30322. Copyright o 1993 by W. B. Saunders Company 0022-3468/93/2809-0029$03.00/O
7188
with using colonoscopy. The cystic, inflammatory, nonneoplastic histological appearance of juvenile polyps distinguishes them from adenomas and has caused most clinicians to feel that there is no risk of malignant transformation. Some have even questioned whether juvenile polyps and adenomas can even coexist in the same patient.6 In contrast to solitary juvenile polyps, the juvenile polyposis syndrome is an uncommon lesion, first described by McCall et al.’ This lesion is characterized by numerous lesions scattered throughout the colon (juvenile polyposis coli) or the entire gastrointestinal (GI) tract (multiple or diffuse juvenile polyposis), and presents with rectal bleeding, abdominal pain and nutritional problems. Several reports of the presence of adenomatous changes in juvenile polyps, adenomas, and adenocarcinomas in the presence of fields of juvenile polyps are found in the literature.8-1y This has caused increasing concern over the management of patients with the more common solitary polyps, as well.‘“J In an effort to clarify the distinction between the solitary polyp and the polyposis condition, we present three cases of juvenile polyposis coli manifesting coexisting adenomatous changes, one of which had carcinoma in situ on biopsy. Recommendations are made regarding management of a patient with these entities. CASE REPORTS
Case 1 An 11-year-old black girl presented with a history of painless bright red blood per rectum resulting in anemia. There was no family history of polyposis or GI problems. The physical examination was noncontributory. An air-contrast enema showed polyps spread diffusely from the rectum to the cecum (Fig 1). She underwent a colonoscopic biopsy which produced an adenomatous polyp with no evidence of atypia. The patient underwent colectomy and ileoanal pullthrough. The histological examination of the colon showed juvenile polyposis coli with occasional polyps having adenomatous changes (Fig 2).
Case 2 A 3-year-old white girl presented with a cramping abdominal pain and a history of bright red blood in her stools for 6 months. The family history was positive for colonic adenocarcinoma in a paternal aunt and multiple forms of GI cancer in maternal relatives. An air-contrast barium enema showed diffuse colonic polyposis. A colonoscopy showed both sessile and pedunculated juvenile polyps, 3 to 15 mm in size. The biopsies were consistent with juvenile polyps with no atypia. A colectomy with endorectal pull-through was performed. The pathologic review of the colon
JournalofPediatric
Surgery, Vol28, No 9 (September),
1993: pp 1188-l 193
1189
MALIGNANT JUVENILE POLYPOSIS COLI
pull-through was performed. The rectal mucosa juvenile nature but was otherwise normal.
had a few polyps of
DISCUSSION
Juvenile polyps are relatively common lesions affecting young people and are the most common form of colonic tumor in children, accounting for > 90% of colonic polyps1 While these polyps are most common in children and young adults, these lesions have been reported in older patients as well. Roth and Helwig22 described a bimodal age distribution in their series of 158 patients with juvenile polyps. The childhood group (60%) had an average age of 4.1 years while the adult group (40%) had an average age of 25.5 years. The incidence of rectal bleeding (80%) and prolapse of an anal mass or passed tissue in the stool (10% to 30%) as the initial presentation was similar in both age groups. Juvenile polyps have been described as retention polyps and inflammatory polyps, and are routinely grouped with hamartomas in the literature. They are smooth and round, bleed easily and frequently show areas of surface ulceration. They may be sessile or
Fig 1. Photograph of a gross colectomy specimen showing pancoIonic juvenile polyposis.
showed pancolonic yps demonstrating studies are being members.
juvenile polyposis with few adenomatous polfocal mild atypia. Subsequent chromosomal investigated for both the patient and family
Case 3 An adopted 9-year-old white girl presented to an outside institution with malnutrition, diarrhea, and rectal bleeding resulting in severe anemia. After transfusion and resuscitation she underwent a contrast enema, which showed diffuse colonic polyposis. She underwent colectomy and ileoproctostomy. The histology of the colon showed juvenile polyps with occasional adenomatous areas and no atypia. Efforts to obtain information regarding the parent’s health was unsuccessful, but there was the suggestion of a possible GI malignancy in a cousin at a young age. The patient had moved to Georgia and was referred to this institution for follow-up, presenting 2 years after the initial diagnosis and treatment. Sigmoidoscopy showed two polyps in the rectum and no lesions in the ileum. The histology of the polyps were adenomas, each showing moderate to severe atypia (Fig 3). Completion endorectal
Fig 2. changes.
Histology of juvenile polyp having foci of adenomatous
1190
MISS
ET AL
tial progression of the histology toward cancer.I(-Iy The dysplasia presents in two forms: the coexistence of adenomatous changes in a juvenile polyp; and coexisting adenomas lacking features of juvenile polyps found in patients with juvenile polyposis syndrome.23 The absence of small adenomas in these latter patients is felt to negate the possibility of an independent process causing adenomas to occur, de novo. Goodman et a123has suggested that juvenile polyps represent one step in a spectrum, beginning with hyperplasia, progressing to typical juvenile polyps which then develop total adenomatous changes and progress eventually to a true adenoma. The substance for this hypothesis is a 23-year-old patient who manifested all these histological findings at the time of her colectomy to treat her adenocarcinoma of the rectum. Several groups have reported the concurrent presence of juvenile and adenomatous polyps in the same patient.8-t9 Indeed, Bussey reported adenomatous tumors in 6 of 37 patients with juvenile polyposis (16%). 24 The St Mark’s registry has reported 1032 polyps found in 87 patients diagnosed with juvenile polyposis. Sixteen percent of these
Fig 3. Adenomatous polyp from case 3 showing severe atypia consistent with carcinoma in situ.
pedunculated. Histologically, there is a continuous single layer of goblet cells, interrupted frequently by ulcerations and chronic inflammation (Fig 4). The sectioned surface show numerous cystic spaces filled with mucus. There is abundant granulation tissue and inflammatory exudate composed of plasma cells, eosinophils, polymorphonuclear cells, and histocytes. Mitoses are uncommon. This description is in contrast to the histology of adenomatous polyps which are neoplastic overgrowths of epithelium with hyperchromatic nuclei, cellular elongation, and few mature cells organized into an arborizing glandular pattern. These may form villi or papillary extensions. Their neoplastic potential has been well described. These two lesions have histologically been viewed as independent and unrelated. Indeed, a study of 50 children reported by Kottmeier and Clatworthy concluded that juvenile and adenomatous polyps did not coexist in the same patient.6 In recent years, this simple view of the benign nature of juvenile polyposis has been complicated by several factors. Several reports have documented the presence of dysplastic changes representing a poten-
Fig 4. Histology of typical juvenile polyp. Note presence of surface ulceration, inflammatory cells, and cystic spaces.
MALIGNANT
JUVENILE
POLYPOSIS
COLI
polyps had adenomatous changes, while 2% were frank adenomas. Interestingly, 18 of the 87 patients have developed large bowel cancer.25 In addition, another group has reported a colon carcinoma arising in an adolescent from a solitary juvenile p01yp.~~ While these several reports appear to lay to rest the issue of whether adenomas and malignancies can arise in the presence of juvenile polyps, this evidence has caused increased concern with regard to the management of patients found to have juvenile polyps of the solitary type, as well. This anxiety has led some authors to suggest that all pediatric patients should have any polyp removed immediately when found unless the child is less than 8 years old, or if the child becomes symptomatic, or if the polyp persists without autoamputation for more than 1 year.*” The very common nature of juvenile polyps in children, in consideration of the rarity of colorectal cancer in children raises some obvious questions as to what management scheme should be persued. The distinction between cancer risk in patients with few polyps as opposed to those with juvenile polyposis should be made. Most children have fewer than five polyps and many have solitary polyps at the time of presentation.*,*’ This is in contrast to the polyposis patient who has fields of colorectal polyps ranging from 50 to 200 in number, some of whom have polyps in the small intestine and stomach as we11.25There has been only one reported case of adenomatous change in a solitary polyp (a 21-year-old patient)** and only two cases of colorectal malignancy documented in the pediatric age group. 26~29 If these very common, solitary juvenile polyps are prone to malignant change, one might wonder why colorectal cancer is so rare in the pediatric population. It seems clear that the risk of malignant change in a solitary juvenile polyp is rare, and a distinction must be made between these lesions and juvenile polyposis, where the risk is more apparent, and there are several documented cases of malignancy.8~y~*4.16~23~25+26~29-31 In order to decrease confusion when discussing patients with juvenile polyps, Jass et a125have suggested a working definition of juvenile polyposis as: (1) more than 5 juvenile polyps of the colon/rectum; (2) juvenile polyps throughout the GI tract; or (3) any number of juvenile polyps with a family history of juvenile polyposis. There are three basic types of juvenile polyposis.3’ The infantile form presents prior to age two with severe rectal bleeding and anemia, severe diarrhea leading to hypoproteinemia, and malnutrition. Recurrent rectal prolapse and bowel obstruction from intussusception are complicating factors. Colectomy has proved curative in a few reported cases, while mortality without surgical intervention is very high.33.74
1191
Autopsy studies have shown juvenile polyps extensively involving the terminal ileum and colon, and on occasion involving the small intestine and stomach. About one third of these patients will have congenital abnormalities such as Meckel’s diverticulum, malrotation of the bowel, and heart lesions.35 Second, juvenile polyposis coli presents with abdominal pain, rectal bleeding or prolapse, and diarrhea. The colon is usually matted with polyps, but polyps elsewhere are rare. Twenty-five percent to SO% of these patients have a family history of juvenile polyp~.~~Some authors have recommended management of this lesion with colonoscopic polyp removal and surveillance, removing the colon only when dysplasia is found.36 Others have performed colectomies with ileoproctomstomy and done surveillance sigmoidoscopy to clear the rectum of p01yps.~’ This has resulted in one irreparabIe rectal cancer due to inadequate following in a 15 year old.25 Others have recommended total colectomy with mucosal proctectomy and endorectal pull-through, thus removing all coionic mucosa and the risk of colonic malignancy.‘x The third form, generalized or diffuse juvenile polyposis presents with symptoms similar to those of juvenile polyposis coli or from gastric bleeding from polyps. Polyps may be present from the stomach to the anus. Surgical therapy is indicated for bleeding, malnutrition and diarrhea. Approximately 25% of these patients may have family members with juvenile polyposis.31 The familial nature of the latter two types of juvenile polyposis has been described in several reports.R.10.‘4.15.Z3,25,32,35,39 The genetic lesion has been described as an autosomal dominant condition. The risk of gastrointestinal malignancies in affected families is greatly increased, indicating that the family, as well as the patient, must be evaluated carefully. Interestingly, the risk of malignancy is as high in the family members without polyposis as in the affected members. In addition, the malignancies have occurred in organs other than the colon. Hence, prophylactic colectomy has not been recommended in the patients with polyposis. From reports discussed above, it seems apparent that the risk of malignancy is dramatically increased in patients with juvenile polyposis coli or generalized juvenile polyposis. The incidence of 18 colorectal cancers in 87 patients on the St Marks’ registry is a dramatic increase in incidence of colon cancer in a limited population. It is noteworthy that the mean age at presentation was 34 years (range, 15 to 59) and that the clinical outcome was usually poor with a high percentage of poorly differentiated or mutinous cancers.25 In this report, Jass et al failed to identify any
1192
HEISS ET AL
markers among their 87 patients that would identify those with increased risk. Thus they conclude that the trigger causing the conversion from a juvenile polyp to a neoplasm is a random event. It is possible that the cancer risk in this group is higher than reported due to the large number of colectomies that were performed to treat unmanageable symptoms or because of confusion at the time of presentation with familial adenomatous polyposis.lo Bentley et aP1 have suggested that the incidence of carcinoma is 20% to 30% in patients with the heterogeneous mixture of both juvenile and adenomatous polyps and that patients with homogeneous juvenile polyps alone are not at risk. If the incidence of heterogeneous patients is 15% as described by Bussey et al, then the risk of carcinoma (3% to 5%) is slightly increased.35 Years of controversy over the true risk of malignancy from juvenile polyps is slowly being sorted out. Bussey et al have suggested that adenomatous changes in juvenile polyps are as common in solitary cases as they are in multiple ~01~~s.~~If true, this suggests that these solitary polyps are self amputating prior to developing atypia and becoming cancerous, since the incidence of adenocarcinoma is rare in children. The risk of cancer from solitary juvenile polyps must be vanishingly small due to its common pediatric presentation and the very small number of documented cancers arising from solitary polyps.
In conclusion, the development of colonoscopy has documented increased incidence of multiple polyps in more proximal locations than previously realized. However, the preferred status of the solitary juvenile polyp as a benign, self-limiting lesion, absent of a malignant potential should be preserved. Solitary or multiple polyps, fewer than five in number, should be removed to resolve symptoms and to establish a diagnosis in situations where concern exists regarding increased risk of familial adenomatous polyposis. Since the risk of recurrence is low, further surveillance by endoscopy is probably unwarranted. Colectomy should be performed in the presence of juvenile polyposis coli when clearing of the polyps by colonoscopy is not possible. The difficulty of screening fields of polyps with random biopsies to establish the absence of adenomatous polyps is significant. While regular colonoscopic surveillance may temporize by removing polyps, in the presence of a large number of lesions, colectomy with endorectal pullthrough could remove the affected organ and bring the risk of colon cancer to zero. This is especially true for familial cases, since these seem to be the conditions in which GI cancers are more common. Juvenile polyposis should be treated as seriously as familial adenomatous polyposis. Family members should be questioned and studied as appropriate.
REFERENCES 1. Gelb A, Minkowitz S, Tresser M: Rectal and colonic polyps occurring in young people. NY State J Med 62:513-518,1962 2. Schermeta DW, Morgan WM, Eggleston J, et al: Juvenile retention polyps. J Pediatr Surg 4:211-2151969 3. Louw JH: Polypoid lesions of the large bowel in children. S Afr Med J 46:1347-1352,1972 4. Mazier WP, MacKeigan JM, Billingham RP, et al: Juvenile polyps of the colon and rectum. Surg Gynecol Obstet 154:829-832, 1982 5. Mestre JR: The changing pattern of juvenile polyps. Am J Gastroenterol81:312-314,1986 6. Kottmeier PK, Clatworthy HW: Intestinal polyps and associated carcinoma in children. Am J Surg 110:709-716,1965 7. McCall I, Bussey HJR, Veale AMC, et al: Juvenile poloposis coli. Proc R Sot Med 57:896-897,1964 8. Smilow PC, Pryor CA, Swinton NW: Juvenile polyposis coli. A report of 3 patients in 3 generations. Dis Colon Rectum 9:248-254,1966 9. Stemper TJ, Kent TH, Summers RW: Juvenile polyposis and gastrointestinal carcinoma. Ann Intern Med 83:639-646, 1975 10. Velcek FT, Coopersmith IS, Chen CK, et al: Familial juvenile adenomatous polyposis. J Pediatr Surg 11:781-787,1976 11. Haggit RC, Pitcock JP: Familial juvenile polyposis of the colon. Cancer 26:1232-1238,197O 12. Kaschula ROC: Mixed juvenile, adenomatous and intermediate polyposis coli: Report of a case. Dis Colon Rectum 14:368374,197l
13. Reed K, Vose PC: Diffuse juvenile polyposis of the colon: A pre-malignant condition? Dis Colon Rectum 24:205-210,198l 14. O’Riordan DS, O’Dwyer PJ, Cullen AF, et al: Familial juvenile polyposis cob and colorectal cancer. Cancer 68:889-892. 1991 15. Grotsky HW, Rickert RR, Smith WD, et al: Familial juvenile polyposis coli: A clinical and pathologic study of a loarge kindred. Gastroenterology 82:494-501, 1982 16. Longo WE, Touloukian RJ, West AB, et al: Malignant potential of the juvenile polyposis coli. Report of a case and review of the literature. Dis Colon Rectum 33:980-984, 1990 17. Sandler RS, Lipper S: Multiple adenomas in juvenile polyposis. Am J Gastroenterol75:361-366,198l 18. Lipper S, Kahn LB, Sandler RS, et al: Multiple juvenile polyposis. A study of the pathogenesis of juvenile polyps and their relationship to colonic adenomas. Hum Pathol12:804-813, 1981 19. Rozen P, Baratz M: Familial juvenile colonic polyposis with associated colon cancer. Cancer 49:1500-1503,1982 20. Rolles CJ: Juvenile intestinal polyps-are they always benign? Br Med J 294:529,1987 21. Gryboski JD: All juvenile Polyps are not benign. Am J Gastroenterol81:397,1986 22. Roth Sl, Helwig EB: Juvenile polyps of the colon and rectum. Cancer 16:468-479, 1963 23. Goodman ZD, Yardley JH, Milligan FD: Pathogenesis of colonic polyps in multiple juvenile polyposis. Report of a case associated with gastric polyps and carcinoma of the rectum. Cancer 43:1906-1913,1979
MALIGNANT
JUVENILE
POLYPOSIS
1193
COLI
24. Bussey HJR: Familial Polyposis. Baltimore, MD, Johns Hopkins, 1975 25. Jass JR, Williams CB, Bussey HJR, et al: Juvenile polyposis-A pre-cancerous condition. Histopathology 13:619-630,198s 26. Liu-TH, Chen MC, Tseng HC: Malignant change of a juvenile polyp of colon: A case report. Chin Med J 4:434-439, 1978 27. Euler AR, Seibert JJ: The role of sigmoidoscopy, radiographs, and colonoscopy in the diagnostic evaluation of pediatric age patients with suspected juvenile polyps. J Pediatr Surg 16:500502,198l 28. Friedman CJ, Fechner RE: A solitary juvenile polyp with hyperplastic and adenomatous glands. Dig Dis Sci 27:946-948,1982 29. Schilla FW: Carcinoma in a rectal polyp. Am J Surg 4:434-439,1954 30. Restrepo C, Moreno J, Duque E, et al: Juvenile colonic polyposis in Columbia. Dis Colon Rectum 21:602-612, 1978 31. Bentley E, Chancrasoma P, Radi R, et al: Generalized juvenile polyposis with carcinoma. Am J Gastroenterol 84:14561459, 1989 32. Sachetallo CR, Griffen WO: Hereditary polypoid diseases of
the gastrointestinal 129:198-203,1975
tract.
A working
classification.
Am J Surg
33. Sachetallo CR, Hahn IS, Carrington CB: Juvenile gastrointestinal polyposis in a female infant: Report of a case and review of the literature of a recently recognized syndrome. Surgery 75:107114,1974 34. Soper RT, Kent Surgery 69:692-698.1971
TH:
Fatal
juvenile
polyposis
in infancy.
35. Bussey HJR, Veale AM, Morson BC: Genetics of gastrointestinal polyposis. Gastroenterology 74:1325-1330. 1978 36. Gilinsky NH, Elliot MS, Price SK, et al: The nutritional consequences and neoplastic potential of juvenile polyposis coli. Dis Colon Rectum 29:417-420,1986 37. Grosfeld J, West K: Generalized Arch Surg 121:530-534, 1986
juvenile
polyposis
cob.
38. Jaxvinen H, Fransilla KO: Familial juvenile Increased risk of colorectal cancer. Gut 25:792-800,
polyposis 1984
coli:
39. Gaithright JB, Cofer TW: Familial incidence polyposis coli. Surg Gynecol Obstet 138:185-188. 1974
of juvenile