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Hereditary polypoid diseases of the gastrointestinal tract
Hereditary Polypoid Diseases of the Gastrointestinal Tract A Working Classification
Charles R. Sachatello, MD, Lexington, Kentucky Ward 0. Grlffen, Jr, MD, Lexington, Kentucky
The overwhelming majority of published cases of polypoid diseases of the gastrointestinal tract can conveniently be classified into a relatively few syndromes [l-4]. (Table I.) This proposed classification is based on the histologic characteristics of the polypoid lesions using the criteria of Morson [5] and Lane, Kaplan, and Pascal [6]. (Table II.) We hope that this classification provides a better understanding of the natural history of these diseases, the potential for meaningful genetic counseling, and a systematic and uniform approach to medical and surgical management. Familial Polyposls of the Colon Description. Familial polyposis of the colon is a hereditary disease transmitted as an autosomal dominant and characterized by the development of numerous adenomatous polyps and subsequent adenocarcinoma of the colon and rectum in the second to fifth decades [1,2,7]. The true adenomatous polyp is confined primarily, if not uniformly, to the large intestine. It is
Fromthe Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky. This work was supported in part by the Newell Fund for the Study of Intestinal Diseases. Reprint requests should be addressed to Dr Charles Ft. Sachatello, Department of Surgery. University of Kentucky Medlcal Center, Lexington, Kentucky. Presented at the Fifteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Francisco, California, May 21 and 22, 1974.
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characterized by dense, closely packed cells with hyperchromatic nuclei. Individual cells are thin, pencil-shaped, and usually very similar. Secretory activity is minimal and goblet type cells appear to be incompletely differentiated. Mitotic figures are frequently seen both in the upper portion of the tubules and on the free surface of the polyps [5,6]. Adenomatous polyps may vary from 1 mm to 5 cm or more. Those measuring more than 1 or 2 cm are located most frequently on a stalk of normal colonic mucosa. There is no recognizable microscopic feature that separates the occasional adenomatous polyp or even multiple adenomatous polyps from the numerous adenomatous polyps so characteristic of familial polyposis of the colon. Adenomatous polyps must carefully be distinguished from metaplastic polyps. Metaplastic polyps are smaller, rarely exceeding 5 mm, are more numerous than adenomatous polyps, and do not show any evidence of mitotic activity in the top third of the lesion or on the luminal surface [5,6]. The typical colon removed from a patient with familial polyposis is characterized by numerous or even uncountable polypoid lesions. Although microscopically most will prove to be adenomatous polyps, an occasional villous adenoma will be encountered in many specimens. A submucosal type of polypoid lymphatic hyperplasia is frequently seen in the ileum [2].
The Amrrlcan Joumal of SUrgary
Juvenile polyps, “hamartomas”
Juvenile polyps, “hamartomas”
_
Generalized gastrointestinal juvenile polyposis
polyposis
Stomach and large and small intestine
Dominant
None specific
None specific
Colon and rectum, small bowel
Uncertain
rarely
High incidence abnormalities
of congenital
High incidence of osteomas and osseous abnormalities especially of skull and mandible, epidermoid inclusion cyst, fibrous tissue abnormalities, “desmoid tumors” Circumoral melanin pigmentation in childhood, blanches with age
Extraintestinal Manifestations
Stomach and large and small intestine
not sex-
Juvenile coli
polyps
Recessive
Familial polyposis of colon
Juvenile polyps, “hamartomas”
~~
Juvenile polyposis of infancy
~__~
Entire gastrointestinal tract, ureter, and bronchus
Tract
Dominant, linked
Genetics
of Gastrointestinal
Hamartomas
Diseases
Peutz-Jeghers syndrome
Histopathology
of Polypoid
Adenomatous
Classification
Dominant, not sex, linked, high penetrance
Disease
I Polyp Distribution __. __~. ~~~~ ~~~~ .~~~ Large intestine; submucosal lymphatic hyperplasia of terminal ileum
TABLE
Adenomatous polyps develop in second to fifth decade More than 90% incidence of colorectal cancer in third to sixth decade Frequently other malignant lesions especially in duodenum Abdominal pain due to intussusception; intestinal obstruction; frequent gastrointestinal bleeding; anemia Moderate increased risk of gastrointestinal cancer; 5% of females have ovarian neoplasms Rectal bleeding, diarrhea; failure to thrive in infancy, inanition; death before age two Rectal bleeding; recurrent numerous juvenile polyps of colon; may require colectomy Upper and lower gastrointestinal bleeding: extensive gastric involvement; small bowel obstruction; no increased risk of ca ricer
Natural History
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TABLE A.
B.
C.
D.
II
Intestinal
Polypoid Lesions
Neoplasms 1. Epithelial a. Adenoma-adenomatous polyp b. Papillary adenoma c. Villous papilloma Hamartomas 1. Juvenile polyps 2. Polyps of Peutz-Jeghers syndrome Inflammatory 1. Pseudopolyps (ulcerative colitis-Crohn’s
disease)
2. Lymphoid polyposis Unclassified or uncertain 1. Metaplastic-hyperplastic-mucosal polyps 2. Polyps of Cronkite-Canada syndrome 3. Fibroinflammatory polyp of terminal ileum
Initially, familial polyposis was thought to represent a disease primarily of the large intestine. More recently, however, it is apparent that the great majority of patients with familial polyposis have extracolonic manifestations such as osteomas, soft tissue tumors, epidermoid inclusion cysts, dental abnormalities, and a tendency toward the development of fibrous tissue over growth or desmoid tumors [ 71. Extracolonic malignancies, especially duodenal, are common [1,2]. Many authors consider that these patients with extracolonic manifestations represent a distinct syndrome, Gardner’s syndrome [ 7,8]. There is simply no evidence that the extracolonic manifestations alter the basic disease, that is, adenomatous polyps and colorectal cancer. More important is the observation that the great majority of kindreds will manifest one or more of these abnormalities when carefully examined. The penetrance of the extracolonic abnormalities is distinctly less than that of the colonic disease. Diagnosis and Treatment. The diagnosis of familial polyposis may be relatively straightforward on the basis of sigmoidoscopic and barium enema studies and a typical family history. Unfortunately, all too often the patient’s symptoms are those of intestinal obstruction or incurable disease. In a few cases, especially those found in the course of family studies, patients will have extensive colonic involvement but minimal, if any, symptoms. More usual, however, is the history of sporadic diarrhea and occasional bloody bowel movements antedating the development of colorectal carcinoma. In a few patients, familial polyposis has initially been misdiagnosed as chronic ulcerative colitis because of the severity of the diarrhea. There are two reasonable alternative forms of operative management: either removal of the abdominal colon and end to end ileoproctostomy or
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proctocolectomy and ileostomy. The arguments for or against either procedure are best considered in the context of the individual patient, the extent of rectal involvement, and the severity of the disease in the family [2]. In some families, cancer is quite common by age thirty whereas in others, cancer rarely develops before the late forties. In a few patients, rectal polyps have disappeared temporarily after abdominal colectomy and ileoproctostomy1 This argument is weakened by the observation that as many as 60 per cent of the patients so treated have .had carcinoma develop in the remaining rectum over a period of two to three decades [9]. Irrespective of the family history, results of barium enema, and sigmoidoscopic appearance, the surgeon should not proceed with colectomy until he has an unquestionably accurate tissue diagnosis. He must be sure that pathologic study has excluded the possibility of metaplastic, lymphoid, juvenile, and pseudopolyposis of the colon. Peutz-Jeghers Syndrome Description. Peutz-Jeghers syndrome is characterized by gastrointestinal polyps and circumoral, buccal, or lingual pigmentation [IO-131. The pigmented lesions resemble freckles but are found in areas where freckles are normally absent, that is, the lips, buccal mucosa, tongue, fingers, and toes. They also differ from freckles in that they are present from childhood whereas freckles are uncommon before age six. The pigmentation appears to fade with age. The polypoid lesions are found most commonly in the intestines but have occurred in the nasal cavity, esophagus, stomach, colon, rectum, ureter, urinary bladder, and bronchus. Peutz-Jeghers polyps appear to represent hamartomas of smooth muscle and are characterized by regular tubular and branching glands surrounded by muscularis mucosa. Individual cells appear normal and are characteristic of the area in which they are found
PI.
Although it was once considered to represent a premalignant disease, Peutz-Jeghers polyposis causes gastrointestinal cancer in only a small percentage of patients [12]. Of interest is the lack of a clear correlation between the frequency distribution of intestinal lesions and subsequent intestinal cancer. Approximately 5 per cent of female patients with Peutz-Jeghers syndrome have been noted to develop ovarian tumors, about half of which represent a sex cord tumor possibly unique to the
The American Journal of Surgery
Polypoid Diseases of Gastrointestinal
Peutz-Jeghers syndrome. A high percentage of these tumors are hormonally active [Id]. There is no evidence that Peutz-Jeghers polyps are present at birth, but several patients were found to have large polyps by age three. Most patients become symptomatic before age twenty-five. Presenting symptoms are those of colicky abdominal pain, and intestinal obstruction and intussusception are common. Operative management should be deliberate and designed to remove the large obvious polypoid lesions with minimal sacrifice of intestine. Several patients with known small bowel polyps have remained relatively asymptomatic for decades. In adult female patients the ovaries should be examined carefully because of the association of this syndrome with ovarian malignancy. The ovarian tumors may be quite small. It appears reasonable to perform prophylactic oophorectomy in older adult females being operated on for the intestinal complications of the Peutz-Jeghers syndrome.
Juvenile Polyposis Description. Juvenile polyps are characterized by a single layer of superficial epithelium comprised of goblet and columnar epithelial cells with the great bulk of the polyp being formed by innumerable and different sized glandular structures scattered in a cellular connective tissue stroma. Some of the glands are cystically dilated with attenuation of the lining epithelium. The lumina of many of the glands are filled with mucus [3,5]. Juvenile polyps vary from a few millimeters to 4 to 5 cm. Large juvenile polyps are usually on a stalk. The single cell layer of lining epithelium frequently becomes ulcerated, leading to infection and hemorrhage. It is these two specific features of juvenile polyps, that is, the stalk and an easily ulcerated mucosa, that account for the natural history and symptoms of juvenile polyposis which include recurrent gastrointestinal bleeding, abdominal pain, intestinal obstruction, intussusception, and autoamputation of larger juvenile polyps. Although as many as forty to fifty patients with multiple juvenile polyps have now been reported on, it is still uncertain whether juvenile polyposis is one syndrome with variable penetrance or several different syndromes [1,3]. Most of the reported cases can conveniently be grouped into one of the three syndromes: (1) juvenile polyposis of infancy; (2) juvenile polyposis coli; (3) generalized juvenile gastrointestinal polyposis.
Volume 129,Docember 1974
Tract
Juvenile polyposis of infancy: Seven infants, six male and one female, have now been recognized to have extensive juvenile polyposis [3]. The clinical picture in these infants was similar. Each had diarrhea, either mucoid or bloody, which developed in the’first few weeks of life. The diarrhea led to the development of anemia, hypoproteinemia, general failure to thrive, and an increased susceptibility to pulmonary infections. Six of the seven infants died before age two. Rectal prolapse developed between age four and nine months and was significant in that the mucosa was studded with polypoid lesions. The rectal prolapse tended to be recurrent and was associated with brisk bleeding from ulcerated and infected juvenile polyps. Several infants required repeated hospitalizations and general anesthesia for reduction of the prolapsed rectal mucosa. Both the morbidity and the parental distress at the unsightly, recurrent, and apparently painful prolapse were emphasized by several investigators. Either rectal bleeding or prolapsed polypoidstudded rectal mucosa prompted sigmoidoscopy, biopsy, and gastrointestinal x-ray studies. In each infant the biopsy specimens were initially interpreted as “adenomas” or adenomatous polyps. Xray studies demonstrated polyps in the stomach and small and large bowel in various combinations. In five of the seven infants intussusception developed leading to death in three. Six of seven infants died before age two years as a result of the combination of repeated episodes of gastrointestinal bleeding, intestinal obstruction, and diarrhea. Six infants had a total of eleven abdominal operations and an undetermined number of rectal fulgurations. Autopsy findings in these six patients demonstrated an uneven distribution of juvenile polyps from the stomach to the anus, with involvement of the terminal ileum and colon being most extensive. The polyps varied from 3 mm to several centimeters and were of uniform histologic appearance irrespective of the site of origin. One patient had left colectomy at age ten months and an abdominal colectomy with a cecorectal anastomosis at age two years. Juvenile polyps were noted in the jejunum and ileum during this latter procedure and nine polyps were removed. Gastrointestinal x-ray studies at age four and subsequently during teenage years demonstrated that some polyps had grown whereas others had apparently sloughed and disappeared. Management of these infants was often compromised by the histologic interpretation of the poly-
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Sachatello and Griffen
poid lesions as representing adenomatous polyps with the unstated implication that this represented preneoplastic involvement of the entire gastrointestinal tract. A more precise understanding of the natural history of individual juvenile polyps and the recognition that the disease may be selflimited warrant more aggressive therapy. Medical management should initially concentrate on delineating the extent of involvement of the stomach and small and large bowel and searching for other congenital abnormalities. Therapy should be directed at control of the diarrhea by medication, a trial of broad spectrum antibiotics, evaluation of the usefulness of an elemental diet on the severity of diarrhea, and intravenous hyperalimentation. Surgical management should concentrate on removal of as many rectal polyps as possible in an attempt at reducing the frequency and severity of rectal prolapse. Elective intestinal resection of the segments that are most extensively involved combined with judicious removal of the larger gastric and small bowel polyps is indicated. Nevertheless a careful review of the available autopsy data suggests that the extent of initial involvement and the tendency for new juvenile polyps to develop will be the prime determinants of longevity. Juvenile polyposis coli: The recognition of juvenile polyposis coli as an entity distinct from familial polyposis of the colon by Morson and his colleagues [15,16] has been of immense value in clarifying the confusing spectrum of polypoid diseases. Although the existence of this disease as an entity is still widely unappreciated, it is likely to be the most common form of juvenile polyposis. The similarity between the polyp distribution in this syndrome and the adenomatous polyps of familial polyposis has resulted in a confused picture of polypoid diseases in children. It is now apparent that juvenile polyps of the colon may occur in a sporadic form with usually only one polyp or in a form in which the colon is almost matted with juvenile polyps. A few patients with extensive juvenile polyps of the colon have had an occasional juvenile polyp of the small bowel, but most have not had polyps elsewhere in the gastrointestinal tract [1,3,4,15,16]. Approximately half the children with juvenile polyposis coli that have been reported on have a family history of juvenile polyps. Most confusing is the association of juvenile polyposis and familial polyposis in the same kindred [15]. Children with juvenile polyposis coli may pre-
202
sent with an asymptomatic prolapsed juvenile polyp or abdominal pain, gastrointestinal bleeding, anemia, diarrhea, and weight loss. Barium enema studies combined with removal of the more accessible rectal polyps and accurate histologic characterization of the polyps will prove to be adequate therapy in most children. Both the rarity of adenomatous polyps in children and the infrequent association of adenomatous and juvenile polyps in the same child are such that higher inaccessible polyps can confidently be considered the same as rectal juvenile polyps. The average patient with juvenile polyposis of the colon will need only intelligent observation and reassurance after the rectal polyps have been removed. Many juvenile polyps of the colon will slough or autoamputate. Although bleeding from juvenile polyps is often bright red and brisk, it is usually episodic and rarely of sufficient magnitude to lead to hypotension. Iron deficiency anemia, however, is common. In a few patients, juvenile polyposis coli is of such severity that colectomy may be indicated. This procedur;? should not be undertaken without an attempt to first remove the larger colonic polyps by colonoscopy. Gathright and Cofer [17] have recently emphasized the familial incidence of this syndrome and stressed the importance of accurate histologic characterization of the polyps prior to definitive treatment. Generalized juvenile gastrointestinal polyposis: A small number of patients have been found
to have juvenile polyps of the stomach and small and large bowel in various combinations. In these patients the gastric and colonic polyps have usually not manifested themselves simultaneously 141. The gastric polyps appear to account for most of the morbidity because of recurrent hemorrhage. The severity of gastric involvement was such that total gastrectomy was necessary in three patients. Two of these patients also had colectomy and multiple operations for excision of small bowel polyps. The similarity of distribution and gross appearance of these polyps and those of the Peutz-Jeghers syndrome is such that there is distinct possibility of misclassifying these two syndromes. The risk of carcinoma in these patients is not increased and specific extracolonic manifestations are inapparent. Summary
Almost ail published cases of hereditary intestinal polypoid diseases can be meaningfully classi-
The American Journal of Surgery
Polypoid Diseases
fied into a relatively few distinct syndromes including familial polyposis of the colon, Peutz-Jeghers syndrome, and juvenile polyposis. Familial polyposis is characterized by the development of numerous adenomatous polyps of the colon and subsequent development of colorectal carcinoma in nearly all patients. Extracolonic manifestations are common but do not influence the premalignant nature of this syndrome. Peutz-,Jeghers syndrome is identifiable by a combination of circumoral melanin pigmentation and hamartomatous polyps. These polypoid lesions have an unusually wide distribution and may occur in t.he respiratory, gastrointestinal, or genitourinary tract. There is a small but definite increased incidence of gastrointestinal cancer in these patients. Juvenile polyposis presents a more variable spectrum. In one form there is extensive intestinal involvement leading to diarrhea, inanition, and increased susceptibility to infection. Another form is limited to the colon and easily confused with familial polyposis. With the third form, there is involvement of the stomach, intestines, and colon, which makes it easily mistaken for the Peutz-Jeghers syndrome. References 1. Bussey HJR: Gastrointestinal polyposis. Gut 11: 978, 1970. 2. Sachatello CR: Familial polyposis of the colon. Cancer 28: 581, 1971.
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of Gastrointestinal
1 racr
3. Sachatello 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. slJrgery75: 107.1974. 4. Sachatello CR, Pickren JW. Grace JT Jr: Generalized juvenile gastrointestinal polyposis. Gastroenferology 58: 699, 1971. 5. Morson BC: Some peculiarities in the histology of intestinal polyps. Dis Colon Rectum 5: 337, 1962. 6. Lane N. Kaplan H, Pascal RR: Minute adenomatous and hyperplastic polyps of the colon: divergent patterns of epithelial growth with specific associated mesenchymal changes. Gastroenterology60: 537, 1971. 7. Smith WG: Familial multiple polyposis. Dis Co/on Rectum 11: 17, 1968. 8. Gardner EJ: Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas. fibromas. and epidermal cysts. Am J Hum Genet 14: 375. 1962. 9. Moertel CG, Hill JR, Adson MA: Management of muttiple polyposis of the large bowel. Cancer 28: 160, 197 1. 10. Godard JE. Dodds WJ, Phillips JC, Scanlon GT: Peutz-Jeghers syndrome: clinical and roentgenographic features. Am J Roentgen01 Radium Ther Nucl Med 113: 3 16, 197 1. 11. Bartholomew LG. Dahlin DC, Waugh JM: Intestinal polyposis associated with mucocutaneous melanin pigmentation (Peutz-Jeghers syndrome). Gastroenterology 32: 434, 1957. 12. Dorois RR, Judd ES, Dahlin DC, Bartholomew LG: Peutz-Jeghers syndrome: is there a predisposition to the development of intestinal malignancy? Arch Surg 98: 509, 1969. 13. McKittrick JE, Lewis WM. Doane WA, Gerwig WH: PeutzJeghers syndrome. Arch Surg 103: 57, 1971. 14. Scully RE: Sex cord tumor with annular tubules: a distinctive ovarian tumor of the Peutz-Jeghers syndrome. Cancer 25: 1107, 1970. 15. Veale AMO, McCall I, Bussey HJR, Morson BC: Juvenile polyposis coli. J Med Genet 3: 5, 1966. 16. McCall I, Bussey HJR, Veale AMO, Morson BC: Juvenile polyposis coli. Proc R Sot Med57: 896, 1964. 17. Gathright JB, Cofer TW: Familial incidence of juvenile polyposis coli. Surg Gynecol Obstet 138: 185. 1974.
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Charles R. Sachatello, MD, Lexington, Kentucky Ward 0. Grlffen, Jr, MD, Lexington, Kentucky
The overwhelming majority of published cases of polypoid diseases of the gastrointestinal tract can conveniently be classified into a relatively few syndromes [l-4]. (Table I.) This proposed classification is based on the histologic characteristics of the polypoid lesions using the criteria of Morson [5] and Lane, Kaplan, and Pascal [6]. (Table II.) We hope that this classification provides a better understanding of the natural history of these diseases, the potential for meaningful genetic counseling, and a systematic and uniform approach to medical and surgical management. Familial Polyposls of the Colon Description. Familial polyposis of the colon is a hereditary disease transmitted as an autosomal dominant and characterized by the development of numerous adenomatous polyps and subsequent adenocarcinoma of the colon and rectum in the second to fifth decades [1,2,7]. The true adenomatous polyp is confined primarily, if not uniformly, to the large intestine. It is
Fromthe Department of Surgery, University of Kentucky Medical Center, Lexington, Kentucky. This work was supported in part by the Newell Fund for the Study of Intestinal Diseases. Reprint requests should be addressed to Dr Charles Ft. Sachatello, Department of Surgery. University of Kentucky Medlcal Center, Lexington, Kentucky. Presented at the Fifteenth Annual Meeting of the Society for Surgery of the Alimentary Tract, San Francisco, California, May 21 and 22, 1974.
198
characterized by dense, closely packed cells with hyperchromatic nuclei. Individual cells are thin, pencil-shaped, and usually very similar. Secretory activity is minimal and goblet type cells appear to be incompletely differentiated. Mitotic figures are frequently seen both in the upper portion of the tubules and on the free surface of the polyps [5,6]. Adenomatous polyps may vary from 1 mm to 5 cm or more. Those measuring more than 1 or 2 cm are located most frequently on a stalk of normal colonic mucosa. There is no recognizable microscopic feature that separates the occasional adenomatous polyp or even multiple adenomatous polyps from the numerous adenomatous polyps so characteristic of familial polyposis of the colon. Adenomatous polyps must carefully be distinguished from metaplastic polyps. Metaplastic polyps are smaller, rarely exceeding 5 mm, are more numerous than adenomatous polyps, and do not show any evidence of mitotic activity in the top third of the lesion or on the luminal surface [5,6]. The typical colon removed from a patient with familial polyposis is characterized by numerous or even uncountable polypoid lesions. Although microscopically most will prove to be adenomatous polyps, an occasional villous adenoma will be encountered in many specimens. A submucosal type of polypoid lymphatic hyperplasia is frequently seen in the ileum [2].
The Amrrlcan Joumal of SUrgary
Juvenile polyps, “hamartomas”
Juvenile polyps, “hamartomas”
_
Generalized gastrointestinal juvenile polyposis
polyposis
Stomach and large and small intestine
Dominant
None specific
None specific
Colon and rectum, small bowel
Uncertain
rarely
High incidence abnormalities
of congenital
High incidence of osteomas and osseous abnormalities especially of skull and mandible, epidermoid inclusion cyst, fibrous tissue abnormalities, “desmoid tumors” Circumoral melanin pigmentation in childhood, blanches with age
Extraintestinal Manifestations
Stomach and large and small intestine
not sex-
Juvenile coli
polyps
Recessive
Familial polyposis of colon
Juvenile polyps, “hamartomas”
~~
Juvenile polyposis of infancy
~__~
Entire gastrointestinal tract, ureter, and bronchus
Tract
Dominant, linked
Genetics
of Gastrointestinal
Hamartomas
Diseases
Peutz-Jeghers syndrome
Histopathology
of Polypoid
Adenomatous
Classification
Dominant, not sex, linked, high penetrance
Disease
I Polyp Distribution __. __~. ~~~~ ~~~~ .~~~ Large intestine; submucosal lymphatic hyperplasia of terminal ileum
TABLE
Adenomatous polyps develop in second to fifth decade More than 90% incidence of colorectal cancer in third to sixth decade Frequently other malignant lesions especially in duodenum Abdominal pain due to intussusception; intestinal obstruction; frequent gastrointestinal bleeding; anemia Moderate increased risk of gastrointestinal cancer; 5% of females have ovarian neoplasms Rectal bleeding, diarrhea; failure to thrive in infancy, inanition; death before age two Rectal bleeding; recurrent numerous juvenile polyps of colon; may require colectomy Upper and lower gastrointestinal bleeding: extensive gastric involvement; small bowel obstruction; no increased risk of ca ricer
Natural History
0
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TABLE A.
B.
C.
D.
II
Intestinal
Polypoid Lesions
Neoplasms 1. Epithelial a. Adenoma-adenomatous polyp b. Papillary adenoma c. Villous papilloma Hamartomas 1. Juvenile polyps 2. Polyps of Peutz-Jeghers syndrome Inflammatory 1. Pseudopolyps (ulcerative colitis-Crohn’s
disease)
2. Lymphoid polyposis Unclassified or uncertain 1. Metaplastic-hyperplastic-mucosal polyps 2. Polyps of Cronkite-Canada syndrome 3. Fibroinflammatory polyp of terminal ileum
Initially, familial polyposis was thought to represent a disease primarily of the large intestine. More recently, however, it is apparent that the great majority of patients with familial polyposis have extracolonic manifestations such as osteomas, soft tissue tumors, epidermoid inclusion cysts, dental abnormalities, and a tendency toward the development of fibrous tissue over growth or desmoid tumors [ 71. Extracolonic malignancies, especially duodenal, are common [1,2]. Many authors consider that these patients with extracolonic manifestations represent a distinct syndrome, Gardner’s syndrome [ 7,8]. There is simply no evidence that the extracolonic manifestations alter the basic disease, that is, adenomatous polyps and colorectal cancer. More important is the observation that the great majority of kindreds will manifest one or more of these abnormalities when carefully examined. The penetrance of the extracolonic abnormalities is distinctly less than that of the colonic disease. Diagnosis and Treatment. The diagnosis of familial polyposis may be relatively straightforward on the basis of sigmoidoscopic and barium enema studies and a typical family history. Unfortunately, all too often the patient’s symptoms are those of intestinal obstruction or incurable disease. In a few cases, especially those found in the course of family studies, patients will have extensive colonic involvement but minimal, if any, symptoms. More usual, however, is the history of sporadic diarrhea and occasional bloody bowel movements antedating the development of colorectal carcinoma. In a few patients, familial polyposis has initially been misdiagnosed as chronic ulcerative colitis because of the severity of the diarrhea. There are two reasonable alternative forms of operative management: either removal of the abdominal colon and end to end ileoproctostomy or
200
proctocolectomy and ileostomy. The arguments for or against either procedure are best considered in the context of the individual patient, the extent of rectal involvement, and the severity of the disease in the family [2]. In some families, cancer is quite common by age thirty whereas in others, cancer rarely develops before the late forties. In a few patients, rectal polyps have disappeared temporarily after abdominal colectomy and ileoproctostomy1 This argument is weakened by the observation that as many as 60 per cent of the patients so treated have .had carcinoma develop in the remaining rectum over a period of two to three decades [9]. Irrespective of the family history, results of barium enema, and sigmoidoscopic appearance, the surgeon should not proceed with colectomy until he has an unquestionably accurate tissue diagnosis. He must be sure that pathologic study has excluded the possibility of metaplastic, lymphoid, juvenile, and pseudopolyposis of the colon. Peutz-Jeghers Syndrome Description. Peutz-Jeghers syndrome is characterized by gastrointestinal polyps and circumoral, buccal, or lingual pigmentation [IO-131. The pigmented lesions resemble freckles but are found in areas where freckles are normally absent, that is, the lips, buccal mucosa, tongue, fingers, and toes. They also differ from freckles in that they are present from childhood whereas freckles are uncommon before age six. The pigmentation appears to fade with age. The polypoid lesions are found most commonly in the intestines but have occurred in the nasal cavity, esophagus, stomach, colon, rectum, ureter, urinary bladder, and bronchus. Peutz-Jeghers polyps appear to represent hamartomas of smooth muscle and are characterized by regular tubular and branching glands surrounded by muscularis mucosa. Individual cells appear normal and are characteristic of the area in which they are found
PI.
Although it was once considered to represent a premalignant disease, Peutz-Jeghers polyposis causes gastrointestinal cancer in only a small percentage of patients [12]. Of interest is the lack of a clear correlation between the frequency distribution of intestinal lesions and subsequent intestinal cancer. Approximately 5 per cent of female patients with Peutz-Jeghers syndrome have been noted to develop ovarian tumors, about half of which represent a sex cord tumor possibly unique to the
The American Journal of Surgery
Polypoid Diseases of Gastrointestinal
Peutz-Jeghers syndrome. A high percentage of these tumors are hormonally active [Id]. There is no evidence that Peutz-Jeghers polyps are present at birth, but several patients were found to have large polyps by age three. Most patients become symptomatic before age twenty-five. Presenting symptoms are those of colicky abdominal pain, and intestinal obstruction and intussusception are common. Operative management should be deliberate and designed to remove the large obvious polypoid lesions with minimal sacrifice of intestine. Several patients with known small bowel polyps have remained relatively asymptomatic for decades. In adult female patients the ovaries should be examined carefully because of the association of this syndrome with ovarian malignancy. The ovarian tumors may be quite small. It appears reasonable to perform prophylactic oophorectomy in older adult females being operated on for the intestinal complications of the Peutz-Jeghers syndrome.
Juvenile Polyposis Description. Juvenile polyps are characterized by a single layer of superficial epithelium comprised of goblet and columnar epithelial cells with the great bulk of the polyp being formed by innumerable and different sized glandular structures scattered in a cellular connective tissue stroma. Some of the glands are cystically dilated with attenuation of the lining epithelium. The lumina of many of the glands are filled with mucus [3,5]. Juvenile polyps vary from a few millimeters to 4 to 5 cm. Large juvenile polyps are usually on a stalk. The single cell layer of lining epithelium frequently becomes ulcerated, leading to infection and hemorrhage. It is these two specific features of juvenile polyps, that is, the stalk and an easily ulcerated mucosa, that account for the natural history and symptoms of juvenile polyposis which include recurrent gastrointestinal bleeding, abdominal pain, intestinal obstruction, intussusception, and autoamputation of larger juvenile polyps. Although as many as forty to fifty patients with multiple juvenile polyps have now been reported on, it is still uncertain whether juvenile polyposis is one syndrome with variable penetrance or several different syndromes [1,3]. Most of the reported cases can conveniently be grouped into one of the three syndromes: (1) juvenile polyposis of infancy; (2) juvenile polyposis coli; (3) generalized juvenile gastrointestinal polyposis.
Volume 129,Docember 1974
Tract
Juvenile polyposis of infancy: Seven infants, six male and one female, have now been recognized to have extensive juvenile polyposis [3]. The clinical picture in these infants was similar. Each had diarrhea, either mucoid or bloody, which developed in the’first few weeks of life. The diarrhea led to the development of anemia, hypoproteinemia, general failure to thrive, and an increased susceptibility to pulmonary infections. Six of the seven infants died before age two. Rectal prolapse developed between age four and nine months and was significant in that the mucosa was studded with polypoid lesions. The rectal prolapse tended to be recurrent and was associated with brisk bleeding from ulcerated and infected juvenile polyps. Several infants required repeated hospitalizations and general anesthesia for reduction of the prolapsed rectal mucosa. Both the morbidity and the parental distress at the unsightly, recurrent, and apparently painful prolapse were emphasized by several investigators. Either rectal bleeding or prolapsed polypoidstudded rectal mucosa prompted sigmoidoscopy, biopsy, and gastrointestinal x-ray studies. In each infant the biopsy specimens were initially interpreted as “adenomas” or adenomatous polyps. Xray studies demonstrated polyps in the stomach and small and large bowel in various combinations. In five of the seven infants intussusception developed leading to death in three. Six of seven infants died before age two years as a result of the combination of repeated episodes of gastrointestinal bleeding, intestinal obstruction, and diarrhea. Six infants had a total of eleven abdominal operations and an undetermined number of rectal fulgurations. Autopsy findings in these six patients demonstrated an uneven distribution of juvenile polyps from the stomach to the anus, with involvement of the terminal ileum and colon being most extensive. The polyps varied from 3 mm to several centimeters and were of uniform histologic appearance irrespective of the site of origin. One patient had left colectomy at age ten months and an abdominal colectomy with a cecorectal anastomosis at age two years. Juvenile polyps were noted in the jejunum and ileum during this latter procedure and nine polyps were removed. Gastrointestinal x-ray studies at age four and subsequently during teenage years demonstrated that some polyps had grown whereas others had apparently sloughed and disappeared. Management of these infants was often compromised by the histologic interpretation of the poly-
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poid lesions as representing adenomatous polyps with the unstated implication that this represented preneoplastic involvement of the entire gastrointestinal tract. A more precise understanding of the natural history of individual juvenile polyps and the recognition that the disease may be selflimited warrant more aggressive therapy. Medical management should initially concentrate on delineating the extent of involvement of the stomach and small and large bowel and searching for other congenital abnormalities. Therapy should be directed at control of the diarrhea by medication, a trial of broad spectrum antibiotics, evaluation of the usefulness of an elemental diet on the severity of diarrhea, and intravenous hyperalimentation. Surgical management should concentrate on removal of as many rectal polyps as possible in an attempt at reducing the frequency and severity of rectal prolapse. Elective intestinal resection of the segments that are most extensively involved combined with judicious removal of the larger gastric and small bowel polyps is indicated. Nevertheless a careful review of the available autopsy data suggests that the extent of initial involvement and the tendency for new juvenile polyps to develop will be the prime determinants of longevity. Juvenile polyposis coli: The recognition of juvenile polyposis coli as an entity distinct from familial polyposis of the colon by Morson and his colleagues [15,16] has been of immense value in clarifying the confusing spectrum of polypoid diseases. Although the existence of this disease as an entity is still widely unappreciated, it is likely to be the most common form of juvenile polyposis. The similarity between the polyp distribution in this syndrome and the adenomatous polyps of familial polyposis has resulted in a confused picture of polypoid diseases in children. It is now apparent that juvenile polyps of the colon may occur in a sporadic form with usually only one polyp or in a form in which the colon is almost matted with juvenile polyps. A few patients with extensive juvenile polyps of the colon have had an occasional juvenile polyp of the small bowel, but most have not had polyps elsewhere in the gastrointestinal tract [1,3,4,15,16]. Approximately half the children with juvenile polyposis coli that have been reported on have a family history of juvenile polyps. Most confusing is the association of juvenile polyposis and familial polyposis in the same kindred [15]. Children with juvenile polyposis coli may pre-
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sent with an asymptomatic prolapsed juvenile polyp or abdominal pain, gastrointestinal bleeding, anemia, diarrhea, and weight loss. Barium enema studies combined with removal of the more accessible rectal polyps and accurate histologic characterization of the polyps will prove to be adequate therapy in most children. Both the rarity of adenomatous polyps in children and the infrequent association of adenomatous and juvenile polyps in the same child are such that higher inaccessible polyps can confidently be considered the same as rectal juvenile polyps. The average patient with juvenile polyposis of the colon will need only intelligent observation and reassurance after the rectal polyps have been removed. Many juvenile polyps of the colon will slough or autoamputate. Although bleeding from juvenile polyps is often bright red and brisk, it is usually episodic and rarely of sufficient magnitude to lead to hypotension. Iron deficiency anemia, however, is common. In a few patients, juvenile polyposis coli is of such severity that colectomy may be indicated. This procedur;? should not be undertaken without an attempt to first remove the larger colonic polyps by colonoscopy. Gathright and Cofer [17] have recently emphasized the familial incidence of this syndrome and stressed the importance of accurate histologic characterization of the polyps prior to definitive treatment. Generalized juvenile gastrointestinal polyposis: A small number of patients have been found
to have juvenile polyps of the stomach and small and large bowel in various combinations. In these patients the gastric and colonic polyps have usually not manifested themselves simultaneously 141. The gastric polyps appear to account for most of the morbidity because of recurrent hemorrhage. The severity of gastric involvement was such that total gastrectomy was necessary in three patients. Two of these patients also had colectomy and multiple operations for excision of small bowel polyps. The similarity of distribution and gross appearance of these polyps and those of the Peutz-Jeghers syndrome is such that there is distinct possibility of misclassifying these two syndromes. The risk of carcinoma in these patients is not increased and specific extracolonic manifestations are inapparent. Summary
Almost ail published cases of hereditary intestinal polypoid diseases can be meaningfully classi-
The American Journal of Surgery
Polypoid Diseases
fied into a relatively few distinct syndromes including familial polyposis of the colon, Peutz-Jeghers syndrome, and juvenile polyposis. Familial polyposis is characterized by the development of numerous adenomatous polyps of the colon and subsequent development of colorectal carcinoma in nearly all patients. Extracolonic manifestations are common but do not influence the premalignant nature of this syndrome. Peutz-,Jeghers syndrome is identifiable by a combination of circumoral melanin pigmentation and hamartomatous polyps. These polypoid lesions have an unusually wide distribution and may occur in t.he respiratory, gastrointestinal, or genitourinary tract. There is a small but definite increased incidence of gastrointestinal cancer in these patients. Juvenile polyposis presents a more variable spectrum. In one form there is extensive intestinal involvement leading to diarrhea, inanition, and increased susceptibility to infection. Another form is limited to the colon and easily confused with familial polyposis. With the third form, there is involvement of the stomach, intestines, and colon, which makes it easily mistaken for the Peutz-Jeghers syndrome. References 1. Bussey HJR: Gastrointestinal polyposis. Gut 11: 978, 1970. 2. Sachatello CR: Familial polyposis of the colon. Cancer 28: 581, 1971.
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3. Sachatello 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. slJrgery75: 107.1974. 4. Sachatello CR, Pickren JW. Grace JT Jr: Generalized juvenile gastrointestinal polyposis. Gastroenferology 58: 699, 1971. 5. Morson BC: Some peculiarities in the histology of intestinal polyps. Dis Colon Rectum 5: 337, 1962. 6. Lane N. Kaplan H, Pascal RR: Minute adenomatous and hyperplastic polyps of the colon: divergent patterns of epithelial growth with specific associated mesenchymal changes. Gastroenterology60: 537, 1971. 7. Smith WG: Familial multiple polyposis. Dis Co/on Rectum 11: 17, 1968. 8. Gardner EJ: Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas. fibromas. and epidermal cysts. Am J Hum Genet 14: 375. 1962. 9. Moertel CG, Hill JR, Adson MA: Management of muttiple polyposis of the large bowel. Cancer 28: 160, 197 1. 10. Godard JE. Dodds WJ, Phillips JC, Scanlon GT: Peutz-Jeghers syndrome: clinical and roentgenographic features. Am J Roentgen01 Radium Ther Nucl Med 113: 3 16, 197 1. 11. Bartholomew LG. Dahlin DC, Waugh JM: Intestinal polyposis associated with mucocutaneous melanin pigmentation (Peutz-Jeghers syndrome). Gastroenterology 32: 434, 1957. 12. Dorois RR, Judd ES, Dahlin DC, Bartholomew LG: Peutz-Jeghers syndrome: is there a predisposition to the development of intestinal malignancy? Arch Surg 98: 509, 1969. 13. McKittrick JE, Lewis WM. Doane WA, Gerwig WH: PeutzJeghers syndrome. Arch Surg 103: 57, 1971. 14. Scully RE: Sex cord tumor with annular tubules: a distinctive ovarian tumor of the Peutz-Jeghers syndrome. Cancer 25: 1107, 1970. 15. Veale AMO, McCall I, Bussey HJR, Morson BC: Juvenile polyposis coli. J Med Genet 3: 5, 1966. 16. McCall I, Bussey HJR, Veale AMO, Morson BC: Juvenile polyposis coli. Proc R Sot Med57: 896, 1964. 17. Gathright JB, Cofer TW: Familial incidence of juvenile polyposis coli. Surg Gynecol Obstet 138: 185. 1974.
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