juvenile colonic polyposis in colombia

Juvenile Colonic Polyposis in Colombia*

CARLOS RESTREPO, M.D.,? JAIME MORENO, M.D.,? EDGAR DUQUE, M.D.,$ CARLOS CUELLO, M.D.,.~ JON AMSEL, Sc .D. ,w PELAYO CORREA, M.D.82

JUVENILE POLYPS of the colon are frequently seen in children and young adults in Colombia. They are also called retention polyps. They usually are not found in adults, apparently because they are self-amputated around the age of 12 years, a~ Most of the patients have only isolated polyps in the rectum. 12"Ir'46 Occa- sionally, patients who have many polyps located in different segments of the large bowel are seen. These cases represent examples of one of the gastrointestinal polyposis syndromes.

Familial adenomatous colonic polyposis is the most common polyposis in many countries? 4'3r It was reported first by Cripps in 1882, and the largest series was that of Bussey, 4 which included more than 600 patients with the disorder and 200 affected families recorded in a specially designed registry begun in 1925. Other well-recognized polyposis syndromes in- clude Gardner's, Turcot's, and Peutz-Jegher's syndromes.

Although man}" reports dealing with colonic polyps in children have included some sporadic mentions of multiple juvenile polyposis, this syndrome was recognized as an independent entity only recently. McColl et al. 29 described it in 1964 and, in 1966, Veale et al. 4s established its familial character. Sachatello et al. at-a9 further described a related syndrome of generalized juvenile gastrointestinal polyposis affecting mainly in- fants.

We have studied a series of cases of juvenile colonic polyposis in Colombia, where this particular syn-

* Received for publication July 17, 1978. t Departments of Pathology and Medicine (Gastroenterology

Section), Universidad de Anitoquia. + Department of Pathology, Universidad del Valle. w School of Public Health, University of Illinois Medical Center. 82 Department of Pathology, Louisiana State University Medical

Center. Supported in part by Public Health Research Contracts NOI-

CP-53521 and NO1-CP-33286 from the Division of Cancer Cause Prevention, National Cancer Institute, with the Louisiana State University Medical Center, and Fundaci6n para la Educaci6n Superior.

Address reprint requests to Dr, Correa: Department of Pathol- ogy, LSU Medical Center, New Orleans, Louisiana 70112.

From the Universidad de Antoquia, MedeU(n, Columbia, and the Universidad del Valle,

Cali, Colombia, South America, The Universi~ of Illinois Medical Center,

Chicago, Illinois, and the Louisiana State University

Medical Center, New Orleans, Louisiana

TABLE 1. Juvenile Polyposis of Colon: Age and Sex Distribution

Age (Years) Male Female Total

0-4 2 - - 2 5-9 4 2 6

10-14 3 6 9 15-19 2 4 6 20-24 2 - - 2 25-29 1 - - 1 30-34 1 - - 1

TOTAL 15 12 27

drome seems to be observed more frequently than other gastrointestinal polyposis syndromes. We present the clinicopathologic and familial features of this series of cases.

Materials and Methods

All colonic polyps in the files of two large departments of pathology in Colombia were reviewed by C.R. Between January 1, 1944, and December 31, 1975, 582 cases were registered in the files of the Instituto de Patologia, Universidad de Antioquia, in Medellin, Colombia. An additional 181 cases, all registered between January 1, 1954, and December 31, 1976, were found in the files of the Department of Pathology, Universidad del Valle, Cali, Colombia. Cases of gastrointestinal p01yposis syndromes totalled 51:14 cases of adenomatous polyposis coli, ten cases of Peutz-Jeghers syndrome, and 27 cases of juvenile polyposis coll. Only the 27 cases of juvenile polyposis coli are included in the present report.

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Fro. 2. (above) Patient 10. Specimen obtained by subtotal colectomy, showing many pedunculated polyps surrounded by normal mucosa. Greater concentra- tion of polyps is noticeable in rectosig- moidal segment.

FIr 3. (below) Close-up view of specimen in Figure 2, showing polyps in the sigmoid colon.

Slides and clinical charts from all 27 cases were reviewed. Interviews were conducted with relatives of patients to collect the necessary pedigree data.

Results

Table 1 shows the distribution by age and sex of patients included in this series. Twenty-three of the 27 patients who had juvenile polyposis (85.2 per cent) were less than 20 years of age the mean age of onset was 8.9 years. There were 15 male and 12 female patients. The most frequent symptoms were passing of blood in stools, bloody diarrhea, and rectal prolapse. Spontane- ous expulsion of polyps occurred frequently in these cases. Mild to severe anemia due to blood loss was frequently observed. X-ray studies of the colon and rectosigmoidoscopy revealed the multiple polyps in 26 patients. One case, in a patient who died of acute intestinal obstruction, was diagnosed only at autopsy.

Family Distribution: Familial transmission of multiple juvenile polyposis of the colon was found in 15

of the 27 cases. Thirteen of these cases were confined to five kindreds; the corresponding pedigrees are shown in Figure 1. Two additional cases suggested a familial tendency, but the necessary' pedigree data

FIG. 4. Patient 23. Rectosigmoid colon, showing many clusters of juvenile polyps surrounded by normal rnucosa.


Fro. 5. Patient I. Juvenile polyp, showing glandular proliferation with well-differentiated mucus-secreting columnar epithelium. Notice prominent stroma made of loose connective tissue with leukocytic infiltrate (hematoxylin and eosin; x 29).

could not be obtained. Of particular interest is Family One, with six recorded cases of multiple juvenile polyposis of the colon in generations III and IV. Five affected members of this family are descendants of one individual in Generation II, known to have multiple adenomatous polyps 25 years before development of cancer in the rectosigmoid colon. Family Two is also remarkable for having four of 51 members of Generation III affected with the disease. Pedigree analysis supports an autosomal dominant mode of inheritance for juvenile polyposis. However, for only Families One and Three are two-generational data available. In Family Three, the condition appears to have skipped a generation. This finding is probably due to incomplete ascertainment rather than to re- duced penetrance. In the remaining families, the pedigree data suggest that a new mutation is respon- sible for the trait.

Gross and Microscopic Features: Total or partial colectomy was performed on 14 of the 27 cases. In one additional case, autopsy material was available for the study. In all cases, numerous peduncu lated

polyps were seen throughout the entire resected segment of the colon as slightly lobulated pedunculated round masses (Figs. 2-4). The mucosa between the polyps was of normal appearanc e , with prominent rugae lacking the typical "cobblestoned" effect of familial adenomatous polyposis. The polyps ranged in size from 0.5 to 3 cm. Many had long slender stalks. Only one of the cases featured clusters o f sessile polyps in the rectum separated by normal-looking mucosa (Fig. 4). Although polyps were seen at all levels of the large bowel, they seemed to be more numerous in the left part of the colon, mainly in the rectum and sigmoid colon. In the remaining cases numerous polyps obtained by endoscopic resection showed similar gross features.

Microscopically, all of these polyps had similar appearances. They showed glandular proliferation with we l l -d i f fe rent ia ted mucus-secret ing co lumnar epithelium (Fig. 5). Dilated glands with epithelial rupture were frequently observed (Figs. 6 and 7). The dilated glands were sur rounded by a prominent stroma showing a dense leukocytic infiltrate, com- posed mainly of neutrophi l ic po lymorphonuc lear

Dis. Col. & Rect. 604 RESTREPO, ET AL. Nov.-Dec. 1978

Fro. 6. Patient 3. Juvenile polyps, showing well differentiated glands, cysts with epithelial rupture, and densely leukocytic infiltrated stroma (hematoxylin and eosin; 29).

cells, a moderate amount of eosinophils, and some lymphocytes and plasma cells (Fig. 7). Many of them showed ulceration and loci of recent hemorrhage. Epi- thelial atypia was not observed. All cases in this series were classified as juvenile polyposis except two. In Patient 6 (IV-6 in Family One) all polyps were of the _juvenile type except one, which was adenomatous. Pa- tient 17, examined by endoscopy and colostomy, had .juvenile-type polyps at 32 years of age; however, cancer of the transverse colon developed in this patient when he was 40 years old, and total colectomy was performed. Examination of the surgical specimen revealed numerous diverticula, a malignant tumor in the transverse colon, and many polyps, of which only three were sampled for histologic study, two of them being of the ` juvenile type, and the third an adenomatous polyp with considerable cellular atypia. This case is also remarkable for being the only exam- ple of carcinoma of the colon arising in association with juvenile polyposis in this series.

Other diseases diagnosed in association with multi- plejuvenile polyposis o f the colon are shown in Table 9.

The not-infrequent diagnosis of congenital heart disease in individuals with juvenile polyps is particu- larly noteworthy. Furthermore, three of the four are thought to represent familial rather than sporadic cases of juvenile polyposis.

Three cases in Family Two (Patients 8, 9 and 11 had acute glomerulonephritis that subsided after clinical treatment. Patients 9 and 11 had this renal ailment in the same period in 1961; it developed in patient 8 in 1973.

The mortality experience for this series is shown in Table 3. The case of Patient 17, a 40-year-old man, is noteworthy because of the diagnosis of .juvenile polyposis had been made 90 years previously.

Fourteen patients were treated with total or subtotal colectomy, while in 12 others, polyp resections were accomplished by endoscopy or co!ostomy. In one case, no specific treatment for polyposis was given, and the syndrome was first diagnosed at autopsy. The cause of death was peritonitis resulting from intestinal occlusion. Twelve patients are known to be alive. Recurrence of polyps in the rectum was observed in

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Fro. 7. Patient 7. Juvenile polyp, showing well-differentiated glands, a glandular cyst, and loose stroma with loci of hemorrhage and slight lenkocytic infiltration (hematoxylin and eosin: x 29).

six patients treated with subtotal colectomy, neces- sitating repeated removal and surgical resection of the rectal mucosa. Follow-up data were not available for nine patients.

TABLE 2. Diseases Diagnosed in Association with Multiple Juvenile Polyposis Coli

Patient Associated Disease

1 Tetralogy of Fallot

6 Coarctation of the aorta; pectus excavatum; osteoma of frontal bone

7, 8, 10 Acute glomerulonephritis

11 Subvalvular aortic stenosis: familial congenital lymphedema

20 Thyroglossal duct cyst

24 Interatrial septat defect

25 Psoriasis

TABLE 3. Mortality Experience of Juvenile Polyposis Cases by Cause of Death

Patient Cause of Death

1

6

12

15

16

23

Unspecified postoperative complications

Suicide

Ileocecal intussusception, acute fibrinous peritonitis

Peritonitis secondary to dehiscent surgical wound

Postoperative septicemia secondary to colectomy for cancer of transverse colon

Unspecified postoperative complications

Discuss ion

The juvenile polyp is the most common type of colonic polyp observed in Colombia, 5'6'9'2~ as well as in some other developing countries. 4~ These polyps occur mainly as isolated lesions in patients less than 15 years of age. Approximately 90 per cent of the polyps


are isolated and are confined to the rectum. In the present series we have analyzed only the microscopically confirmed cases of multiple juveni le polyposis of the colon.

Multiple polyposis of the colon, juvenile type, is observed mainly in children, with the mean age of onset of first symptoms 8.9 years. Early clinical manifesta- tion of the disease is highly characteristic of this syndrome, unlike the situation with adenomatous polyps, the symptoms of which appear, in general, in the third decade of life. a's'a~ The symptoms most fie- quently observed in patients diagnosed to have multi- pie juvenile polyposis were rectal bleeding, bloody diarrhea, and prolapsed rectal mucosa. Spontaneous expulsion of polypoid masses was frequently recorded. Grossly, numerous pedunculated polyps were scattered throughout the colon, although the}" tended to concentrate in the left side, mainly the sigmoid colon and rectum. Most of the polyps were larger than 1 cm in diameter. A normal mucosa, lacking the characteristic "cobblestoned" appearance of adenomatous multiple polyposis, surrounded the polyps. In general, most of the patients examined had more than 25 polyps, but in no instance did the number of polyps exceed 100, falling short of the least number of polyps required by Bussey 4 for the diagnosis of polyposis of the colon.

The microscopic features were similar to those previously described. 15,*9,-~~ 23.27.2S.35.42.43 Juvenile polyps characteristically contain glandular retention cysts. Roth and Helwig ~ believe they result from al- ternating cycles of ulceration and regeneration of the mucosa with blockage dilation of glands. Horrilleno et al . "-~ also considered juvenile polyps to be retention polyps. Conversely, Morson and Bussey a~ believe that juvenile polyps represent hamartomatous growths of intestinal mucosa. Kozuka "4 has advanced the view thatjuvenile poIyps represent an immature var- iant of adult adenomatous polyps. Finally, it has been suggested that some pathogenic relationship might exist between juvenile polyps and a prolonged history of allergy?

Juvenile polyps are not generally thought of as being precancerous, aa Yet in two cases in the present series (Patients 6 and 17), adenomatous proliferation with pseudostratification of the glandular epithelium (showing mild to severe atypia) was observed in isolated polyps, with development of cancer of the transverse colon in one case (Patient 17). The coincidental finding of adenomatous and juvenile polyposis has been reported. -%r''''zS,aa' 36,38,39.41,45, 47,49,51 In our experience, this is unusual, and patients having such coincidental findings are the only ones in whom cancer of the colon associated with juvenile polyposis

developed later. At present, it is not clear which of the following possibilities explain the coincidental finding of juvenile and adenomatous polyps in the same patient: 1) the two types of polyposis of the colon develop independently of one another, and it is a chance phenomenon that they occur coincidently in the same patient; 2)juvenile polyps, under appropriate condi- tions, are potentially malignant, and adenomatous polyps represent one of the initial transitory stages.

A definite familial pattern was observed for 13 of the cases, which were confined to five families. In two additional cases of familial pattern was suggested, but could not be documented with adequate pedigree data.

Our findings are consistent with earlier reports that this condition segregates as an autosomal dominant trait.a.4,~o,l,, 14, t6,18,29,34,44,50 In Families Two, Four, and Five, the cases seemed to represent new muta- tions.

However, the genetics of juvenile polyposis of the colon appear to be more complicated than suggested by its conventionally accepted mode of inheritance. Considerable intrafamilial variability has charac- terized not only the present case series, but previously reported familial aggregations as well. ~~ ls,a2,a4.44,50 Examples illustrating this variability in- clude: I)juvenile polyposis coli occurring in some families in which adenomatous polyposis or colonic cancer, or both, have occurred; 2) isolated juvenile polyps undergoing adenomatous changes in some affected family members with multiple juveni le polyposis of the colon; 3) the appearances of juvenile polyps, ranging from their being isolated to being multiple within the same family. The pedigree of Family' One is quite remarkable in showing this intrafamilial variability. One patient, who is not included in this series, had adenomatous polyposis with severe atypia of the rectum diagnosed microscopically 25 years before development of cancer of the rectosigmoid colon. Patient IV-6, in the same family, was remarkable for showing adenomatous changes in one of many juvenile polyps that were microscopically examined.

Several alternative genetic models can, at least con- ceptually, explain the phenomenon of more than one type of polyposis occurring in the same kindred. These models are: 1) a modifying allele at the polyposis locus (allelic interaction); 2) genes at other loci interacting with the polyposis gene (nonallelic interaction, or epistasis); and 3) more than one polyposis gene segregating in the same family.

It is unlikely, however, that the first model, similar in substance to that proposed by Veale et al . , 4s is cor- rect, in that it assumes a mutational frequency at a

Volume 21 Number 8 JUVENILE POLYPOSIS 1N COLOMBIA 607

single locus, which is highly unlikely. The second model is more reasonable, provided there is loose linkage between the epistatic and polyposis genes. I f tight linkage existed, it would be extremely difficult to distinguish between allelic and nonallelic interactions. The third and final model is self-explanatory.

The coincidental finding of congenital malformations in some of the patients included in this series has been observed previously, a, ~'29' 48 Veale et al. 4s stressed the sporadic rather than familial nature of these cases. We were unable to confirm this. Rather, three of the four patients with juvenile polyposis, for whom there was a coincidental finding of a congenital mal- formation, had relatives who were also affected with juvenile polyposis. In all instances, however, there was a negative family history o f congenital malformations.

Previous investigators have repor ted d i f ferent types of malformations in association with juvenile polyposis; however, our patients were diagnosed as having mainly cardiac anomalies. The prevalence of congenital heart disease in our limited case series g-reatly exceeds the expected number, based on prevalence estimates of congenital heart disease for the general population of Colombia. Even though only Patients 7 and 12 had cardiac lesions that were similar in their embryologic derivation (i.e., both being de- fects of the arterial wall and intracardiac connective tissue), further study of this preliminary finding is warranted. The coexistence of juvenile polyposis and congenital heart disease may represent a distinctly new syndrome, but this can be investigated only with the accumulation of additional cases. Regardless of the direction of future studies, however, it is clear at the present t ime that the genetics o f juven i le polyposis are complicated by this finding.

In one family, glomerulonephrit is was associated with juvenile polyposis in three cases, coinciding in time in two of the cases and observed ten years later in the third case. Laryngeal polyps were also seen in one member of the same family.

The cases reported in the present series represent examples of juvenile polyposis of the colon proper, and should be distinguished from two other syndromes reported in the medical literature featuring juvenile polyps. ''r''5'aa'a


ment. Baltimore, The Johns Hopkins University Press, 1975, 104 pp

5. Cabrera A, LegaJ: Polyps of the colon and rectum in children. AmJ Surg 100: 551, 1960

6. Cabrera A, Restrepo C, Lega J: Polipos del recto y porcidn distal del colon. Rev Lat Am Patol 3: 55, 1959

7. Campanello N: Poliposi intestinale diffusa in un lattante. Rev Assoc Med Bras 17: 299, 1940

8. Chevrel JP, Amouroux J, Gverand JP: La polypose juvenile. bled Chir Dig 5: 47, 1976

9. Correa P, Duque E, Cuello C, et al: Polyps of the colon and rectum in Call, Colombia. Int J Cancer 9: 86, 1972

10. DeCosse JJ, Adams biB, Condon RE: Familial polyposis. Cancer 39: 267, 1977

1I. Devadason I: Colonic juvenile polyps in a family. Australas Radiol 20: 125, 1976

12. Duhamel J: Colo-rectal polyps in adolescence. Am J Proctol 26:36 (Dec) 1975

13. Elston RC, Yelverton KC: General models for segregation analysis. Am J Hum Genet 27: 31, 1975

14. Erbe RW: Current concepts in genetics: Inherited gastrointestinal polyposis syndromes. N EnglJ bled 294:1101, 1976

15. Franklin R, blcSwain B: Juvenile polyps of the colon and rectum. Ann Surg 175: 887, 1972

t6. Gathright JB Jr, Corer TW Jr: Familial incidence of juvenile polyposis coli. Surg Gynecol Obstet 138: 185, 1974

17. Gelb AM, Minkowitz S, Tresser M: Rectal and colonic polyps occurring in young people. NY StateJ Med 62: 513, 1962

18. Haggitt RC, Pitcock JA: Familial juvenile polyposis of the colon. Cancer 26: 1232, 1970

19. Holgersen LO, bliller RE, Zintel HA: Juvenile polyps of the colon. Surgery 69: 288, 1971

20. Horrilleno EG, Eckert C, Ackerman LV: Polyps of the rectum and colon in children. Cancer 10: 1210, 1957

21. Kaschula RO: Mixed juvenile, adenomatous and intermediate polyposis coli: Report of a case. Dis Colon Rectum 14: 368. 1971

92. Kissane Jbl, Smith biG: Patholo~ of Infancy and Childhood. St. Louis, The C. V. blosby Company, 1967, p 223

23. Knox WG, Miller RE, Begg CF, et al: Juvenile polyps of the colon: A clinicopathologic analysis of 75 polyps in 43 patients. Surgery 48: 201, 1960

24. Kozuka S: Nature of juvenile polyps in the large intestine. Acta Pathol Jpn 26: 509, 1976

25. Lefevre HWJr, Jacques TF: blultiple polyposis in an infant of four months. Amj Surg 81: 90, I951

96. Lega J, Restrepo C: Polipos deI recto y de la porcidn distal del colon. Antioquia bled 7: 2, 1957

27. blallam AS, Thomson SA: Polyps of the rectum and colon in children: A ten year review at the Hospital for Sick Chil- dren. Can J Surg 3: 17, 1959

28. Mauro J, Prior JT: Gastrointestinal polypoid lesions in childhood. Cancer 10: 131, 1957

29. blcColl I, Bussey HJ, Veale AM, et al: Juvenile polyposis coll. Proc R Soc bled 57: 896, 1964

30. Morson BC: Genesis of colorectal cancer. Clin Gastr0enterol 5:505 (Sept) 1976

31. Morson BC, Bussey HJ: Predisposing causes of intestinal cancer. Curt Probl Surg (Feb) 1970, p 8

32. Raskin JB, Dodd H II: Juvenile polyposis coil concurrent with neurofibromatosis. South bled J 69: 1374, 1976

33. Ravitch MNI: Polypoid adenomatosis of the entire gastrointestinal tract. Ann Surg 128: 283, 1948

34. Ray JE, Heald RJ: Growing up with juvenile gastrointestinal polyposis: Report of a case. Dis Colon Rectum 14: 375, 1971

35. Roth SI, Helwig EB: Juvenile polyps of the colon and rectum. Cancer 16: 468, 1963

36. Ruymann FB: Juvenile polyps with cachexia: Report of an infant and comparison with Cronkhite-Canada syndrome in aduIts. Gastroenterology 57: 431, 1969

37. Sachatello CR, Griffen WOJr: Hereditary polypoid diseases of the gastrointestinal tract: A working classification. Am J Surg 129: 198, 1975

38. 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. Surgery 75: 107, 1974

39. Sachatello CR, Pickren JW. Grace JT Jr: Generalized juvenile gastrointestinal polyposis: A hereditary syndrome. Gas- troenteroIogy 58: 699, 1970

40. SalasJ: Patolog~a de los polipos de colon en nifios yen adultos. Rev Lat Am Patol 9: 3, 1970

41. Schwartz AM, blcCauley RG: Juveni le gastrointest inal polyposis. Radiology 121: 441, 1976

42. Shermeta DW, blorgan WW, Eggleston J, et al: Juvenile retention polyps. J Pediatr Surg 4: 211, 1969

43. Silverberg SG: "Juvenile" retention polyps of the colon and rectum. Am J Dig Dis 15:'617, 1970

44. Smilow PC, Pryor CA Jr, Swinton NW: Juvenile polyposis cole A report of three patients in three generations of one family. Dis Colon Rectum 9: 248, 1966

45. Soper RT, Kent TH: Fatal juvenile polyposis in infancy. Surgery 69: 692, 197I

46. Spencer R: gastrointestinal hemorrhage in infancy and childhood: 476 cases. Surgery 55: 718, 1964

47. Stemper TJ, Kent TH, Summers RW: Juvenile polyposis and gastrointestinal carcinoma: A study of a kindred. Ann Intern Med 83: 639, 1975

48. Veale AM, McColl I, Bussey H J, et al: Juvenile polyposis coli. J bled Genet 3: 5, 1966

49. Velcek FT, Coopersmith IS, Chen CK, et al: FamiIial juvenile adenomatous polyposis, j Pediatr Surg 1 I: 781, 1976

50. Wennstrom J, Pierce ER, McKusick VA: Hereditary begnign and malignant lesions of the large bowel. Cancer 34: 850, 1974

51. Williams AO, Prince DL: Intestinal polyps in the Nigerian Af- rican. J Clin Pathol 28: 367, 1975

52. Yone,noto RH, Slayback JB, Byron RL Jr, et al: Familial polyposis of the entire gastrointestinal tract. Arch Surg 99: 427, 1969

APPENDIX

Report of 27 Cases

Patient 1 (Subject IV-12). The propositus in Family One, the 9-year-old grandson of II-7, was evaluated in 1973 for intermittent rectal bleeding, rectal prolapse, recurrent crises of abdominal pain, anemia and diarrhea of three years' duration. Numerous polyps were seen on sigmoidoscopic and barium-enema examinations. The patient had a congenical heart condition, which was clinically diagnosed as tetraloD of Fallot, and marked clubbing of fingers. Several polyps removed at endoscopy showed microscopic features of juvenile polyps (Fig. 5). Total colectomy was performed. There

were more than 40 polyps in the surgical specimen. The patient died three months after operation. Autopsy was not performed.

The 43-year-old grandfather of Patient 1 was first examined in 1951 because of rectal bleeding, and many rectal polyps were found by endoscopy. Biopsies of several of them revealed adenomatous polyps with villous changes and extremely severe atypia (Fig. 8). Twenty-four years later, in 1975, the now 67-year- old patient had acute intestinal obstruction. Laparotomy disclosed a large tumor in the sigmoid colon, which was considered unresect-

Volume 21 Number 8 JUVENILE POLYPOSIS IN' COLOMBIA 609

Fic.. 8. Adenomatous polyp removed from the grandfather of patient 1 at the age of 43 years, showing marked glandular dysplasia (hematoxylin and eosin; 29).

able, and colostomy was done. Histolo~c diagnosis was undiffer- entiated carcinoma. X-ra~ studies confirmed the presence of tumor in the sigmoid colon and numerous polyps at different levels. Mi- croscopic study of polyps removed at operation and by endoscopy afterwards confirmed their adenomatous type. The patient died ten months after operation.

Patient 2 (Subject IV-8, Family One). A 15-year-old sister of Patient 1, with mild symptoms, was examined for polyposis in 1974. Many polyps were seen on barium-enema examination (Fig. 9) and endoscopy. Microscopic study of several rectal polyps removed by endoscopy revealed that they were the juvenile type. Operation has not been performed, and the patient has been followed in the hospital clinics.

Patient 3 (Subject I\:-9, Famil} One). A 14-year-old sister of Patients I and 3 was examined for polyposis in 1974. Numerous rectal polyps were disclosed by endoscopy. Rectal polyps removed for microscopic study were of the juvenile type (Fig. 6). No major operation has been performed for the polyposis, and the patient has been followed in the hospital clinics.

Patient 4 (Subject IV-10, Family One). A 13-year-old sister of Patient 1 was examined for polyposis in 1974. Sigmoidoscopy revealed man? rectal polyps which, on microscopic study, were of the juvenile type. No major operation was performed, and the patient is being followed.

Patient 5 (Subject IV-6, Family One). A 9-year-old boy, a cousin of Patient 1. was examined in 1973 because of intermittent rectal bleeding, rectal prolapse, and a fi~e-year history of expulsion of poiypoid masses. Barium-enema examination and endoscop} revealed numerous polyps. Sixteen polyps were removed by endoscop}, 15 of which proved to be of the juvenile type on microscopic study. One of the polyps contained loci of adenomatous changes

with slight atypia. No major operation has been performed, and the patient is being followed.

There are five more siblings in the family of Patient 6, none of whom has shown symptoms of polyposis.

Patient 6 (Subject III-14, Family One). A 15-year-old boy second cousin of the preceding patients, was first examined in 1956 because of intermittent rectal bleeding and recurrent rectal prolapse. An excavated sternum was observed on physical examination. Many colonic polyps were seen on barium-enema examination and endoscopy. Numerous polyps were removed by endoscopy over a three-year period, until the patient reached the age of 20 years. Total colectomy with ileorectal anastomosis was then per- ~Cormed, and there were many polyps throughout the colon. A review of available slides showed exclusively juvenile polyps. Shortly after the operation, sinusitis developed, and a ~'rontal osteoma was diagnosed by x-ra~. A year later, at the age of 21 }'ears. the patient was diagnosed as having aortic coarctation with marked clubbing of the fingers; a successful surgical correction was carried out two months later. Recurrent rectal polyps, which proved to be of the juvenile type, were removed on many subsequent occasions. The patient was admitted several times in 1965 at the age of 24 years, in 1972 at the age of 31 years, and in 1974. for repeated bouts of intestinal obstruction secondary to peritoneal adhesions. His condition was treated by continued suction and other therapeutic meas- ures. The patient married at 25 ?,'ears of age and fathered a daughter, who has not shown symptoms of disease. He committed suicide at the age of 34 years.

Patient 7 (Subject III-40). The propositus in Family Two was first seen at the age of 8 years in 1972 because he had had sudden onset of cramping abdominal pain, persistent nausea and ~omiting, and rectal bleeding of short duration. Many polyps were found bv

Dis, Col. & Rect. 6 1 0 RESTREPO, ET AL. No,.-Dec. 1978

FIG. 9. Patient 2. Roentgenogram (double-contrast technique), revealing multiple colonic polyps.

endoscopy and barium-enema examination. Numerous polyps removed showed microscopic features ofjuvenile polyps. Total colectomy with ileostomy was performed. A total of 31 polyps was found scattered throughout the colon (Fig. 7). A month later, the patient had acute intestinal obstruction due to intussusception, which was treated by surgical resection of the ileostomy stump. When the patient was 10 years old, he had acute glomerulonephritis, with complete spontaneous regression. He was followed for more than two years after operation.

Three siblings of Patient 7 have had a similar condition. His father had a history of laryngeal polyps, but did not have colonic polyps.

Patient 8 (Subject IIi-34, Family Two). A brother of Patient 8 was first evaluated in 1960 when he was 11 years old. He had had intermittent rectal bleeding, diarrhea, and prolapse of rectal polyps for several years. Many polyps were removed by endoscopy and were classified as the juvenile type after a review of the microscopic slides. Subtotal colectomy was carried out when the patient was 15 years old. There were numerous polyps in the surgical specimen found to be of the juvenile type by histologic study. A year later, recurrent rectal polyps were removed at endoscopy. Later, the pa* tient had acute glomerulonephritis with hypertension, which subsided completely spontaneously. Three years after subtotal colectomy, when the patient was 19 years of age, another partial colonic resection was performed. The patient was followed for seven years after the last surgical procedure, and many recurrent rectal polyps were removed each year; all of them were of the juvenile type.

Patient 9 (Subject III-35, Family Two). Another brother of Pa- tient 8, was first seen at tile age of ten years in 1960 because of intermittent rectal bleeding and rectal prolapse of four years' duration. Many colonic polyps were seen on barium-enema examination and endoscopy. Several which were removed by laparotomy were microscopically classified as the juvenile type. Total colectomy was carried out when the patient was 13 years old, and the surgical specimen then contained multiple juvenile polyps also. No recnr- rence was recorded on follow up. Ten years after colectomy the patient was admitted again because of drug addiction.

Patient 10 (Subject III-36, Family Two). This patient, also a brother of Patient 8, was seen at the age of 5 years in 1959, because of recurrent abdominal cramps, bloody diarrhea, and frequent prolapse of the rectum for two years before admission. Many polyps of the colon were seen on roentgenograms. Subtotal colectomy was performed when the patient was 6 years old. Surgical specimens (Figs. 2 and 3) contained about 60 polyps, which were microscopically classified as the juvenile type. A year after operation, acute glomerulonephritis developed, but the patient recovered fnlly. He had recurrent rectal polyps, which were treated by three subsequent endoscopic resections and then surgical removal of the complete rectal mucosa. At his last follow-up examination, at the age of 91 years, the patient was free of symptoms.

Patient 11 (Subject III-10, Family Three). A 13-year-old girl was first seen in 1973 because of rectal bleeding, diarrhea and tenesmus, which she had had for three years before admission. Endoscopy revealed many clusters of polyps, which completely en- circled the intestinal lumen. All polyps taken for microscopic study showed juvenile features. This patient also has congenital heart disease, which was diagnosed as subvalvular aortic stenosis associated with familial congenital lymphedema. In 1977, when the patient was 17 years old, resection of the rectal mucosa was carried out. The surgical specimen contained more than 30 polyps, ranging in size from 0.3 to 9 cm. Slides were reviewed and all polyps were of the juvenile type.

The patient's maternal grandmother had a long history of in- termit tent rectal bleeding, which was highly suggestive of polyposis; she has not been examined, however. Three of her siblings, who had similar symptoms, were not studied, either.

Patient 1'2 (Subject III-4, Family Four). A 10-year-old girl was admitted to the hospital in 1964 because of acute onset of abdominal cramping pain, persistent vomiting, spastic contractures of hands and wrists, and irregular movements of the eyeballs. Medical treatment was unsuccessful, and the patient died shortly after admission. Autopsy revealed ileocecal intussusception, dilatation of small intestinal loops, and acute fibrinous peritonitis. Many pedun- culatedjuvenile polyps were found scattered throughout the colon. No polyps were seen in the upper gastrointestinal tract.

The patient's 11-year-old brother was treated in the hospital because of similar symptoms due to solitary juvenile polyp of the rectum.

Patient 13 (Subject II-5, Family Five). A 6-year-old girl was admitted to the hospital in 1973 because of rectal bleeding of one year's duration. Sigmoidoscopy revealed numerous polyps which, upon microscopic examination, proved to be of the juvenile type.

An 8-year-old brother of this patient was also treated in the hospital because of juvenile polyps of the rectum.

Patient 14. An 18-year-old youth with a long history of rectal bleeding, diarrhea, and rectal prolapse was examined in 1960; endoscopy showed many polyps. Barium-enema examination also revealed numerous polyps in the entire colon, associated with many diverticula. Total colectomy was performed. The surgical specimen contained about 100 polyps. All the lesions had typical microscopic features of juvenile polyps. After one year postoperatively, when the patient was last seen, follow-up information was not available.

A brother, paternal grandfather, and two uncles of Patient 14 had symptoms highly suggestive of polyposis. Unfortunately, we could not locate their household to build up the family pedigree.

Patient 15. In 1974, a 16-year-old boy was admitted to the hospital because of a long history of bloody diarrhea, tenesmus, rectal bleeding, and frequent passing of polyps by rectum. The patient had begun to show symptoms at 4 years of age. Total colec-


tomy with ileorectal anastomosis was performed. There were many polyps in the colon which on microscopic examination were all classified as juvenile. The patient had an agonizing postoperative course and died ten days after the operation because of peritonitis secondary to dehiscence of the surgical wound. Autopsy was not performed.

A paternal aunt of this patient is known to have had multiple polyposis of the colon and was operated on for it. Slides were not available for review.

Patient 16. A 19-year-old youth was first seen in 1950 because of intermittent rectal bleeding and prolapse of rectal mucosa. En- doscopy revealed many polyps, which were classified as the juvenile type on the basis of microscopic examination. Further treatment was not given at that time. The patient was treated from the age of 20 years to the age of 32 years. At the age of 26 years he had renal tuberculosis, which was successfully treated. Repeated endoscopic resections for polyps were performed. He was seen again in 1963, when nine polyps were removed; all of them showed microscopic features of the juvenile type. In 1971, when the patient was 40 years old, a diagnosis of cancer of the transverse colon was made on the basis of roentgenographic examination. Total colectomy was performed. The patient's condition was poor after the operation. Empyema of the right pleural cavity and severe infection developed, and he died on postoperative day 21. Autopsy was not performed. Examination of the surgical specimen showed a tumor mass encircling the transverse colon, associated with multiple polyps and diverticula. A polyp was found in the appendiceal mucosa. Slides from three polyps were reviewed. Two had distinctive features of juvenile polyps, and the third was an adenomatous polyp with severe atypia. This is the only case in this series showing an association between juvenile polyposis and cancer of the colon. Only one of all the polyps from this patient that were examined showed adenomatous features.

Patient 17. In a 12-year-old girl who had a long history of rectal bleeding, numerous colonic polyps were found by endoscopy and barium-enema examination. Total colectomy was performed in 1959. The patient recovered uneventfully and was discharged from the hospital. No follow-up information is available. The surgical specimen contained many pendunculated polyps, scattered throughout the colon. All of them had microscopic characteristics of juvenile polyps.

No family history of polyposis was elicited in this case. Patient 18, A 22-year-old man was first seen at the hospital

because of a long history of rectal bleeding, bloody diarrhea, and tenesmus. Barium-enema examination and endoscopy showed many rectal polyps. Total colectomy was carried out in 1960. The surgical specimen contained many polyps on the left side (splenic flexure, descending colon, and sigmoid), all of them of the juvenile type. After the operation the patient was followed for two years. Endoscopic removal of recurrent rectal polyps was necessary on several occasions; on one, more than 30 polyps were resected. No follow-up information is available.

There was no family history of the disease. Patient 19. A 12-year-old girl was seen in 1956 because of a

long history of intermittent rectal bleeding and prolapse of the rectal mucosa, blany rectal polyps were found by endoscopy. Nine- teen polyps were removed, and all proved to be juvenile polyps on review of the slides. The patient has been lost to follow up.

No family history of the disease was found. Patient 20. A 12-year-old girl was first seen in 1973 because of

repeated rectal prolapse which had begun in 1968, when she was 7 years old. Endoscopy and x-ray revealed numerous colonic polyps. Thirty polyps were removed by endoscopy, and all proved to be of the juvenile type on microscopic examination. The patient was seen agama year later because of similar complaints, and more juvenile polyps were removed at endoscopy. A small nodule removed from the midline of the neck proved to be a thyroglossal duct cyst.

There was no family history of the disease. Patient 21. A 6-year-old boy was first seen in 1968 because of

rectal bleeding of two years' duration. Many rectal polyps removed on two occasions by endoscopy proved to be of the juvenile type of

Fro. 10. Patient 24. Close-up view of specimen obtained by subtotal colectomy, showing many hemorrhagic pedunculated juvenile polyps.

microscopic examination. The patient has been lost to follow up since the end of 1968.

A sibling of this patient has had similar complaints, which suggests a familial trend; this was not investigated further.

Patient 22. A 3-year-old boy was seen in 1965 because of intermittent rectal bleeding, which had been present almost since birth, and frequent spontaneous expulsion of polypoid masses by rectum. Several rectal polyps were removed for microscopic examination and were found to be of thejuvenile type. The patient was lost to follow up.

There was no family history of the disease in this case. Patient 23. A 25-year-old fnan was seen in 1973 because of a

long history of rectal bleeding, bloody diarrhea, and tenesmus. Endoscopy revealed numerous rectal polyps, some of which were removed for microscopic study and were diagnosed as juvenile polyps. Anterior resection of the rectosigmoid colon was carried out five months after the initial examination. The patient's condition was poor after operation, and he died two weeks later. The surgical specimen (Fig. 4) contained many clusters of juvenile polyps, most of them sessile, surrounded by normal mucosa. The rest of the colon was examined at autopsy, and only one juvenile polyp was found in the ascending colon. This patient also had a long history of psoriasis since the age of 12 years, and had had recurrent psychiatric problems for which he had sought treatment repeatedly between the ages of 20 and 25 years. The clinical record also revealed a seven-year history of rectal bleeding and diarrhea, beginning at age 19 years, which had been treated as idiopathic ulcerative colitis. Review of slides of three successive rectal biopsies revealed at least one distinctive juvenile polyp.

Patient 24. An &year-old girl was seen in t970 because of a two-year history of rectal prolapse and intermittent rectal bleeding. Many rectal polyps were found at endoscopy and resected, blicro- scopic examination showed that all of them were juvenile polyps. One and three years later, numerous rectal polyps were again found and resected by endoscopy. Subtotal colectomy with preser- vation of the sigmoid colon and rectum was carried out in 1973, when the patient was 12 years old. Examination of the surgical specimen revealed about 50 pedunculated juvenile polyps, scattered throughout the colon (Fig. 10). The patient sought treatment again a year after operation, and numerous juvenile polyps of the remaining rectum were removed. This patient was known to have had congenital heart disease, diagnosed as interatrial septal defect, since she was 2 months old; it was successfully corrected surgically in 1970.

Dis. Col & Rect. 612 RESTREPO, ET AL. Nov.-Dec. 1978

Three siblings of this patient were free of disease. The maternal grandfather had died of gastric cancer; his age was not stated.

Patient 25. A 7-year-old girl was first examined in 1965 because of a two-year history of abdominal cramping pains, rectal bleeding, diarrhea, tenesmt,s, anorexia, and weight loss. Many rectal polyps were found at endoscopy and removed for microscopic examination. Partial colectomy was carried out in 1966. The surgical specimen contained numerous pedunculated polyps. The patient was seen again three times during the following year, and on each occasion recurrent rectal polyps were removed. All showed microscopic features of juvenile polyps. The patient had been treated at the age of 2 years for chronic mastoiditis. She was last seen in 1967 and was afterwards lost to follow up.

Patient 25 was an only daughter. Her father had a long history of

rectal bleeding, but was not investigated for polyposis. Patient 26. A 19-year-old girl was seen in 1957 because of a

history of bloody diarrhea and tenesmus of almost a year's duration. Endoscopy revealed many rectal polyps, which were removed and proven to be juvenile polyps on microscopic examination. The patient was lost to follow up.

Patient 27. A 10-year-old boy was seen in 1959 because of severe rectal bleeding and spontaneous expulsion of rectal polyps. Many polyps were found by endoscopy and removed for microscopic examination. Three months later, the patient had a similar episode of rectal bleeding, with prolapse of rectal mucosa; he went into irreversible shock and died. Autopsy was not per formed. All polyps were of the juvenile type.

There was no family history.

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juvenile colonic polyposis in colombia

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