Adenocarcinoma of an Ileostomy in a Patient with Familial Adenomatous Polyposis Report of a Case Thomas P. Gilson, M.D.,* Larry L. Sollenberger, M.D.-~ From the *Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, and the ~Department of Surgery, MS Hershey Medical Center, Penn State University, Hershey, Pennsylvania A case of adenocarcinoma arising in an ileostomy of 39 years' duration is presented. The patient had undergone proctocolectomy in 1949 for familial adenomatous polyposis, with subsequent ileostomy in 1950, and presented in April 1989 with bleeding and a mass at the stoma site. Biopsy of the mass revealed adenocarcinoma. Adenocarcinoma of an ileostomy is a rare but well-documented complication, with the present patient bringing the total number of reported cases to 18. The literature is reviewed, and surveillance measures are suggested. [Key words: Adenocarcinoma; Ileostomy; Familial adenomatous polyposis] Gilson TP, Sollenberger LL. Adenocarcinoma of an ileostomy in a patient with familial adenomatous polyposis: report of a case. Dis Colon Rectum 1992;35:261-265. A
denocarcinoma of an ileostomy is a rare but . well-documented complication which tends t o occur many years after stomal maturation. As of this writing, 17 cases have been reported, 141-11 of which involved an ileostomy fashioned after treatment for ulcerative colitis (UC) and 3 l~ after treatment for familial adenomatous polyposis (FAP). We present the case of a male who develo p e d adenocarcinoma of the ileostomy 39 years after a total proctocolectomy for FAP, and we review the previously described 17 cases. R E P O R T O F A CASE A 69-year-old black male with a history of diabetes and chronic pancreatitis secondary to alcohol abuse was admitted in April 1989 to the Harrisburg Hospital for recurrent abdominal pain and bleeding from the ileostomy site. He had required hospitalization twice over the preceding four months
Address reprint requests to Dr. Gilson: Departmentof Pathology and LaboratoryMedicine, Universityof Cincinnati Medical Center, 231 BethesdaAvenue, Cincinnati, Ohio 45267-0529. 261
for abdominal pain secondary to the pancreatic disease. There was no report of bleeding during these previous hospitalizations. The patient has a family history of FAP; his father underwent colon resection in 1947 for "multiple polyposis with early malignant change." The patient himself presented in 1949 with rectal bleeding and was noted to have multiple polyps on sigmoidoscopic examination. Biopsy of a rectal polyp revealed adenomatous change. He underwent proctocolectomy with ileoanal anastomosis at that time. No slides of the specimen were available for review, but the pathology report notes "multitudes of small polyps" throughout the entire colon, with "several small sessile polyps" in the portion of the ileum resected at the time of surgery. Microscopically, the polyps showed adenomatous change with marked mucosal atypia, but no invasion of the muscularis was seen on multiple sections. The final pathologic diagnosis was familial polyposis of the colon. One year later, the patient required diverting ileostomy for multiple perianal fissures and abscesses along with gangrene of the terminal ileum. The patient subsequently did well and was followed closely for FAP. In 1964, he had four small polyps removed from his ileostomy. These were reported to show adenomatous change with no evidence of invasion. On a subsequent examination in 1971, 13 polyps were removed from the stoma and also showed adenomatous change. During this time period, he was also followed for adenomatous polyposis of the stomach and duodenum. In 1983, the patient moved from New York City to Pennsylvania and was initially seen on a routine
262
GILSON AND SOLLENBERGER
Dis Colon Rectum, March 1992
Figure 1. Ileostomy with mass on medial aspect.
Figure 2. Ileostomy mass with mucinous adenocaminoma (hematoxylin and eosin, x4).
clinic visit in 1984, at which time his ileostomy was reported to be functioning well but was slightly stenotic. He was lost to follow-up until September 1987, when he was hospitalized with chronic pancreatitis. His ileostomy was reported to be functioning well and normal in appearance at this time. The patient was hospitalized again in April 1989 with recurrent abdominal pain which had been felt to be secondary to the chronic pancreatitis. A car-
cinoembryonic antigen (CEA) level obtained during this admission was 5.0 ng/ml (normal, 2.0-5.0 ng/ml). He presented with cachexia, abdominal tenderness in the epigastrium, and a 2.5-cm mass on the medial aspect of the ileostomy, located in the right lower quadrant (Fig. 1). Flexible ileoscopy was performed, and multiple small polyps were present in the ileum. Biopsies were taken of these polyps as well as the mass on the ileostomy
Vol. 35, No. 3
ADENOCARCINOMA OF AN ILEOSTOMY
263
Figure 8. Representative adenomatous polyp in ileum (hematoxylin and eosin, x4). surface. On microscopic examination, the polyps revealed inflammation with adenomatous changes, while the ileostomy mass was positive for adenocarcinoma. The patient was taken to the operating room, where he underwent resection of 30 cm of terminal ileum through a wide eliptical skin incision. A new Brooke ileostomy was fashioned in the left lower quadrant. No evidence of metastatic disease was seen intraoperatively. The patient pursued an unremarkable postoperative course and was discharged on the eighth postoperative day. At a twoyear follow-up, he remains well with a functional ileostomy.
Pathology Pathologic examination of the resected specimen revealed a mucinous,-moderately differen-
tiated adenocarcinoma with extension into the muscularis propria (Fig. 2). Multiple additional adenomatous and villoglandular polyps were noted in the remaining ileum (Fig. 3). The skin margins, the proximal margin of resection, and one mesenteric lymph node were negative for tumor. Interestingly, no adenomatous elements were noted at the base of the tumor or in any of the sections through the mass. DISCUSSION Since the original description of adenocarcinoma in an ileostomy by Sigler and Jedd 1 in 1969, a total of 18 cases, including the present one, have been reported. 1-13 Fourteen of the patients had !JC, while the remaining three required ileostomy for treatment of FAP, as did the patient in this case
264
GILSON AND SOLLENBERGER
Dis Colon Rectum, March 1992
Table 1. Summary of Patient Data Source
Underlying
Disease
Stoma Duration*
(years)
Sigler and Jedd 1 Cuesta and Donner2 Johnson et aL a
UC UC UC
19 6 3
Roth and Logio 13
FAP
7
Baciewicz et aL 4 Bedetti and DeRisio 6 Vasilevsky and Gordon 7
UC UC UC UC
20 13 23 38
Primrose et.al. TM Smart et al. ~ Roberts et aL 9 (2)
FAP UC UC
18 28 34
UC UC FAP UC
23 25 29 30
UC
34
Carter et all1
UC
36
Present study
FAP
39
Stryker 5
Suarez et al.l~ (4)
Presenting Symptoms Small bowel obstruction
Local irritation Pain, bleeding, local irritation Pain, local irritation, mass Pain, local irritation Bleeding, mass Pain, bleeding, mass Bleeding, mass, difficulty with adherence Bleeding, local irritation Bleeding, mass Local irritation, difficulty with adherence Difficulty with adherence Mass Mass Local irritation Pain, local irritation,
bleeding Bleeding, mass, difficulty with adherence Bleeding, mass
Biopsy Resultst
Not done Negative x3 Negative Positive Negative Positive Positive Positive Negative Negative Positive Positive Positive Positive Negative x l Positive Positive Refused Positive
* Stoma duration from last revision until diagnosis of adenocarcinoma.
t Biopsy results for adenocarcinoma. Biopsies showing dysplastic changes are recorded as negative. report. One UC patient was felt to have developed adenocarcinoma from contiguous spread of a rectal tumor, 3 but, in the remaining cases, the tumor was felt to have arisen spontaneously at the ileostomy site. The data on all patients are summarized in Table 1. Benign neoplastic polyps of the small bowel in patients with FAP are recognized, and malignancies related to them have been described. TM The present patient was known to have adenomatous polyps in the colon, stomach, duodenum, and ileostomy site. In the previously described cases of ileostomyassociated adenocarcinomas arising in patients with FAP, a pre-existing adenoma could be identified. However, in the present case, no such source was apparent. This suggests that the patient's tumor may represent an atypical response of the ileal mucosa to chronic irritation rather than a manifestation of his primary disease. Several authors T M have suggested chronic irritation in various forms (preoperative "backwash" ileitis, external trauma, chemical exposure via stoma adhesives, etc.) as a
potential factor in the etiology of ileostomy-associated adenocarcinoma in patients with UC. However, given the size of the mass in the present case, it seems more likely that the adenocarcinoma has overgrown a pre-existing adenomatous source and that the pathogenesis of malignancy in FAP is distinct from UC. In the three years prior to the writing of this article, the number of reported cases has doubled, and one author has suggested that the incidence of ileostomy adenocarcinoma may be increasing because of the increasing duration of ileostomies. 1~ The present patient had his ileostomy for 39 years, which is the longest duration of any case heretofore reported. Excluding the case of contiguous spread of a rectal cancer and including the present case, the average duration of the ileostomy prior to diagnosis of adenocarcinoma is approximately 25 years (FAP, 23 years; UC, 26 years). Although the numbers of cases and reported follow-ups are limited, it would seem reasonable to routinely examine all ileostomies of a duration greater than 20
ADENOCARCINOMA OF AN ILEOSTOMY
Vol. 35, No. 3
years, possibly on a biannual basis, since the tum o r s do not a p p e a r to be aggressive in the majority of r e p o r t e d cases regardless of u n d e r l y i n g disease. Likewise, it w o u l d s e e m a p p r o p r i a t e to aggressively pursue any mass at an i l e o s t o m y site or c o m p l a i n t s of bleeding, pain, or n e w onset of local irritation in patients with a long-standing ileostomy. T h o r o u g h biopsy, especially of the stomae p i d e r m a l junction, must b e b a l a n c e d with high clinical suspicion b e c a u s e greater than 30 p e r c e n t of all biopsies r e p o r t e d have b e e n falsely negative for a d e n o c a r c i n o m a . I l e o s c o p y m a y play an adjunct role in cases w h e r e biopsies are negative or no mass lesion is apparent. CEA level has not thus far p r o v e d to be a helpful adjunct in diagnosis, since, in the p r e s e n t case and in three others p r e v i o u s l y reported, 6'9 it has b e e n normal. ACKNOWLEDGMENTS The authors w o u l d like to thank Dr. Philip Wiedel for his assistance. REFERENCES l. Sigler L, Jedd FL. Adenocarcinoma of the ileostomy occurring after colectomy for ulcerative colitis: report of a case. Dis Colon Rectum 1969;12:45-8. 2. Cuesta MA, Donner R. Adenocarcinoma arising at an ileostomy site: report of a case. Cancer 1976;37: 949-52. 3. Johnson WR, McDermott FT, Pihl E, Hughes ES. Adenocarcinoma of an ileostomy in a patient with ulcerative colitis. Dis Colon Rectum 1980;23:351-2.
265
4. Baciewicz F, Sparberg M, Lawrence UJ, Poticha SM. Adenocarcinoma of an ileostomy site with skin invasion: a case report. Gastroenterology 1983;84: 168-70. 5. Stryker SJ. Primary stoma adenocarcinoma: an unusual complication of ileostomy. Dis Colon Rectum 1983;26:47-9. 6. Bedetti CD, DeRisio VJ. Primary adenocarcinoma arising at an ileostomy site: an unusual complication after colectomy for ulcerative colitis. Dis Colon Rectum 1986;29:572-5. 7. Vasilevsky CA, Gordon PH. Adenocarcinoma arising at the ileocutaneous junction occurring after proctocolectomy for ulcerative colitis. Br J Surg 1986; 73:378. 8. Smart PJ, Sastry S, Wells S. Primary mucinous adenocarcinoma developing in an ileostomy stoma. Gut 1988;29:1607-12. 9. Roberts PL, Veidenheimer MC, Cassidy S, Silverman ML. Adenocarcinoma arising in an ileostomy. Arch Surg 1989;124:497-9. 10. Suarez V, Alexander-Williams J, O'Connor HJ, et aL Carcinoma developing in ileostomies after 25 or more years. Gastroenterology 1988;95:205-8. 11. Carter D, Choi H, Otterson M, Telford G, Primary adenocarcinoma of the ileostomy after colectomy for ulcerative colitis. Dig Dis Sci 1988;33:509-12. 12. Primrose JN, Quirke P, Johnston D. Carcinoma of the ileostomy in a patient with familial adenomatous polyposis. Br J Surg 1988;75:384. 13. Roth JA, Logio T. Carcinoma arising in an ileostomy stoma: an unusual complication of adenomatous polyposis coll. Cancer 1982;49:2180-4. 14. Ross JE, MaraJE. Small bowel polyps and carcinoma in intestinal polyposis. Arch Surg 1974;108:736-8.
denocarcinoma of an ileostomy is a rare but . well-documented complication which tends t o occur many years after stomal maturation. As of this writing, 17 cases have been reported, 141-11 of which involved an ileostomy fashioned after treatment for ulcerative colitis (UC) and 3 l~ after treatment for familial adenomatous polyposis (FAP). We present the case of a male who develo p e d adenocarcinoma of the ileostomy 39 years after a total proctocolectomy for FAP, and we review the previously described 17 cases. R E P O R T O F A CASE A 69-year-old black male with a history of diabetes and chronic pancreatitis secondary to alcohol abuse was admitted in April 1989 to the Harrisburg Hospital for recurrent abdominal pain and bleeding from the ileostomy site. He had required hospitalization twice over the preceding four months
Address reprint requests to Dr. Gilson: Departmentof Pathology and LaboratoryMedicine, Universityof Cincinnati Medical Center, 231 BethesdaAvenue, Cincinnati, Ohio 45267-0529. 261
for abdominal pain secondary to the pancreatic disease. There was no report of bleeding during these previous hospitalizations. The patient has a family history of FAP; his father underwent colon resection in 1947 for "multiple polyposis with early malignant change." The patient himself presented in 1949 with rectal bleeding and was noted to have multiple polyps on sigmoidoscopic examination. Biopsy of a rectal polyp revealed adenomatous change. He underwent proctocolectomy with ileoanal anastomosis at that time. No slides of the specimen were available for review, but the pathology report notes "multitudes of small polyps" throughout the entire colon, with "several small sessile polyps" in the portion of the ileum resected at the time of surgery. Microscopically, the polyps showed adenomatous change with marked mucosal atypia, but no invasion of the muscularis was seen on multiple sections. The final pathologic diagnosis was familial polyposis of the colon. One year later, the patient required diverting ileostomy for multiple perianal fissures and abscesses along with gangrene of the terminal ileum. The patient subsequently did well and was followed closely for FAP. In 1964, he had four small polyps removed from his ileostomy. These were reported to show adenomatous change with no evidence of invasion. On a subsequent examination in 1971, 13 polyps were removed from the stoma and also showed adenomatous change. During this time period, he was also followed for adenomatous polyposis of the stomach and duodenum. In 1983, the patient moved from New York City to Pennsylvania and was initially seen on a routine
262
GILSON AND SOLLENBERGER
Dis Colon Rectum, March 1992
Figure 1. Ileostomy with mass on medial aspect.
Figure 2. Ileostomy mass with mucinous adenocaminoma (hematoxylin and eosin, x4).
clinic visit in 1984, at which time his ileostomy was reported to be functioning well but was slightly stenotic. He was lost to follow-up until September 1987, when he was hospitalized with chronic pancreatitis. His ileostomy was reported to be functioning well and normal in appearance at this time. The patient was hospitalized again in April 1989 with recurrent abdominal pain which had been felt to be secondary to the chronic pancreatitis. A car-
cinoembryonic antigen (CEA) level obtained during this admission was 5.0 ng/ml (normal, 2.0-5.0 ng/ml). He presented with cachexia, abdominal tenderness in the epigastrium, and a 2.5-cm mass on the medial aspect of the ileostomy, located in the right lower quadrant (Fig. 1). Flexible ileoscopy was performed, and multiple small polyps were present in the ileum. Biopsies were taken of these polyps as well as the mass on the ileostomy
Vol. 35, No. 3
ADENOCARCINOMA OF AN ILEOSTOMY
263
Figure 8. Representative adenomatous polyp in ileum (hematoxylin and eosin, x4). surface. On microscopic examination, the polyps revealed inflammation with adenomatous changes, while the ileostomy mass was positive for adenocarcinoma. The patient was taken to the operating room, where he underwent resection of 30 cm of terminal ileum through a wide eliptical skin incision. A new Brooke ileostomy was fashioned in the left lower quadrant. No evidence of metastatic disease was seen intraoperatively. The patient pursued an unremarkable postoperative course and was discharged on the eighth postoperative day. At a twoyear follow-up, he remains well with a functional ileostomy.
Pathology Pathologic examination of the resected specimen revealed a mucinous,-moderately differen-
tiated adenocarcinoma with extension into the muscularis propria (Fig. 2). Multiple additional adenomatous and villoglandular polyps were noted in the remaining ileum (Fig. 3). The skin margins, the proximal margin of resection, and one mesenteric lymph node were negative for tumor. Interestingly, no adenomatous elements were noted at the base of the tumor or in any of the sections through the mass. DISCUSSION Since the original description of adenocarcinoma in an ileostomy by Sigler and Jedd 1 in 1969, a total of 18 cases, including the present one, have been reported. 1-13 Fourteen of the patients had !JC, while the remaining three required ileostomy for treatment of FAP, as did the patient in this case
264
GILSON AND SOLLENBERGER
Dis Colon Rectum, March 1992
Table 1. Summary of Patient Data Source
Underlying
Disease
Stoma Duration*
(years)
Sigler and Jedd 1 Cuesta and Donner2 Johnson et aL a
UC UC UC
19 6 3
Roth and Logio 13
FAP
7
Baciewicz et aL 4 Bedetti and DeRisio 6 Vasilevsky and Gordon 7
UC UC UC UC
20 13 23 38
Primrose et.al. TM Smart et al. ~ Roberts et aL 9 (2)
FAP UC UC
18 28 34
UC UC FAP UC
23 25 29 30
UC
34
Carter et all1
UC
36
Present study
FAP
39
Stryker 5
Suarez et al.l~ (4)
Presenting Symptoms Small bowel obstruction
Local irritation Pain, bleeding, local irritation Pain, local irritation, mass Pain, local irritation Bleeding, mass Pain, bleeding, mass Bleeding, mass, difficulty with adherence Bleeding, local irritation Bleeding, mass Local irritation, difficulty with adherence Difficulty with adherence Mass Mass Local irritation Pain, local irritation,
bleeding Bleeding, mass, difficulty with adherence Bleeding, mass
Biopsy Resultst
Not done Negative x3 Negative Positive Negative Positive Positive Positive Negative Negative Positive Positive Positive Positive Negative x l Positive Positive Refused Positive
* Stoma duration from last revision until diagnosis of adenocarcinoma.
t Biopsy results for adenocarcinoma. Biopsies showing dysplastic changes are recorded as negative. report. One UC patient was felt to have developed adenocarcinoma from contiguous spread of a rectal tumor, 3 but, in the remaining cases, the tumor was felt to have arisen spontaneously at the ileostomy site. The data on all patients are summarized in Table 1. Benign neoplastic polyps of the small bowel in patients with FAP are recognized, and malignancies related to them have been described. TM The present patient was known to have adenomatous polyps in the colon, stomach, duodenum, and ileostomy site. In the previously described cases of ileostomyassociated adenocarcinomas arising in patients with FAP, a pre-existing adenoma could be identified. However, in the present case, no such source was apparent. This suggests that the patient's tumor may represent an atypical response of the ileal mucosa to chronic irritation rather than a manifestation of his primary disease. Several authors T M have suggested chronic irritation in various forms (preoperative "backwash" ileitis, external trauma, chemical exposure via stoma adhesives, etc.) as a
potential factor in the etiology of ileostomy-associated adenocarcinoma in patients with UC. However, given the size of the mass in the present case, it seems more likely that the adenocarcinoma has overgrown a pre-existing adenomatous source and that the pathogenesis of malignancy in FAP is distinct from UC. In the three years prior to the writing of this article, the number of reported cases has doubled, and one author has suggested that the incidence of ileostomy adenocarcinoma may be increasing because of the increasing duration of ileostomies. 1~ The present patient had his ileostomy for 39 years, which is the longest duration of any case heretofore reported. Excluding the case of contiguous spread of a rectal cancer and including the present case, the average duration of the ileostomy prior to diagnosis of adenocarcinoma is approximately 25 years (FAP, 23 years; UC, 26 years). Although the numbers of cases and reported follow-ups are limited, it would seem reasonable to routinely examine all ileostomies of a duration greater than 20
ADENOCARCINOMA OF AN ILEOSTOMY
Vol. 35, No. 3
years, possibly on a biannual basis, since the tum o r s do not a p p e a r to be aggressive in the majority of r e p o r t e d cases regardless of u n d e r l y i n g disease. Likewise, it w o u l d s e e m a p p r o p r i a t e to aggressively pursue any mass at an i l e o s t o m y site or c o m p l a i n t s of bleeding, pain, or n e w onset of local irritation in patients with a long-standing ileostomy. T h o r o u g h biopsy, especially of the stomae p i d e r m a l junction, must b e b a l a n c e d with high clinical suspicion b e c a u s e greater than 30 p e r c e n t of all biopsies r e p o r t e d have b e e n falsely negative for a d e n o c a r c i n o m a . I l e o s c o p y m a y play an adjunct role in cases w h e r e biopsies are negative or no mass lesion is apparent. CEA level has not thus far p r o v e d to be a helpful adjunct in diagnosis, since, in the p r e s e n t case and in three others p r e v i o u s l y reported, 6'9 it has b e e n normal. ACKNOWLEDGMENTS The authors w o u l d like to thank Dr. Philip Wiedel for his assistance. REFERENCES l. Sigler L, Jedd FL. Adenocarcinoma of the ileostomy occurring after colectomy for ulcerative colitis: report of a case. Dis Colon Rectum 1969;12:45-8. 2. Cuesta MA, Donner R. Adenocarcinoma arising at an ileostomy site: report of a case. Cancer 1976;37: 949-52. 3. Johnson WR, McDermott FT, Pihl E, Hughes ES. Adenocarcinoma of an ileostomy in a patient with ulcerative colitis. Dis Colon Rectum 1980;23:351-2.
265
4. Baciewicz F, Sparberg M, Lawrence UJ, Poticha SM. Adenocarcinoma of an ileostomy site with skin invasion: a case report. Gastroenterology 1983;84: 168-70. 5. Stryker SJ. Primary stoma adenocarcinoma: an unusual complication of ileostomy. Dis Colon Rectum 1983;26:47-9. 6. Bedetti CD, DeRisio VJ. Primary adenocarcinoma arising at an ileostomy site: an unusual complication after colectomy for ulcerative colitis. Dis Colon Rectum 1986;29:572-5. 7. Vasilevsky CA, Gordon PH. Adenocarcinoma arising at the ileocutaneous junction occurring after proctocolectomy for ulcerative colitis. Br J Surg 1986; 73:378. 8. Smart PJ, Sastry S, Wells S. Primary mucinous adenocarcinoma developing in an ileostomy stoma. Gut 1988;29:1607-12. 9. Roberts PL, Veidenheimer MC, Cassidy S, Silverman ML. Adenocarcinoma arising in an ileostomy. Arch Surg 1989;124:497-9. 10. Suarez V, Alexander-Williams J, O'Connor HJ, et aL Carcinoma developing in ileostomies after 25 or more years. Gastroenterology 1988;95:205-8. 11. Carter D, Choi H, Otterson M, Telford G, Primary adenocarcinoma of the ileostomy after colectomy for ulcerative colitis. Dig Dis Sci 1988;33:509-12. 12. Primrose JN, Quirke P, Johnston D. Carcinoma of the ileostomy in a patient with familial adenomatous polyposis. Br J Surg 1988;75:384. 13. Roth JA, Logio T. Carcinoma arising in an ileostomy stoma: an unusual complication of adenomatous polyposis coll. Cancer 1982;49:2180-4. 14. Ross JE, MaraJE. Small bowel polyps and carcinoma in intestinal polyposis. Arch Surg 1974;108:736-8.
