Malignancy associated with a long-standing ileostomy is a rare event. Of the four primary small bowel malignancies (adenocarcinoma, lymphoma, carcinoid, and leimyosarcoma/stromal cell tumors), adenocarcinoma and lymphoma are the most common.1 Peristomal small bowel cancers tend to arise in a setting of preexisting disease such as Crohn’s, celiac sprue, and familial polyposis, which may predispose the small bowel epithelium to malignant transformation. Immunoproliferative small bowel disease and celiac sprue are well-known to increase the incidence of small bowel lymphoma.2,3 It has been postulated the mucosal environment associated with a long-standing stoma may favor malignant transformation4,5; the milieu of altered intestinal flora and chronic exposure to bile acids are the proposed inciting agents.5-7 Patients with inflammatory bowel disease also may have an increased risk of intestinal lymphoma; a large population-based series7 estimated the relative risk between 0.4 and 2.4. This risk may be associated with long-term use of azathioprine or 6-mercaptopurine.8 Importantly, all types of ileostomy-associated malignancy have an insidious presentation marked by peristomal skin changes unresponsive to conservative measures. The wound, ostomy, continence (WOC) nurse plays a pivotal role in making the diagnosis, because these patients most commonly present to their ostomy care nurse as the first step in management.
Lymphoma. There have been two previously reported cases of lymphoma arising from an ileostomy,9,10 although malignancy associated with a long-standing ileostomy has been well described.5-7,11-14 Levecq et al9 reported a high-grade B-cell lymphoma arising in an ileostomy after only 2 years in a patient with indeterminant colitis and transfusion-related acquired immune deficiency syndrome. Pranesh10 reported a case of a B-cell nonHodgkins lymphoma in an ileostomy arising 20 years after a total proctocolectomy for ulcerative colitis.
Given the paucity of cases of ileostomy-associated lymphoma, treatment is extrapolated from sporadic lymphoma occurring in the small intestine, which can be either primary or secondary, as a consequence of systemic lymphoid malignancy. Previous literature reviews15 of gastrointestinal lymphomas estimate that primary small intestinal lymphoma accounts for 25% to 30% of all small bowel malignancies, with the gastrointestinal tract the most common site of primary extranodal lymphoma. Virtually all of these neoplasms are nonHodgkins lymphomas and, apart from T-cell lymphomas arising in the setting of celiac sprue, most are of a B-cell origin.16 The tumors arise from the mucosa-associated lymphoid tissue of the small bowel.16 Evaluation of these tumors requires a high index of suspicion. In the authors’ experience, traditional diagnostic techniques such as endoscopy, sonography, and axial imaging may not yield conclusive results. The uptake of 18-F fluorodeoxyglucose on positron emission tomography is a useful means of diagnosing intestinal lymphoma.17
The American Society of Clinical Oncology (ASCO) consensus considers the Musshoff modification of Ann Arbor Staging,18 which takes into account depth of tumor invasion and its effect on prognosis, the most widely accepted staging system for primary gastrointestinal lymphoma. Treatment is based on the stage of the disease (see Table 1), with a combination of surgery and polychemotherapy reserved for patients with Stage I and II disease and polychemotherapy alone for patients with Stage III and IV lymphoma.
Select patients with primary small bowel lymphoma who have disseminated disease may be candidates for surgical resection. The use of radiation therapy with or without surgical resection also has been reported in the treatment of Stage I and II disease; however, this strategy has the potential for significant radiation enteritis to surrounding small and large intestine and is utilized in select patients only. Response to therapy is correlated with stage of disease. The overall 5-year survival rate is 59% to 75%.18,19 Patients with Stage I and II disease have a 5-year survival approaching 82%, while patients with disseminated disease fare worse.20 Recent retrospective case series and cohort studies21-24 suggest a regimen of chemotherapy alone with dose-intensified doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone is superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus involved-field radiotherapy for the treatment of localized lymphoma.
Squamous cell carcinoma. Although exceedingly rare, squamous cell carcinoma at the mucocutaneous junction of an ileostomy has been reported in five instances as a late complication of end ileostomy following total proctectomy and once following ileal urinary conduit following cystoprostatectomy.25,26 No large series exist, but of the previously reported cases, the mean age at diagnosis was 72.5 with the earliest occurrence 26 years following creation of ileostomy, suggesting a chronic pathologic process. In addition, most cases report long-standing peristomal skin irritation with associated granulation, ulceration, stricture requiring revision of the ileostomy, or chronic bacterial infection of an ileal urinary conduit before squamous cell carcinoma developed.27-29
All reports revealed well-differentiated squamous cell carcinoma arising at the mucocutaneous junction. Management involved multidisciplinary teams and relied on wide local excision to the level of the fascia and resiting of the ileostomy in four cases, local excision and ileostomy reconstruction in another, and palliative radiotherapy in another.25
Adenocarcinoma. Adenocarcinoma arising in abnormally placed small intestinal mucosa (ileal anal pouch, ileostomy, and ileal conduit) has been increasingly reported. The latent period between ileostomy formation and the development of adenocarcinoma ranged from 3 to 51 years.29-31 The mechanism of this increased risk is not entirely clear, but the “colonization” that occurs in the epithelium may predispose it to the metaplasia-dysplasia sequence. The change in bacteriology associated with a chronic ileostomy was first reported by Gorbach et al4 and has a putative role in the increased risk of malignant transformation. Chronic physical and chemical irritation also may be a risk factor.5
Treatment of small bowel adenocarcinoma relies on aggressive surgical resection often followed by adjuvant chemotherapy. Due to the rarity of the condition, data regarding adjuvant therapy for primary small bowel adenocarcinoma are limited. Therapy modalities are extrapolated from other primary GI cancers. A multicenter phase II clinical trial32 of chemotherapy (fluorouracil [5FU]) and radiation in duodenal and periampullary carcinoma showed no significant survival benefit as adjuvant therapy. Recent advances in adjuvant chemotherapy protocols including folinic acid, fluorouracil, and oxaliplatin (FOLFOX); folinic acid, fluorouracil, and irinotecan (FOLFIRI); and other platinum-based therapy with or without irinotecan have shown promise in treating unresectable GI adenocarcinoma. However, these adjuvant therapies are not well studied in primary small bowel malignancies.33,34
Prognosis is based on the status of the surgical margins, presence of extramural venous spread, lymph node status, tumor differentiation, and depth of tumor invasion. Five- and 10-year survival rates are reported to be 52% and 47%, respectively.22
Due to the rarity of these tumors, two additional cases of rare primary gastrointestinal tumors arising in close proximity to small bowel ostomy sites are presented.