Mixed Neuroendocrine Carcinoma and Adenocarcinoma in a Patient With Ileal Pouch-Anal Anastomosis

ABSTRACT

Neoplasia of the ileoanal pouch is uncommon, occurring in fewer than 1% of patients. Neuroendocrine carcinoma (NEC) is a rare neoplastic complication and can be difficult to diagnose due to symptoms overlapping with inflammatory pouch disorders. We describe a 36-year-old man with ileal pouch-anal anastomosis complicated by Crohn's-like disease of the pouch who underwent pouch excision for refractory disease. Histopathology revealed mixed poorly differentiated adenocarcinoma and NEC. Management may involve surgical resection for localized disease and systemic therapy for advanced stages. This case highlights the need to consider neoplastic processes, including NECs, in patients with persistent or atypical pouch symptoms.

INTRODUCTION

Ileal pouch-anal anastomosis (IPAA) is the treatment of choice in patients with medically refractory ulcerative colitis.^1,2 This involves creation of a distal ileal reservoir, subsequently anastomosed to the anal canal.³ Although IPAA improves quality of life, complications include pouchitis, pouch failure, Crohn's-like disease (CD) of the pouch, and rarely neoplasia (3.3% at 20 years postoperatively), with adenocarcinoma representing the most common histological subtype.⁴ We present a 36-year-old man with history of IPAA found to have poorly differentiated adenocarcinoma with neuroendocrine carcinoma (NEC) involving the pouch, underscoring the importance of considering neoplastic processes in patients with persistent or atypical pouch symptoms.

CASE REPORT

A 36-year-old man with a history of 2-stage IPAA (performed 16 years ago for medically refractory ulcerative colitis), complicated by CD of the pouch, presented with abdominal pain of 3 months' duration involving the mid-epigastric and periumbilical regions. He was receiving ustekinumab 90 mg subcutaneously every 4 weeks for CD of the pouch. Computed tomography enterography and pouchoscopy demonstrated active inflammation of the prepouch ileum with stricturing at the previous enteroenterostomy site and pouch inlet. In addition, a fistulous tract extending from the prepouch ileum and posterior pouch to the presacral space was identified. Given concerns for CD of the pouch refractory to ustekinumab, along with subtherapeutic trough levels, his treatment was transitioned to combination therapy with infliximab and azathioprine.

Despite 4 months of combination therapy with infliximab and azathioprine, his disease remained refractory, and he continued to experience abdominal pain. Given the risk of obstruction secondary to stricturing at the enteroenterostomy, surgical management was pursued. Intraoperatively, there was marked active disease involving the neoterminal ileum, characterized by creeping fat and bowel wall thickening. The pouch itself was significantly inflamed and not amenable for salvage. As a result, pouch excision was performed with the creation of an end ileostomy.

Histopathological examination of the resected pouch revealed a 1.8 cm mass consistent with mixed poorly differentiated adenocarcinoma and NEC. Ki-67 proliferative index was not performed. Immunohistochemical staining was positive for synaptophysin, chromogranin, and mucicarmine (Figure 1). Although regional lymph nodes were negative for malignancy, microscopic involvement of the surgical margin could not be excluded. His postoperative course was complicated by pain, surgical site infection, and Clostridioides difficile infection, all managed with appropriate medical therapy. He also developed small bowel obstruction requiring an ileoscopy with dilation of a stricture at the ileo-ileal anastomosis.

Figure 1.

Representative hematoxylin and eosin (A) histology image (10×) demonstrating mixed poorly differentiated adenocarcinoma and neuroendocrine carcinoma with positive immunostains for synaptophysin (B) and chromogranin (C). Mucicarmine stain (D) demonstrating the presence of signet ring cells. Pathologic stage I (pT1, pN0, cM0), histologic grade 3, and residual tumor (R) R1 (microscopic).

Oncology was consulted for further evaluation and management of carcinoma. A positron emission tomography-computed tomography scan demonstrated small fluorodeoxyglucose–avid mesenteric nodes and peritoneal nodules suspicious for metastases (Figure 2). He subsequently underwent exploratory laparotomy with biopsy of the peritoneum, omentum, and mesenteric nodules. Histopathology revealed fibroadipose tissue with fat necrosis and organizing abscess, without evidence of malignancy. The adenocarcinoma component was staged at pT1N0 and the neuroendocrine component was classified as grade 3, no systemic chemotherapy was recommended. Given the R1 (microscopic) resection margin with absence of regional lymph node involvement and metastatic disease, oncology recommended surveillance with serial abdominal and pelvic computed tomography imaging , initially at 6 months followed by annual imaging thereafter. He continues to undergo surveillance imaging and, at 1-year follow-up, has no evidence of recurrent or metastatic disease.

Figure 2.

PET-CT with a small fluorodeoxyglucose-avid abdominal soft tissue nodule subjacent to the right anterior abdominal wall (A) and prominent node in central mesentery (B) suspicious for metastasis. PET-CT, positron emission tomography-computed tomography.

DISCUSSION

Neuroendocrine tumors (NET) arise from enterochromaffin and other neuroendocrine cells throughout the gastrointestinal tract. Many are nonfunctional, presenting with nonspecific symptoms such as abdominal pain, change in bowel habits, and obstruction.^5,6 Functional tumors may manifest with hormone-related syndromes, although these are less common in gastrointestinal NETs.^5,6 Neuroendocrine neoplasms are graded by differentiation, ranging from well-differentiated NET to poorly differentiated, high-grade NEC, as seen in our case.^5,6

Neoplasia involving the ileoanal pouch is uncommon, with pathogenesis thought to be multifactorial, involving chronic inflammation secondary to pouchitis, previous colorectal dysplasia, and pouch construction techniques.^4,7 In contrast, neuroendocrine neoplasms of the pouch do not follow the inflammation-dysplasia-carcinoma sequence, yet their presentation frequently overlaps with inflammatory pouch disorders, creating diagnostic challenges.^4,7,8

Distinguishing inflammatory pouch disorders from neoplastic changes remains difficult as both can present with nonspecific symptoms including increased stool frequency, urgency, abdominal pain, and obstruction.^4,8 Endoscopically, both can demonstrate erythema, ulceration, friability, and stricturing.^4,8 This overlap was evident in our case, as the patient developed a stricture at the enteroenterostomy site and inflammation in the pre-pouch ileum. These findings were attributed to active CD of the pouch, and biopsies were not obtained at that time. Advanced endoscopic imaging techniques such as chromoendoscopy and narrow band imaging can improve detection, but their use has not been standardized in patients with IPAA.^4,9 Histopathological evaluation is the gold standard for diagnosis, though interpretation can be difficult in chronic inflammation, as reactive epithelial atypia can mimic dysplasia and early neoplasia may be difficult to distinguish from inflammatory change.^4,9,10 Owing to substantial overlap, management frequently focuses on intensifying inflammatory control, which may delay oncological diagnosis.

The majority of pouch neuroendocrine neoplasms described in the literature have been incidental discoveries made during evaluation for nonspecific symptoms (Table 1).^11–15 Unlike the well-differentiated NETs described in previous reports, our patient's tumor was an NEC admixed with adenocarcinoma, which, to our knowledge, has not been previously reported in the ileal pouch. Diagnosis is often made histologically during surveillance pouchoscopy or investigation of refractory symptoms. These are often similar to other gastrointestinal neuroendocrine neoplasms, staining positive for chromogranin and synaptophysin.^4,16 Management is dependent on staging. For localized and well-differentiated lesions, surgical resection is the primary treatment, while advanced metastatic disease may require medical therapies including somatostatin analogs, targeted agents, and cytotoxic chemotherapy.^4,16,17 In our patient, despite high-grade NEC and signet ring cell adenocarcinoma histology, the localized stage (pT1N0) and absence of distant metastasis supported surveillance over chemotherapy, even with the R1 margin. Multidisciplinary tumor board review is recommended for complex cases. Although no established surveillance protocol for pouch NEC exists, high-risk patients are advised to undergo annual pouchoscopy with random biopsies of the pouch, cuff, and afferent limb.^4,8 This case illustrates the diagnostic challenges in distinguishing inflammatory from neoplastic pouch conditions.

Table 1.

Reported cases of ileal pouch associated with neuroendocrine tumor

Case	Age (yr)	Sex	Presenting symptoms	Detection	NET characteristics	Treatment	References
1	81	Female	Crampy lower abdominal pain	CT showed pouch wall mass, followed by endoscopy and biopsy confirmed NET	1.5 cm, well-differentiated NET, no metastasis	Pouch excision with permanent ileostomy	11
2	46	Male	Abdominal pain and rectal bleeding	Routine endoscopy found ulcerated polyp, repeat biopsy confirmed NET	3 cm ulcerated polyp, no metastasis	Pouch excision with new pouch construction and temporary loop ileostomy	12
3	34	Male	Incidental finding during routine endoscopy	Routine endoscopy found an ulcerated lesion, biopsy confirmed NET	4 cm, no metastasis	Pouch excision with permanent ileostomy	13
4	35	Male	Asymptomatic	Routine endoscopy showed normal mucosa, but biopsy was positive for NET	2 mm, grade 1 well-differentiated NET, no metastasis	Active endoscopic surveillance every 6 mo	14
5	42	Male	Abdominal pain, intestinal obstruction, perianal Crohn's disease	Histology incidentally revealed NET during pouch excision for pouch failure	Size is not available, no metastasis	Pouch excision and end ileostomy	15

CT, computed tomography; NET, neuroendocrine tumor.

DISCLOSURES

Author contributions: PR Ramesh: Data interpretation; data acquisition; drafting of the manuscript; critical revision of the manuscript for important intellectual content; final approval of the manuscript. V. Chedid: Conception and design; critical revision of the manuscript for important intellectual content; final approval of the manuscript. SA Urquhart: Data interpretation; critical revision of the manuscript for important intellectual content; final approval of the manuscript. S.A. Urquhart is the article guarantor.

Financial disclosure: None to report.

Previous presentation: Presented at the American College of Gastroenterology Annual Scientific Meeting, October 27, 2025; Phoenix, AZ.

Informed consent was obtained for this case report.

ABBREVIATIONS:

CD

Crohn's disease

FDG

fluorodeoxyglucosep

IPAA

ileal pouch-anal anastomosis

NEC

neuroendocrine carcinoma

NET

neuroendocrine tumor

PET-CT

positron emission tomography–computed tomography