Mucinous Carcinoma Arising Within Perianal Fistula in a Crohn’s Patient: A Challenging Diagnosis That Often Fails Biopsy Detection

Background: Anorectal fistulas are well-established complications of Crohn’s disease (CD), occurring in 20-40% of patients. Compared to the general population, patients with CD are also at increased risk for cancers due to chronic inflammation. Malignancy occurring within a chronic perianal fistula is overall very rare. Mucinous adenocarcinoma (MA) is a less common subtype of colorectal cancer that is discerned by the presence of extracellular mucin in over 50% of tissue. Methods: We report a unique case of fistula-associated perianal mucinous adenocarcinoma that required resection for definitive diagnosis as multiple biopsies failed to confirm histologic diagnosis of malignancy. Case: A 58-year-old male with ileocolonic CD diagnosed in childhood was seen in the clinic after previously being lost to follow up and without therapy for multiple years. His CD was complicated by colovesicular fistula requiring ileocectomy at age 45. Colonoscopy was performed revealing ulceration at the anastomosis without evidence of perianal disease. Vedolizumab was subsequently initiated, with clinical improvement and symptom resolution within 9 months. Results: Repeat colonoscopy 15 months later revealed a 9mm inflamed polyp at the entry of a perianal fistula 4mm from the dentate line, and persistent anastomotic ulceration. Pathology showed polypoid high-grade dysplasia with mucosal and submucosal mucin pools associated with underlying fistula, however, could not exclude carcinoma. Flexible sigmoidoscopy 2 months later showed an ulcerated pedunculated lesion 4mm from the dentate line which could not be lifted for resection. Biopsies showed low-grade dysplasia associated with mucin pools without definitive invasive carcinoma. EUS revealed a 23x18mm complex, round heterogenous lesion contiguous with the rectal wall and involving all layers without identifiable fistula. Again, pathology showed high-grade dysplasia with mucin pools but could not exclude invasive carcinoma. He was referred to colorectal surgery and MRI of the pelvis was done showing a 4.5 cm semi-circumferential mucinous mass 3 cm from the anal verge invading the external sphincter. Patient underwent transanal excision of the rectal mass and pathology revealed invasive moderately differentiated mucinous adenocarcinoma with positive deep and peripheral margins. He subsequently completed adjuvant chemoradiation, and is currently planned to undergo abdominoperineal resection with end colostomy. Conclusions: Perianal mucinous carcinoma arising in a chronic fistula associated with CD is an extremely rare occurrence, with an incidence of less than 1%. The pathogenesis of carcinoma associated with perianal fistula is controversial and thought to be caused by dysplastic changes from constant regeneration of fistula mucosa or delayed wound healing in the setting of immunosuppressant use. Diagnosis is challenging and may be delayed due to symptoms mimicking those of typical fistulas, as well as difficulties in obtaining malignant cells by biopsy alone. Currently there are no definitive guidelines for the management of these particular malignancies, though surgery is the primary therapeutic option with or without chemoradiation. This case highlights the importance of early consideration of surgery, as repeat biopsies may remain undiagnostic. Additionally, it is crucial to have a high index of suspicion for malignancy when evaluating abnormal mucosa associated with perianal fistula, as carcinoma may occur even in the absence of known chronic fistula, as in our case.