Wide Local Excision of Perianal Mucinous Adenocarcinoma

Case Report

A 67-year-old man was seen in surgical oncology clinic with a 6-month history of intermittent hematochezia and a new, palpable perineal mass (Fig 1). His previous surgical history was notable for two prior perineal abscesses. The first was 10 years prior and resolved after incision and drainage. The second was 3 years prior to this visit and did not respond to incision and drainage, requiring subsequent draining seton placement. The operative findings at that time revealed a complicated, intersphincteric fistula in ano. He was discharged from surgery clinic after an appropriate convalescence at 2 weeks.

Fig 1.

He had no interval follow-up for 3 years until he presented with hematochezia. He had no change in stool caliber or constitutional symptoms. His past medical history was notable for diabetes, cerebrovascular accident, and hyperlipidemia. There was no family history of colon cancer.

Physical exam was remarkable for a 6 × 5-cm lesion in the left anterior perineum extending to the base of the scrotum, near the anal verge, and grossly separate from his anal canal. Laboratory findings included carcinoembryonic antigen of 2.0 ng/mL (normal, < 2.5 ng/mL). Punch biopsy of the perianal mass performed at initial presentation demonstrated adenomatous polypoid lesions with ulceration of the surrounding epidermis and dermis but no evidence of invasion of those polypoid lesions into dermal connective tissue. Colonoscopy revealed two diminutive hyperplastic polyps. No fistula or malignant intraluminal colorectal mass was found. Endoscopic ultrasound (EUS) was performed and did not show extension of this mass into the anal canal. Core biopsies guided by palpation were performed at the time of his colonoscopy and once again showed adenomatous tissue without evidence of invasion into adjacent dermal structures.

Management options discussed included abdominoperineal resection (APR) or wide local excision. The patient was counseled that APR is generally offered as definitive therapy for perianal adenocarcinoma when it involves the anal canal. In his case, because there was no gross evidence of anal canal involvement, wide local excision could be considered for definitive diagnosis and as potential therapy. He strongly declined a permanent colostomy. He thus underwent successful and uncomplicated wide local excision of the perineal mass. Pathology demonstrated invasive adenocarcinoma, well-differentiated with endophytic (Figs 2A) and exophytic qualities (Fig 2B). Abundant mucin was noted in association with the sub-epithelial component. There were scattered foci showing desmoplastic response with morphologic features consistent with progression from a tubulovillous adenoma. However, no colonic mucosa was present in association with the mass. It had features of invasion into dermal connective tissue and focally into skeletal muscle. The margins were negative with the closest being to the external sphincter surface at approximately 1 mm.

Fig 2.

Postoperatively, the patient underwent adjuvant treatment with capecitabine and concurrent external beam radiation therapy to 50.4 Gy, on the basis of multidisciplinary review and National Comprehensive Cancer Network rectal cancer protocols. Surveillance has included clinical evaluation every 6 months with perineal and inguinal nodal exams as well as anoscopy. Follow-up colonoscopy was performed and did not demonstrate any polyps. He has remained free of disease as of 28 months.

Discussion

Perianal mucinous adenocarcinoma can be classified as anal duct, ectopic perianal/ischiorectal, or associated with fistula in ano¹ (Fig 3; WLE, wide local excision). The latter two subtypes have been grouped by the World Health Organization as extramucosal adenocarcinoma and currently are pathologically indistinguishable.² Historically, these pathologic terms have been used interchangeably, resulting in a singular management strategy. Differentiating these subtypes allows for more individualized treatment options.

Fig 3.

Mucinous adenocarcinoma of the perineum was first described by Rosser³ in 1934. Recognizing that adenocarcinomas may originate from chronic fistulous disease, Rosser established three criteria for perianal adenocarcinoma associated with fistula in ano: that the fistula precede the carcinoma by at least 10 years, that the internal opening of the fistula is in the anal canal and outside the tumor itself, and that the only tumor present in the rectum or anal canal should be secondary to direct extension from the carcinoma in the fistula.¹ Subsequent case reports have identified other types of perianal mucinous adenocarcinoma, such as those associated with anal ducts or ectopic anal glands.^1,4,5 However, no formal diagnostic or classification criteria have been established.

Although the exact incidence is not known, all types of perianal mucinous adenocarcinoma represent approximately 3% to 11% of perianal cancers.^6–8 Risk factors include inflammatory bowel disease, prior fistulous disease, and diabetes.^4,9,10 Patients may present with anal pain, perianal mass, or rarely, with bleeding or obstruction.^4,6 Persistent fistulous disease should raise suspicion of an underlying malignant process. Preoperative work-up consists of laboratory studies, colonoscopy, EUS, and/or magnetic resonance imaging. Carcinoembryonic antigen level can be elevated and may serve as a marker of metastasis. EUS delineates anatomy and extent of disease.⁶ A hyperintense T2 image on magnetic resonance imaging with enhanced solid component is suggestive of perianal mucinous adenocarcinoma.¹¹

Core or punch biopsies may fail to reveal an invasive component of disease. Invasion can be demonstrated by findings in the subepithelial tissue of globules of mucin and/or invasion into dermal elements or skeletal muscle.¹² Consideration can be made for incisional biopsy, but it may be limited by healing potential of ulcerated epidermis and dermis. In the absence of a definitive tissue specimen, the next step should be excision with the goal to achieve negative microscopic margins. Excisional biopsy with positive margins will mandate additional treatment, potentially an APR if the anal canal seems involved.

Anal duct adenocarcinoma, originating from nonectopic tissue, is often an aggressive subtype warranting APR and adjuvant chemoradiotherapy with consideration for neoadjuvant therapy. This subtype represents approximately 10% to 20% of all anal carcinoma. Likewise, perianal adenocarcinoma associated with ectopic or remnant anal glands can have high local recurrence and warrants APR with wide local excision of perianal tissue to achieve negative margins. However, extramucosal adenocarcinoma originating from a fistula in ano represents a different pathologic subtype that may be amenable to wide excision only. It is critical to distinguish the origin of malignant cells in extramucosal perianal mucinous adenocarcinoma associated with a fistula as from either migration of an anal duct or rectal carcinoma or chronic stimulation and mucosal dysplastic changes in the fistulous tract.^4,9,13–18

In the first subtype, malignant cells arise from colorectal mucosa via adenomatous changes and then migrate to seed a granulating fistula in ano.^4,13–16 This pathologic subtype warrants aggressive surgical resection of the primary colorectal or anal tumor site and the satellite disease in the fistula in ano. The second source of malignant cells is dysplastic degeneration in recurrent or persistent fistulous disease. Chronic inflammation creates an immunologic privileged site as lymphatics are disrupted and surveillance is impaired.¹⁹ Mucosal irritation may cause either adenomatous dysplasia (eg, mucosal adenocarcinoma with cutaneous extension at the mucocutaneous junction of an ileostomy) or squamous dysplasia (eg, Marjolin's ulcer).^9,20–22 Distinguishing between these two origins of dysplastic cells is relevant and directly impacts management.

The natural history and prognosis are not well known. Local spread does occur as the tumor invades into dermal structures then into adjacent organs.³ There are limited case reports of metastases to lymph nodes.^6,23 However, because of disrupted lymphatics, there is no clear role for sentinel lymph node biopsy. While some reports claim an indolent course after diagnosis, others describe almost 100% mortality within one year.² It is probable these disparate histories correlate more with histologic subtypes rather than the management approach.

Regardless of the subtype, APR was historically considered the standard of care, particularly after early case series reported high likelihood of local recurrence.²⁴ Sphincter-sparing wide local excision can be considered, particularly in the elderly, but long-term outcomes are not known.²⁵ In this case, when malignant transformation arose in the setting of chronically inflamed tissue and was grossly separate from the anal duct, definitive diagnosis and management was achieved with wide local excision to negative margins. This treatment approach can be further substantiated by the favorable prognosis associated with the similar management of ileostomy-associated mucinous adenocarcinoma.²²

The roles for neoadjuvant and adjuvant therapy are also unclear. Generally, locoregional recurrence carries a poor prognosis in rectal cancer with some case series suggesting a similar outcome for perianal adenocarcinoma.^6,26,27 Intestinal adenocarcinomas are sensitive to chemoradiotherapy, which has been validated in rectal cancer to reduce locoregional recurrence.^27,28 Likewise, adjuvant chemoradiotherapy can be used in perianal adenocarcinoma associated with fistula in ano with the goal to reduce locoregional recurrence and improve survival; prospective data regarding this recommendation are needed.

Perianal mucinous adenocarcinomas represent disparate clinical entities depending on pathophysiology and biology. Extramucosal mucinous adenocarcinoma associated with fistula in ano represents one specific subtype that may be amenable to wide local excision rather than APR. Diagnosis is made clinically and can be challenging because tissue samples may not reveal the presence or extent of invasion. If there is no evidence of anal canal involvement and the pathophysiology reflects chronic local inflammation, it is reasonable to proceed with wide local excision and a goal of negative margins. Adjuvant therapy can be used to reduce the likelihood of local recurrence. It is critical to state there are a limited number of case reports and this management decision should be made after counseling the patient and with multidisciplinary review. In the appropriate situation, the patient may be offered a sphincter-sparing procedure and achieve the goal of curative resection.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.