Figure 70-30. Perianal Paget disease. Paget cells are above the basal layer.

Figure 70-31. Epidermoid cancer of the anal canal. Courtesy of Dr. Mariana Berho.

Anal Canal Tumors

Epidermoid or Squamous Cell Carcinoma

Cancers that arise within the anal canal differ in treatment and prognosis from tumors that occur in the

perianal skin. Epidermoid cancer of the anal canal has various microscopic appearances, including

squamous cell (large cell keratinizing), transitional zone (large cell nonkeratinizing), basaloid, or

mucoepidermoid epithelium (Fig. 70-31). The term cloacogenic carcinoma has also been used for

basaloid and transitional carcinomas. The clinical presentation, treatment, and prognosis are similar

among the different forms of epidermoid carcinomas.

Patients with anal canal tumors typically present with bleeding and pruritus. As with anal margin

tumors, these symptoms are often initially misdiagnosed as hemorrhoids or fissure. Digital examination

of the anal canal will often demonstrate an indurated mass. Anoscopy allows for visualization of the

tumor and biopsy to confirm the diagnosis. Physical examination should also include palpation of the

inguinal region to evaluate for enlarged lymph nodes. Although there is no association between

epidermoid anal cancer and colorectal cancer, most clinicians recommend a colonoscopy to evaluate the

colon and rectum.

Staging of squamous cell cancer of the anal canal is based on the size of the primary tumor and

evidence of lymph node and distant metastases and is detailed in Table 70-6. Although endoanal

ultrasound may demonstrate the depth of invasion and enlarged perirectal lymph nodes, these variables

are not part of the TNM staging system. Enlarged or suspicious groin lymph nodes should be biopsied,

either by excision or fine-needle aspiration. Computed tomography of the abdomen and pelvis is

indicated to detect for distant metastatic disease. PET scanning is not typically done as part of the initial

staging, however it may be useful in assessing persistent or recurrent disease after treatment. HIV

testing should be considered in those patients who are at higher risk.

Prior to 1975, the treatment of anal canal squamous cell cancer included surgery alone or radiation

therapy alone. Early-stage lesions were treated by local excision while patients with more advanced

tumors underwent abdominoperineal resection. Local recurrence rates approached 50% and 5-year

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survival was 40% to 70%.50 Nigro et al. treated patients with preoperative chemotherapy and radiation

prior to APR in an effort to decrease recurrence rates and discovered that the majority of these tumors

had completely regressed at the time of surgery. This finding led them to recommend treatment with

chemoradiation alone with surgery reserved for patients with residual disease, commonly referred to as

the Nigro Protocol. This regimen includes external beam radiation to the primary carcinoma as well as

the pelvic and inguinal lymph nodes, combined with intravenous 5-fluorouracil and mitomycin C. A

typical modified Nigro regimen is summarized in Table 70-7. Since the initial report, multiple studies

have confirmed these results, including two randomized trials.51,52

Patients who are treated with chemoradiation should be followed closely to detect any evidence of

recurrence. This includes physical examination and anoscopy with biopsy of any suspicious areas. In

patients with persistent or recurrent disease, abdominoperineal resection is recommended. Studies of

patients who underwent salvage APR show better survival in recurrent rather than persistent disease,

with a 57% 5-year survival rate.53 Inguinal node metastasis at initial presentation prior to treatment

with chemoradiation is also associated with poor outcome after APR for treatment failure.54 It is

important to consider that perineal wound complication rates are high in patients who undergo APR for

recurrent anal cancer after treatment with chemoradiation,55 and reconstruction with a rectus abdominis

myocutaneous flap should be considered. Radical groin dissection may also be considered in patients

with symptomatic inguinal disease after chemoradiation.

Adenocarcinoma

Anal canal adenocarcinomas are relatively rare, accounting for less than 10% of all anal carcinomas.56

Their presentation is similar to squamous cell cancers of the anal canal, with pain, bleeding, pruritus,

and a palpable mass, although these tumors tend to have a more aggressive natural history than SCC.

These tumors tend to present in the seventh decade of life and occur equally in males and females.57

Adenocarcinomas of the anal canal are classified according to their cell of origin. Rectal-type

adenocarcinomas arise from the transitional zone in the upper anal canal and are indistinguishable from

adenocarcinoma of the distal rectum. These tumors are treated in a similar manner as rectal cancer,

with chemoradiation followed by abdominoperineal resection; local excision may be an option in small,

early stage tumors that do not invade the anal sphincter complex. Anal gland-type adenocarcinomas

arise from the mucin-secreting goblet cells that line the glands within the anal canal. These tumors may

develop in an extramucosal manner without involvement of the anal canal epithelium. There have also

been reports of mucinous adenocarcinoma developing in the setting of a chronic anal fistula, although

the likely origin of these tumors is also the goblet cells within the anal glands. Anal gland-type

adenocarcinomas have a lower response rate to chemoradiation than SCC of the anal canal, and these

tumors are therefore best treated with combined chemoradiation and abdominoperineal resection.

Melanoma

Melanoma occurs most commonly in the skin and eyes, but can also develop from the transitional

epithelium within the anal canal or the anoderm at the anal verge. This tumor is more common in

females than in males and is relatively rare, accounting for less than 1% of all anal malignancies.

Symptoms are typically pain, pruritus, and bleeding. Most lesions are pigmented, and may frequently be

incorrectly diagnosed as a thrombosed hemorrhoid. Some anal melanomas may not contain pigment and

can be difficult to differentiate from SCC.

Anal canal melanomas spread submucosally into the rectum, but do not typically invade other organs.

Lymphatic spread to mesenteric lymph nodes is present in up to 35% of patients at the time of

diagnosis,58 and hematogenous spread to distant sites is common as well. Melanomas of the anal canal

do not respond to chemotherapy or radiation, making surgery the only chance for cure. Options include

wide local excision or abdominoperineal resection, however the prognosis is extremely poor, with 5-

year survival rates of less than 30%.59 While APR may help to reduce local recurrence, survival rates do

not differ from wide local excision and most authors therefore advocate for local excision to avoid the

morbidity of a permanent colostomy.60

STAGING AND CLASSIFICATION

Table 70-6 American Joint Committee on Cancer Staging Classification for

Squamous Cell Carcinoma of the Anal Canal

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TREATMENT

Table 70-7 Modified Nigro Regimen for Squamous Cell Carcinoma of the Anal

Canal

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