Diagnosis


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Physical examination

Upon examination, the anus should be inspected to look for masses, fissures, hemorrhoids, anal warts, or fistulas. A digital examination, a proctoscope, and a flexible or rigid proctosigmoidoscope should help to visualize a carcinoma, although distal lesions can be missed on endoscopy.

Histopathology

The distribution of the histological types of anal cancer is as follows: Squamous cell carcinoma 47%, Transitional (cloacogenic or synonymously known as basaloid) carcinoma 27%, Adenocarcinoma 15%, Carcinoma, NOS 3%, Papillary villous (adeno) carcinoma 3%, Mucinous adenocarcinoma 2%, Melanoma 1%, Other 2%.17

Squamous cell carcinoma

The World Health Organization classification recommends that the term “squamous carcinoma” can be used to cover all histological types of SCC of the anal canal. However, due to the appearances being variable, a number of variants exist. The common variants observed include small cystic foci lines by mucin-producing cells. Some areas of the tumor can also be pleomorphic.18,19

Basaloid carcinoma

This tumor may be entirely submucosal and surround the anal canal and lower rectum, or occasionally is seen as a penetrating ulcer at the level of the dentate line. While it arises from cells of the anal transition alone, it is best considered as a variant of SCC for means of treatment and prognosis.

It can arise from any of the different epithelial cells of the anal transition zone. Well-differentiated varieties may resemble basal cell carcinomas of skin or transitional cell carcinoma of the bladder. Mixed types also occur, and poorly differentiated ones can be difficult to distinguish from squamous carcinoma.20

The histology consists of a proliferation of palisading tumor cells. Small foci of necrosis can be present at areas of large cells, and basaloid appearances can also be seen in the same umour.21

Staging and prognosis

The staging system that is internationally used is the classification by the American Joint Committee on Cancer, 7th edition, 2010 (Table 1).22 After diagnosis is confirmed, staging investigations should be undertaken, including computed tomography (CT) scan of chest, abdomen, and pelvis for assessment of the primary tumor and for signs of metastastic disease,22 as well as magnetic resonance imaging (MRI) of the pelvis for more accurate local staging of primary tumor.

MRI can show the extent of tumor invasion into the external sphincter and perirectal tissues. MRI is advantageous over CT as it has the ability to differentiate between soft tissues and define structures more clearly.23

TABLE 1. WHO histological classification of tumors of the anal canal.

1. Epithelial tumors
    a. Intraepithelial neoplasia, (dysplasia)
    b. Squamous or transitional epithelium
    c. Glandular
    d. Paget’s disease
2. Carcinoma
    a. Squamous cell carcinoma
    b. Adenocarcinoma
    c. Mucinous adenocarcinoma
    d. Small cell carcinoma
    e. Undifferentiated carcinoma
    f. Others
3. Carcinoid tumor
4. Malignant melanoma
5. Non-epithelial tumors
6. Secondary tumors

Positron emission tomography CT is believed to help in determining the nature of any suspicious lymphadenopathy or other possible metastatic lesions.24

Centers outside the UK also use transrectal or three-dimensional ultrasound for staging and for follow-up, which also gives good anatomical detail, especially for small tumors.25,26

Grading

Anal cell carcinoma is graded histologically based on the degree of differentiation of the tumor, as described in Table 2.27 If there is any variation within the tumor, the highest grade is recorded as the final grade.28However, it is debatable whether the highest grade of histology or the grading is believed to have any significance on prognosis due to the subjectivity and imprecision in grading.

TABLE 2. Staging and grading of anal cancers.

Primary tumor
TX  Primary tumor cannot be assessed
T0  No evidence of primary tumor
Tis  Carcinoma in situ (Bowen’s disease), high grade- squamous intraepithelial lesion (HISL), AIN II–III
T1  Tumor 2 cm or less
T2  Tumor more than 2 cm but no more than 5 cm
T3  Tumor more than 5 cm
T4  Tumor of any size invades adjacent organ(s), eg, vagina, urethra, bladder (direct invasion) of rectal wall, peri-rectal skin, subcutaneous tissue, or sphincter muscle is not classified as T4
Regional lymph nodes (N)
NX  Regional lymph nodes cannot be assessed
N0  No regional lymph node metastasis
N1  Metastasis in peri-rectal lymph node(s)
N2  Metastasis in unilateral internal iliac and/or inguinal lymph nodes
N3  Metastasis in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes
Distant metastases (M)
M0  No distant metastasis
M1  Distant metastasis

Management

There has been a paradigm shift in the treatment of anal cancer over the last 30 years from radical surgery to primary chemoradiotherapy, resulting in reduced permanent colostomy rates.

For all four stages of anal SCC except for small T1 tumors of the anal margin, concurrent chemotherapy and radiotherapy are recommended over radiotherapy alone. Otherwise, radical surgery is recommended to improve local control.