MEDICAL AND SURGICAL REVIEW TOPICS

Malignancies of the anal cancer are relatively uncommon and represent only 2-3% of all anorectal carcinomas.

The position of the tumor in the anal canal relative to the dentate line is important with regard to the biologic behavior of the tumor.

This is based on the lymphatic drainage in these two areas.

Most tumors spread by direct extension and lymphatic drainage.

Hematologic spread is less common.

Anal tumors are classified into two groups based on location: 1) anal cana tumors  2) anal margin tumors

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- Epidermoid carcinoma (1-2% of all colorectal carcinomas) are referred to as squamous, basaloid, cloacogenic, or transitional carcinomas.

- Although each has different histologic features, they exhiit similar biologic behavior and are thus grouped together.

- typically seen in patients 50-70 years of age

- seen more frequently in women

- two cell types – squamous cell (keratinizing) and transitional cell (nonkeratinizing)

- rectal pain, bleeding, or mass are common presenting symptoms

- 40-50% have pelvic lymph node involvement at diagnosis, whereas 15-36% have inguinal nodal involvement and 10% have distant metastasis

- excellent prognosis when discovered prior to nodal involvement and invasion to adjacent structures.

- 80% of tumors are cured by chemotherapy/radiation therapy alone

- chemotherapy with mitomycin C and 5-fluorouracil combined with radiation is the treatment of choice.

- this may be followed by surgical rsection

- abdominoperineal resection is indicated for residual disease or recurrence

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- 0.5-1% of malignant anal tumors

- anal canal is the 3rd most common site after skin and eyes

- typically occurs adjacent to the dentate line

- rectal bleeding is the most frequent complaint

- most are not highly pigmented, and diagnosis is difficult

- tumor is aggressive and often widely metastatic. abdominoperineal resection is indicated in selected patients.

- tumors often radioresistant and unresponsive to chemotherapy

- 5-yaer survival is <15%

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squamous cell carcinoma, basal cell carcinoma, bowen’s disease, paget’s disease of bone

squamous cell carcinoma, basal cell carcinoma, bowen’s disease, paget’s disease of bone

- these tumors are similar to skin tumors elsewhere and are treated likewise

- include squamous cell and basal cell carcinomas, Bowen’s disease, and Paget’s disease of bone

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ANAL CANCER and BOWEN DISEASE

Anatomy-loosely speaking, above dentate line is columnar, below is squamous.  A 1cm transition zone (cloacogenic zone) is present which can contain columnar, cuboidal, or transitional epithelium.

Anal canal = 4cm tube from anal verge (what you see looking from outside) to anorectal ring (about 2cm above dentate line)

Anal margin = skin from anal verge to point 5cm away circumferentially.  Is the intersphincteric space.

Dentate line = transition point, located about 2cm above anal verge.

Term “anal cancer” comprises 2 entities: anal canal cancer (anal verge to 2cm above dentate line) and anal margin (anal verge out to 5cm skin) cancer.  Overlapping behavior and treatment.  Typically well-differentiated and slow growing.

Epidemiology: F:M 5:1, mean age 60s.  Associated with HPV genotypes 16 and 18, anal receptive intercourse, immunosuppressed states (HIV, organ transplant)

SSx: change in bowel habits, hematochezia, pain, urgency, tenesmus, pruritis.

Workup: punch or wedge biopsy diagnostic. Stage with EUS, exam of inguinal nodes with FNA for suspicious nodes, CT abdomen/pelvis, CXR.

ANAL CANAL LESIONS

EPIDERMOID (SQUAMOUS) CARCINOMA

Arises from the cloacogenic zone.  Includes

squamous cell carcinoma

basaloid carcinoma

cloacogenic

mucoepidermoid carcinoma.

generally spread to inguinal LNs. higher incidence of superior rectal LN metastasis.

Staging of anal canal cancers

T1  Tumor <2cm

T2  Tumor 2-5cm

T3  Tumor >5cm

T4  Tumor of any size with invasion into adjacent organ

N1 Perirectal nodes

N2  Unilateral internal iliac or inguinal lymph nodes

N3  N1 and N2, or bilateral N2.

M1 diatant metastases

Stage I  T1N0M0

Stage II T2-3 N0M0

Stage IIIa T1-3N1M0, T40M0

Stage IIIb T4N1M0, anyT N2-3 M0

Stage IV  M1

Treatment is wide local excision for small, well-differentiated, localized tumors confined to submucosa.  All others receive Nigro protocol. Historically, anal canal cancers were treated with APR but results were poor: 50% recurrence rates, 5-yr survival 24-62%.   In 1970s, sensitivity to chemoXRT established.

NIGRO protocol:

chemoradiation of 30Gy XRT of tumor, pelvic, and inguinal nodes from day 1 to 21, plus 5FU 1000mg/m^2 days 1-4 and 28-31 plus mitomycin C 15mg/m^2 on day1

If grossly disease disappears, no further treatment is necessary.  LNs treated as well regardless of status, outcomes as good as formal LAN. Repeat Biopsy at 6wks. If pos,

perform APR 4-6weeks after completion of radiation therapy OR repeat chemo (first line choice).  Complete response >90%.  5yr sur 85%.

Surveillance:

Most recurrences are locoregionally. If nodal recurrence, treat with chemoXRT.

anoscopy  q3mos x 2years, then q6mos

PE            q3mos x 2years, then q6mos

CT, LFTs, EUS: surveillance debatable.

ANAL MARGIN LESIONS

BASAL CELL CARCINOMA

Rare. Local excision.

BOWEN DISEASE

SSx: discrete scaly, crusty, or moist plaques surrounding the anus.  Diagnose with skin biopsy.  Treat with wide local excsion.

PERIANAL PAGET’S DISEASE

Rare intraepidermal neoplasm of apocrine glands.  Long preinvasive phase.  PE reveals scaly or red plaque.  Dx with biopsy.  Workup with full colonoscopy because 50% incidence of synchronous adenocarcinoma.  Rx with wide local excision.  Negative margins a must.  If underlying carcinoma, APR is required.

SQUAMOUS CELL CARCINOMA

Rare.  Less aggressive than SCCs of the anal canal.  Treat with local excision, not Nigro protocol.  Metastasizes to inguinal LNs.

BUSCHKE-LOWENSTEIN TUMOR – giant condyloma acuminatum.  Tend to erode into adjacent sturctures.  Local excision.  Consider chemoXRT for larger lesions.

A 57 year old woman sees blood on the toilet paper. Her doctor notes the presence of an excoriated bleeding 2.8cm mass at the anus. Boipsy confirms the clinical suspicoin of anal cancer. In planning the management of a 2.8cm epidermoid carcinoma of the anus, which of the following is the best initial mangement strategy?

a. Abdominoperineal resection

b. Wide local resection with bilateral inguinal node dissection

c. Local radiation therapy

d. Systemic chemotherapy

e. Combined radiation therapy and chemotherapy

The aswer is e. (Greenfield, pp1131-1136)

Epidermoid cancers of the anal canal metastasize to inguinal nodes as well as to the perirectal and mesenteric nodes.

The results for local radical surgery have been disappointing.

Combined external radiation with synchronous chemotherapy (fluorouracil and mitomycin), also known as the Nigro protocol, has been used as the standard treatment of the disease, whereas radical surgical approaches are now generally reserved for treatment failures and recurrences.

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