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Image of squamous cell carcinoma courtesy of David E. Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Anal cancer is a rare neoplasm that accounts for 2% of all gastrointestinal cancers. Approximately 9400 new cases are diagnosed each year in the United States, with over 1500 estimated deaths in 2022.[1] The male-to-female ratio is 2:3.5 and the median age at diagnosis is 65 years.[1] Risk is significantly elevated in persons with HIV infection but has been slowly decreasing in this population, possibly due to the use of antiretroviral therapy and human papillomavirus (HPV) vaccine.[2] The most common type of anal cancer is squamous cell carcinoma (SCC), which is the main focus of this presentation.

Image courtesy of Dreamstime / Medscape.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Anal cancer may involve the anal canal, the anal margin (including the perianal skin over a radius of 5-6 cm from the squamous-mucocutaneous junction), or both.[3]

Image courtesy of David E. Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Infection with HPV is the single greatest risk factor for the development of anal cancer. Other risk factors include, but are not limited to[4-6]:

  • Age >55 years
  • Receptive anal intercourse
  • Concomitant sexually transmitted disease (STD)
  • Immunosuppression (as in transplant recipients or individuals with HIV infection)
  • Pelvic irradiation
  • Smoking

At-risk populations should be screened carefully, with early referral to colorectal surgeons.

Digital rectal exam image (left) courtesy of Dreamstime; anoscope image (right) courtesy of Edward Fazendin, MD.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Signs and symptoms of anal cancer include:

  • Bleeding per rectum
  • Peri-anal mass/lump
  • Peri-anal pain or pressure
  • Itching or discharge from the anus
  • A change in bowel habits

The workup and evaluation of anal cancer begins with a detailed history and physical exam, including a digital rectal examination (DRE). Referral to a colorectal surgeon for anoscopy with biopsy and colonoscopy (beneficial as a screening tool for concomitant colon cancer) is the next key step.[4-6] Testing for related conditions, such as HPV infection and other STDs, can also aid in determining associated risk factors.

Image courtesy of Wikimedia Commons.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Colorectal surgeons commonly use the following two methods to evaluate anal lesions:

  • High-resolution anoscopy (HRA)
  • Anoscopy with targeted destruction of lesions

HRA (shown), similar to colposcopy, uses acetic acid to identify dysplasia in the perianal area and anal canal. Anoscopy with targeted destruction uses electrocauterization and excisional biopsy both to remove lesions and to provide tissue for biopsy. The two methods are equally effective in diagnosing anal cancer or dysplasia.[4]

Anal cancer staging image courtesy of Medscape.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

In the staging of anal cancer, computed tomography (CT) of the abdomen and pelvis is the most useful tool for evaluating distant metastases to solid organs and lymph nodes, as well as local invasion into nearby organs. Endoanal ultrasonography (EAUS) is an adjunctive tool used to assess the depth of invasion of cancers and spread to local lymph nodes. Positron emission tomography (PET)/CT may be of use if CT findings are unclear.[3-4]

Image courtesy of Medscape.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

The gold standard for treatment of SCC of the anal canal is the Nigro protocol, which combines external radiation therapy and systemic chemotherapy with mitomycin C and 5-fluorouracil (5-FU). Combined radiation and chemotherapy yields complete remission rates of up to 80%.[7] The approximate duration of therapy is 4 weeks. SCC responds slowly, decreasing in size for up to 26 weeks after therapy.[8]

EAUS of an anal-canal cancer; image courtesy of David E Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Close surveillance is required after therapy to monitor for recurrence. For patients deemed to have a complete clinical response after completion of chemoradiation (Nigro protocol), surveillance consists of re-evaluation every 3-6 months with DRE, anoscopy, and inguinal node palpation for a total of 5 years. In addition, CT or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis are obtained annually for 3 years.[9]

Image courtesy of David E. Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Persistent or recurrent disease can be treated with radical surgical resection (eg, abdominoperineal resection [APR]). This procedure involves removal of the anus, the rectum, and a portion of the perineum, as well as creation of a permanent colostomy. For perianal SCC, wide local excision (shown) is the treatment of choice.[3,4,8, 10] Potential complications of treatment fall into the following three main categories:

  • Radiation-related - Ulceration, skin damage, anal stenosis
  • Chemotherapy-related - Nausea, hair loss, lung inflammation
  • Surgical - Bleeding, infection, damage to normal healthy tissue
Image courtesy of David E Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Other Anal Cancers

Adenocarcinoma accounts for approximately 3-9% of all anal cancers. It has three subtypes:

  • Rectal type (most common)
  • Anal gland type
  • Anorectal fistula type

Rectal-type adenocarcinoma arises in the upper anus and is not distinguishable from adenocarcinoma of the lower rectum, so it is treated according to rectal cancer protocols. APR is the most definitive surgical therapy for it; in addition, it often requires neoadjuvant chemoradiation.[3,4]

Other cancers of the anus are exceptionally rare. The slide depicts a case of anal leukemia.

Image courtesy of David E Stein, MD, MHCM.

Anal Cancer: The Fundamentals

Anyelin Almanzar, MD; Edward A. Fazendin, MD; Alexander J. Crean, MD; David E. Stein, MD, MHCM | May 9, 2022 | Contributor Information

Melanoma accounts for less than 1% of anal malignancies, but the anal canal is the third most common location for melanoma, after the skin and eyes. Anal melanoma can often masquerade as a deeply pigmented hemorrhoid. Pathologic diagnosis requires examination under anesthesia and biopsy. Unfortunately, anal melanoma does not respond to the therapy typically used for melanoma; surgical excision is the only treatment, and it offers minimal survival benefit.[3,4]

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