Types and Stages of Anal Cancer

Anal cancer is an atypical type of cancer that starts in the anus. The anus is the opening at the end of the intestines connecting to the outside of the body. The anus is connected to the rectum by the anal canal, it has two sphincter muscles that are in the shape of a ring. The anal canal and skin outside the anus are connected by the anal verge, the skin around the anal verge is called perianal skin. The inner lining of the anal canal is mucosa, and most anal cancers start from the mucosal cells.

There are many cells in the anal canal, from the rectum to the anal verge:

• The cells in the anal canal close to the rectum are shaped like tiny columns.
• The cells in the middle (transitional zone) of the anal canal are called transitional cells and are in the shape of a cube.
• Below the dentate line (midway down the anal canal) there are flat squamous cells.
• The cells of the perianal skin (skin around the anal verge) are squamous.

The symptoms generally include bleeding from the anus or rectum, anal itching, pain in the area of the anus, and a mass or growth in the anal canal.

The cause of anal cancer can be a genetic mutation, where the healthy cells grow and multiply out of control, and they don't die accumulating into a mass (tumor). These cancer cells invade nearby tissues and can separate from an initial tumor to spread elsewhere in the body (metastasize). Also, anal cancer is closely related to Human papillomavirus (HPV), a sexually transmitted infection as a majority of anal cancer cases have evidence of HPV infection.

The risk factors include aging, promiscuity, smoking, history of anal cancer (relapsing), Human papillomavirus (HPV), and Drugs or conditions that suppress the immune system.

Types of Anal cancer

Anal cancer is often categorized into two types they are, Cancers of the anal canal (above the anal verge), and Cancers of the perianal skin (below the anal verge).

• Squamous cell carcinoma: It is the most common type of anal cancer. The tumors start in the squamous cells that line most of the anal canal and the anal margin.
• Adenocarcinoma: A rare type of cancer, the cancers start in cells that line the upper part of the anus near the rectum, and also can start in the glands under the anal mucosa (that release secretions into the anal canal). Adenocarcinoma is often confused with Paget's disease, which is a different disease and is not cancer.
• Basal cell carcinoma: It is a type of skin cancer that can develop in the perianal skin. They are often treated with surgery to remove the cancer. It is a rare type of anal cancer.
• Melanoma: The cancer starts in cells of the anal lining that make the brown pigment called melanin. Melanomas are more common on the skin of other parts of the body. Anal melanomas are hard to see and are found at a later stage.
• Gastrointestinal stromal tumor (GIST): The GIST is common in the stomach or small intestine, and rarely starts in the anal region. If the tumors are found at an early stage, they are removed with surgery. If they have spread beyond the anus, they can be treated with drug therapy.
• Polyps(Benign anal tumors): Small, bumpy, or mushroom-like growths that form in the mucosa. There are many kinds including fibroepithelial polyps, inflammatory polyps, and lymphoid polyps.
• Skin tags(Benign anal tumors): The benign growths of connective tissue that are covered by squamous cells. Skin tags are often confused with haemorrhoids (swollen veins inside the anus or rectum).
• Anal warts(Benign anal tumors): Also called condylomas, They're caused by Human papillomavirus infection. The growths that form just outside the anus and in the lower anal canal below the dentate line, also just above the dentate line
• Leiomyomas(Rare form of Benign anal tumors): Developed from smooth muscle cells.
• Granular cell tumors (Rare form of Benign anal tu): Developed from nerve cells and are composed of cells that contain lots of tiny spots (granules).
• Lipomas(Rare form of Benign anal tumors): Start from the fat cells.
• Low-grade SIL (or grade 1 AIN) (pre-cancer anal condition): Pre-cancers might also be called dysplasia. Dysplasia in cells of the anus is called anal intraepithelial neoplasia (AIN)or anal squamous intraepithelial lesions (SILs). The cells in low-grade SIL look like normal cells, and often go away without treatment and have a low chance of turning into cancer.
• High-grade SIL (or grade 2 AIN or grade 3 AIN) (pre-cancer anal condition): The cells in high-grade SIL look abnormal, with time could become cancer, and need treatment.

Also Read: Types and Stages of Anal Cancer

Anal Cancer Stages

Staging cancer is the process of trying to figure out the spread if any, and if so, how far. It helps to determine how serious the cancer is and choose the best treatment option. The earliest stage anal cancers are called stage 0 and then range from stages I through IV. The lower the number, the less cancer has spread. The higher the number, such as stage IV, means cancer has spread more.

According to the American Joint Committee on Cancer (AJCC), the staging system used is the TNM system. Once T, N, and M categories are determined, the information is combined in a process called stage grouping to indicate an overall stage.

• The extent (size) of the tumour(T):What is the size of cancer? Has the cancer reached nearby structures or organs?
• The spread to nearby lymph nodes(N): Has the cancer spread to nearby lymph nodes?
• The spread (metastasis) to distant sites(M): Has the cancer spread to distant lymph nodes or distant organs such as the liver or lungs?

Treatment is done according to the anal cancer stage

• Stage 0: Can often be removed completely by surgery, and Radiation therapy or chemotherapy (chemo) are rarely needed.
• Stages I and II: Small tumors that do not involve a sphincter muscle can be removed by the surgery. In some cases, this may be followed with Radiation therapy and chemotherapy (chemo). The standard treatment for anal cancer without harming the anal sphincter is chemoradiation, which is a combination of external beam radiation therapy (EBRT) and chemo. In certain cases, only a local resection might be needed. Most of the time, a surgery called Abdominoperineal resection (APR).
• Stages IIIA, IIIB, and IIIC: As cancer has grown into nearby organs or spread to nearby lymph nodes, and not distinct organs. The first treatment in most cases is chemoradiation a combination of radiation therapy and chemo. If some cancer remains (after 6 months) after the chemoradiation, a surgery called an abdominoperineal resection (APR) is done, and radiation therapy.
• Stage IV: As the cancer has spread to distinct organs, the treatment is very unlikely to cure these cancers. Instead, treatment is aimed at controlling the disease for as long as possible, along with the standard treatment (Chemo with radiation therapy). For some advanced anal cancers that have grown on chemotherapy, immunotherapy is recommended.
• Recurrent anal cancer: Cancer is called recurrent when it comes back after treatment, it can be local or distinct. If chemoradiation is done, then it is treated with surgery and/or chemo. If surgery is done at first, then chemoradiation is done. Treating recurrent anal cancer often requires a surgery called an abdominoperineal resection(APR).

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Reference

1. Gondal TA, Chaudhary N, Bajwa H, Rauf A, Le D, Ahmed S. Anal Cancer: The Past, Present and Future. Curr Oncol. 2023 Mar 11;30(3):3232-3250. doi:10.3390/curroncol30030246. PMID: 36975459; PMCID: PMC10047250.