by Jason Wasserman MD PhD FRCPC
July 6, 2023
What is anal intraepithelial neoplasia?
Anal intraepithelial neoplasia (AIN) is a precancerous growth made up of abnormal squamous cells in the anus or anal canal. If left untreated, AIN can turn into a type of anal cancer called squamous cell carcinoma over time. Another name for AIN is squamous intraepithelial lesion (SIL).
Where does anal intraepithelial neoplasia start?
AIN starts from squamous cells that cover the inside surface of the anus and anal canal. The squamous cells form a thin layer of tissue called the epithelium. The term “intraepithelial” means that the abnormal cells in AIN are still located entirely within the epithelium.
What are the symptoms of anal intraepithelial neoplasia?
AIN does not typically cause any symptoms and the condition is usually during routine screening of the anus or when the anus or anal canal are examined for another reason. However, for some patients, AIN is associated with symptoms such as bleeding from the anus or itchiness of the anus or surrounding skin.
What causes anal intraepithelial neoplasia?
Most causes of AIN are caused by long-standing infection with human papillomavirus (HPV). Low grade AIN (AIN1) is typically associated with low-risk subtypes of HPV (6, 11, 42, 43, 44) whereas high grade AIN (AIN2 and AIN3) is typically associated with high-risk subtypes of HPV (subtypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, 68).
Is anal intraepithelial neoplasia a type of cancer?
No. AIN is not a type of cancer. However, AIN is an abnormal growth that can change into a type of anal cancer called squamous cell carcinoma over time.
How is anal intraepithelial neoplasia graded?
Anal intraepithelial neoplasia is divided into three categories – AIN1, AIN2, and AIN3 – based on the degree of cytologic atypia, the location of the abnormal cells within the epithelium, and the number and location of mitotic figures (cells dividing to create new cells). The grade is important because the chance of developing anal cancer from AIN is much greater for AIN2 and AIN3 compared to AIN1.
Anal intraepithelial neoplasia 1 (AIN1)
The abnormal cells in AIN1 are located within the lower 1/3 of the epithelium. Abnormal squamous cells infected with HPV called koilocytes are often seen. Another name for AIN1 is low grade squamous intraepithelial lesion (LSIL). AIN1 that sticks out from the surface of the anus or anal canal is called condyloma acuminatum.
Anal intraepithelial neoplasia 2 (AIN2)
The abnormal cells in AIN2 involve the lower 2/3 of the epithelium and the cells often appear larger and darker than the cells in AIN1. An increased number of mitotic figures (cells dividing to create new cells) are also typically seen. Another name for AIN2 is high grade squamous intraepithelial lesion (HSIL).
Anal intraepithelial neoplasia 3 (AIN3)
The abnormal cells in AIN3 involve almost the entire epithelium and the cells are larger and darker than the cells in AIN1 and AIN2. A large number of mitotic figures (cells dividing to create new cells) are also typically seen. Another name for AIN3 is high grade squamous intraepithelial lesion (HSIL).
What is p16 and why is it important?
Cells infected with high-risk types of human papillomavirus (HPV) produce large amounts of a protein called p16 and increased p16 is commonly seen in AIN2 and AIN3. For this reason, pathologists perform a test called immunohistochemistry that allows them to see if the cells are producing extra p16. Pathologists use the term positive or reactive to describe cells that show increased amounts of p16. A positive result supports the diagnosis of AIN2 or AIN3 and helps exclude other conditions that can look like these conditions under the microscope.
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