Penile intraepithelial neoplasia (PeIN)

by Jason Wasserman MD PhD FRCPC and Trevor Flood MD FRCPC
November 2, 2022

What is penile intraepithelial neoplasia (PeIN)?

Penile intraepithelial neoplasia (PeIN) is a non-invasive precancerous disease that involves the penis. It is called “non-invasive” because the abnormal cells are only found in the skin on the surface of the penis. If left untreated, PeIN can turn into a type of penile cancer called squamous cell carcinoma over time.

What causes penile intraepithelial neoplasia?

Infection with the sexually transmitted virus human papillomavirus (HPV) is the most common cause of PeIN. The virus infects cells on the surface of the penis. Over time, the virus causes changes inside the infected cells that lead to the development of PeIN. A subtype of PeIN called ‘differentiated PeIN’ is associated with conditions that cause long-stand inflammation including lichen sclerosus, phimosis, and balanoposthitis.

How is the diagnosis of penile intraepithelial neoplasia made?

The diagnosis of PeIN is usually made after a small piece of tissue is removed in a procedure called a biopsy. The tissue is then sent to a pathologist for examination under the microscope. After the diagnosis is made, your doctor may recommend a second surgical procedure to remove any remaining abnormal tissue.

What does it mean if penile intraepithelial neoplasia is positive for p16?

p16 is a protein that is produced by normal cells throughout the body. Compared to normal cells, precancerous and cancerous tumours caused by HPV produce extra p16 which builds up inside the tumour cells. In order to determine if a group of cells has been infected with HPV, pathologists perform a test called immunohistochemistry to see how much p16 protein the cells are making and where the protein is located inside the cell. Tumours that are caused by HPV are almost always positive or reactive for p16. Tumours caused by other factors are typically negative or non-reactive for p16.

What are the types of HPV-associated penile intraepithelial neoplasia?

Pathologists divide PeIN into two types based on the way the cells look when examined under the microscope. The two most common types are called basaloid (or undifferentiated) and warty. Other less common types are clear cell, pagetoid, and spindle cell.

What does it mean if penile intraepithelial neoplasia is described as differentiated?

‘Differentiated’ PeIN means that the tumour cells look similar to the squamous cells normally found in the skin on the surface of the penis. Unlike the undifferentiated type of PeIN, differentiated PeIN is not caused by HPV.

What stage is penile intraepithelial neoplasia?

All PeIN are staged as Tis. This tumour stage is used to describe an ‘in situ’ or non-invasive disease.