Intraductal carcinoma of the prostate gland

by Jason Wasserman MD PhD FRCPC and Trevor Flood MD FRCPC
August 19, 2024

Background:

Intraductal carcinoma of the prostate gland is a noninvasive tumour characterized by the proliferation of malignant cells within the ducts and acini of the prostate gland. Unlike invasive prostate cancer, the tumour cells in intraductal carcinoma are found within the ductal system and do not invade the surrounding prostate tissue. However, this condition is important because it is almost always associated with higher-grade invasive prostatic adenocarcinoma.

What are the symptoms of intraductal carcinoma?

Intraductal carcinoma itself may not cause specific symptoms, particularly in its early stages. However, when it is associated with invasive prostate cancer, symptoms may include difficulty urinating, a weak urine stream, frequent urination, particularly at night, and blood in the urine or semen. Some patients may also experience pain in the pelvic area or back. Often, intraductal carcinoma is discovered incidentally during a biopsy for other prostate issues.

What causes intraductal carcinoma?

The exact cause of intraductal carcinoma is not well understood. It is thought to arise due to a combination of genetic factors and environmental influences. The development of intraductal carcinoma likely involves mutations in key genes that regulate cell growth and division, leading to the uncontrolled proliferation of abnormal cells within the prostate ducts.

What genetic changes are associated with intraductal carcinoma?

Intraductal carcinoma is associated with several genetic alterations that are also seen in high-grade invasive prostate cancers. These include mutations in the PTEN gene, loss of TP53 (a tumour suppressor gene), amplification of the MYC oncogene, loss of BRCA2, and rearrangements involving the ERG gene. These genetic changes contribute to the aggressive behaviour of the associated invasive cancer and the poor prognosis often seen in these cases.

How is the diagnosis of intraductal carcinoma made?

The diagnosis of intraductal carcinoma can be made either after a biopsy or after the entire prostate gland has been removed during surgery. A pathologist then examines the tissue under a microscope. Given its frequent association with high-grade invasive cancer, finding only intraductal carcinoma in a biopsy often prompts further investigations and more aggressive management to ensure that any associated invasive cancer is appropriately treated.

What is the relationship between intraductal carcinoma and invasive prostate cancer?

Intraductal carcinoma is strongly associated with invasive prostate cancer, particularly with high-grade forms of the disease. While intraductal carcinoma itself is noninvasive, its presence is a marker of aggressive disease and indicates a high likelihood of concurrent or subsequent invasive adenocarcinoma.

What are the microscopic features of intraductal carcinoma?

Under the microscope, intraductal carcinoma is characterized by the proliferation of tumour cells within preexisting ducts and acini of the prostate gland. The cells typically show marked cytologic atypia, meaning they appear abnormal with enlarged nuclei, prominent nucleoli, and increased mitotic activity. A key feature of intraductal carcinoma may include the presence of comedonecrosis, where areas of dead cells (necrosis) are seen within the ducts, often surrounded by a ring of tumour cells. The tumour cells may fill and expand the ducts, sometimes leading to a cribriform pattern (a sieve-like structure), which is also a characteristic finding.

Immunohistochemistry

Immunohistochemistry (IHC) is a technique used by pathologists to detect specific proteins in a tissue sample. Pathologists often perform immunohistochemistry to help distinguish between intraductal carcinoma and invasive prostatic adenocarcinoma. In intraductal carcinoma, the basal cells surrounding the ducts express p63 and Ker903, which confirms the tumour’s noninvasive nature. In contrast, invasive prostatic adenocarcinoma typically lacks these basal cell markers.

Is intraductal carcinoma given a Gleason grade?

Intraductal carcinoma is not assigned a Gleason grade on its own. The Gleason grading system is used to evaluate the aggressiveness of invasive prostate cancer based on its microscopic appearance. However, when intraductal carcinoma is found in association with invasive adenocarcinoma, it is assigned a Gleason grade pattern 4 or 5. This classification reflects the aggressive nature of the associated invasive cancer and its potential impact on prognosis and treatment decisions.

Prognosis for patients diagnosed with intraductal carcinoma

The prognosis for patients diagnosed with intraductal carcinoma of the prostate is generally more guarded compared to those with only invasive prostate cancer. This is because intraductal carcinoma is almost always associated with a higher grade and stage of disease. However, the exact prognosis can vary depending on the extent of the disease and the presence of concurrent invasive cancer. Early detection and more aggressive treatment are typically warranted, and most patients benefit from a combination of surgery, radiation, and hormone therapy to control the disease.

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