Ductal adenocarcinoma of the prostate gland

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


Background:

Ductal adenocarcinoma is a rare type of prostate cancer that arises in the glands of the prostate. These glands are small round structures that produce seminal fluid. Ductal adenocarcinoma grows in complex patterns and is generally more aggressive than the more common acinar adenocarcinoma.

male genital tract

What are the symptoms of ductal adenocarcinoma?

The symptoms of ductal adenocarcinoma can be similar to other types of prostate cancer. These include difficulty urinating, weak urine flow, blood in the urine or semen, and pain in the lower back or pelvis. Some patients may experience no symptoms at all, especially in the early stages of the disease.

What causes ductal adenocarcinoma?

The exact cause of ductal adenocarcinoma is not well understood. Like other types of prostate cancer, it is thought to result from a combination of genetic factors, hormonal influences, and environmental exposures. Older age and a family history of prostate cancer may increase the risk of developing this type of cancer.

What is the difference between the prostate gland’s ductal adenocarcinoma and acinar adenocarcinoma?

Ductal adenocarcinoma and acinar adenocarcinoma are similar in that they both arise from glands in the prostate. However, ductal adenocarcinoma tends to grow in more complex patterns and present at a higher stage, meaning it may be more advanced when diagnosed.

Mixed ductal and acinar adenocarcinoma

Ductal adenocarcinoma is frequently seen in combination with the more common acinar adenocarcinoma of the prostate gland. In these cases, ductal adenocarcinoma often makes up a minority of the tumour. Pathologists often use the term prostatic adenocarcinoma with ductal features when examining a biopsy to describe a tumour resembling ductal adenocarcinoma. However, once the entire tumour has been surgically removed, the diagnosis of ductal adenocarcinoma is used when more than half of the tumour shows ductal features. It is important to recognize this mixed pattern because even a small component of ductal adenocarcinoma can influence the overall behaviour and treatment of the cancer.

How is this diagnosis made?

Most tumours in the prostate are found after a doctor manually examines your prostate gland. This procedure is called a digital rectal examination. If an unusual lump is found, the next step is to take several small tissue samples from the prostate in a procedure called a core needle biopsy. Most biopsies usually involve 10 to 15 samples of tissue taken from different parts of the prostate. A biopsy can also be done after a blood test shows high levels of the prostate-specific antigen (PSA).

Your pathologist will then examine the tissue samples under a microscope.  What they see (the microscopic features) will help them predict how the disease will behave. These same features will help you and your doctors decide which treatment options are best for you.  These options may include active surveillance, radiation, or surgery to remove the tumour.

What are the microscopic features of ductal adenocarcinoma?

Under the microscope, ductal adenocarcinoma is characterized by tumour cells often arranged in cribriform (cells connected to form slit-like space) or papillary structures. The tumour cells are typically tall columnar cells with prominent nucleoli. Some areas of the tumour may show comedonecrosis, which is the presence of dead cells within a larger group of viable (living) cells. These features help pathologists distinguish ductal adenocarcinoma from the more common acinar adenocarcinoma.

This image shows ductal adenocarcinoma of the prostate gland viewed through the microscope.
This image shows ductal adenocarcinoma of the prostate gland viewed through the microscope.

What Gleason grade is ductal adenocarcinoma?

The Gleason grading system is used to grade prostate cancer based on how the cancer cells look under the microscope. It is based on their growth patterns, with higher scores indicating more aggressive cancer.

In the Gleason system, cancers are assigned a score based on the two most common patterns of growth seen in the tumour, with each pattern given a grade from 1 to 5. The two grades are then added together to give a Gleason score. Cancers with a higher Gleason score tend to grow and spread more quickly.

Ductal adenocarcinoma is generally given a Gleason grade of 4, the second highest grade, because of its typically complex growth patterns. The presence of comedonecrosis, which is a marker of even more aggressive cancer, leads to a Gleason grade of 5. This means that ductal adenocarcinoma is typically associated with a more aggressive clinical course than lower Gleason score prostate cancers.

Tumour quantification

Tumour quantification is the percentage of the prostate replaced by cancer cells. This gives an estimate of how big the tumour is. Your pathology report will describe how many tissue samples show cancer cells. Your report will also explain what percentage of each sample was replaced by cancer cells. This information will help your doctor, and you decide which treatment options are best for you.

Extraprostatic extension​​

Extraprostatic extension describes cancer cells that have moved outside the prostate and into the surrounding tissue. If cancer cells are seen in the tissue outside the prostate, they will be described in your report. Extraprostatic extension is associated with a worse prognosis and is used to determine the tumour stage.

Seminal vesicle invasion​

The seminal vesicles are organs located behind the bladder and above the prostate. Each person has two seminal vesicles, one on each side of the prostate. These organs produce and store the fluid sent to the prostate to feed and move sperm. Seminal vesicle invasion means that cancer cells have spread directly from the prostate into the seminal vesicles. Seminal vesicle invasion is associated with a worse prognosis and is used to determine the tumour stage (see Pathologic stage below).

Bladder neck invasion

​The bladder rests above the prostate gland. Bladder neck invasion means that cancer cells have spread directly from the prostate into the lower part of the bladder, known as the bladder neck. Invasion of the bladder neck is associated with a worse prognosis and is used to determine the tumour stage.

Perineural invasion

Pathologists use the term “perineural invasion” to describe a situation where cancer cells attach to or invade a nerve. “Intraneural invasion” is a related term that specifically refers to cancer cells inside a nerve. Nerves, resembling long wires, consist of groups of cells known as neurons. These nerves, present throughout the body, transmit information such as temperature, pressure, and pain between the body and the brain. Perineural invasion is important because it allows cancer cells to travel along the nerve into nearby organs and tissues, raising the risk of the tumour recurring after surgery.

Perineural invasion

Lymphovascular invasion

Lymphovascular invasion occurs when cancer cells invade a blood vessel or lymphatic channel. Blood vessels, thin tubes that carry blood throughout the body, contrast with lymphatic channels, which carry a fluid called lymph instead of blood. These lymphatic channels connect to small immune organs known as lymph nodes, scattered throughout the body. Lymphovascular invasion is important because it enables cancer cells to spread to other body parts, including lymph nodes or the lungs, via the blood or lymphatic vessels.

Lymphovascular invasion

Margins

In pathology, a margin is the edge of tissue removed during tumour surgery. The margin status in a pathology report is important as it indicates whether the entire tumour was removed or if some was left behind. This information helps determine the need for further treatment.

Pathologists typically assess margins following a surgical procedure like an excision or resection, which removes the entire tumour. Margins aren’t usually evaluated after a biopsy, which removes only part of the tumour. The number of margins reported and their size—how much normal tissue is between the tumour and the cut edge—vary based on the tissue type and tumour location.

Pathologists examine margins to check if tumour cells are at the tissue’s cut edge. A positive margin, where tumour cells are found, suggests that some cancer may remain in the body. In contrast, a negative margin, with no tumour cells at the edge, suggests the tumour was fully removed. Some reports also measure the distance between the nearest tumour cells and the margin, even if all margins are negative.

Margin

Lymph nodes

Lymph nodes are small immune organs found throughout the body. Cancer cells can spread through small lymphatic vessels from a tumour to lymph nodes. For this reason, lymph nodes are commonly removed and examined under a microscope to look for cancer cells. The movement of cancer cells from the tumour to another part of the body, such as a lymph node, is called a metastasis.

Cancer cells typically spread first to lymph nodes close to the tumour, although lymph nodes far away can also be involved. For this reason, the first lymph nodes removed are usually close to the tumour. Lymph nodes further away from the tumour are only typically removed if they are enlarged and there is a high clinical suspicion that there may be cancer cells in them.

If any lymph nodes were removed from your body, they will be examined under the microscope by a pathologist, and the results of this examination will be described in your report. “Positive” indicates that cancer cells were found in the lymph node. “Negative” indicates that no cancer cells were found. If cancer cells are found in a lymph node, the size of the largest group of cancer cells (often described as “focus” or “deposit”) may also be included in your report. Extranodal extension means that the tumour cells have broken through the capsule on the outside of the lymph node and have spread into the surrounding tissue.

The examination of lymph nodes is important for two reasons. First, this information determines the pathologic nodal stage (pN). Second, finding cancer cells in a lymph node increases the risk that cancer cells will be found in other parts of the body in the future. As a result, your doctor will use this information when deciding if additional treatment, such as chemotherapy, radiation therapy, or immunotherapy, is required.

Lymph node

extranodal extension

Pathologic stage (pTNM)

​​The pathologic stage for ductal adenocarcinoma of the prostate gland is based on the TNM staging system, an internationally recognized system created by the American Joint Committee on Cancer. This system uses information about the primary tumour (T), lymph nodes (N), and distant metastatic disease (M)  to determine the complete pathologic stage (pTNM). Your pathologist will examine the tissue submitted and give each part a number. In general, a higher number means a more advanced disease and a worse prognosis.

Tumour stage (pT)

Your pathologist will assign your tumour a stage between T2 and T4 based on what they observe after examining your prostate specimen under the microscope. The stage is based on how far the cancer cells have spread outside of the prostate.

  • T2 – The tumour is found inside the prostate only.
  • T3 – The cancer cells have spread outside of the prostate and into the fat, seminal vesicles, and/or into the bladder neck.
  • T4 – The cancer cells have spread into other nearby organs or tissues such as the rectum or pelvic wall.​
Nodal stage (pN)

Ductal adenocarcinoma of the prostate gland is given a nodal stage of N0 or N1 based on the presence of cancer cells in a lymph node. If no lymph nodes contain cancer cells, the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined, and it is listed as NX.

Other helpful resources

Atlas of Pathology
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