by Jason Wasserman MD PhD FRCPC
March 14, 2023
Adenocarcinoma is a type of cervical cancer. It develops from glandular cells normally found in a part of the cervix called the endocervical canal. Most tumours develop from a non-invasive type of cancer called endocervical adenocarcinoma in situ (AIS).
The most common symptom of adenocarcinoma of the cervix is abnormal uterine bleeding. Less common symptoms include pelvic pain and pressure.
The most common cause of adenocarcinoma of the cervix is infection with high-risk types of human papillomavirus (HPV), specifically types 16, 18, and 45. These tumours account for about 80 to 85% of cases worldwide. At present, doctors do not know what causes the other 15 to 20% of cases that are not associated with HPV.
The diagnosis of adenocarcinoma of the cervix is usually made after some cells are removed from the cervix during a Pap test. The diagnosis can also be made after a larger sample of tissue is removed in a biopsy or resection. After the initial diagnosis is made, most patients are offered surgery to remove the entire tumour.
Cells infected with high-risk types of HPV typically produce large amounts of a protein called p16. Pathologists can see this protein inside cells by performing a test called immunohistochemistry. When immunohistochemistry is performed, most adenocarcinomas of the cervix are positive for p16. As a result, this test is used to confirm the diagnosis of adenocarcinoma and rule out other conditions that can look like adenocarcinoma under the microscope.
Pathologists divide adenocarcinoma of the cervix into three levels or grades based on how much of the tumour is making glands similar to those normally found in the cervix. The three levels are called well differentiated, moderately differentiated, and poorly differentiated. The differentiation of the tumour is important because less differentiated tumours (for example, those that are poorly differentiated) tend to grow faster and are more likely to spread to other parts of the body.
The tumour is measured in three dimensions – length, width, and depth of invasion. These measurements are important because they are used to determine the pathologic tumour stage (pT).
Adenocarcinoma starts within the cervix however larger tumours can grow to involve nearby organs such as the endometrium, vagina, bladder, or rectum or supporting tissues such as the parametrium. Pathologists use the term tumour extension to describe how far the cancer cells have spread from their starting point in the cervix into surrounding organs and tissues. Tumour extension into other organs or the parametrium around the cervix is important because it is associated with a worse prognosis and is used to determine the tumour stage.
The tissue that covers the inside surface of the cervix is called the epithelium while the tissue just below the epithelium is called the stroma. Adenocarcinoma of the cervix starts in the epithelium but as the tumour grows, the cells spread into the stroma. This is called stromal invasion.
Most pathology reports will describe the amount of stromal invasion in two directions:
The size of stromal invasion is not the same as the tumour size because the tumour size also includes any AIS that may be above the area of invasion. For that reason, the size of the tumour may be larger than the size of the stromal invasion.
The amount of stromal invasion is important because it is used to determine the pathologic tumour stage (pT). In general, less stromal invasion is associated with a better prognosis while more invasion is associated with a worse prognosis.
Lymphovascular invasion means that cancer cells were seen inside a blood vessel or lymphatic vessel. Blood vessels are long thin tubes that carry blood around the body. Lymphatic vessels are similar to small blood vessels except that they carry a fluid called lymph instead of blood. The lymphatic vessels connect with small immune organs called lymph nodes that are found throughout the body. Lymphovascular invasion is important because cancer cells can use blood vessels or lymphatic vessels to spread to other parts of the body such as lymph nodes or the lungs.
Lymph nodes are small immune organs found throughout the body. Cancer cells can spread from a tumour to lymph nodes through small vessels called lymphatics. 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.
Lymph nodes examined are usually divided into those found in the pelvis and those found around a large blood vessel in the abdomen called the aorta. The lymph nodes found around the aorta are called para-aortic. Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.
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. Most reports will include the total number of lymph nodes examined, where in the body the lymph nodes were found, and the number (if any) that contain cancer cells.
If cancer cells are found in a lymph node, the size of the area involved by cancer will be measured and described in your report.
The examination of lymph nodes is important for two reasons. First, this information is used to determine 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.
What does it mean if a lymph node is described as positive?
Pathologists often use the term “positive” to describe a lymph node that contains cancer cells. For example, a lymph node that contains cancer cells may be called “positive for malignancy” or “positive for metastatic carcinoma”.
What does it mean if a lymph node is described as negative?
Pathologists often use the term “negative” to describe a lymph node that does not contain any cancer cells. For example, a lymph node that does not contain cancer cells may be called “negative for malignancy” or “negative for metastatic carcinoma”.
A margin is any tissue that has to be cut by the surgeon in order to remove the tumour from your body. If you underwent a surgical procedure to remove the entire tumour from your body, your pathologist will examine the margin closely to make sure there are no cancer cells at the cut edge of the tissue. A margin is considered positive when the cancer cells are seen at the edge of the cut tissue. If AIS is seen at the margin that will also be described in your report. Finding cancer cells at the margin increases the risk that the tumour will grow back in that location.
The number and type of margins described in your report will depend on the type of procedure performed to remove the tumour from your body. Pap smears do not have margins.
Typical margins include:
The pathologic stage for adenocarcinoma of the cervix is based on the TNM staging system, an internationally recognized system originally 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.
The pathologic tumour stage for adenocarcinoma of the cervix is based on the size of the depth and horizontal spread of invasion and the extension of tumour into surrounding organs or tissue.
The pathologic stage is based on the examination of lymph nodes for cancer cells.
Adenocarcinoma of the cervix is given a metastatic stage of 0 or 1 based on the presence of cancer cells at a distant site in the body (for example the lungs). The metastatic stage can only be assigned if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely present, the metastatic stage cannot be determined and is listed as MX.