This article was last reviewed and updated on July 26, 2019.

by Jason Wasserman, MD PhD FRCPC

Quick facts:

• ​​Clear cell carcinoma is a type of cancer that starts in the endometrium, the tissue that lines the inside of the uterus.

• Clear cell carcinoma is an aggressive cancer that is more common in older women.

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The normal uterus

The uterus is a pear-shaped hollow organ found in the female pelvis between the rectum (the end of the large bowel) and the urinary bladder. The upper part of the uterus (fundus) is attached to the fallopian tubes while the lower part is connected to the vagina through the uterine cervix.

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The walls of the uterus are made up of three layers: 

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• Endometrium – The endometrium is the tissue on the inner surface of the uterus. The endometrium is made up of endometrial glands lined by one layer of cells that form a barrier called the epithelium. The epithelium is surrounded by supporting tissue called endometrial stroma.

• Myometrium – The myometrium is the middle layer and is made up of smooth muscle which allows the uterus to change size and contract. 

• Serosa – The serosa is a thin layer of tissue that surrounds the outside of the uterus.

 

What is clear cell carcinoma?

Clear cell carcinoma is a type of cancer (a malignant tumour) that develops from glands in the endometrium. The name comes from the fact that many of the cells look clear when examined under the microscope.

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Clear cell carcinoma is usually diagnosed after a small sample of tissue is taken from the endometrium in a procedure called a biopsy or curettage. After the diagnosis, the tumour is removed in surgical procedure called a hysterectomy.​

Myometrial invasion

The myometrium is a thick band of muscle just below the endometrium. The movement of cancer cells from the endometrium into the myometrium is called myometrial invasion.

 

The amount of myometrial invasion will be described in millimeters and as a percentage of the total myometrial thickness.

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Myometrial invasion is usually only described in your report after the entire tumour has been removed.

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Why is this important? Myometrial invasion is an important prognostic feature and is used to determine the tumour stage (see Pathological stage below).

Cervical stromal involvement

The cervix is a structure at the very bottom of the uterus. The cervix connects directly with the endometrium. The wall of the cervix is made up of a type of tissue called stroma.

 

Clear cell carcinoma may grow from the endometrium into the cervix. After the tumour is removed completely, your pathologist will carefully examine the tissue from the cervix to see if there are any cancer cells in the cervical stroma.

Why is this important? Finding cancer cells in the cervical stroma increases the tumour stage (see Pathologic stage below).

Other tissues or organs involved

Several other organs and tissues are directly attached or very close to the uterus including the ovaries, fallopian tubes, vagina, bladder, and rectum.

 

Why is this important? Cancer cells directly growing into any of these structures by clear cell carcinoma is associated with poor prognosis and will be described in your report.

Lymphovascular invasion

Blood moves around the body through long thin tubes called blood vessels. Another type of fluid called lymph which contains waste and immune cells moves around the body through lymphatic channels.

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Cancer cells can use blood vessels and lymphatics to travel away from the tumour to other parts of the body. The movement of cancer cells from the tumour to another part of the body is called metastasis.

 

Before cancer cells can metastasize, they need to enter a blood vessel or lymphatic. This is called lymphovascular invasion.

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Why is this important? Lymphovascular invasion increases the risk that cancer cells will be found in a lymph node or a distant part of the body such as the lungs.

Margins

A margin is the normal tissue that surrounds a tumour and is removed with the tumour at the time of surgery. The margins will only described in cases where the tumour extends into the cervical stroma or other tissues surrounding the uterus and after the entire tumour has been removed.

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The type and number of margins described in your report will depend on the type of surgical procedure performed to remove the tumour.

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Why is this important? Cancer cells found at the margin (positive margin) increase the risk that the tumour will grow back after treatment.

Tumour size

This is the size of the tumour measured in millimeters. The tumour size is only measured after the entire tumour has been removed.

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel from the tumour to a lymph node through lymphatic channels located in and around the tumour (see Lymphovascular invasion above). The movement of cancer cells from the tumour to a lymph node is called a metastasis. 

Your pathologist will carefully examine all lymph nodes for cancer cells. Lymph nodes that contain cancer cells are often called positive while those that do not contain any cancer cells are called negative. Most reports include the total number of lymph nodes examined and the number, if any, that contain cancer cells.

 

Lymph nodes on the same side as the tumour are called ipsilateral while those on the opposite side of the tumour are called contralateral.

 

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.

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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.
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• Isolated tumour cells - The area inside the lymph node with with cancer cells is less than 0.2 millimeters in size.

• Micrometastases - The area inside the lymph node with with cancer cells is more than 0.2 millimeters but less than 2 millimeters in size.

• Macrometastases - The area inside the lymph node with with cancer cells is more than 2 millimeters in size.

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Why is this important? Cancer cells found in a lymph node is associated with a higher risk that the cancer cells will be found in other lymph nodes or in a distant organ such as the lungs. The number of lymph nodes with cancer cells is also used to determine the nodal stage (see Pathologic stage below).

Pathologic stage​

​The pathologic stage for clear cell carcinoma 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 more advanced disease and worse prognosis.

 

Pathologic stage is not reported on a biopsy specimen. It is only reported when the entire tumour has been removed in an excision or resection specimen.
 

Tumour stage (pT)

Clear cell carcinoma is given a tumour stage between 1 and 4 based on the depth of myometrial invasion and growth of the tumour outside of the uterus.

 

• T1 - The tumour only involves the uterus.

• T2 - The tumour has grown to involve the cervical stroma.

• T3 - The tumour has grown through the wall of the uterus and is now on the outer surface of the uterus OR it has grown to involve the fallopian tubes or ovaries.

• T4 - The tumour has grown directly into the bladder or the colon.

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Nodal stage (pN)

Clear cell carcinoma is given an nodal stage of 0 to 2 based on the following microscopic features:

 

• The presence of cancer cells in a lymph node,

• The size of the area with cancer cells inside the lymph node,

• The location of the lymph nodes that contain cancer cells.

 

If no lymph nodes are involved the nodal stage is N0. If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as NX.
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Metastatic stage (pM)

Clear cell carcinoma is given an 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 determined 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.

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