Learn about your diagnosis

Ovary – Clear cell carcinoma

by Jason Wasserman, MD PhD FRCPC, updated on July 27, 2019

Quick facts:
  • Clear cell carcinoma is a type of ovarian cancer.
  • Clear cell carcinoma is an aggressive cancer that has often spread to other organs in the pelvis or abdomen by the time it is first detected and diagnosed.
  • Patients with Lynch syndrome are at higher risk for developing clear cell carcinoma.

In this article you will learn about:

  • The normal ovary
  • What is clear cell carcinoma?
  • How do pathologists make this diagnosis?
  • Tumour size
  • Cancer cells on the surface of the ovary or fallopian tube
  • Intact or ruptured tumours
  • Other organs or tissues involved
  • Lymph nodes
  • Treatment effect
  • Pathologic stage
  • Mismatch repair testing
The normal ovary

The ovaries are part of the female reproductive tract. The ovaries are small organs that are attached to the uterus by the fallopian tubes. The outer surface of the ovaries are lined by specialized cells called epithelial cells that form a barrier called an epithelium.

Gynecological tract

What is clear cell carcinoma?

Clear cell carcinoma is a type of cancer that starts either on the outer surface of the ovary or within the tissue below the surface of the ovary.

In many cases, patients with clear cell carcinoma have a history of endometriosis or their ovaries will show evidence of endometriosis. For this reason, it is believed that in some women, endometriosis acts as the ‘seed’ for the development of clear cell carcinoma in the future. However, the vast majority of women who have endometriosis will never develop clear cell carcinoma so the risk associated with endometriosis is still quite low.​

How do pathologists make this diagnosis?

Because it often spreads to the peritoneum, clear cell carcinoma can be diagnosed after fluid is removed from the abdominal cavity in a procedure called a fine needle aspiration (FNA). The fluid is then sent to a pathologist who examines the cells in the fluid under the microscope.

The diagnosis of clear cell carcinoma can also be made after a small sample of tissue is removed in a procedure called a biopsy. In this procedure, a small sample of tissue from the pelvis or abdomen is removed. The ovary itself is not usually biopsied.

For some women, the diagnosis of clear cell carcinoma is only made when the entire tumour has been surgically removed and sent to a pathologist for examination. The ovary is usually removed along with the fallopian tube, and uterus.

In many cases, the surgeon will request an intraoperative or frozen section consultation from your pathologist. The diagnosis made by your pathologist during the intraoperative consultation can change the type of surgery performed or the treatment offered after the surgery is completed.​

Tumour size

This is the size of the tumour measured in millimeters. The size of the tumour will only be included in your report after the entire tumour has been removed.

Cancer cells on the surface of the ovary or fallopian tube

The cancer cells in clear cell carcinoma can spread from the ovary to another nearby organ such as the fallopian tube or the ovary on the other side of the body.

If cancer cells are seen on the surface of the fallopian tube or ovary, it suggests that they have traveled there from another site.

Why is this important? This information is important because a tumour that has spread from one organ to another is given a higher tumour stage (see Pathologic stage below) .

Intact or ruptured tumours

All ovarian tumours are examined to see if there are any holes or tears in the outer surface of the tumour or ovary. The outer surface is referred to as the capsule. The capsule is described as intact if no holes or tears are identified. The capsule is described as ruptured if the outer surface contains any large holes or tears.

Why is this important? This information is important because a capsule that ruptures inside the body may spill cancer cells into the abdominal cavity. A ruptured capsule is associated with worse prognosis and is used to determine the  tumour stage (see Pathologic stage below).

Other organs or tissues involved

Small samples of tissue are commonly removed in a procedure called a biopsy to see if cancer cells have spread to the pelvis or abdomen. These biopsies which are often called omentum or peritoneum are sent for pathological examination along with the tumour.

Other organs (such as bladder, small intestine, or large intestine) are not typically removed and sent for pathological examination unless they are directly attached to the tumour. In these cases your pathologist will examine each organ under the microscope to see if there are any cancer cells attached to those organs.

Why is this important? Cancer cells in other organs are used to determine the tumour stage (see Pathologic stage below).​

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.

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.​

  • 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.

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).

Treatment effect

If you were treated with chemotherapy (or other drugs designed to kill cancer cells) prior to surgical removal of your tumour, your pathologist will examine the tumour to determine the percentage of the tumour that is still alive (viable).

The response will be categorized as follows:​

  1. No/minimal response – Most of the tumour is alive.
  2. Appreciable response – Some of the tumour is dead and some is alive.
  3. Complete response – Almost all or all of the tumour is dead.
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)
  • T0 – After careful examination of the tissue, no primary tumour is found. This can happen if you received treatment (for example chemotherapy) before surgery and the tumour shows complete response (see Treatment effect above).
  • T1a – The tumour is found only in one ovary or fallopian tube.
  • T1b – The tumour is found in both ovaries or fallopian tubes.
  • T1c – The tumour is found in only one ovary or fallopian tube but the tumour capsule is broken OR cancer cells were found in fluid taken out of the abdomen or pelvis.
  • T2a – The tumour extends to the uterus or cancer cells were found on the surface of the ovaries, fallopian tubes, or uterus (implants).
  • T2b – The tumour extends to other parts of the pelvis or cancer cells were found on the surface of tissues in the pelvis (implants).
  • T3 – Cancer cells are found outside of the pelvis in the tissues of the abdomen.
Nodal stage (pN)
  • NX – No lymph nodes were sent to pathology for examination.
  • N0 – No cancer cells are found in any of the lymph nodes examined.
  • N0(i+) -Only isolated cancer cells are found in a lymph node (see Lymph nodes above).
  • N1a – Cancer cells are found in a lymph node but the area with cancer cells is not greater than 10 millimeters.
  • N1b – Cancer cells are found in a lymph node and the area with cancer cells is greater than 10 millimeters.
Metastatic stage (pM)

Clear cell carcinoma is given a metastatic stage between 0 and 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 sent for pathological examination.

Mismatch repair testing

​Each cell in your body contains a set of instructions that tell the cell how to behave. These instructions are written in a language called DNA and the instructions are stored on 46 chromosomes in each cell. Because the instructions are very long, they are broken up into sections called genes and each gene tells the cell how to produce piece of the machine called a protein.

If the DNA becomes damaged or if it cannot be read accurately, the cell will be unable to produce the proteins it requires to function normally. An area of damaged DNA is called a mutation and mutations are one of the most common causes of cancer in humans.

For most patients, clear cell carcinoma arises as a result of both environmental factors and genetic factors. These tumours are said to be ‘sporadic’ because they cannot be totally predicted.

Lynch syndrome

Some patients, however, inherit particular genes that put them at a much higher risk for developing clear cell carcinoma. These people are said to have a syndrome and the most common syndrome associated with endometrial carcinoma is called Lynch.

Lynch syndrome is caused by the loss of one of 4 special proteins (MSH2, MSH6, MLH1, and PMS2) that normally function to remove errors from the genetic material (DNA) in your cells. When one of these proteins is lost, mutations start to accumulate and the normal cell can eventually turn into cancer.

As a precaution, pathologists test all clear cell carcinomas for Lynch syndrome using a test called mismatch repair. This test looks at the activity of MSH2, MSH6, MLH1, and PMS2 and if one or more of them is lost, additional testing may be performed to assess your risk for Lynch syndrome.

Why is this important? The diagnosis of Lynch syndrome is important not only for the patient but also for the patient’s family who may also be at risk of cancer as a result of the syndrome.

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