Your diagnosis

Clear cell carcinoma of the ovary

This article will help you read and understand your pathology report for clear cell carcinoma of the ovary.

by Sandra Lee MD FRCPC (updated May 31, 2021)

Quick facts:
  • Clear cell carcinoma is a type of ovarian cancer.
  • Endometriosis is found in over 50% of clear cell carcinomas and is the most important risk factor for clear cell carcinoma.
  • Patients with Lynch syndrome are at higher risk for developing clear cell carcinoma.
The ovary

The ovaries are part of the female reproductive tract. The ovaries are small organs that are located at the ends of the fallopian tubes and are attached to the uterus by the ovarian ligaments. The outer surface of the ovaries is lined by specialized cells called epithelial cells that form a barrier called an epithelium. The epithelial cells on the surface of the ovary are also called the capsular surface. The tissue below the epithelium is called the stroma.

Gynecological tract

What is clear cell carcinoma of the ovary?

Clear cell carcinoma is a type of cancer that can start from the epithelial cells normally found on the surface of the ovary. Clear cell carcinoma can also start in the ovary from the cells associated with endometriosis.

Endometriosis is the presence of endometrial tissue (which is normally found in the uterus) outside of the uterus and the ovary is a common location to find endometriosis. About 1% of patients with endometriosis will develop a tumour related to their endometriosis and these tumours most commonly occur in the ovary.

How do pathologists make this diagnosis?

For most 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.

Often your 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.

If the clear cell carcinoma has spread outside of the ovary, it 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.

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 travelled there from the tumour. The movement of cancer cells from the tumour to another body site is called metastasis.

This information is important because a tumour that has spread or metastasized from one organ to another is given a higher tumour (T) 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 (capsular) surface of the ovary. The capsular surface is described as intact if no holes or tears are identified. The capsular surface is described as ruptured if it contains any large holes or tears. If the ovary or tumour is received in multiple pieces, it may not be possible for your pathologist to tell if the capsular surface has ruptured or not.

This information is important because a capsular surface that ruptures inside the body may spill cancer cells into the abdominal cavity. A ruptured capsule is associated with a worse prognosis and is used to determine the tumour (T) 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 outside of the ovary. These biopsies, which are often from the peritoneum, are sent to your pathologist to see if the tumour has spread or metastasized. The omentum is an abdominal organ that is a common site of tumour spread or metastasis. This organ is often entirely removed and examined by your pathologist.

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

The presence of cancer cells in other organs is used to determine the tumour (T) stage and distant metastatic disease (M) stage (see Pathologic stage below).

Lymph nodes

Lymph nodes are small immune organs located throughout the body. Cancer cells can travel or metastasize from the tumour to a lymph node through lymphatic channels located in and around the tumour.

Lymph node

Your pathologist will carefully examine all the lymph nodes removed by your surgeon for cancer cells. If cancer cells are found in a lymph node, the size of the area found is important and is used to determine the lymph node (N) stage (see Pathologic stage below). The size of the area in the lymph node involved by cancer and the number of lymph nodes involved by cancer will be described in your report.

  • Isolated tumour cells – The area inside the lymph node with cancer cells is less than 0.2 millimeters in size. Lymph nodes with isolated tumour cells are considered to be negative lymph nodes.
  • Micrometastases – The area inside the lymph node with cancer cells is more than 0.2 millimeters but less than 2 millimeters in size. Lymph nodes with micrometastases are considered to be positive lymph nodes.
  • Macrometastases – The area inside the lymph node with cancer cells is more than 2 millimeters in size. Lymph nodes with macrometastases are considered to be positive lymph nodes.

Isolated tumour cells are recorded in your pathology report as N0 (ITC+) or N0 (i+). The presence of isolated tumour cells in a lymph node does not affect the Pathologic stage for clear cell carcinoma.

Micro and macrometastases found in a lymph node are associated with a worse prognosis and are used to determine the lymph node (N) stage (see Pathologic stage below).

Normal lymphatics of pelvis

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. The instructions are broken up into sections called genes and each gene tells the cell how to produce a protein. Proteins allow cells to live and to work properly.

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

When DNA becomes damaged, there are proteins that try to fix the damaged areas/mutations. Mismatch repair proteins are a set of proteins that normally function to remove certain types of damage/mutations from the DNA in your cells. The four main mismatch repair proteins are MLH1, PMS2, MSH2, and MSH6. When one of these proteins does not work properly, mutations in other genes can start to accumulate and a normal cell can eventually turn into a cancer cell. Pathologists can test the mismatch repair proteins to see if they are working properly. If one or more of the mismatch repair proteins is not working properly this is called mismatch repair deficiency.

In most tumours, mismatch repair deficiency is somatic, which means the mutation is only present in your tumour cells. Somatic mutations can result from both environmental and complex genetic factors, and it is very difficult to determine the exact reason why the mismatch repair protein stopped working properly.

Sometimes mismatch repair protein mutations are inherited. Inherited mutations are also called germline mutations. Germline mutations are mutations that are present in all of the cells in your body as well as your tumour cells. They can be passed down/inherited from your parents and they can also be passed down/inherited to your children. A person who inherits a mismatch repair protein that does not work properly has a higher risk of developing certain cancers and is said to have a cancer syndrome called Lynch syndrome.

In clear cell carcinomas of the ovary, mismatch repair deficiency occurs in a small percentage of cases (about 6%). Most of these are due to somatic mismatch repair protein mutations. A small number of clear cell carcinomas with mismatch repair deficiency are related to germline mismatch repair protein mutations (Lynch syndrome). In some hospitals, ovarian clear cell carcinomas are tested by your pathologist for mismatch repair deficiency. If mismatch repair deficiency is identified in your tumour, additional testing may be done to assess your risk for Lynch syndrome.

Because Lynch syndrome results from an inherited gene mutation, the diagnosis of Lynch syndrome is important not only for you but also for your family. If additional testing confirms you have Lynch syndrome, your family members may want to have additional testing to see if they also have Lynch syndrome.

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.

Tumour stage (pT)ovary cancer T1 T2 T3
Nodal stage (pN)

Node stage ovary cancer

Metastatic stage (pM)

ovary cancer M stage

References

WHO Classification of Tumours. Female Genital Tumours. 5th Edition (Vol 4). Lyon (France): International agency for research on cancer. 2020.

College of American Pathologists Cancer Protocols

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