by Sandra Lee MD FRCPC
March 7, 2023
Clear cell carcinoma is a type of ovarian cancer. Most clear cell carcinomas are associated with a condition called 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.
For most women, the diagnosis of clear cell carcinoma of the ovary is only made when the entire tumour has been surgically removed and sent to a pathologist for examination. If the tumour has spread outside of the ovary, the diagnosis can also be made 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.
An intraoperative consultation, also known as a frozen section, is an opportunity for your surgeon and pathologist to examine the tumour, lymph nodes, or other tissue samples at the time of surgery. During this consultation, a frozen section may be performed where the tissue is quickly examined under the microscope. The purpose of an intraoperative consultation and frozen section is to provide your surgeon with information that will help guide decisions made at the time of surgery.
The tumour 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 tumour cells are seen on the surface of the fallopian tube or ovary, it suggests that they have travelled there from the tumour. The spread of 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).
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 tumour 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).
Small samples of tissue are commonly removed in a procedure called a biopsy to see if tumour 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 presence of tumour cells in other organs is used to determine the tumour (T) stage and distant metastatic disease (M) stage.
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.
Lymph nodes are small immune organs located throughout the body. Tumour cells can travel or metastasize from the tumour to a lymph node through lymphatic channels located in and around the tumour. Your pathologist will carefully examine all the lymph nodes removed by your surgeon for tumour cells. If tumour cells are found in a lymph node, the size of the area found is important and is used to determine the lymph node (pN) stage. The size of the area in the lymph node involved by the tumour and the number of lymph nodes with tumour cells will be described in your report.
For clear cell carcinoma of the ovary, pathologists divide lymph nodes with tumour cells into three categories:
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).
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.