Invasive lobular carcinoma of the breast

by Jason Wasserman MD PhD FRCPC
April 4, 2022


What is invasive lobular carcinoma?

Invasive lobular carcinoma is a type of breast cancer. Invasive lobular carcinoma commonly starts from a non-cancerous growth of abnormal breast cells called lobular carcinoma in situ (LCIS). LCIS can be present for months or years before turning into invasive lobular carcinoma. In addition, patients with a previous diagnosis of LCIS have a higher risk of developing invasive lobular carcinoma.

What genetic syndromes increase the risk of developing invasive lobular carcinoma?

Some genetic syndromes are also associated with an increased risk of developing invasive lobular carcinoma. If you or a family member have been diagnosed with breast and ovarian cancer syndrome (BRCA2) or a syndrome related to changes in the CDH1 gene, you should talk with your doctor about your risk of developing breast cancer.

How do pathologists make the diagnosis of invasive lobular carcinoma?

The diagnosis of invasive lobular carcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy. Tests for breast prognostic markers such as estrogen receptor (ER), progesterone receptor (PR), and HER2 may be performed on the biopsy and included in the biopsy report.

Surgery is then performed to remove the entire tumour which is sent to a pathologist for examination under the microscope. Depending on the amount of breast tissue removed, the surgery performed may be called a ‘lumpectomy’ (which means removal of the ‘lump’) or a ‘mastectomy’ which means removal of the entire breast.

After the tumour is removed it will be sent to a pathologist who will look for additional features such as the tumour size, tumour extension, lymphovascular invasion, perineural invasion, and the presence of tumour cells in lymph nodes. All of these features are described in more detail in the sections below.

lobular carcinoma breast

Are there different types of invasive lobular carcinoma?

Yes, there are two different types of invasive lobular carcinoma, classic type and pleomorphic type. Your pathologist will determine the type based on how the cancer cells look when examined under a microscope.

  1. Classic type – This is the most common type of invasive lobular carcinoma. The cancer cells are small and they travel through the tissue as single cells (they are not attached to the other cancer cells).
  2. Pleomorphic type – The cancer cells in the pleomorphic type are larger and more abnormal-looking than the cells in the classic type. The nucleus of the cell (the part of the cell that holds most of the genetic material) is also hyperchromatic (darker) and larger than the nucleus in the classic type. Compared to the classic type of invasive lobular carcinoma, the pleomorphic type is more likely to spread to lymph nodes and other parts of the body.
What is the Nottingham grade and why is it important?

Pathologists use a system called the Nottingham grading system to divide invasive lobular carcinoma into three levels or grades – 1, 2, and 3. The grade is important because grade 2 and grade 3 tumours tend to grow more quickly and are more likely to spread to other parts of the body such as lymph nodes.

How do pathologists determine the Nottingham grade for invasive lobular carcinoma?

The grade can only be determined after the tumour is examined under the microscope. When examining the tumour, pathologists look for the following four microscopic features:

  1. Tubule – A tubule is a group of cells connected together to form a round, ring-like structure. Tubules look similar but are not exactly the same as the glands that are normally found in the breast. A score of 1 to 3 is given based on the percentage of cancer cells forming tubules. Tumours made up mostly of tubules are given a score of 1 while tumours made up of very few glands are given a score of 3. The cells in invasive lobular carcinoma do not form glands and always receive a score of 3 for this feature.
  2. Nuclear pleomorphism – The nucleus is a part of the cell that holds most of the cell’s genetic material (DNA). Pleomorphism (or pleomorphic) is a word pathologists use when the nucleus of one tumour cell looks very different from the nucleus in another tumour cell. A score of 1 to 3 is given for nuclear pleomorphism. When most of the cancer cells are small and look very similar to each other, the tumour is given a score of 1. When the cancer cells are very large and abnormal-looking, the tumour is given a score of 3.
  3. Mitotic rate – Cells divide in order to create new cells. The process of creating a new cell is called mitosis, and a cell that is dividing is called a mitotic figure.  Your pathologist will count the number of mitotic figures in a specific area (called a high powered field) and will use that number to give a score between 1 and 3. Tumours with very few mitotic figures are given a score of 1 while those with many mitotic figures are given a score of 3.​

The score from each category is added to determine the overall grade as follows:

  • Grade 1 (low-grade) – Score of 3, 4, or 5.
  • Grade 2 (high-grade) – Score of 6 or 7.
  • Grade 3 (high-grade) – Score of 8 or 9.
What are breast prognostic markers?

Prognostic markers are proteins or other biologic elements that can be measured to help predict how a disease such as cancer will behave over time and how it will respond to treatment. The most commonly tested prognostic markers in the breast are the hormone receptors estrogen receptor (ER) and progesterone receptor (PR) and the growth factor HER2.

Hormone receptors

ER and PR are proteins that allow cells to respond to the actions of the sex hormones estrogen and progesterone. ER and PR are made by normal breast cells and by some breast cancers. Cancers that make ER and PR are described as ‘hormone sensitive’ because they depend on these hormones to grow.

Your pathologist will perform a test called immunohistochemistry to see if the cells in the tumour are making ER and PR. This test is often performed on the biopsy sample. However, in some situations, it may only be performed after the entire tumour is removed.

Pathologists determine the ER and PR score by measuring the percentage of tumour cells that have protein in a part of the cell called the nucleus and the intensity of the stain. Most reports give a range for the percentage of cells that show nuclear positivity while the intensity is described as weak, moderate, or high.

HER2

HER2 is a protein that is made by normal, healthy cells throughout the body. The tumour cells in some types of cancer make extra HER2 and this allows the cells in the tumour to grow faster than normal cells.

There are two tests that are commonly performed to measure the amount of HER2 in tumour cells. The first test is called immunohistochemistry and it allows your pathologist to see the HER2 protein on the surface of the cell. This test is given a score of 0 through 3.

HER2 immunohistochemistry score:

  • Negative (0 and 1) – A score of 0 or 1 means the tumour cells are not making extra HER2 protein.
  • Equivocal (2) – A score of 2 means the cells may be making extra HER2 protein and another test called fluorescence in situ hybridization (see below) will need to be performed to confirm the results.
  • Positive (3) – A score of 3 means the cells are making extra HER2 protein.

The second test that is used to measure HER2 is called fluorescence in situ hybridization (FISH). This test is usually only performed after a score of 2 on the immunohistochemistry test. Instead of looking for HER2 on the outside of the cell, FISH uses a probe that sticks to the HER2 gene inside the nucleus of the cell. Normal cells have 2 copies of the HER2 gene in the nucleus of the cell. The purpose of the HER FISH test is to identify tumour cells that have more copies of the HER2 gene which allows them to make more copies of the HER2 protein.

Tumour cells that make extra HER2 will also have more DNA instructions for HER2. Pathologists call this change a translocation.

HER2 FISH score:

  • Positive (amplified) – The tumour cells have extra copies of the HER2 gene. These cells are most likely making extra HER2 protein.
  • Negative (not amplified) – The tumour cells do not have extra copies of the HER2 gene. These cells are most likely not making extra HER2 protein.
Has the tumour spread outside of the breast?

Invasive lobular carcinoma starts inside the breast but the tumour may spread into the overlying skin or the muscles of the chest wall. The finding of cancer cells in either skin or chest wall is called tumour extension.

Tumour extension increases the tumour stage (see Pathologic stage below). It is also associated with a higher risk that the tumour will grow back after treatment or that cancer cells will spread to a distant body site such as the lung.

What does lymphovascular invasion mean?

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. 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. 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.

lymphovascular invasion

What are 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 metastasis.

Lymph node

Your pathologist will carefully examine each lymph node 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.

There are three types of lymph nodes that may be described in your report:

  • Sentinel axillary lymph node – This is the first lymph node in the chain of lymph nodes that drains fluid from the breast. If cancer is going to be found in the axilla, it will usually be found in the sentinel node first.
  • Non-sentinel axillary lymph node – This type of lymph node is located after the sentinel lymph node in the axilla. Cancer cells usually travel to these lymph nodes after passing through the sentinel lymph node.
  • Internal mammary lymph node – This type of lymph node is found in the breast itself. Cancer cells may travel to these lymph nodes if the lymph node is found close to the tumour.

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 as follows:

  • Isolated tumour cells – The area of tumour cells measure less than 0.2 millimetres and have less than 200 tumour cells.​
  • Micrometastases – The area of tumour cells measures more than 0.2 millimetres but less than 2 millimetres.
  • Macrometastases – The area of tumour cells measures more than 2 millimetres.

Finding cancer cells in a lymph node is associated with an increased risk that cancer will come back at a distant body site such as the lungs in the future. This information is also used to determine the nodal stage (see Pathologic stage below).

What is a margin?

A margin is any tissue that was cut by the surgeon in order to remove the tumour from your body. Whenever possible, surgeons will try to cut tissue outside of the tumour to reduce the risk that any cancer cells will be left behind after the tumour is removed.

Margin

Your pathologist will carefully examine all the margins in your tissue sample to see how close the cancer cells are to the edge of the cut tissue. Margins will only be described in your report after the entire tumour has been removed.

A negative margin means there were no cancer cells at the very edge of the cut tissue. If all the margins are negative, most pathology reports will say how far the closest cancer cells were to a margin. The distance is usually described in millimetres.

A margin is considered positive when there are cancer cells at the very edge of the cut tissue. A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

​What does treatment effect mean?​

If you received treatment (either chemotherapy or radiation therapy) for your cancer prior to the tumour being removed, your pathologist will examine all of the tissue submitted to see how much of the tumour is still alive (viable). Lymph nodes with cancer cells will also be examined for treatment effect.

The treatment effect will be reported as follows:

  1. No residual tumour – all the cancer cells are dead
  2. Probable effect – some of the cancer cells are dead but some are still alive
  3. No definitive response – most of the cancer cells are still alive

How do pathologists determine the pathologic stage (pTNM) for invasive lobular carcinoma?

​The pathologic stage for invasive lobular 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 a worse prognosis.

Tumour stage (pT) for invasive lobular carcinoma

Lobular carcinoma is given a tumour stage between 1 and 4 based on the size of the tumour and the presence of cancer cells in the skin or muscles of the chest wall.

breast cancer pathologic stage

Nodal stage (pN) for invasive lobular carcinoma

Lobular carcinoma is given a nodal stage between 0 and 3 based on the number of lymph nodes that contain cancer cells, the size of the group of cancer cells found in the lymph node, and the location of the lymph nodes with cancer cells.​

Metastatic stage (pM) for invasive lobular carcinoma

Lobular carcinoma 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 determined if tissue from a distant site is submitted for pathological examination. Because this tissue is rarely sent, the metastatic stage cannot be determined and is listed as pMX.

A+ A A-