Breast -

Invasive lobular carcinoma

This article was last reviewed and updated on August 13, 2019.
by Jason Wasserman, MD PhD FRCPC

Quick facts:

  • Invasive lobular carcinoma is a type of breast cancer.

  • Unlike other types of breast cancer, the cells in lobular carcinoma do not stick together as the tumour grows.

  • Your pathology report will include important information such as the tumour nuclear grade and hormone receptor status.

The normal breast

Adult breast tissue is composed of small structures called glands which are organized into groups called lobules. Under certain conditions, these glands can produce milk, which is transported to the nipple by a series of small channels called ducts.  

 

The inside of both glands and ducts is lined by specialized cells called epithelial cells which form a barrier called the epithelium. The tissue surrounding glands and ducts is called stroma and contains long, thin cells called fibroblasts.

What is invasive lobular carcinoma?

Invasive lobular carcinoma is a type of a breast cancer (a malignant tumour). The tumour develops from the epithelial cells in the glands and ducts of the breast.

Invasive lobular carcinoma often starts from a non-cancerous growth of abnormal breast cells called lobular carcinoma in situ (LCIS). Lobular carcinoma in situ can be present for months or years before turning into invasive lobular carcinoma.

 

When examined under a microscope, the abnormal cells in lobular carcinoma in situ are only found inside the glands and ducts. In order to become invasive lobular carcinoma, the abnormal cells have to break out of the glands and ducts and enter the stroma. The movement of abnormal cells from the glands and ducts into the stroma below is called invasion.

 

Patients with a previous diagnosis of lobular carcinoma in situ have a higher risk for developing invasive lobular carcinoma.

 

Some genetic syndrome are also associated with an increased risk for 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 the CDH1 gene, you should talk with your doctor about your risk for developing breast cancer. 

The diagnosis of lobular carcinoma is usually made after a small sample of tissue is removed in a procedure called a biopsy. The tumour is later removed in an excision or resection. Depending on the amount of breast tissue removed, the resection specimen may be called a 'lumpectomy' (which means removal of the 'lump') or a 'mastectomy'.

Tumour size

This is the size of the tumour. Tumour size will only be described in your report after the entire tumour has been removed. The tumour is usually measured in three dimensions but only the largest dimension is described in your report. For example, if the tumour measures 4.0 cm by 2.0 cm by 1.5 cm, your report will describe the tumour as being 4.0 cm.

 

A tumour measuring 0.1 cm or less is usually called microinvasive.


Only the invasive part of the tumour is included in the size.

Why is this important? The tumour size is used to determine the tumour stage (see Pathologic stage below) and larger tumours are associated with worse prognosis.

Histologic type

There are two different types of lobular carcinoma based on how the cancer cells look when examined under a microscope.

 

  1. Classic type - This is the most common type of lobular carcinoma. The cancer cells are small and they travel through the tissue as single cells (they are not attached 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 darker and larger than the nucleus in the classic type.

Why is this important? Compared to the classic type of lobular carcinoma, the pleomorphic type of lobular carcinoma is a more aggressive tumour and is associated with worse prognosis.

Histologic grade (Nottingham or Scarff-Bloom-Richardson grading system)

Pathologists use the word grade to describe the difference between the cancer cells and the normal epithelial cells that line the inside of the ducts and glands in the breast.

 

The grade can only be determined after the tumour has been examined under the microscope. Your pathologist will look for the following three microscopic features to determine the grade.

  1. Glands - A score of 1 to 3 is given based on the percentage of cancer cells forming glands. Tumours made up mostly of glands are given a score of 1 while tumours made up of very few glands are given a score of 3. The cells in 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 cells genetic material (DNA). Pleomorphism (or pleomorphic) is a word pathologists use when the nucleus of one tumour cells 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 one and other, the tumour is given a score of 1. When the cancer cells are very large and abnormal looking, the tumor is given a score of 3.

  3. Mitotic rate - A cell that is dividing to create a new cell 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 histologic grade as follows:

  • Grade 1 - Score of 3, 4, or 5.

  • Grade 2 - Score of 6 or 7.

  • Grade 3 - Score of 8 or 9.

 

Why is this important? Compared to low grade tumours (grades 1 and 2), high grade tumours (grade 3) are associated with worse prognosis.

Tumour extension

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.

 

Why is this important? 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 travel (metastasize) to a distant body site such as the lung.

Multiple tumours

If more than one tumour is found in your tissue sample, each will be described separately. The tumour stage (see Pathologic stage below) is based on the largest tumour identified.

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.


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.


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 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. 

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 margin is considered positive when there are cancer cells at the very edge of the cut tissue. 

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 millimeters.

Why is this important? A positive margin is associated with a higher risk that the tumour will grow back (recur) in the same site after treatment.

Treatment effect

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).

 

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

 

Lymph nodes with cancer cells will also be examined for treatment effect.

Estrogen receptor (ER), progesterone receptor (PR), and HER2 status

Estrogen and progesterone receptors are proteins that are produced by normal breast cells which allow the cells to respond to the hormones estrogen and progesterone. HER2 is a special type of protein that allows cancer cells to grow faster than normal cells.

 

Your pathologist will test your tumour to see if it makes ER, PR or HER2. Tumours that make ER or PR are said to be hormone positive while those that make extra HER2 are called HER2 positive. Tumours that do not make any of these proteins are called triple negative.

Most lobular carcinomas make ER and PR and very few make extra HER2.

Why is this important? Tumours that make ER, PR, or HER2 are treated with special medication that targets the activity of these proteins. After reviewing your pathology report, your doctor will talk with you about the treatment options best suited for you.

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 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 millimeters and have less than 200 tumour cells.​

  • Micrometastases - The area of tumour cells measures more than 0.2 millimeters but less than 2 millimeters.

  • Macrometastases - The area of tumour cells measures more than 2 millimeters.

Why is this important? Finding cancer cells in a lymph node is associated with an increased risk that the 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).

Pathologic stage

​The pathologic stage for 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 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) 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.

 

  • T1 - The tumour is less than or equal to 20 millimeters in size.

  • T2 - The tumour is greater than 20 millimeters but no more than 50 millimeters in size.

  • T3 - The tumour is greater than 50 millimeters in size.

  • T4 - The tumour has grown into the skin of the breast or the muscles behind the breast or has caused a change in the skin called 'inflammatory carcinoma'.

 

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 amount of cancer cells found in the lymph node, and the location of the lymph nodes with cancer cells.

  • N0 - No cancer cells are found in any of the lymph nodes examined.

  • N0(i+) - Only isolated cancer cells were found in a lymph node. 

  • N1mi - Micrometastases. Cancer cells were found in a lymph node but the group of cancer cells is not bigger than 2.0 millimeters.

  • N1a - Cancer cells were found in 1 to 3 lymph nodes from the axilla (under the arm) and at least one group of cancer cells is larger than 2.0 millimeters.

  • N1b - Cancer cells were found in an internal mammary sentinel lymph node.

  • N1c - Cancer cells were found in a lymph node from the axilla and an internal mammary lymph node.

  • N2a - Cancer cells were found in 4 to 9 axillary lymph nodes and at least one group of cancer cells was larger than 2.0 millimeters.

  • N2b - Cancer cells were found in internal mammary lymph nodes after imaging of the breast.

  • N3a - Cancer cells were found in 10 or more axillary lymph nodes and at least one group of cancer cells is larger than 2.0 millimeters OR  cancer cells were found in a lymph node below the clavicle.

  • N3c - Cancer cells were found in a lymph node above the clavicle.

 

If no lymph nodes are sent for pathological examination, the nodal stage cannot be determined and the nodal stage is listed as pNX.


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.

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