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What is a pathology test & report?

When a breast lump is biopsied, or tissue removed during surgery samples are sent for testing. Basic testing consists of studying the cancer cells under the microscope by a specialized doctor called a pathologist. A pathologist is a physician specializing in the diagnosis of disease based on examination of tissues and fluids removed from the body. Pathology tests involve evaluation of small samples of cells under a microscope to determine whether they are cancerous by identifying structural abnormalities.

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Additional testing of the cancers genetics may also be performed using Next Generation Sequencing (NGS) at specialized laboratories. Both the pathologist and the specialized labs send your doctor a report that gives a diagnosis for each sample taken. Information in this report is used to help determine treatment.

Different parts of your pathology report results will come back over time because some tests take longer than others, and not all tests are done by the same lab. In the few weeks after surgery, you may see a few different reports from different labs. Waiting can be very difficult, and it may be tempting to fixate on each piece of information by itself. However, you and your doctor need the complete pathology report to truly understand the cancer and decide on a treatment plan.

After any biopsy or excision, you should request a copy of the pathology report for your records so that you have documentation of your pathologic diagnosis. In addition, it is helpful to have a copy of the pathology report to refer to when you are researching your disease.

The Basic Pathology Report

The pathology report is a critical component of the diagnostic process. Your primary doctor will use this report in conjunction with other relevant test results to make a final diagnosis and develop a treatment strategy. By having a basic understanding of what the pathologist is looking for and the structure of the report, you may better understand your pathology report. Having a copy of your pathology report for your personal records is highly recommended. You may want to start a folder or binder containing copies of all your test results

Understanding your Pathology Report

Although pathology reports are written by physicians for physicians, you may be able to decipher some of the medical jargon provided by the report. The structure and information provided in your pathology report may vary, and the following sections are usually included.

Demographics: This section includes the patient’s name and date of procedure. You should check that this information is correct to ensure that you have the correct pathology report.

Specimen: The specimen section describes the origin of the tissue sample(s).

Clinical History: The clinical history section provides a brief description of the patient’s medical history relevant to the tissue sample that the pathologist is examining.

Clinical Diagnosis (Pre-Operative Diagnosis): The clinical diagnosis describes what the doctors are expecting before the pathologic diagnosis.

Procedure: The procedure describes how the tissue sample was removed.

Gross Description (Macroscopic): The gross description refers to the pathologist’s observations of the tissue sample using the naked eye. It may include size, weight, color or other distinguishing features of the tissue sample. If there is more than one sample, this section may designate a letter or number system to distinguish each sample.

Microscopic Description: In the microscopic description, the pathologist describes how the cells of the tissue sample appear under a microscope. Specific attributes that the pathologist may look for and describe may include cell structure, tumor margins, vascular invasion, depth of invasion and pathologic stage.

Non-Invasive or Invasive Breast Cancer Breast cancer usually begins either in the cells of the lobules, which are milk-producing glands, or the ducts, the passages that drain milk from the lobules to the nipple. The pathology report will tell you whether or not the cancer has spread outside the milk ducts or lobules of the breast where it started.

  • Non-invasive cancers stay within the milk ducts or lobules in the breast and do not grow into or invade normal tissues within or beyond the breast.
  • Invasive cancers do grow into normal, healthy tissues. Most breast cancers are invasive.
  • Mixed A breast cancer also may be a “mixed tumor,” meaning that it contains a mixture of cancerous ductal cells and lobular cells. This type of cancer is also called “invasive mammary breast cancer” or “infiltrating mammary carcinoma.” It would be treated as a ductal carcinoma.
  • Multifocal If there is more than one tumor in the breast, the breast cancer is described as either multifocal or multicentric. In multifocal breast cancer, all of the tumors arise from the original tumor, and they are usually in the same section of the breast. If the cancer is multicentric, it means that all of the tumors formed separately, and they are often in different areas of the breast.

Breast Cancer is Classified as one of the following.

  • DCIS (Ductal Carcinoma in Situ) - a non-invasive cancer that stays inside the milk duct.
  • LCIS (Lobular Carcinoma in Situ) - an overgrowth of cells that remain inside the lobule. It is not a true cancer, but individuals are at an increased risk for developing an invasive cancer in the future in either breast.
  • Invasive Ductal Carcinoma - The most common type of breast cancer, invasive ductal carcinoma begins in the milk duct but has grown into the surrounding normal tissue inside the breast.
  • Inflammatory Breast Cancer - Inflammatory breast cancer is a fast-growing form of breast cancer that usually starts with the reddening and swelling of the breast, instead of a distinct lump.
  • Invasive Lobular Carcinoma - These start inside the lobule but grows into the surrounding normal tissue inside the breast.
  • Metastatic Breast Cancer - Breast cancer that has returned after previous treatment or has spread beyond the breast to other parts of the body.
  • Triple Negative Breast Cancer - Approximately 12% of all breast cancers are TNBC, meaning that they are estrogen-receptor negative (ER-), progesterone-receptor negative (PR-), and human epidermal growth factor receptor 2-negative (HER2-). This means that TNBC is not stimulated to grow from exposure to the female hormones estrogen or progesterone, nor through an overactive HER2 pathway.

Cell Structure or “Grade”

Cell Structure: A pathologist examines the cell structure and microscopic attributes of cancer and assigns a histologic “grade” to the cancer. The Grade is a “score” that tells you how different the cancer cells appear from normal, healthy breast cells. The grade will be on a scale from 1 to 3 or as well differentiated, moderately differentiated, or poorly differentiated. Grade is NOT the STAGE Stage is based on the size of the cancer and how far it has spread beyond the breast.

  • Grade 1 or well-differentiated: Cells appear normal and are not growing rapidly.
  • Grade 2 or moderately-differentiated: Cells appear slightly different than normal.
  • Grade 3 or poorly differentiated: Cells appear abnormal and tend to grow and spread more aggressively.

Tumor Margins: If cancerous cells are present at the edges of the sample tissue, then the margins are described as “positive” or “involved.” If cancerous cells are not present at the edges of the tissue, then the margins are described as “clear,” “negative” or “not involved.”

Vascular Invasion: Pathologists will describe whether or not blood vessels are present within the tumor.

Depth of Invasion: The depth of invasion may not be applicable to all tumors, but is used to describe invasion of the tumor.

Pathologic Stage: The clinical stage is determined from the pathologic stage as well as other diagnostic tests such as X-rays. The pathologic stage, designated with a “p,” describes the extent of the tumor as determined from the pathology report only. The staging system most often used by pathologists is based on the American Joint Commission on Cancer’s (AJCC) TNM (tumor, node invasion, metastasis) system.

Size measures the cancer at its widest point and is used to help determine the stage of the breast cancer.

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Diagnosis (Summary): The final diagnosis is the section where the pathologist compiles the information from the entire pathology report into a concise pathologic diagnosis. It includes the tumor type and cell of origin.

Special Tests or Markers:

Your pathology report may include information about the rate of cancer cell growth. A higher percentage suggests a faster-growing cancer. Tests that can measure the rate of growth include:

  • S-phase fraction: S-phase is short for “synthesis phase,” which happens just before a cell divides into two new cells. S-phase is the percentage of cells in the sample that are in the process of copying their DNA. More than 10% is considered high.
  • Ki-67: Ki-67 is a protein in cells that increases as the cells prepare to divide into new cells. The percentage of cells that are positive for Ki-67 can be measured - .the more positive cells the more quickly they are dividing and forming new cells. A result of more than 20% is considered high.

Tumor Necrosis If the pathology report says that tumor necrosis is present, this means that dead breast cancer cells can be seen within the tissue sample.

Vascular or Lymphatic System Invasion The breast has a network of blood vessels (called the vascular system) and lymph channels (lymphatic system) that carry blood and fluid back and forth from your breast tissue to the rest of the body. They are the "highways" that bring in nourishment and remove used blood and the waste products of cell life.

Vascular or lymphatic system invasion happens when breast cancer cells break into the blood vessels or lymph channels. This increases the risk of the cancer traveling outside the breast or coming back in the future. Doctors can recommend treatments to help reduce this risk.

Your pathology report will say “present” if there is evidence of vascular or lymphatic system invasion. If there is no invasion, your report will say “absent.” Lymphatic invasion is different from lymph node involvement. The lymph channels and lymph nodes are part of the same system, but they are looked at and reported separately.

Ploidy (Number of Chromosomes) A pathologist may look at whether the cancer cells contain the normal amount of DNA. To do this, the pathologist looks at the number of chromosomes in the cancer cells and reports them as:

  • Diploid: This means that a proportion of cancer cells have the same number of chromosomes as normal, healthy cells (two sets of 23 each). They tend to be slower-growing, less aggressive cancers.
  • Aneuploid: This means that a proportion of cancer cells have too many or too few chromosomes. When cancer cells are rapidly dividing, mistakes in the distribution of chromosomes can happen, resulting in some cells having too many chromosomes and others too few. An aneuploid cancer may be more aggressive than a diploid cancer.

Test That Determine Your Treatment

Hormone Receptor Status - a test that tells you whether or not the breast cancer cells have receptors for the hormones estrogen and progesterone is performed. Hormone receptors for estrogen and progesterone can be found in and on some breast cells and these receptors are where hormones signal the breast cells to grow. A cancer is called estrogen-receptor-positive (or ER+) if it has receptors for estrogen and progesterone-receptor-positive (PR+) if it has progesterone receptors.

HER2 (human epidermal growth factor receptor 2) is a gene that plays a role in the development of breast cancer. All breast cancers are tested for HER2. The HER2 gene makes HER2 protein receptors on breast cells. In about 10% to 20% of breast cancers, the HER2 gene doesn't work correctly and makes too many copies of itself (known as HER2 gene amplification). All these extra HER2 genes tell breast cells to make too many HER2 receptors (HER2 protein over-expression). This makes breast cells grow and divide in an uncontrolled way. Breast cancers with HER2 gene amplification or HER2 protein over-expression are called HER2-positive in the pathology report. There are several tests used to find out if breast cancer is HER2-positive. How your results appear in the report will depend on the test you have. Two of the most common tests are:

PDL-L1

Cancer immunotherapy known as programmed cell death 1 (PD-L1) has generated great excitement for its ability to help the immune system recognize and attack breast cancer cells. PD-L1 is a protein that inhibits certain types of immune responses. Drugs that block PD-L1 are called checkpoint inhibitors and may enhance the ability of the immune system to fight cancer. A CPS score which measures the amount of PD-L1 expression on cancer cells is also reported and the higher the CPS score the more effective the checkpoint inhibitor medication.

Genomic Assays

Genomic assays analyze a sample of breast cancer cell DNA. Genomic tests are used to help make decisions about whether more treatments after surgery would be beneficial. Genomic and genetic testing are very different and often confuse patients. A genetic testing is done on a sample of your blood, saliva, or other tissue and can tell you if you have a mutation in a gene that is linked to a higher risk of breast cancer. Genomic testing is performed on the cancer cell and can help predict the risk of recurrence and potential benefit from treatment. Genomic tests can be done on a sample of preserved tissue that was removed from the breast during the original biopsy or surgery. The Oncotype DX test is the most widely used genomic test to estimate a woman’s risk of recurrence of early-stage, hormone-receptor-positive breast cancer, as well as how likely she is to benefit from chemotherapy after breast cancer surgery.

BRCA1 and BRCA2 Testing

Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene 1) or BRCA2 (BReast CAncer gene 2). BRCA1/2 are human genes that produce proteins involved in DNA repair. When either of these genes is altered or mutated, DNA repair may not progress correctly. This can lead to the development of certain types of cancer such as breast cancer. BRCA mutations can be hereditary (germline) or occur spontaneously (somatic). Together, BRCA1 and BRCA2 mutations account for about 25 to 30% of hereditary breast cancers and about 5 to 10% of all breast cancers.

The poly ADP-ribose polymerase (PARP) enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. PARP inhibitors target and inhibit this enzyme and may contribute to cancer cell death and increased sensitivity to chemotherapy. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.

Pathologist Signature: The report is signed by the pathologist responsible for its contents.

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Reference:

American Cancer Society. Breast Cancer Facts & Figures 2019-2020. Available at: www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf