In November, 2013 (and issued several weeks earlier as an early on-line release), The American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued a joint, updated guideline aimed at improving the accuracy and reporting of human epidermal growth factor receptor 2 (HER2) testing in patients with invasive breast cancer.
The guideline, originally issued in 2007, provides new and revised recommendations on HER2 testing to identify patients who can benefit from effective HER2-targeted therapies, such as trastuzumab (Herceptin), pertuzumab (Perjeta), lapatinib (Tykerb), and T-DM1 (Kadcyla). These treatments can substantially improve survival in patients with HER2-positive invasive breast cancer. It is important to accurately determine the HER2 status to ensure that patients most likely to benefit are offered an HER2-targeted treatment, and those that are unlikely to benefit can avoid costs and side effects associated with those drugs.
The new guideline revised scoring for HER2 immunohistochemistry (IHC) stains and also revised scoring cutoffs for HER2 in-situ hybridization (ISH) testing. It also increased the upper end of the range of optimal fixation time for specimens used for HER2 testing to 72 hours. Testing is now recommended for primary invasive breast carcinomas, recurrences, and metastases. In addition, the new guideline stresses repeat testing if HER2 results are discordant with other clinical or histologic findings. If a patient’s initial tumor was HER2 negative and a patient has disease recurrence with clinical behavior suggesting of HER2 positive or triple negative disease, repeat HER2 testing should be strongly considered. Repeat testing should be performed for tumors with discordance between histologic findings and HER2 results (i.e. a low grade tumor that is HER2 positive). Repeat HER2 testing should be performed on tumor-containing excisions if a prior biopsy showed high grade (grade 3) tumor that was HER2 negative (0 or 1+), if the amount of tumor in the prior biopsy was small, if the re-excision specimen contains high grade tumor morphologically different from the tumor in the initial biopsy, if HER2 by IHC and FISH testing was equivocal (2+) in the initial specimen, or if there is doubt about appropriate handling of the prior specimen or about test results of the prior biopsy specimen.
Pathology Associates implemented the updated ASCO/CAP guideline recommendations soon after their release. Our laboratory is accredited by the College of American Pathologists. In addition to strict quality control measures for our HER2 stains, we participate in laboratory inspections and proficiency testing as well as perform ongoing validation of our breast panel (ER,PR,HER2) results to ensure reliability and accuracy of our test results.
(Archives of Pathology 137(11)2013)
Clinical Oncology 31(31) 2013: 3997-4013
To diagnose cancer, a sample of tissue, called a biopsy is taken from a patient and examined by a pathologist to determine if cancer cells are present. A pathologist is a doctor who specializes in the diagnosis and classification of diseases by looking at cells under a microscope and through medical laboratory tests. The pathologist determines whether a tumor is benign or cancerous, and if cancerous, the exact cell type, and grade. The pathologist writes the pathology report and is a member of your medical care team to help treat and care for you as a patient. The following information has been developed for you by the College of American Pathologists to help you better understand your diagnosis and evaluate important treatment options.
Surgical pathology reports vary somewhat regarding the information that they contain; however, each report will document the significant details that affect the management of your diagnosed condition or disease process. Typically, a surgical pathology report is divided into a minimum of four to five sections:
Sometimes a comment section is included, which may note a specific scientific reference or journal article.
To ensure that the report is about you and your diagnosis, each pathology report has your patient identifiers. This is specific information that relates directly to you and includes your name, your birth date, and your hospital or medical record number. In addition, your pathologist’s signature and the name and address of the laboratory, will appear on the report.
When a specimen is sent to the pathology laboratory, the container is also identified with your patient identifiers and matched to your medical record to ensure that the specimen is from you. After the specimen arrives in the lab and is processed, and the final pathology report is prepared, these identifiers are checked repeatedly to ensure the correct information is related to your doctor for your care.
Each pathology department has a numbering system that is used so that they can specifically label each patient specimen. These numbers are called accession or surgical numbers, and they help identify your specimen as it is processed by the pathology laboratory. All the microscope slides made from your specimen will also have your accession or surgical number on them. Your individual accession or surgical number will correlate with your patient identifiers.
Sometimes your doctor may supply additional clinical information about you or your specimen that your primary care physician feels will help your pathologist when they examine the specimen. This may include your symptoms or medical conditions, possible disorders your doctor would like your pathologist to look for, or special studies your primary care physician would like run on your specimen.
The specimen section refers to the anatomic location (place on the body) of the tissue or name of the organ. For example, a skin biopsy would be designated, skin, forehead or the organ removed, such as gallbladder, or appendix. This section is important as an incorrect description or designation (such as to right or left) can be detrimental with grave consequences. Much attention to detail is given to ensure that the appropriate designation is documented.
The gross description section describes how a specimen looks to the “naked eye” and details what tissue is to be examined under the microscope. It includes the size, color, number of tissue samples, and when appropriate, the weight of the specimen. Gross descriptions of a small biopsy specimen are typically short. However, a more complex specimen may require a more detailed description.
Usually, if there are multiple tissues or organs in the specimen, they are each described and samples taken for microscopic examination. Even for a single organ, different portions of the organ are often sampled, and include any area that looks abnormal or different that what is usually seen in a healthy organ. Each of these samples will be used to make a microscope slide and will be listed in your pathology report.
For each cancer, there are standardized criteria that vary depending on the location of the cancer and the type of cancer. The details are documented so as to stage the cancer, which directly affects the patient’s prognosis and subsequent treatment. Read an example of the type of information that a gross description for a breast removed for cancer would include.
The microscopic description details how the specimen looks under the microscope and how it compares with normal cells. The section describes if the cancer has invaded nearby tissues. This microscopic description is then used, along with the gross description and your clinical history to make the pathologic diagnosis.
A microscopic examination of a specimen is always performed. However, a microscopic description is not always included on the pathology report. Pathologists, who do not describe the microscopic features in the report, may include findings that are outside of the norm or would directly affect the patient’s care within the diagnosis section or as a comment.
The microscopic description is also used by the pathologist to note small incidental findings that may not be important to the patient’s care, but may be of interest to other pathologists who may see the case. This could include the results of special studies or microscopic stains that were performed that help confirm the diagnosis, or rule out a different diagnosis.
The diagnosis section represents the final medical diagnosis that is established after thorough examination of the specimen. The pathologist is the doctor who makes the diagnosis. Some diagnoses are very short, such as “acute appendicitis.” Other diagnoses can be quite lengthy as they need to describe many aspects of the cancer that will affect the patient’s treatment and outcome.
In these cancer cases, there often will be additional information, called cancer staging that are included in the diagnosis. This describes what type of cancer is present, how the cancer looks (cancer grade) how far in the specimen has the cancer spread (cancer stage), and other aspects of the cancer, such as if the cancer is present in blood vessels. The diagnosis will also include whether the surgical margins (the edges or borders of a tumor) contain cancer. All this information helps determine what additional treatments (if any) are needed for the patient, and help predict how the patient will do over time (outcome).
Sometimes there are diseases which are subtle, difficult to diagnose or the disease process is considered controversial – or unclear. Many pathologists tend to utilize the “comment section” to explain the intricacies when this type of issue arises. In addition, if the diagnosis is not clear, rare, or associated with new information or technology, the comment section is used to list the possible diagnoses; recommendation for additional testing; or studies that may be helpful in finding the correct diagnosis.
In summary, the surgical pathology report represents a description, which includes the location of the specimen and what the specimen looks like both with the naked eye, as well as when examined under a microscope. This information is then integrated with the clinical information by the pathologist to make a pathologic diagnosis. The pathologic diagnosis is then given to the clinician so they can proceed with the appropriate treatment and continued care of the patient.