Physicians use a variety of tests to accurately diagnose cancer, determine prognosis, and monitor cancer for progression and side effects. Precision cancer medicines are targeted drugs and immunotherapies engineered to directly attack cancer cells with specific abnormalities, leaving normal cells largely unharmed. Individuals with cancer should discuss the role of genomic – biomarker testing with their physician. Genomic markers can be tested for in a tissue biopsy sample or in the blood using a “liquid biopsy.”
- Pathology Report and Testing
- Genomic – Biomarker Testing
- The Complete Blood Count
- Other Blood Tests
What is a pathology test?
Pathology is the historical test standard for the diagnosis of cancer and one of the more important diagnostic tools that physicians use to diagnose caner. 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 a small sample of cells under a microscope to determine whether they are cancerous by identifying structural abnormalities.1,2,3,4,5,6,7,8,9,10,11,12,13
How are tissue samples obtained?
Most cancer patients will undergo a biopsy or other procedure to remove a sample of tissue for examination by a pathologist in order to diagnose their disease. There are a variety of methods used to obtain samples, including a typical biopsy, fine needle aspiration, or a biopsy with the use of an endoscope. The method used to gain a tissue sample depends on the type of mass and location in the body.
A typical biopsy involves the surgical removal of a mass of abnormal cells. Fine needle aspiration involves guiding a thin needle into the cancer and gently sucking out cells for microscopic evaluation. An endoscope is a lighted tube that can be guided into the body through an orifice, such as the mouth or anus, and is used to perform a biopsy. It allows the physician to see the cells in question and then “scrape” the abnormal cells in order to get a sample. For example, throat cells may be sampled in this way.
A physician may also perform a bone marrow biopsy, which uses a large needle to remove a sample of the bone marrow. The purpose of this procedure is to diagnose lymphoma and leukemia or determine whether certain types of cancer, such as breast or prostate, have spread to the bones. Bone marrow biopsies are usually performed in the bones of the rear hip. This procedure may also be called a bone marrow aspiration.
Once a tissue sample is obtained, it is then “fixed”, meaning it is treated in a way that stops degradation and prevents the cells in the sample from changing characteristics. Next, the sample is stained so that the pathologist can see the cell structure under a microscope and determine whether the cells are exhibiting cancerous characteristics.
What Is a Liquid Biopsy?
A liquid biopsy is performed by testing a sample of blood for the presence of circulating cancer cells, known as circulating tumor cells. Perhaps more importantly, samples of blood obtained from a liquid biopsy can also be tested for cell-free tumor DNA (cfDNA), which are fragments of DNA shed by cancer cells into a patient’s bloodstream.
Because cancer cells are constantly “shedding” parts of their DNA, specific genetic mutations (alterations) within these pieces of DNA can provide invaluable information to healthcare providers and ultimately help guide optimal treatment options for each patient.
Importantly, the bits of cf DNA obtained from a liquid biopsy can provide information to healthcare providers in the following areas:
- If or to what extent the cancer is responding to treatment
- Optimal treatment options specific to the DNA mutations of the cancer cells
- Earlier detection of cancer compared with standard screening measures
- Molecular and genetic real-time changes occurring in a patient’s cancer cells in response to treatment and growth
The Pathology Report
Once a tissue sample is obtained, the pathologist will examine the tissue sample under the microscope in order to determine if it contains normal, pre-cancerous or cancerous cells. The pathologist then writes a pathology report summarizing his or her findings.
The pathology report is a critical component of the diagnostic process. The primary doctor will use this report in conjunction with other relevant test results to make a final diagnosis and develop a treatment strategy.
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.
Genomic-biomarker testing report
Tissue or blood is also used to test for known cancer driving mutations and markers that can help determine which drug or immunotherapy can best target the cancer. A report listing all mutations tested will be provided.
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 also highly recommended. Your primary doctor should be able to address specific questions you have about your pathology report.
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. Your primary doctor should be able to address specific questions you have about your pathology report; however, it is helpful to have a basic understanding of what the pathologist is looking for. The structure and information provided in your pathology report may vary, but 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.
Cell Structure: Using a microscope, the pathologist examines the cell structure and microscopic attributes of the tissue sample and assigns a histologic grade to the tumor. The histologic grade helps the pathologist identify the type of tumor. The grade may be described numerically with the Scarff-Bloom-Richardson system1,2,3 or as well-differentiated, moderately-differentiated or poorly differentiated.
* 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.
Special Tests or Markers: Depending on the tissue sample, the pathologist may conduct tests to further determine whether or not specific proteins or genes are present, as well as how fast cells are growing.
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.
Pathologist Signature: The report is signed by the pathologist responsible for its contents
The Role of Genomics in Diagnosing and Monitoring Cancer
Cancer is the result of genetic abnormalities that affect the function of particular genes. Genes determine the form, function, and growth patterns of cells. Those that accelerate or suppress growth are often involved in cancer. For example, many cancers have an abnormality in a gene that is responsible for stimulating cellular growth and/or the gene that normally prevents cancer is not working properly. Both of these genetic abnormalities can result in uncontrolled and excessive cellular growth, the hallmark trait of cancer. Genomic tests, or assays as they are called by scientists, are a tool for identifying the specific genes in a cancer that are abnormal or are not working properly. In essence, this is like identifying the genetic signature or fingerprint of a particular cancer.
Genomic testing can help doctors to:
- Determine a patient’s prognosis (potential outcome)
- Determine whether a cancer is aggressive/fast growing or slow growing
- Choose the most effective treatment for each individual cancer
- Monitor patients who are undergoing treatment to determine if the treatment is working
- Monitor patients who are in remission to catch a potential disease progression early when it is more treatable
Perhaps the greatest promise of genomic testing is its potential for individualizing treatment. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy that attacks a specific mutation or other cancer-related change in the DNA programming of the cancer cells can be developed or selected for treatment.
Not all cancer cells are alike. They may differ from one another based on what genes have mutations that are responsible for the growth of the cancer. Testing is performed to identify genetic mutations or the proteins they produce that drive the growth of the cancer. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells.
Because precision cancer medicine seeks to define the genomic alterations that are driving a specific cancer, rather than relying on a simple broad classification of cancer solely based on its site of there is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with cancer originating in the same tissue or organ, the behavior of the cancer and its response to treatment can vary widely.
Tissue biopsy-based tests are invasive, can have serious complications, are time-consuming, and the specimens are often inadequate to test for all the relevant mutations. A liquid biopsy test can be performed quicker and is performed on a blood sample avoiding the need to obtain a biopsy or tissue sample. Although not yet standard, liquid biopsies are increasingly used in the management of cancer.
It’s important to understand that genomic testing is different from genetic testing. Genetic tests are typically used to determine whether a healthy individual has an inherited trait (gene) that predisposes them to developing cancer. Genomic tests evaluate the genes in a sample of diseased tissue from a patient who has already been diagnosed with cancer. In this way, genes that have mutated, or have developed abnormal functions, are identified in addition to those that may have been inherited.
The Complete Blood Count & Other Blood Tests
Blood tests are used to measure the number of blood cells in circulation and the levels of chemicals, enzymes, proteins, and organic waste products that are normally found in the blood. The levels of blood cells, such as red blood cells, white blood cells and platelets, may be low in patients receiving treatment for cancer. Also, the levels of some chemicals normally found in the blood may be either too high or too low as a result of the cancer or its treatment. There are two types of blood tests typically performed during cancer treatment: the complete blood count (CBC) and a blood chemistry panel.
Complete Blood Count (CBC)
The CBC measures the levels of the three basic blood cells: red blood cells, white blood cells, and platelets. In the United States, the CBC is typically reported in the format shown in Table 1 below. It is important to understand not only which blood counts are being tested, but also how those results are reported. You will want to pay careful attention to the results column, which shows any results that are normal and the flag column, which shows any results that are abnormal.
Table 1: CBC with results and reference interval
White Blood Count
Red Blood Count
Result column: The result column shows counts that fall within the normal range.
Flag column: The flag column shows counts that are lower (“L”) or higher (“H”) than the normal range.
Reference interval (or reference range) column: The reference interval shows the normal range for each measurement for the lab performing the test. Different labs may use different reference intervals.
White blood cells: White blood cells help protect individuals from infections. The above CBC report shows that the patient’s total white cell count is 1.5, which is lower than the normal range of 4.0-10.5. The low white cell count increases the risk of infection.
Absolute neutrophil count: Neutrophils are the main white blood cell for fighting or preventing bacterial or fungal infections. In the CBC report, neutrophils may be referred to as polymorphonuclear cells (polys or PMNs) or neutrophils. The absolute neutrophil count (ANC) is a measure of the total number of neutrophils present in the blood. When the ANC is less than 1,000, the risk of infection increases. The ANC can be calculated by multiplying the total WBC by the percent of polymorphonuclear cells. For example, this patient’s ANC is 0.34, which equals (WBC) 1.5 x 23%.
Red blood cells: Red blood cells carry oxygen from the lungs to the rest of the body. The above CBC report indicates that the patient has a red cell count of 3.5, which is lower than the normal range of 4.70-6.10, and therefore, shown in the flag column.
Hemoglobin (Hb or Hgb): Hemoglobin is a protein in the red cell that carries oxygen. The above CBC report indicates that the patient’s Hb count is 10.8, which is below the normal range of 14.0-18.0. The hematocrit (HCT), another way of measuring the amount of Hb, is also low. This means that the patient has mild anemia and may be starting to notice symptoms.
Platelets: Platelets are the cells that form blood clots that stop bleeding. The above CBC report indicates that the platelet count for this patient is normal.
Blood Chemistry Panel: The blood chemistry panel measures the levels of chemicals, enzymes, and organic waste products that are normally found in the blood. The results of a blood chemistry panel are typically reported with the name of the substance, the result, and the reference interval, as shown in Table 2. The reference interval is the normal range for that laboratory. Reference intervals may vary between laboratories. Substances that are typically measured in cancer patients are as follows:
Table 2: Sample blood chemistry panel with results and reference interval
Lactate dehydrogenase (LDH)
Albumin is the most prevalent protein in the blood. It is synthesized in the liver and removed from circulation by the kidney, which causes it to be excreted in the urine. Albumin is often measured in order to detect liver damage or kidney damage, either of which may be a side effect of cancer or cancer treatment.
Alanine aminotransferase (ALT) is an enzyme in the liver that rearranges the building blocks of proteins. It is released from damaged liver cells. Cancer patients may experience liver damage as a side effect of some cancer treatments or due to spread of cancer to their liver. ALT may also be referred to as SGPT (serum glutamic pyruvic transferase.)
Aspartate aminotransferase (AST) is an enzyme in the liver that rearranges the building blocks of proteins. It is released from damaged liver cells. Cancer patients may experience liver damage as a side effect of some cancer treatments or due to spread of cancer to their liver. AST may also be referred to as SGOT (serum glutamic oxaloacetic transaminase.)
Alkaline phosphatase is an enzyme is that involved in bone growth. It is processed in the liver and excreted into the digestive tract in the bile. A higher than normal amount of alkaline phosphatase indicates bone or liver problems. In cancer patients, elevated alkaline phosphatase may indicate that cancer has spread to the bones or that liver damage, possibly due to some chemotherapy drugs, has caused problems with bile excretion.
Bilirubin is a substance that is formed from broken down red blood cells. It becomes part of bile, which is produced by the liver. A build-up of bilirubin can cause jaundice and may be measured to test for liver or bile duct function, which may be compromised if there is cancer in the liver or if there is liver damage. Some chemotherapy drugs may cause liver damage.
BUN (blood urea nitrogen) is a part of urea, the waste product that is left over from the breakdown of protein. Urea circulates in the blood until it is filtered out by the kidneys and excreted in the urine. If the kidneys are not functioning properly, there will be excess urea in the bloodstream, resulting in higher than normal BUN levels. Cancer patients may have elevated BUN if they have been treated with certain chemotherapy drugs that may cause kidney damage.
Calcium is a chemical that is necessary for muscle contraction, nerve function, blood clotting, cell division, healthy bones and teeth. An increased level of calcium in the bloodstream is a possible complication of cancer and is referred to as hypercalcemia. In its severe form, hypercalcemia may be a life-threatening emergency.
Chloride is a chemical that helps maintain fluid balance in the body. Low chloride levels may be caused by vomiting or diarrhea.
Creatinine is a compound that is produced by the body and excreted in the urine. Compounds that leave the body in the urine are processed by the kidney, therefore creatinine may be used to monitor for kidney function. Some cancer treatments may cause kidney damage.
Glucose is the simplest form of sugar that the body uses for energy. The body requires insulin to move sugar from the bloodstream into the cells for energy production. An abnormal glucose reading may signify a problem with insulin production, which occurs in the pancreas.
Lactate dehydrogenase (LDH) is involved in producing energy and is released from damaged cells in many areas of the body, including the heart and liver. Cancer patients may have an elevated LDH due to spread of cancer to their liver or damage to their liver from certain cancer treatments. For more information, go to Liver Damage. LDH is also considered a tumor marker, which is a substance that occurs at higher than normal amounts in the presence of cancer.
Magnesium is a chemical that is necessary for muscle contraction, nerve function, heart rhythm, bone strength, generating energy, and building protein.
Potassium is a chemical that regulates heart contraction and helps maintain fluid balance. Low sodium levels may be caused by vomiting or diarrhea.
Sodium is a chemical that helps maintain fluid balance and is necessary for muscle contraction and nerve function. Low sodium levels may be caused by vomiting or diarrhea.
Uric Acid is the end product of the digestion of certain proteins and is normally eliminated through the urine. Excess uric acid may be a side effect of some cancer treatments, and may lead to a condition called tumor lysis syndrome. When excess uric acid is present, it is converted to crystal. These crystals may be deposited in the tiny tubes that are part of the kidney and cause acute kidney damage, which can ultimately lead to kidney failure.
Additional results that are sometimes included in the blood chemistry panel are measures of the blood’s clotting capacity. Some cancer treatments reduce the number of platelets in circulation, which can cause the blood to clot more slowly so that the patient is more susceptible to excessive bleeding.
Table 3: Measures of the blood’s clotting capacity
Prothrombin time (PT)/INR
Activated Partial Thromboplastin Time (aPTT) is a measure of bleeding and clotting and is used to evaluate unexplained bleeding or monitor heparin treatment. Heparin is a drug that is administered to increase the clotting capacity of a patient’s blood. Some cancer patients may receive heparin as treatment for a low platelet count, or thrombocytopenia, which is a side effect of some cancer treatments. This condition can lead to more easy bruising and bleeding.
Prothrombin time (PT) is the most common way to express the clotting capacity of blood. PT results are reported as the number of seconds the blood takes to clot when mixed with a thromboplastin reagent. The International Normalized Ratio (INR) was created by the World Health Organization because PT results can vary depending on the thromboplastin reagent used. The INR is a conversion unit that takes into account the different sensitivities of thromboplastins. The INR is widely accepted as the standard unit for reporting PT results. Cancer patients may have an abnormally low PT/INR due to a lower than normal platelet count. Platelets are the components of blood that stop bleeding by clotting the blood. A low platelet count, also called thrombocytopenia, and a low PT may lead to more frequent bruising and bleeding.
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