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Diagnosis

Diagnosis of a disease is different from its detection. Cancer is detected when symptoms or abnormalities, such as a lump or growth, are recognized by a patient or doctor. But even after it is detected, it needs careful diagnosis. Effective diagnostic testing is used to confirm or eliminate the presence of disease, monitor the disease process, and to plan for and evaluate the effectiveness of treatment. A diagnosis is an identification of a particular type of cancer. When making a diagnosis, the initial signs and symptoms are investigated through a variety of tests in order to identify whether cancer is causing them and, if so, what type of cancer it is.

There is no single test that can accurately diagnose cancer. The complete evaluation of a patient usually requires a thorough history and physical examination along with diagnostic testing. Many tests are needed to determine whether a person has cancer, or if another condition (such as an infection) is mimicking the symptoms of cancer. In some cases, it is necessary to repeat testing when a person’s condition has changed, if a sample collected was not of good quality, or an abnormal test result needs to be confirmed.

Diagnostic procedures for cancer may include imaging, laboratory tests (including tests for tumor markers), tumor biopsy, endoscopic examination, surgery, or genetic testing.

Step 1: Medical history and physical exam

If you're experiencing signs or symptoms that may indicate cancer, a doctor typically starts by asking about your medical history and giving you a physical examination. Medical information that your doctor may ask about may include detailed accounts of:

  • Your current health, including any current physical complaints
  • Your past health, including prior medical conditions
  • Your family's history of illness, including cancer
  • Any environmental exposures that might have put you at risk of cancer
  • A physical exam allows the doctor to further evaluate your overall health and may help him to assess the spread of the disease. The doctor may examine your entire body or focus on areas of concern.

Step 2: Investigative Procedures

Diagnosing cancer involves the use of a variety of tests that provide details about the abnormality, which may have been detected through routine medical check-up, through self-examination or reported symptoms. Human body as we know is made of small building blocks called cells. The cells perform various functions to keep us healthy. They often multiply for growth and repair of tissues. Normally cell growth or multiplication is balanced by cell loss or cell death. Cancer is a group of diseases characterized by uncontrolled growth and spread of cells. More information about these cells must be gathered in order to identify them as malignant (cancerous) or non-malignant (non-cancerous), and if they are malignant, to determine how serious (aggressive) the particular cancer cells are. Aggressive cancers grow and spread more quickly than less-aggressive or “indolent” cancers.

There are many types of laboratory tests specifically designed to evaluate cancer which can be broadly categorized as:

  • A Histopathology / Cytopathology report is based on observation of abnormal cells seen under a microscope.
  • Blood tests measure substances in the blood that may indicate how advanced the cancer is or other problems related to the cancer.
  • Diagnostic imaging involves visualization of abnormal masses using high tech machines that create images, such as x-rays, computed tomography (CT), positron emission test (PET), magnetic resonance imaging (MRI), and combined PET/CT.
  • Tumor marker tests detect substances in blood, urine, or other tissues that occur in higher than normal levels with certain cancers.
  • Genetic Markers in which special laboratory evaluation of DNA involving the identification of the genetic make-up—the DNA—of the abnormal cells is done.

The correct diagnosis is necessary in order to determine treatment. In addition to a complete medical history and physical examination, diagnostic procedures for cancer may include one or more of the following common laboratory tests:

A) Laboratory Tests

Clinical chemistry uses chemical processes to measure levels of chemical components in body fluids and tissues. The most common specimens used in clinical chemistry are blood and urine. If your medical history and physical exam suggest the need for further testing, your doctor may use blood and urine tests to help rule out or diagnose disease. Small amounts of blood and urine are collected and then, in a laboratory, are analyzed for abnormalities.

Blood is typically obtained from one of your veins — such as a vein inside your forearm — by using a thin needle inserted through your skin. In some instances, blood may be obtained by pricking your fingertip. For a urine test, you collect a urine sample in a small container.

Afterward, your blood and urine are tested in a lab. If the doctor finds abnormal types of cells or cancer cells, too many or too few cells, or if any of various other substances are detected, it may indicate cancer. For example, if you have leukemia — a blood cancer — cancerous white blood cells can be seen under a microscope.

Blood Analysis: A complete blood count (CBC) measures the size, number, and maturity of the different blood cells in a specific volume of blood. This is one of the most common tests performed. Abnormal cells may indicate cancer. Variation in the normal number, size, and maturity of cells may indicate a problem. Red blood cells are important for carrying oxygen and fighting anemia and fatigue; the hemoglobin portion of the CBC measures the oxygen carrying capacity of the red blood cells while the hematocrit measures the percentage of red blood cells in the blood. White blood cells fight infection. Increased numbers of white blood cells, therefore, may indicate the presence of an infection. However white blood cells in excess may indicate leukemia.  Platelets prevent the body from bleeding and bruising easily.

A variety of blood tests are used to check the levels of substances in the blood that indicate how healthy the body is and whether infection is present. For example, blood tests revealing elevated levels of waste products, such as creatinine or blood urea nitrogen (BUN), indicate that  either the kidneys are not working efficiently to filter those substances out ( i.e. a renal disease) or these substances are being produced in excess in the body. Other tests check the presence of electrolytes - chemical compounds such as sodium and potassium that are critical to the body's healthy functioning. Coagulation studies determine how quickly the blood clots and gives the status of the coagulation factors in the body.

Urine analysis: Urinalysis tests the components of urine to check for the presence of drugs, blood, protein, and other substances. Blood in the urine (hematuria) may be the result of a benign (noncancerous) condition, but it can also indicate infection of the urinary system or other problem. High levels of protein in the urine (proteinuria) may indicate a kidney or cardiovascular problem.

Spinal Tap / Lumbar puncture: A procedure to evaluate the fluid around the spine and brain for pressure and/or infection and to detect any abnormal cells. A special needle is placed into the lower back, into the spinal canal. This is the area around the spinal cord. Cerebral spinal fluid CSF is the fluid that bathes your brain and spinal cord. The pressure in the spinal canal and brain can then be measured. A small amount of CSF can be removed and sent for testing to determine if there is an infection or other problem.

Tumor markers: Tumor markers are substances either released by cancer cells into the blood or urine or substances created by the body in response to cancer cells. Tumor markers are used to evaluate how well a patient has responded to treatment and to check for tumor recurrence. Research is currently being conducted on the role of tumor markers in detection, diagnosis, and treatment of cancers.

Tumor markers are useful in identifying potential problems, but they must be used with other tests for the following reasons:

  • People with benign conditions may also have elevated levels of these substances in their blood.
  • Not every person with a tumor has tumor markers.
  • Some tumor markers are not specific to any one type of tumor.

The following is a brief description of some of the more useful tumor markers:

CA 125 – Ovarian cancer is the most common cause of elevated CA 125, but cancers of the uterus, cervix, pancreas, liver, colon, breast, lung, and digestive tract can also raise CA 125 levels. Several noncancerous conditions can also elevate CA 125. CA 125 is mainly used to monitor the treatment of ovarian cancer.

Prostatic Acid Phosphatase (PAP) – PAP originates in the prostate and is normally present in small amounts in the blood. In addition to prostate cancer, elevated levels of PAP may indicate testicular cancer, leukemia, and non-Hodgkin’s lymphoma, as well as some noncancerous conditions.

Prostate-specific Antigen (PSA) – Prostate-specific antigen is always present in low concentrations in the blood of adult males. An elevated PSA level in the blood may indicate prostate cancer, but other conditions such as benign prostatic hyperplasia (BPH) and prostatitis can also raise PSA levels. PSA levels are used to evaluate how a patient has responded to treatment and to check for tumor recurrence.

Carcinoembryonic Antigen (CEA) – CEA is normally found in small amounts in the blood. Colorectal cancer is the most common cancer that raises this tumor marker. Several other cancers can also raise levels of carcinoembryonic antigen.

Human Chorionic Gonadotropin (HCG) – HCG is another substance that appears normally in pregnancy and is produced by the placenta. If pregnancy is ruled out, HCG may indicate cancer in the testis, ovary, liver, stomach, pancreas, and lung. Marijuana use can also raise HCG levels.

Alpha-Fetoprotein (AFP) – Alpha-fetoprotein is normally elevated in pregnant women since it is produced by the fetus. However, AFP is not usually found in the blood of adults. In men, and in women who are not pregnant, an elevated level of AFP may indicate liver cancer or cancer of the ovary or testicle. Noncancerous conditions may also cause elevated AFP levels.

CA 19-9 – This marker is associated with cancers in the colon, stomach, and bile duct. Elevated levels of CA 19-9 may indicate advanced cancer in the pancreas, but it is also associated with noncancerous conditions, including gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis.

CA 15-3 – This marker is most useful in evaluating the effect of treatment for women with advanced breast cancer. Elevated levels of CA 15-3 are also associated with cancers of the ovary, lung, and prostate, as well as noncancerous conditions such as benign breast or ovarian disease, endometriosis, pelvic inflammatory disease, and hepatitis. Pregnancy and lactation also can raise CA 15-3 levels.

CA 27-29 – This marker, like CA 15-3, is used to follow the course of treatment in women with advanced breast cancer. Cancers of the colon, stomach, kidney, lung, ovary, pancreas, uterus, and liver may also raise CA 27-29 levels. Noncancerous conditions associated with this substance are first trimester pregnancy, endometriosis, ovarian cysts, benign breast disease, kidney disease, and liver disease.

Lactate Dehydrogenase (LDH) – LDH is a protein that normally appears throughout the body in small amounts. Many cancers can raise LDH levels, so it is not useful in identifying a specific kind of cancer. Measuring LDH levels can be helpful in monitoring treatment for cancer. Noncancerous conditions that can raise LDH levels include heart failure, hypothyroidism, anemia, and lung or liver disease.

Neuron-specific Enolase (NSE) – NSE is associated with several cancers, but it is used most often to monitor treatment in patients with neuroblastoma or small cell lung cancer.

Abnormal levels of the chemical components in blood and/or urine, higher than normal levels of certain antigens, proteins and other substances (tumor markers) in your blood or urine also might suggest the presence of cancer. However, tumor marker test results need to be interpreted carefully, as noncancerous conditions also can cause abnormal results.

B) Diagnostic Imaging

Diagnostic imaging tools, such as X-ray and magnetic resonance imaging (MRI), allow your doctor to create pictures of your bones, organs and other areas inside your body. These images can help your doctor determine whether you have a tumor, where in your body it's located, how large it is and if it has spread. Your doctor determines which areas of your body to examine and which tests to use based on your particular situation. Commonly used imaging techniques include:

X-ray – X-rays use invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film. X-rays may be taken of any part of the body to detect tumor (or cancer) cells. X-rays are often used to examine cancers of the lungs, intestines, stomach, kidneys and breasts.

Ultrasound (Also called Sonography) – This technology bounces high-frequency sound waves off tissues in the body to create images of blood vessels, tissues, and organs on a small monitor that looks like a television screen. They are used to view internal organs as they function, and to assess blood flow through various vessels. Ultrasound is helpful in diagnosing cancers found in soft tissues. Tumors in the abdomen, liver, and kidneys can often be seen with an ultrasound.

Computerized Tomography – CT or CAT Scan uses a combination of x-rays and computer technology to produce cross-sectional images (often called slices), both horizontally and vertically, of the body including the bones, muscles, fat, and organs. CT scan can pinpoint a tumor or infection deep in the brain, abdomen or chest and is the best way to evaluate the lungs for evidence of tumor spread. CT scans are also used to examine your liver, pancreas, adrenal glands and bones.

Magnetic Resonance Imaging – Like computerized tomography, MRI also gives a detailed glimpse inside the body. It uses a combination of large magnets, radiofrequencies, and a computer to produce detailed images of organs and structures within the body. MRI uses an much stronger magnet than X-rays. In some cases, MRI can even be more sensitive than CT. MRI is often used to detect cancer of the brain, spinal cord, head and neck, liver and soft tissues.

Radionuclide Scanning – In a radionuclide scan, your doctor injects a small, safe amount of radioactive material into your bloodstream. All of your tissues and bones absorb some of this material. Tumors may absorb more or less of it, however, and appear different from surrounding, healthy tissue. Radionuclide scans can help your doctor locate tumors, particularly of your bones or thyroid.

Positron Emission Tomography – PET is a type of radionuclide scan in which your doctor injects a small amount of a radioactive tracer — typically a form of glucose — into your body. All tissues in your body absorb some of this tracer, but tissues that are using more energy, including tumors, absorb greater amounts, allowing them to be seen on the scan. Doctors use PET scans to determine the location of a tumor and see if it has spread.

Lymphangiogram (LAG) - an imaging study that can detect cancer cells or abnormalities in the lymphatic system and structures. It involves a dye being injected into the lymph system.

Bone Scans - pictures or x-rays taken of the bone after a dye has been injected that is absorbed by bone tissue. These scans are used to detect tumors and bone abnormalities.

Single Photon Emission Computed Tomography – Similar to a PET scan, the SPECT scan uses radioactive tracers to help spot cancer in your body. The tracers used in a SPECT scan contain antibodies that stick to tumors. Those spots show up on the scan. SPECT scans are used to spot metastases — cancers that have spread.

Keep in mind that all cancers can't be seen through imaging. For instance, a tumor may be too small or in a location that's difficult to see. Other tests may prove more useful in these instances.

C) Biopsy

A biopsy — the removal of a sample of tissue for study, generally under a microscope — is always necessary to make a cancer diagnosis. Sample tissue may be removed by using techniques that commonly include:

Needle Biopsy – Your doctor uses a thin needle and a syringe to remove small pieces of tissue from a tumor. Two types of needle biopsy exist — fine-needle aspiration cytology (FNAC) and core biopsy. These procedures are essentially the same, but core biopsy involves using a slightly larger needle to remove a small, solid core of tissue. Any tissue can be biopsied, including the liver, lung, brain and bone marrow.

Endoscopic Biopsy – Your doctor inserts a thin, flexible tube (endoscope) into a natural opening in your body, such as your rectum or mouth and throat. The endoscope contains a fiber-optic light and a video camera at its tip. The camera lens transmits images to an external monitor so that your doctor can look closely at areas inside your body. If the doctor sees abnormal looking tissue, he or she can insert instruments through the endoscope to remove sample tissue

Surgical Biopsy – Your doctor makes an incision through your skin and removes either an entire tumor (excisional biopsy) or a portion of a tumor (incisional biopsy). In some cases you may only need local anesthesia. Other times, such as when a tumor is inside your chest, your doctor may use general anesthesia.

Bone Marrow Biopsy – Bone marrow aspiration and/or biopsy - a procedure that involves taking a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (called a core biopsy), usually from the hip bones, to be examined for the number, size, and maturity of blood cells and/or abnormal cells.

After your doctor obtains a tissue sample, it's generally chemically treated and sliced into very thin sections. These sections are placed on glass slides, stained — to enhance contrast — and studied under a microscope by a person who specializes in examining body tissues (pathologist) or a specialist in blood and blood-forming tissues (hematologist), or both. This allows your doctor to determine exactly where the cancer came from.

Biopsy also helps your doctor determine the cancer's grade — an assigned number on a scale of one to four that refers to the appearance of cancer cells under the microscope. Grade 1 cancers are generally the least aggressive and grade 4 cancers, the most aggressive. This information may help guide treatment options.

Step 3: Diagnosis determines Treatment

A combination of pathological assessment (laboratory evaluation using a microscope) and diagnostic imaging and other investigations are used not only to identify the type of cancer but also it’s its stage, and then the treatment.

Stage indicates how extensive the cancer is and how much it has spread. Staging usually involves determining the size of the primary tumor and evaluating whether it has remained in the tissue in which it started, whether it has invaded other nearby organs or tissues, and whether cancer cells have spread to distant locations in the body. The cancer is then assigned a stage on a predetermined scale of numbers and letters, for example stage I, II, IIIa, IIIb, IV, etc. The higher number and letter combination indicates more extensive spread, and therefore a more serious condition. Treatment is often selected based on the stage of disease. Higher stage cancers typically receive very aggressive treatments and lower stage disease less aggressive treatment.

Cancer Staging

With the information gathered during tests such as imaging and biopsy, your doctor then determines the stage of your cancer. Staging is a system of classifying information about cancer, including the size of your tumor, how much it has spread in your body and to where it has spread. Roman numerals between 0 and IV are used to describe stages — 0 being least advanced and IV being the most advanced. Your doctor uses this information to determine what treatment you need and to evaluate how your cancer might progress. For example, if you have an advanced cancer, you might choose a more aggressive treatment than would someone with an early-stage cancer.

Following a diagnosis of cancer, the most important step is to accurately determine the stage of cancer. Stage describes how far the cancer has spread. (Some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to know the correct stage of your cancer.

There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, lower the stage, better the treatment prognosis (outcome).

Stage 0 – precancer
Stage 1 – small cancer found only in the organ where it started
Stage 2 – larger cancer that may or may not have spread to the lymph nodes
Stage 3 – larger cancer that is also in the lymph nodes
Stage 4 – cancer in a different organ from where it started

However, research has indicated that identifying the stage of disease may not be the most accurate technique for determining how aggressive it is. For example, some early stage diseases may recur or progress even after treatment, while some late stage cancers may stay in remission. These findings suggest that there may be factors other than how the cancer looks under a microscope and how far it has spread at the time of diagnosis that may better indicate the likelihood that a given cancer will recur and/or progress.

How is prognosis determined?

The probable course and/or outcome of the cancer is called the prognosis. Identifying factors that indicate a better or worse prognosis may help you and your doctor plan your treatment. Your doctor will evaluate all possible factors to determine your prognosis, which include:

  • Your age
  • Your level of physical fitness
  • Size of your cancer
  • Stage of your cancer
  • Aggressiveness of your cancer (cancer cells that are growing and dividing rapidly are considered more aggressive)

Human genomics, which is the study of the entire genetic material of humans, has provided invaluable tools for identifying the genetic components of cancers. The mapping of the human genome, which consists of 30,000 to 70,000 genes, has laid the ground work for understanding the role those genes play in human health and disease. Cancer is many different diseases; however, one aspect of all cancers that is similar is damage to the DNA resulting in uncontrolled cell growth. Identifying the genes for each cancer type that are involved in the capacity growth and spread may provide valuable prognostic information.

Recently, the genetic make-up of cancer is being increasingly recognized as an important prognostic factor. For example, some genes have been associated with an aggressive course or tendency to recur. Identification of these in an early stage cancer may indicate a poor prognosis. Some research suggests that the genetic make-up of cancer may be even more important for determining prognosis than the stage of cancer.

As improvements are made in the special laboratory techniques used to identify the genetic make-up of cancers, this genetic information may become a better predictor of cancer aggressiveness and outcome than stage, which has been the diagnostic indicator of choice in the past. Additionally, this genetic information will likely play an increasing role in directing treatment. Specifically, the genes involved in each cancer may indicate more aggressive treatment for some cancers and less aggressive treatment for others.

 
 
 
     
 
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