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| Testing Biopsy and Cytology Specimens for Cancer |
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Waiting out a possible cancer diagnosis can be a very stressful experience. A better understanding of the tests doctors use to diagnose cancer may relieve some of your stress. Learning about this process can also help you understand how these tests affect treatment options, and can help you work together with your doctors to make informed decisions about your diagnosis and treatment.
Much of the testing process takes place "behind the scenes." You will have a chance to meet and ask questions of your surgeon, medical oncologist, radiation oncologist, oncology nurses, and many other members of the cancer care team. You will be able to see at least parts of what these professionals do. On the other hand, you rarely meet the pathologists, histotechnologists, cytotechnologists, and medical laboratory technologists whose work leads to a diagnosis of malignant (cancerous) or benign (noncancerous).
This essay follows a tissue or cell sample along the diagnostic process, starting with the biopsy (removal of a tissue sample) procedure. It then explains what is done to the sample in the laboratory during the testing process. Finally, this document explains what type of information the pathology report contains, the impact of the information in making treatment decisions, and definitions of some of the medical terms used in these reports.
How Is Cancer Diagnosed?
A diagnosis of cancer is nearly always based on examination of cell or tissue samples under a microscope. The procedure that takes a sample for this testing is called a biopsy, and the tissue sample is called the biopsy specimen. The testing process is sometimes referred to as pathology.
Although lumps that might be malignant (cancerous) can be detected by imaging (radiology) studies or felt as masses during a physical examination, they nonetheless must be sampled and examined under a microscope to determine their exact nature. Not all lumps are malignant. In fact, most tumors are benign. A cancerous tumor is able to spread into surrounding tissues and even to distant parts of the body. A benign tumor does not have this capability.
Types of Tissue and Cell Samples
Tissue or cell samples can be removed from almost any part of the body. The actual procedures used will depend on the location of the tumor and what type of cancer is suspected. For instance, the procedures for skin biopsies clearly need to be different from the procedures for brain biopsies. And, there are several types of skin biopsy procedures. Doctors choose the one best suited to the type of skin tumor suspected. While shave biopsies that remove the outer layers of skin are fine for some basal cell or squamous cell skin cancers, they are not recommended for suspected melanomas of the skin. Punch biopsies or excisional biopsies remove deeper layers of the skin, and can determine how deeply a melanoma has penetrated the skin -- an important factor in selecting treatment for that type of cancer.
Overview of biopsy types
Some types of biopsies involve operations to remove an entire organ, and are done only by surgeons. Other types of biopsies are less invasive and may remove tumor samples through a thin needle or through an endoscope (a flexible lighted tube). These biopsies are sometimes performed by surgeons, but can also be done by other doctors such as radiologists, oncologists, pulmonologists (lung specialists), gastroenterologists (digestive system specialists) or pathologists. The most common biopsy types used in cancer diagnosis are discussed in this section. For more complete information, refer to the diagnosis section of American Cancer Society documents on specific types of cancer.
Needle biopsy: The 2 types of needle biopsies are fine needle biopsies and core needle biopsies. Fine needle aspiration (FNA) uses a very thin needle and a syringe to withdraw a small amount of fluid and very small pieces of tissue from the tumor mass. The doctor can aim the needle while feeling a suspicious tumor or area near the surface of the body. If the tumor is deep inside the body and cannot be felt, the needle can be guided while it is viewed by imaging procedures such as an ultrasound or a computed tomography (CT) scan. The main advantage of FNA is that it does not require an incision (cutting through the skin). The disadvantage is that in some cases this needle cannot remove enough tissue for a definite diagnosis. Although FNA is a type of biopsy, it is also classified as a cytology test (see next section).
The needles used for a core biopsy are slightly larger than those used in FNA. They remove a small cylinder of tissue (about 1/16 inch in diameter and 1/2 inch long). The core needle biopsy is done using local anesthesia (numbing medication) in the doctor's office or clinic. Like FNA, a core biopsy can sample tumors felt by the doctor as well as smaller ones viewed by imaging studies.
Excisional or incisional biopsy: A surgeon cuts through the skin to remove the entire tumor (excisional biopsy) or a small part of a large tumor (incisional biopsy). This often can be done using local anesthesia or regional anesthesia (numbing medication). If the tumor is inside the chest or abdomen, general anesthesia is used (the patient is asleep).
Endoscopic biopsy: This procedure is done using a thin, flexible lighted tube with a viewing lens or a video camera. If a video camera is used, it is connected to a screen that allows the doctor to clearly see any masses in the area. The endoscope can be passed through natural body openings to view suspicious areas in the gastrointestinal tract, genitourinary tract, and the respiratory tract. Advantages of endoscopy include the opportunity to see the cancer directly and the ability to take a tissue sample through the endoscope to determine if cancer is present and, if so, the cell type.
Laparoscopy and thoracoscopy: Laparoscopy is similar to endoscopy but is used to examine the contents of the abdomen and remove tissue samples. The tube is passed through a small incision in the abdomen. A similar procedure to view the inside of the chest is called thoracoscopy.
Laparotomy and thoracotomy: A laparotomy is a surgical technique that involves an incision into the abdomen, usually a midline incision from upper to lower abdomen. This may be done when there is uncertainty about a suspicious area that cannot be diagnosed by less invasive tests. During the laparotomy, a biopsy of a suspicious area can be done and an assessment can be made about the location, size, and involvement of surrounding areas. General anesthesia is used for this technique. A similar operation, which examines inside the chest is called thoracotomy.
Overview of cytology types
Diagnosis of diseases based on examination of individual cells and small clusters of cells, called cytology or cytopathology, has become increasingly important in cancer diagnosis over the past few decades. While the pieces of tissue in biopsy samples may be as small as 1/16 inch or much larger (several inches), the individual cells and the cell clusters in cytology samples are placed in fluid and are usually too small to see without a microscope. Sometimes, as in some FNA samples, only one drop of blood or tissue fluid is taken. On the other hand, some pleural fluid or peritoneal fluid cytology samples may include a quart or more of fluid.
A cytology specimen usually is easier to obtain, causes less discomfort to the patient, is less likely to result in serious complications, and is less expensive than a tissue biopsy. The disadvantage is that, in some situations, a biopsy result is more accurate. In many clinical situations, however, the accuracy is the same. Sometimes, an excisional biopsy is the only treatment needed to remove a cancer -- an obvious advantage. In other situations, a cancer might be better treated by chemotherapy or radiation therapy, and surgery might be done after these treatments. In such cases, excisonal biopsy would not be the best choice and a cytology sample, endoscopic biopsy, or incisional biopsy would be a good idea. As you can see, choices of tests are not simple -- the doctors consider many factors in the context of the specific type of cancer suspected and what organ is affected.
Cytology tests may be used in two ways -- for diagnosis or for screening. Diagnostic tests are used for people who have signs, symptoms, or some other indication that a particular disease such as cancer is likely to be present. The purpose of a diagnostic test is to determine if a disease is present and, if so, to classify it precisely and accurately. A screening test is used to identify people who might have a certain disease even before they develop symptoms of that condition. A screening test is expected to identify nearly all people who are likely to have the disease, but it does not conclusively prove that the disease is present. Therefore, a diagnostic test is used if a screening test is positive. Some cytology tests, such as the Pap test, are mainly used for screening but, in many cases can accurately identify cancers. Nonetheless, a biopsy is generally done to confirm abnormal findings of a Pap test before treatment, such as surgery, is started.
Fine needle aspiration biopsy (FNA): FNA is sometimes considered a cytology test and is sometimes called a biopsy. It is discussed in this document in the previous section "Overview of Biopsy Types."
Body cavity fluids: This term refers to fluid from cavities and spaces in the body. These fluids can be tested to see if cancer cells are present. Some of the body cavity fluids tested in this way include:
- Urine
- Sputum (phlegm)
- Spinal fluid, also known as cerebrospinal fluid or CSF (from the space surrounding the brain and spinal cord)
- Pleural fluid (from the cavity around the lungs)
- Pericardial fluid (from the sac surrounding the heart)
- Ascitic fluid, also known as ascites or peritoneal fluid (from the abdominal or peritoneal cavity)
Scrape or brush cytology: Another cytology technique is to gently scrape or brush some cells from the organ or tissue being tested. The best-known cytology test that samples cells by scraping or brushing is the Pap test. Pap test samples are taken by using a small spatula and/or brush to remove cells from the cervix (lower part of the uterus or womb). Other areas that can be brushed or scraped include the esophagus, stomach, bronchi (breathing tubes that lead to the lungs), and mouth.
What Happens to Biopsy and Cytology Specimens After They Are Removed From the Patient?
Routine biopsy processing
Standard procedures and methods are applied to nearly all types of biopsy samples. Additional procedures, which are described later in this document, may also be performed on certain types of samples (such as lymph nodes and bone marrow). After the biopsy specimen is obtained by the doctor, it is placed in a container with formalin (a combination of water and formaldehyde) or another preservative fluid. The container is labeled to indicate the patient's name and other identifying information (hospital number and birthdate, for example), site of biopsy (exactly where on the body it was taken from), and then sent to the pathology laboratory with a pathology requisition form. The requisition form also identifies who submitted the biopsy, the date of the biopsy procedure, and pertinent clinical history (information about the patient's symptoms, other abnormal test results, and what type of disease the doctor expects the biopsy may show). Next the pathologist or an assistant examines the specimen without a microscope. The appearance of the sample before further processing is called the "gross description" and includes the tissue sample's size, color, consistency, and other characteristics. The specimen may even be photographed for documentation.
The gross examination is important since the pathologist often recognizes features suspicious for malignancy. This will determine which parts of a large biopsy are the most critical to study under a microscope. For small biopsies, for example, a punch biopsy of skin or a core needle biopsy of any site, the entire specimen is examined under a microscope. The tissue to be examined microscopically is placed into small containers called cassettes. The cassettes hold the tissue securely while it is processed, and prevents small samples from getting lost during that process. After processing, which may take a few hours but is usually done overnight, the tissue sample is placed into a mold with hot paraffin wax. The wax cools to form a solid block that protects the tissue. This paraffin wax block with the embedded tissue is placed on an instrument called a microtome, which the histotechnologist uses to cut very thin slices of the tissue. These thin slices of the specimen are placed on glass slides, and dipped into a series of stains or dyes to alter the color of the tissue, making its appearance more distinctive when viewed under a microscope. For most biopsy specimens, routine processing as described above is all that is technically required. At this point (usually the day after the biopsy was performed), the pathologist examines the tissue under a microscope.
Intraoperative consultation (Frozen section)
Sometimes a surgeon needs information about a tissue sample during surgery, so that decisions can be made about immediate surgical treatment. The surgeon cannot wait until the next day as is the case for routine biopsies. He or she will request an intraoperative (during surgery) pathology consultation. This consultation is often called a frozen section examination.
When a frozen section examination is performed, fresh tissue is sent from the operating room directly to the pathologist. Because the patient is often under general anesthesia it is important that a frozen section examination be completed as quickly as possible. This usually takes 10 to 20 minutes. The fresh tissue is grossly examined by the pathologist to decide which part of the tissue sample should be examined under the microscope. Instead of processing the tissue in wax blocks, the tissue is quickly frozen in a special solution, forming what looks like an ice cube around the tissue sample. It is then thinly sectioned (sliced) on a refrigerated microtome, quickly stained (dipped in a series of dyes), and examined under the microscope. Although the frozen sections usually do not display features of the tissue as clearly as sections of tissue embedded in wax, they are usually clear enough for an interpretation that helps the surgeon decide what type of operation, if any, is best for the patient.
Frozen sections are often used to evaluate how completely a cancer has been removed. For example, if a lobe of a lung is removed due to cancer, the surgeon will want to know whether the bronchial (breathing tube) margin surrounding the remaining tissue which remains of that lobe is cancer-free. A slice of the surgical margin tissue surrounding the cancer is then submitted for a frozen section diagnosis. If there is no cancer, no further surgery is necessary. But, if cancer cells are found, the surgeon will remove more tissue, in order to reduce the likelihood of cancer growing back.
Intraoperative consultations do not always provide a definite answer. In some cases, a piece of tissue will require routine or even special processing to arrive at a clear answer. In such cases, the surgeon will usually close the surgical incision. When the results are available in a few days, another operation may be needed.
Cytology specimen processing
Processing of cytology specimens depends greatly on their type. Some specimens are smeared directly on glass microscope slides by the doctor who obtains the sample. The slides are then sent to the cytology laboratory where they are dipped into a series of stains (colored dyes), similar to those used for biopsy samples. Other specimens, such as body cavity fluids, cannot be easily placed on a glass microscope slide by the doctor because they are too dilute (too few cells are present in a large volume of fluid). Several methods are used in cytology lab's to concentrate the cells on a glass slide before staining. After processing and staining, the samples are examined under a microscope by a cytotechnologist, who will identify any abnormal cells and mark their location with a special pen. A pathologist will then review the marked cells and decide on a diagnosis.
What do doctors look for under the microscope?
General principles: Over a hundred years ago, scientists realized that various tissues and organs look different when viewed under a microscope. This is because they are formed by different cell types and because the cells are arranged differently. Even more importantly, it was discovered that the usual appearance of each type of tissue or organ is changed by certain diseases such as cancer. During the past century, this science, known as pathology, has been greatly refined.
Most tissue and cell samples are examined by pathologists (doctors who specialize in diagnosing diseases by laboratory tests). Sometimes, other doctors will also examine specimens or tissues of organs related to their area of expertise. For example, hematologists often examine blood and bone marrow samples from their patients, and some dermatologists will examine their patients' skin biopsy specimens.
The details of how doctors distinguish normal tissue from cancer, and recognize the different types of cancer, are the subject of many thousands of pages of medical textbooks and journals. Some features that doctors look for under a microscope are important only when found in 1 or 2 types of tissue, while others will be more important if found in almost all tissues. There a few general concepts that can be explained in nontechnical terms and can help you to better understand how doctors determine if cancer is present.
- The overall size and shape of cancer cells are often abnormal. They may be either smaller or larger than normal cells. Normal cells often have characteristic shapes that help them perform specific roles in the body. Cancer cells usually do not function in a useful way and their shapes are often distorted. Unlike normal cells that tend to have the same size and shape, cancer cells often are quite variable in their sizes and shapes.
- The size and shape of the nucleus of a cancer cell is often abnormal. The nucleus is the center of the cell that contains the cell's DNA (deoxyribonucleic acid). The nucleus is surrounded by cytoplasm. Some types of cells can be imagined as looking like a fried egg, in which the central yolk represents the nucleus and the surrounding white is the cytoplasm (this is only a way of imagining cells, and does not truly reflect cell composition). Cancer cells typically have a nucleus that is larger than that of a normal cell. And, like the overall cell size and shape, the size and shape of the cell nucleus is generally similar among normal cells of each tissue but can vary greatly among cancer cells. Another feature of the nucleus of a cancer cell is that it appears darker when viewed under a microscope after being stained with certain dyes. The larger size and darker shade of many cancer cells is due to the fact that they often contain too much DNA.
- Cancer cells do not relate to each other normally. Normal tissues are formed by a very orderly arrangement of cells. The arrangement of normal cells reflects the function of each tissue. For instance, cells of some glands form ducts that carry substances secreted by the cells to other parts of the tissue. Breast tissue is organized into lobules, which, during breast-feeding can produce milk, and ducts that carry milk from the lobules to the nipple. Cells of the stomach also form glands, to produce enzymes, acid, and mucus that digest the food and protect the stomach lining from digesting itself. When cancers develop in the breast, stomach, and many other tissues, the cancer cells do not form glands as they should. Sometimes the cancer cells form abnormally distorted glands and sometimes they form cell clumps that do not resemble glands at all. Another feature that reflects the abnormal interactions among cancer cells is that cancer cells invade other tissues. Normal cells stay where they belong within a tissue, while the ability of cancer cells to invade reflects the fact that their growth and movement is not coordinated with their neighboring cells. This ability to invade is how cancer spreads to and damages nearby tissues. And, unlike normal cells, cancer cells can metastasize (spread through blood vessels or lymph vessels) to distant parts of the body. Knowing this helps doctors recognize cancers under a microscope, because finding cells where they don't belong is a useful clue that they might be cancerous.
Classification of various types of cancer: There are several basic kinds of cancers, which doctors can further classify into hundreds or even thousands of types, based on their appearance under a microscope. Cancers are named according to which type of normal cells and tissues they most closely resemble. For example, cancers that resemble glandular tissues are called adenocarcinomas. Other cancers that resemble certain immune system cells are called lymphomas, and those that look like bone or fat tissue are osteosarcomas and liposarcomas, respectively.
Grading a cancer: In addition to identifying the cell type or tissue a cancer resembles, doctors determine how close that resemblance is -- the grade of the cancer. Cancers that look more like normal tissues are called low grade and those that do not resemble normal tissues are high grade. A high grade cancer tends to grow and spread more quickly than a low grade cancer. Patients with high grade cancers tend to have a poorer prognosis (outlook for survival).
Special studies in cancer diagnosis
Although the type and grade of a cancer is usually apparent when it is viewed under a microscope after routine processing and staining, this is not always the case. Sometimes the pathologist may need additional laboratory methods to make a diagnosis.
Histochemical stains: These tests use a variety of chemical dyes that are attracted to certain substances found in some types of cancer cells. An example is the mucicarmine stain, which is attracted to mucus. Droplets of mucus inside a cell that are exposed to this stain will appear pink-red under a microscope. This stain is useful if the pathologist suspects, for example, an adenocarcinoma (a glandular type of cancer) in a lung biopsy. Adenocarcinomas can produce mucus, so finding pink-red spots in lung cancer cells will tell the pathologist that the diagnosis is adenocarcinoma.
Besides being helpful in distinguishing different tumors, other types of special stains are used in the laboratory to identify microorganisms (germs) like bacteria and fungi in tissue sections. This is important to people with cancer, who may develop infections as a side effect of chemotherapy. It is also important in cancer diagnosis because some infectious diseases cause lumps to form which might initially be confused with a cancer, until these histochemical stains prove that the patient has an infection and not cancer.
Immunohistochemical stains: Immunohistochemical or immunoperoxidase stains are another very useful category of special tests. The basic principle of this method is that an antibody will attach itself to some substances called antigens. Each type of antibody recognizes and attaches to specific antigens. Certain types of normal cells and cancer cells contain unique antigens, which can be recognized by specific antibodies. If cells have a specific antigen, they will attract a specific antibody. To determine if the antibodies have been attracted to the cells, chemicals will be added that cause the cell to change color only if an antibody (and, therefore, the antigen) is present.
Immunohistochemical stains are very useful in identifying certain types of cancers. For example, a routinely processed biopsy of a lymph node may contain cells that clearly appear cancerous, but the pathologist cannot tell whether the cancer started in the lymph node or started elsewhere in the body and later spread to the lymph nodes. If the cancer started in the lymph node, the diagnosis would be lymphoma. If the cancer started in another part of the body and spread to the lymph node, it might be metastatic cancer. This distinction is of great importance to the patient and the doctor, since treatment depends on the type of cancer as well as other factors.
There are hundreds of antibodies used for immunohistochemical tests by laboratories at cancer centers. Some are quite specific, meaning that they react only with one type of cancer. Others may react with a few types of cancer, so a decision about a cancer's type is made by testing with several antibodies. By considering these results in the context of the cancer's appearance after routine processing, its location and other information about the patient (age, gender, etc.), it is often possible to classify the cancer in a way that can help the oncologist select the best treatment.
Electron microscope: The typical medical lab microscope uses a beam of ordinary light to view specimens. A much more complex, larger, and more expensive instrument called an electron microscope uses beams of electrons. The electron microscope's magnifying power is about one thousand times greater than that of an ordinary light microscope. This degree of magnification is rarely useful in determining if a cell is cancerous. But, it sometimes helps find very tiny details of a cancer cell's structure that provide clues to the exact type of the cancer. For instance, melanoma, a highly aggressive cancer of the skin, is notorious for its ability to mimic other types of cancer when viewed under the ordinary light microscope. Although there are some exceptions, melanomas usually can be recognized by certain immunohistochemical stains. In such exceptional cases, the electron microscope may be used to identify tiny bodies located in melanoma cells called melanosomes, thereby establishing the type of cancer and helping the oncologist choose the best treatment for the patient.
Flow cytometry: This test is often used to examine the cells from bone marrow, lymph nodes, and blood samples. It is very accurate in determining the exact type of leukemia or lymphoma, and in distinguishing lymphomas from noncancerous diseases of lymph nodes. A sample of cells from a biopsy, cytology specimen, or blood specimen is treated with special antibodies and passed in front of a laser beam. Each antibody sticks only to certain types of cells that contain specific antigens. If the sample contains those cells, the laser will cause them to give off light that is measured and analyzed by a computer.
Flow cytometry can also be used to measure the amount of DNA in cancer cells. Instead of using antibodies to detect protein antigens, cells can be treated with special dyes that react with DNA before being analyzed. In this way, one can measure the ploidy of cancer cells, which reflects the amount of DNA they contain. If there's a normal amount of DNA, the cells are said to be diploid. If the amount is abnormal, then the cells are described as aneuploid. Aneuploid cancers of most (but not all) organs tend to be more aggressive than diploid ones. Another use of flow cytometry is to measure the S-phase fraction, which is the percentage of cells in a sample that are in a certain stage of cell division called the synthesis (or S) phase. The more cells that are in the S-phase, the faster the tissue is growing and the more aggressive the cancer is likely to be.
Image cytometry: Like flow cytometry, this test uses dyes that react with DNA. But, instead of suspending the cells in a stream of liquid and analyzing them with a laser, image cytometry uses a digital camera and a computer to measure the amount of DNA in cells on a microscope slide. Like flow cytometry, image cytometry can determine the ploidy of cancer cells.
Cytogenetics: Normal human cells contain 46 chromosomes (pieces of DNA and protein that control cell growth and metabolism). Some types of cancer have characteristic abnormalities of their chromosomes. Recognizing these changes helps in identifying certain types of cancer. This is especially useful in diagnosing some lymphomas, leukemias, and sarcomas. Even if a patient is known to have a particular type of cancer, cytogenetic studies may help in predicting the outlook for survival or even which chemotherapy drugs the cancer is likely to respond to.
Several types of chromosome changes can be found in cancer cells:
- A translocation means part of one chromosome has broken off and is now located on another chromosome.
- An inversion means that part of a chromosome is upside down (now in reverse order) but still attached to the chromosome where it originated.
- A deletion indicates part of a chromosome has been lost.
- An addition happens when all or part of a chromosome has been duplicated, and too many copies of it are found within the cell.
Cytogenetic testing usually takes about 3 weeks, because the cancer cells must grow in laboratory dishes for about 2 weeks before their chromosomes are ready to be viewed under the microscope.
Molecular genetic studies: DNA and RNA tests can be used to find most of the translocations that are identified by cytogenetic tests. They can also detect some translocations involving parts of chromosomes too small to be seen with usual cytogenetic testing under a microscope. This sophisticated testing is helpful in classifying some leukemias and, less often, some sarcomas. These tests are also useful after treatment to find small numbers of remaining leukemia cancer cells that may be missed under a microscope.
Molecular genetic tests can also identify mutations (abnormal changes) in certain areas of DNA that are responsible for regulating cell growth. Some of these mutations may cause cancers to be especially aggressive in growing and spreading. But, testing for these mutations is not routine practice and is usually done only in research studies. Some gene mutations can be inherited from parents and cause a person to have a greater risk of developing certain cancers. Unlike acquired gene mutations that only affect the abnormal cells of the tumor, inherited mutations affect all cells of a person's body. These inherited mutations can often be identified by genetic testing on blood samples. Genetic counseling and testing may be recommended for some people with a strong family history of cancer. Because these tests do not analyze the cancerous tissue, they are not discussed further in this document.
Reverse transcription polymerase chain reaction (RTPCR) is a very sensitive molecular genetic test for finding small numbers of cancer cells in blood or tissue samples. RTPCR is a method for detecting small amounts of RNA, a substance related to DNA that is needed for cells to produce proteins. There are specific RNAs for each protein in our body. RTPCR tests for cancer cells specifically look for the RNA sequences that are responsible for making substances found in cancer cells but not in most normal cells. This method is being tested for detecting the spread of prostate cancer, colon cancer, and melanoma of the skin. A potential advantage of this test is that it can detect very small numbers of cancer cells in the blood or tissue samples that would be missed by other tests. The disadvantage is that doctors are still not sure whether having a few cancer cells in the bloodstream or a lymph node means that a patient will actually develop distant metastases that grow enough to cause symptoms or affect survival. It is still uncertain how or if the test should be used in considering treatment options.
Certain substances, called antigen receptors, occur on the surface of immune system cells called lymphocytes Normal lymph node tissue contains cells with many different antigen receptors, which help the body respond to infection. Some types of lymphoma and leukemia, however, start from a single abnormal lymphocyte, so all their cells have the same antigen receptor. Laboratory tests of the DNA that contains information on each cell's antigen receptors are a very sensitive way to diagnose and classify these cancers.
How Long Does Biopsy and Cytology Testing Take?
The uncertainty you feel waiting for biopsy and cytology test results can be a source of much anxiety. Not knowing when the results will be ready, and not understanding why testing sometimes takes longer than expected can cause extra concern.
Most routine biopsy and cytology results are available 1or 2 days after the sample is received in the laboratory. There are many reasons why some cases take considerably longer to complete.
Often, there are "technical" reasons for delays in reporting. For example, bone and other hard tissues that contain lots of calcium need to be specially handled. These tissues must be treated with strong acids or other chemicals to remove the minerals so that the tissue becomes soft enough to be thinly sectioned (sliced) on the microtome. Another technical reason for delay is that the formalin solution used for preserving tissues takes longer to penetrate samples with lots of fatty tissue (such as breast biopsies). An additional day of fixation (formalin treatment) is sometimes necessary. Large samples, such as those resulting from removal of an entire organ may also require more than one day for the formalin to adequately penetrate the tissue. If formalin does not completely penetrate the sample, cells may appear disturbed under the microscope and testing is more difficult and/or less accurate.
For most large samples, only selected areas are processed and examined under the microscope. After examination of the first microscopic sections of tissue, the pathologist may want to examine more sections for an accurate diagnosis. In these cases, processing of extra pieces of tissue may be needed. Or, the lab may need to make additional slices of the tissue that has already been embedded in wax blocks. Either of these situations can add 1or 2 days to the testing time.
Although most cancers can be identified by examination of routinely stained sections, other studies such as those already described, may be needed for some specimens. For example, histochemical stains or immunoperoxidase stains usually delay a case for another day. Other sophisticated studies like flow cytometry, electron microscopy, and molecular pathology techniques can take even longer, sometimes days, before obtaining results.
Another important reason for delaying a pathology report is that the pathologist may seek a second opinion from an expert. Unlike some chemical tests done in the laboratory that measure the amount of a specific substance or determine whether a substance is present or absent, testing tissue or cell samples for cancer is based on the professional opinion of the pathologist viewing the sample under the microscope. Although the abnormal features of some cancers are obvious, some cases have features that are very difficult to recognize. Also, pathologists are often understandably reluctant to diagnose certain very rare types of cancer without a second opinion from experts who specialize in that area. There are pathology experts specializing in almost every organ system (digestive, head and neck, breast, bone, reproductive, etc.). When difficult or rare cases are encountered, slides are usually sent to experts by overnight mail. Such review can delay the case for additional days.
Finally, patients should realize that delays might occur for reasons that are neither technical nor medical. For example, typing the report takes time. Some laboratories send results directly to doctors' office computer systems or fax machines, but a hospital mail system or US mail is still often used and can delay availability of results.
What Can You Do To Learn More About Your Pathology Results?
Pathology results have a key role in making decisions about treatment, and many patients want to learn more about their test results. You should feel free to ask your doctors to explain these results in a way that you can understand, focusing on how the results influence treatment options and help predict your outlook for survival. Some pathologists will speak with you to help you understand your pathology reports. But, some other pathologists believe that your oncologist, primary care doctor, or other doctors are better able to explain the results in the context of your overall medical situation. Also, doctors who already know you well are often best able to discuss the complex personal issues affected by your pathology results.
You may request copies of your pathology reports, and you may find it useful to keep a folder or notebook with your pathology, radiology, and other test results. If you see additional doctors in the same hospital where your cancer was diagnosed, the new doctors will have access to the original pathology report and other medical records. If consulting doctors (such as those sought for second opinions) practice at other facilities, it is usually necessary to send copies of pathology reports and other medical records.
Some cancer centers have a policy requiring that microscope slides of the patient's cancer be reviewed by the pathologists at their own institution. Some pathology laboratories will give copies of microscope slides to you if you are about to visit another cancer center for a second opinion or consultation. Other laboratories prefer to mail the slides directly to the consulting cancer center's pathology department.
If you or your doctors have any concerns about your pathology diagnosis, you can have your microscope slides reviewed by a consulting pathologist for a second opinion. Your oncologist or surgeon or the pathologist who initially examined your specimen can often suggest a consultant with special qualifications in examining samples such as yours. Or, you can have your slides sent to the pathology department of a medical school or cancer center you have confidence in.
What Information Is Included in a Pathology Report?
The pathology report of surgical specimens is often quite long and complex. It is typically divided into numerous subheadings.
Patient, doctor, and specimen identification: The general identifying information includes the patient's name, medical record number issued by the hospital, the date when the biopsy or surgery was performed and the unique number of the specimen issued in the laboratory.
Clinical information: The next portion of the report often contains information about the patient provided by the doctor who removed the tissue sample. Such information may include a pertinent medical history and special requests made to the pathologist. For example, if a lymph node sample is being removed from a patient already known to have cancer in another organ, the doctor will indicate the type of the original cancer. This information is often useful in guiding the pathologist's selection of special studies needed to determine whether any cancer in that lymph node is a metastasis from the prior cancer or is a new cancer that developed in the lymph node.
Gross description: The next part of the report is called the gross description. The medical meaning of "gross" differs from the common usage of the word, and refers to features that can be identified without a microscope (by simply looking at, measuring, or feeling the tissue).
For a small biopsy, this description is a few sentences indicating its size color, and consistency. This section also records the number of tissue-containing cassettes submitted for processing.
Larger biopsy or tissue specimens, for example, a mastectomy for breast cancer, will have much longer descriptions including the size of the entire breast, size of the cancer, how close the cancer is to the nearest surgical margin or edge of the specimen, how many lymph nodes were found in the underarm area, and the appearance of noncancerous breast tissue. A summary of exactly where tissue was taken from for processing is included.
For cytology specimens, the gross description is very short and usually indicates the number of slides or smears made by the doctor. If the sample is a body fluid, its color and volume are noted.
Microscopic description: This description records what the pathologist saw under the microscope. The appearance of the cancer cells, how they are arranged together, and the extent to which the cancer penetrates nearby tissues in the specimen are usually included in the microscopic description. For typical cases of common cancers or for benign tissues, a microscopic description may not be included in the report. Results of any additional studies (histochemical stains, flow cytometry, etc.) performed in the case are documented in the microscopic description or in a separate section.
Diagnosis: The most important part of the pathology report is the final diagnosis. It is, in essence, the "bottom line" of the testing process, although this section may appear at the bottom or the top of the page. The patient's doctor relies upon this final diagnosis to help in choosing appropriate treatment for the patient. If the diagnosis is cancer, this section will indicate the exact type of cancer that is present and will usually include the cancer's grade.
Comment: After the final diagnosis is made, the pathologist may wish to communicate additional information to the doctors taking care of the patient. The comment section is often used to clarify a concern or make recommendations for further testing.
Summary: Some pathology reports for cancers contain a summary of findings most relevant to making treatment decisions.
Revised: 11/20/01
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