CHAPTER 165
Symptoms and Diagnosis of Cancer
Cancer can produce many different symptoms, some subtle and some not at all subtle. Some symptoms develop early in the course of cancer and are therefore important warning signs that should be evaluated by a doctor. Other symptoms develop only after the cancer progresses and are therefore not helpful in the early detection of cancer. Still other symptoms, such as nausea, loss of appetite, fatigue, and vomiting, may be the result of the cancer or its treatment, may be warning signs, or may even result from conditions other than cancer. Some symptoms occur with many or almost all cancers, and others are specific to the type of cancer and where it is growing.
Screening programs allow early detection and diagnosis of cancer. The earlier cancer is diagnosed, the more effective treatment is likely to be.
Symptoms
At first, cancer, as a tiny mass of cells, produces no symptoms whatsoever. As a cancer grows, its physical presence can affect nearby tissues. Also, some cancers secrete certain substances or trigger immune reactions that cause symptoms in other parts of the body that are not near to the cancer (paraneoplastic syndromes).
Cancer affects nearby tissues by growing into or pushing on them, thus irritating or compressing them. Irritation typically causes pain. Compression may keep tissues from performing their normal functions. For example, a bladder cancer or a cancerous lymph node in the abdomen may compress the tube (ureter) connecting a kidney with the bladder, blocking the flow of urine. A lung cancer may block airflow through one segment of a lung, causing partial lung collapse and predisposing to infection. Cancer anywhere may compress a blood vessel, shutting off blood flow or causing bleeding. When cancer grows in an area with a lot of space, such as in the wall of the large intestine, it may not cause any symptoms until it becomes quite large. In contrast, a cancer growing in a more restricted space, such as on a vocal cord, may cause symptoms (such as hoarseness) when it is relatively small. If a cancer spreads (metastasizes) to other parts of the body, the same local effects of irritation and compression eventually occur, but in the new location, so the symptoms may be quite different. Cancers that involve the membrane covering the lungs (pleura) or the baglike structure that surrounds the heart (pericardium) often ooze fluid, which collects around those organs; large fluid collections can interfere with breathing or the pumping of the heart.
Warning Signs of Cancer
Because cancer is more likely to be cured if less advanced when treatment is begun, it is critical that cancer be discovered early. Some symptoms may give early warning of cancer and should, therefore, trigger a person to seek medical care. Fortunately, most of these symptoms are usually caused by far less serious conditions. Nonetheless, the development of any of the warning signs of cancer should not be ignored.
Some of the warning signs are general. That is, they are vague changes that do not help pinpoint any particular cancer. Still, their presence can help direct doctors to do the physical examinations and laboratory tests necessary to exclude or confirm a diagnosis. Other symptoms are much more specific and steer doctors to a particular kind of cancer or location. Some warning signs of cancer are
Weight loss
Fatigue
Night sweats
Loss of appetite
New, persistent pain
Recurrent nausea or vomiting
Blood in urine
Blood in stool (either visible or detectable by special tests)
Sudden depression
A recent change in bowel habits (constipation or diarrhea)
Recurrent fever
Chronic cough
Changes in the size or color of a mole or changes in a skin ulcer that does not heal
Enlarged lymph nodes
Pain
Cancers are typically painless at first. As they grow, the first symptom is often a mild discomfort, which may steadily worsen into increasingly severe pain as the cancer enlarges. The pain may result from the cancer compressing or eroding into nerves or other structures. However, not all cancers cause severe pain. Similarly, lack of pain does not guarantee that a cancer is not growing or spreading.
Bleeding
At first, a cancer may bleed slightly because its cells are not well attached to each other and its blood vessels are fragile. Later, as the cancer enlarges and invades surrounding tissues, it may grow into a nearby blood vessel, causing bleeding. The bleeding may be slight and undetectable or detectable only with testing. Such is often the case in early-stage colon cancer. Or, particularly with advanced cancer, the bleeding may be more significant, even massive and life threatening.
The site of the cancer determines the site of the bleeding. Cancer anywhere along the gastrointestinal tract can cause bleeding in the stool. Cancer anywhere along the urinary tract can cause bleeding in the urine. Other cancers can bleed into internal areas of the body. Bleeding into the lungs can cause the person to cough up blood.
Weight Loss and Fatigue
Commonly, a person with cancer experiences weight loss and fatigue, which can worsen as the cancer progresses. Some people notice weight loss despite a good appetite. Others lose their appetite and may even become nauseated by food or have difficulty swallowing. They may become very thin; the loss of underlying fat is particularly noticeable in the face. People with advanced cancer are often very tired and sleep many hours a day. If anemia develops, these people may find that they feel tired or become short of breath with even slight activity.
Swollen Lymph Nodes
As a cancer begins to spread around the body, it may first spread to nearby lymph nodes, which become swollen. The swollen lymph nodes may be painless or tender, and they may feel hard or rubbery. They may be freely moveable, or if the cancer is more advanced, they may be stuck to the skin above, to the deeper layers of tissue below, or to each other.
SOME COMPLICATIONS OF CANCER
| COMPLICATION | DESCRIPTION |
| Cardiac tamponade | Fluid accumulates in the baglike structure surrounding the heart (pericardium, or pericardial sac). This fluid puts pressure on the heart and interferes with its ability to pump blood. Fluid can accumulate when a cancer invades the pericardium and irritates it. |
| Pleural effusion | Fluid accumulates in the baglike structure around the lungs (pleural sac), causing shortness of breath. |
| Superior vena cava syndrome | Cancer partially or completely blocks the vein (superior vena cava) that drains blood from the upper part of the body into the heart. Blockage of the superior vena cava causes the veins in the upper part of the chest and neck to swell, resulting in swelling of the face, neck, and upper part of the chest. |
| Spinal cord compression | Cancer compresses the spinal cord or the spinal cord nerves, resulting in pain and loss of function (such as urinary or fecal incontinence). The longer the compression of the spinal cord or spinal cord nerves persists, the less likely normal nerve function will return when the compression is relieved. |
| Brain dysfunction | The brain functions abnormally as a result of a cancer growing within it, either as a primary brain cancer or more commonly as a metastasis from a cancer elsewhere in the body. Many different symptoms can occur, including confusion, drowsiness, agitation, headaches, abnormal vision, abnormal sensations, weakness, nausea, vomiting, and seizures. |
| Bleeding | Cancer grows into and erodes nearby blood vessels. Serious, even fatal, bleeding can result from cancers in areas containing many large blood vessels, such as the neck and chest. |
Depression
Cancer often results in depression. Depression can be related to the symptoms of the illness, a fear of dying, or a loss of independence. Additionally, some cancers may produce substances that directly cause depression by affecting the brain.
Neurologic and Muscular Symptoms
Cancer can grow into or compress nerves, causing any of several neurologic and muscular symptoms, including a change in sensation (such as tingling sensations) or muscle weakness. When a cancer grows in the brain, symptoms may be hard to pinpoint but can include confusion, dizziness, headaches, nausea, changes in vision, and seizures. Neurologic symptoms may also be part of a paraneoplastic syndrome.
Respiratory Symptoms
Cancer can compress or block structures, such as the airways in the lungs, causing shortness of breath, cough, or pneumonia. Shortness of breath can also occur when the cancer causes a large pleural effusion, bleeding into the lungs, or anemia.
Diagnosis
Cancer is suspected based on a person’s symptoms, the results of a physical examination, and sometimes the results of screening tests. Occasionally, x-rays obtained for other reasons, such as an injury, show abnormalities that might be cancer. Confirmation that cancer is present requires other tests (termed diagnostic tests). After cancer is diagnosed, it is staged. Staging is a way of describing how advanced the cancer has become, including such criteria as how big it is and whether it has spread to neighboring tissues or more distantly to lymph nodes or other organs.
SCREENING
Screening tests serve to detect the possibility that a cancer is present before symptoms occur. Screening tests usually are not definitive; results are confirmed or disproved with further examinations and tests. Diagnostic tests are performed once a doctor suspects that a person has cancer.
Although screening tests can help save lives, they can be costly and sometimes have psychologic or physical repercussions. Screening tests can produce false-positive results—results that suggest a cancer is present when it actually is not. False-positive results can create undue psychologic stress and can lead to other tests that are expensive and risky. Screening tests can also produce false-negative results—results that show no hint of a cancer that is actually present. False-negative results can lull people into a false sense of security. For these reasons, there are only a small number of screening tests that are considered reliable enough for doctors to use routinely.
What Are Paraneoplastic Syndromes?
Paraneoplastic syndromes occur when a cancer produces one or more substances that circulate in the bloodstream to cause symptoms at sites distant from the tumor. These substances can affect the function of other tissues and organs, resulting in a variety of symptoms. Paraneoplastic syndromes may affect many different organ systems, including the nervous system and the endocrine (hormone) system, causing such problems as low blood sugar, diarrhea, or high blood pressure.
General syndromes such as the development of fever, night sweats, and loss of weight and appetite can be experienced by many people with cancer. Most of the syndromes discussed below are uncommon, and most cancer patients do not experience these more specific paraneoplastic syndromes.
Neurologic syndromes: Polyneuropathy is a dysfunction of peripheral nerves, resulting in weakness, loss of sensation, and reduced reflexes. Subacute sensory neuropathy is a rare form of polyneuropathy that sometimes develops before the cancer is diagnosed. It causes a disabling loss of sensation and incoordination but little weakness.
Paraneoplastic cerebellar degeneration occurs rarely in patients with breast cancer, ovarian cancer, small cell carcinoma of the lung, or other solid tumors. This disorder may be caused by an autoantibody (an antibody that attacks the body’s own tissues) that destroys the cerebellum. Symptoms can include unsteadiness in walking, incoordination of the arms and legs, difficulty speaking, dizziness, and double vision. Symptoms may appear before the cancer is detected.
Uncontrollable eye movements (opsoclonus) and quick contractions of the arms and legs (myoclonus) can occur in some children with neuroblastoma.
Subacute motor neuronopathy occurs in some people with Hodgkin and non-Hodgkin lymphoma. The nerve cells of the spinal cord are affected, weakening the arms and legs.
Eaton-Lambert syndrome occurs in some people with small cell carcinoma of the lung. This syndrome is characterized by extreme muscle weakness caused by lack of proper activation of the muscle by the nerve.
Thymoma is a rare tumor that can be associated with myasthenia gravis, a syndrome of weakness resulting from antibodies that damage the nerve connections in muscle tissue.
Endocrine syndromes: Small cell carcinoma of the lung may secrete a substance that stimulates the adrenal gland to produce increased hormone levels, which can cause weakness, weight gain, and high blood pressure (Cushing’s syndrome). Small cell carcinoma of the lung may also produce antidiuretic hormone, causing water retention, decreased sodium levels, weakness, confusion, and seizures in some people.
Very high calcium levels in the blood (hypercalcemic syndrome) may occur in people with solid tumors or leukemias. This can occur when the cancer secretes a hormone-like substance in the blood that causes release of calcium from bone. High calcium levels may also result if the cancer directly invades bone, thereby releasing calcium into the bloodstream. As a result of the high calcium levels in the blood, the person develops confusion, which can progress to coma and even death.
Excessive production of other hormones can cause carcinoid syndrome—flushing, wheezing, diarrhea, and heart valve problems.
Other syndromes: Polymyositis is muscle weakness and soreness resulting from muscle inflammation. When polymyositis is accompanied by skin inflammation, the condition is called dermatomyositis.
Hypertrophic osteoarthropathy can occur in people with lung cancer. This syndrome alters the shape of the fingers and toes and can cause painful swelling of some joints.
Doctors determine whether a particular person is at special risk for cancer—because of age, sex, family history, previous history, or lifestyle—before they choose to perform screening tests. The American Cancer Society has provided cancer screening guidelines that are widely used. Other groups have also developed screening guidelines. Sometimes recommendations vary among different groups, depending on how the groups’ experts weigh the relative strength and importance of available scientific evidence.
In women, two of the most widely used screening tests are the Papanicolaou (Pap) test to detect cervical cancer and mammography to detect breast cancer. Both screening tests have been successful in reducing the death rates from these cancers in certain age groups.
In men, prostate-specific antigen (PSA) levels in the blood may be used to screen for prostate cancer. PSA levels are high in men with prostate cancer, but levels also are elevated in men with noncancerous (benign) enlargement of the prostate. As such, the main drawback to its use as a screening test is the large number of false-positive results, which generally lead to more invasive tests. Whether the PSA test should be used routinely to screen for prostate cancer is unresolved, with varying recommendations from different groups. Men over 50 should discuss the PSA test with their doctor.
A common screening test for colon cancer involves checking the stool for blood that cannot be seen by the naked eye (occult blood). Finding occult blood in the stool is an indication that something is wrong somewhere in the gastrointestinal tract. The problem may be cancer, although many other disorders, such as ulcers, hemorrhoids, diverticulosis (small pouches in the colon wall), and abnormal blood vessels in the intestinal walls, can also cause small amounts of blood to leak into the stool. In addition, taking an aspirin or another nonsteroidal anti-inflammatory drug (NSAID) or even eating red meat can temporarily produce a positive result. Positive results on the most commonly used test can occasionally be caused by consuming certain raw fruits and vegetables (turnips, cauliflower, broccoli, melons, radishes, and parsnips). Some people with blood in the stool may have negative test results because they have consumed vitamin C. Newer screening tests for occult blood that use a different technique are much less susceptible to such errors but are somewhat more costly. Outpatient procedures such as sigmoidoscopy and colonoscopy are also often used for colon cancer screening.
Some screening tests can be done at home. For example, monthly breast self-examinations may help women detect breast cancer. Periodically examining the testes may help men detect testicular cancer, one of the most curable forms of cancer, especially when diagnosed early. Checking the mouth for sores may help detect mouth cancer in an early stage.
Tumor markers are substances secreted into the bloodstream by certain tumors. It was first thought that measuring levels of these markers would be an excellent way to screen asymptomatic people for cancer. However, tumor markers are often present to some extent in the blood of people who do not have cancer. Finding a tumor marker does not necessarily mean a person has cancer, and tumor markers have a very limited role in cancer screening.
DIAGNOSTIC TESTS AND STAGING
Diagnosis
Usually, when a doctor first suspects cancer, some type of imaging study, such as x-ray (see page 2042), ultrasonography (see page 2044), or computed tomography (CT—see page 2037), is performed. For example, a person with chronic cough and weight loss might have a chest x-ray; a person with recurrent headaches and trouble seeing might have a CT scan or magnetic resonance imaging (MRI—see page 2040) of their head. Although these tests can show the presence, location, and size of an abnormal mass, they cannot confirm that cancer is the cause. Cancer is confirmed by finding cancer cells on microscopic examination of samples from the suspected area. Usually, the sample must be a piece of tissue, although sometimes examination of the blood is adequate (such as in leukemia). Obtaining a tissue sample is termed a biopsy. Biopsies can be performed by cutting out a small piece of tissue with a scalpel, but very commonly the sample is obtained using a hollow needle. Such tests are commonly done without the need for an overnight hospital stay (outpatient procedure). Doctors often use ultrasonography or a CT scan to guide the needle to the right location. Because biopsies can be painful, the person is usually given a local anesthetic to numb the area.
In people with findings on examination or imaging tests that suggest cancer, measuring blood levels of tumor markers may provide additional evidence for or against the diagnosis of cancer. In people who have been diagnosed with certain types of cancer, tumor markers may be useful to monitor the effectiveness of treatment and to detect possible recurrence of the cancer. For some cancers, the level of a tumor marker drops following treatment and increases if the cancer recurs.
Staging
When cancer is diagnosed, staging tests help determine how extensive the cancer is in terms of its location, size, growth into nearby structures, and spread to other parts of the body. People with cancer sometimes become impatient and anxious during staging tests, wishing for a prompt start of treatment. However, staging allows doctors to determine the most appropriate treatment as well as help to determine prognosis.
Staging may use scans or other imaging tests, such as x-ray, CT, MRI, bone scintigraphy, or positron emission tomography (PET). The choice of staging test(s) depends on the type of cancer. CT is used to detect cancer in many parts of the body, including the brain and lungs and parts of the abdomen, including the adrenal glands, lymph nodes, liver, and spleen. MRI is of particular value in detecting cancers of the brain, bone, and spinal cord.
CANCER SCREENING RECOMMENDATIONS*
| PROCEDURE | FREQUENCY |
| Skin cancer | |
| Physical examination | Should be part of a routine checkup May be needed more frequently by people at high risk of developing skin cancer |
| Whole-body photography | Not routinely needed; may be helpful for people with multiple moles or in whom examination of the skin is difficult |
| Lung cancer | |
| Chest x-ray | Not recommended on a routine basis |
| Sputum cytology | Not recommended on a routine basis |
| Low-dose spiral computed tomography | Not recommended on a routine basis, but is under investigation |
| Rectal and colon cancer | |
| Stool examination for occult blood | Yearly after age 50† |
| Sigmoidoscopic or colonoscopic examination | Every 5 years beginning at age 50 (sigmoidoscopy)† Every 10 years beginning at age 50 (colonoscopy) |
| Prostate cancer | |
| Rectal examination | Yearly after age 50 |
| Blood test for prostate-specific antigen | Yearly after age 50 |
| Cervical cancer | |
| Papanicolaou (Pap) test | Annual regular Pap test (or newer liquid-based Pap test every 2 years) beginning between ages 18 and 21. Some women 70 years of age or older who have had 3 or more normal Pap tests in a row may choose to stop having cervical cancer screening. For women over 30, some doctors recommend testing every 3 years with a conventional Pap test plus the human papillomavirus DNA test |
| Breast cancer | |
| Breast self-examination | Consideration of monthly self-examinations after age 20 |
| Breast physical examination by health care provider | Every 3 years between ages 20 and 39, then yearly |
| Mammography | Yearly, starting at age 40 |
| *Recommendations for screening are influenced by many factors. These screening recommendations, based primarily on those of the American Cancer Society, are for asymptomatic people with an average risk of cancer. For people with a higher risk, such as those with a strong family history of certain cancers or those who have had a previous cancer, screening may be recommended more frequently or to start at a younger age. Screening tests other than those listed here may also be recommended. Furthermore, other organizations, such as the U.S. Preventive Services Task Force, may have slightly different recommendations. A person’s physician can help the person decide when to begin screening and which tests should be used. †The combination of yearly stool examination for occult blood and sigmoidoscopy every 5 years is preferred over either of these options alone. |
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Biopsies are often needed for staging and can sometimes be done together with the initial surgical treatment of a cancer. For example, during a laparotomy (an abdominal operation) to remove colon cancer, a surgeon removes nearby lymph nodes to check for spread of the cancer. During surgery for breast cancer, the surgeon biopsies or removes lymph nodes located in the armpit to determine whether the breast cancer has spread there. This information, along with features of the primary tumor, helps the doctor determine whether further treatment is needed. When staging is based only on initial biopsy results, physical examination, and imaging, the stage is referred to as clinical. When the doctor uses results of a surgical procedure or additional biopsies, the stage is referred to as pathologic. The clinical and pathologic stage may differ.
SELECTED TUMOR MARKERS*
| TUMOR MARKER | DESCRIPTION | COMMENT ABOUT TESTING |
| Alpha-fetoprotein (AFP) | Elevated AFP levels often are found in the blood of people with liver cancer (hepatoma). In addition, elevated AFP is often found in people with certain cancers of the ovary or testis. | Testing can be useful in diagnosing these cancers and in monitoring treatment. |
| Beta-human chorionic gonadotropin (β-HCG) | This hormone is produced during pregnancy but also occurs in women who have a cancer originating in the placenta and in men with various types of testicular cancer. | Testing can be useful in diagnosing such cancers and in monitoring treatment. |
| Beta2 (β2)-microglobulin | Levels may be elevated in people with multiple myeloma or other cancers of blood cells. | This test cannot be recommended for cancer screening. |
| Calcitonin | Calcitonin is produced by certain cells in the thyroid gland (C cells). Blood levels are elevated in medullary thyroid cancer. | This test may be used to monitor response to treatment of medullary thyroid cancer. |
| Carbohydrate antigen 125 (CA-125) | Levels may be elevated in women with a variety of gynecologic diseases, including ovarian cancer. | This test is not recommended for routine cancer screening. |
| Carbohydrate antigen 19-9 (CA 19-9) | Levels may be elevated in people with cancers of the digestive tract, particularly pancreatic cancer. | This test cannot be recommended for cancer screening. |
| Carbohydrate antigen 27.29 (CA27.29) | Levels may be elevated in people with breast cancer. | This test cannot be recommended for cancer screening. |
| Carcinoembryonic antigen (CEA) | Levels may be elevated in the blood of people with cancer of the colon. Blood levels may also be elevated in patients with other cancers or noncancerous conditions. | After surgery for colon cancer, testing can be useful in monitoring treatment and detecting recurrence. |
| Lactate dehydrogenase | Levels can be elevated for a variety of reasons. | This test cannot be recommended for cancer screening. However, it is useful in assessing prognosis and monitoring treatment, particularly for people with testicular cancer, melanomas, or lymphomas. |
| Prostate-specific antigen (PSA) | Levels are elevated in men with noncancerous (benign) enlargement of the prostate and often are considerably higher in men with prostate cancer. What constitutes a meaningfully abnormal level is somewhat uncertain, but men with an elevated PSA level should be evaluated further by a doctor. | Testing can be useful in screening for cancer and in monitoring its treatment. |
| Thyroglobulin | Elevated blood levels may occur in people with thyroid cancer or benign thyroid conditions. | This test cannot be recommended for routine screening but may be helpful for monitoring response to treatment of thyroid cancer. |
| *Because tumor markers can also be produced by noncancerous tissue, doctors generally do not use them to screen healthy people. Exceptions may include PSA for prostate cancer and AFP for people at risk of hepatoma. In families with inherited medullary thyroid cancer, a rare condition, calcitonin blood levels also may be a useful screening test. | ||
In addition to imaging tests, doctors often obtain blood tests to see if the cancer has begun to affect the liver, bone, or kidneys.