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A diagnosis of cancer may be suspected based on history and physical examination but requires confirmation by tumor biopsy and histopathologic examination.
A complete history and physical examination may reveal unexpected clues to early cancer.
History
Physicians must be aware of predisposing factors and must specifically ask about familial cancer, environmental exposure (including smoking history), and prior or present illnesses (eg, autoimmune disorders, previous immunosuppressive therapy, hepatitis B or hepatitis C, HIV infection, abnormal Papanicolaou test, human papillomavirus infection). Symptoms suggesting occult cancer can include
Physical examination
Particular attention should be paid to skin, lymph nodes, lungs, breasts, abdomen, and testes. Prostate, rectal, and vaginal examinations are also important. Findings help direct further testing, including x-rays and biopsies.
Testing
Tests include imaging tests, serum tumor markers, and biopsy.
Imaging
tests often include plain x-rays, ultrasonography, CT, and MRI. These tests assist in identifying abnormalities, determining qualities of a mass (solid or cystic), providing dimensions, and establishing relationship to surrounding structures, which may be important if surgery or biopsy is being considered.
Serum
tumor markers may offer corroborating evidence in patients with findings suggestive of a specific cancer (see Tumor Immunology: Tumor Immunodiagnosis). With some exceptions (eg, prostate-specific antigen [PSA]), these markers do not have enough sensitivity and specificity to be used for screening. They are the most useful in detecting early relapse and monitoring response to therapy. Useful examples include
Biopsy to confirm the diagnosis and tissue of origin is almost always required when cancer is suspected or detected. The choice of biopsy site is usually determined by ease of access and degree of invasiveness. If lymphadenopathy is present, fine-needle or core biopsy may yield the tumor type; if nondiagnostic, open biopsy is done. Other biopsy routes include bronchoscopy for easily accessible mediastinal or central pulmonary tumors, percutaneous liver biopsy if liver lesions are present, and CT- or ultrasound-guided biopsy. If these procedures are not suitable, open biopsy may be necessary.
Grading is a histologic measure of tumor aggressiveness and provides important prognostic information. It is determined by examining the biopsy specimen. Grade is based on the morphologic appearance of tumor cells, including the appearance of the nuclei, cytoplasm, and nucleoli; frequency of mitoses; and amount of necrosis. For many cancers, grading scales have been developed
Molecular tests such as chromosomal analogues, fluorescent in situ hybridization (FISH), PCR, and cell surface antigens (eg, in lymphomas, leukemias) delineate the origin of metastatic cancers originating from an unknown primary cancer or assist in recognizing chemotherapy resistance (eg, in acute myelogenous leukemia).
Staging
Once a histologic diagnosis is made, staging (ie, determination of the extent of disease) helps determine treatment decisions and prognosis. Clinical staging uses data from the history, physical examination, imaging tests, laboratory tests, and biopsy of bone marrow, lymph nodes, or other sites of suspected disease. For staging of specific neoplasms, see details in the organ-relevant chapter.
Imaging
tests
Imaging tests, especially CT and MRI, can detect metastases to brain, lung, or abdominal viscera, including the adrenal glands, retroperitoneal lymph nodes, liver, and spleen. MRI (with gadolinium contrast) is the procedure of choice for recognition and evaluation of brain tumors, both primary and metastatic. PET scanning is increasingly being used to determine the metabolic activity of a suspect lymph node or mass. Integrated PET–CT can be valuable, especially in lung, head and neck, and breast cancer and in lymphoma.
Ultrasonography can be used to study orbital, thyroid, cardiac, pericardial, hepatic, pancreatic, renal, and retroperitoneal areas. It may guide percutaneous biopsies and differentiate renal cell carcinoma from a benign renal cyst.
Nuclear scans can identify several types of metastases. Bone scans identify abnormal bone growth (ie, osteoblastic activity) before it is visible on plain x-ray. Thus, this technique is useless in neoplasms that are purely lytic (eg, multiple myeloma); routine bone x-rays are the study of choice in such diseases.
Laboratory
tests
Serum chemistries and enzymes may help staging. Elevated liver enzyme (alkaline phosphatase, LDH, ALT) levels suggest the presence of liver metastases. Elevated alkaline phosphatase and serum Ca may be the first evidence of bone metastases. Elevated BUN or creatinine levels may indicate an obstructive uropathy secondary to a pelvic mass, intrarenal obstruction from tubular precipitation of myeloma protein, or uric acid nephropathy from lymphoma or other cancers. Elevated uric acid levels often occur in myeloproliferative and lymphoproliferative disorders.
Invasive tests
Mediastinoscopy (see Diagnostic and Therapeutic Pulmonary Procedures: Mediastinoscopy and Mediastinotomy) is especially valuable in the staging of non–small cell lung cancer. When mediastinal lymph node involvement is found, patients do not usually benefit from thoracotomy and lung resection but may benefit from chemoradiation and subsequent tumor resection.
Bone marrow aspiration and biopsy are especially useful in detecting metastases from malignant lymphoma and small cell lung cancer, and their role in breast and prostate cancer staging is expanding. Marrow biopsy is positive at diagnosis in 50 to 70% of patients with malignant lymphoma (low and intermediate grade) and in 15 to 18% of patients with small cell lung cancer. Bone marrow biopsy should be done in patients with hematologic abnormalities (ie, anemia, thrombocytopenia, pancytopenia) that cannot be explained by other mechanisms.
Biopsy of regional lymph nodes is part of the evaluation of most tumors, such as breast, lung, or colon cancers.
Last full review/revision August 2008 by Bruce A. Chabner, MD; Elizabeth Chabner Thompson, MD, MPH
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