In 1947, the American Cancer Society began a public education campaign about the signs and symptoms of cancer, describing them as “Cancer’s Danger Signals,” ranging from “unusual bleeding or discharge” to “nagging cough or hoarseness.” This approach has evolved over the decades, with the improvement in diagnostic techniques that has made it possible to rapidly diagnose cancer in patients with minimal symptoms or none at all. The primary care physician and geriatrician are on the front lines of diagnosing cancer, especially in its earliest and most treatable stages.
The number of individuals older than 65 years in the United States is expected to more than double over the next 30 years, with the largest increase occurring in the subsegment of individuals aged 75 to 84. More than 60% of new cancers and 70% of cancer deaths occur in people older than 65 years. The primary care physician or geriatrician must not only manage the chronic comorbid medical conditions of older patients, but also display vigilance in the medical examination of this high-cancer-risk population. The evaluation can often be complex, involving multiple imaging modalities, specialized blood tests, and biopsy procedures, and has the potential to be an emotionally distressing experience for the patient. When cancer is suspected in an older patient, a logical and targeted plan of medical tests must be constructed that takes into consideration the impact on the patient’s current performance status, his or her goals of care, and the associated financial costs.
Cancer is one of the most common diseases that drastically diminish quality of life and life expectancy. According to the American Cancer Society, over 1.4 million new cancer diagnoses will be made in the United States in 2009. This number does not include basal and squamous cell skin cancers or in situ carcinoma (except bladder). Cancer is the second most common cause of death next to heart disease and accounts for nearly one of every four deaths. The most common sites of new cancer cases for men are prostate (25%), lung/bronchus (15%), and colorectal (10%). For women, they are breast (27%), lung/bronchus (14%), and colorectal (10%). The leading cause of cancer deaths for both men and women was lung cancer, which accounted for 30% of male cancer deaths and 26% of female cancer deaths. Aging and cancer are complex processes that are regulated by multiple factors. Extensive research into the molecular mechanisms of both aging and cancer has demonstrated the convergence of many common biological pathways. The most critical of these pathways are those activated by DNA damage, inflammation, depletion of stem cells, and oxidative stress. Hence, cancer can be truly thought of as a disease of aging. The National Cancer Institute, Surveillance Epidemiology and End Results program has found, from data collected between 2003 and 2007, that the median age for cancer diagnosis for prostate is 67 years; for breast, 61 years; for colon/rectum, 70 years; for lung, 71 years; and for leukemia, 66 years. Furthermore, 68.4% of lung cancer diagnoses and 63.4% of colorectal cancer diagnoses were made in patients older than 65 years.
Major Imaging Modalities in Cancer Diagnosis
Cancer imaging studies have a fundamental role in the diagnosis and management of many types of cancers. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound are widely used to help distinguish between malignant and benign lesions, to accurately stage a newly diagnosed cancer, and to provide objective information on tumor size that can be used to determine the response to treatment. Specialized plain film x-ray imaging such as mammography has been established as an important screening method and posttreatment surveillance program for breast cancer. The recent improvements in functional imaging, such as PET-CT scanning, have made it possible to obtain important additional information for treatment decisions.
A.J. is a 78-year-old widowed man with a past medical history of coronary artery disease, hypertension, and glaucoma who presents to his geriatrician with 4 months of epigastric abdominal pain that radiates to the back, along with episodes of nausea. He also reports an 8-pound weight loss over the past 2 months. On physical examination, he has no signs of ascites or gastrointestinal obstruction. Laboratory studies disclosed the following values: hemoglobin, 10.5 g/dL; white blood cell count, 10,500/μL; platelet count, 330,000/μL; total bilirubin, 2.50 mg/dL; direct bilirubin, 1.50 mg/dL; aspartate aminotransferase, 109 U/L; alanine aminotransferase, 115 U/L; alkaline phosphatase, 467 U/L; lactate dehydrogenase, 503 U/L; and CA 19-9, 82 U/mL. The patient’s geriatrician orders an upper endoscopy, which is within normal limits.
Plain X-rays
Traditional plain film x-rays are widely used for the detection of lung cancers and bone cancers. This form of imaging provides high resolution, but with only limited contrast if there are no calcifications located in the tumor. Chest x-ray screening has not been demonstrated to be effective at reducing mortality from lung cancer. A solitary pulmonary nodule 8 mm or larger in diameter requires further evaluation, including repeat chest x-ray, computed tomography, and possibly biopsy. The skeletal survey, which includes plain x-ray films of the skull, axial skeleton, pelvis, and bilateral extremities, has a key role in the evaluation of patients suspected of having osseous involvement from multiple myeloma.
Mammography
Mammography is the main imaging modality used for the early detection of breast cancer. Mammographic screening programs have been shown to save lives when compared with unscreened populations. Mammography has an overall sensitivity of less than 50%, and efforts are underway to improve its effectiveness as a screening tool. Most mammography performed today is based on newer digital imaging systems. A recently completed trial involving over 50,000 women (Digital Mammographic Imaging Screening Trial) found comparable efficacy compared to plain x-ray mammography. Digital mammography is superior for woman with radiodense breasts and those younger than age 50. The sensitivity for digital mammograms is 41%, with 98% specificity and a positive predictive value of 12%. A newer mammographic imaging technique, tomosynthesis, which generates a number of “slices” of the breast for analysis, has shown encouraging results.
Ultrasound
Ultrasound produces high-resolution images from high-frequency sound waves, and its use has many applications in cancer diagnosis. This form of imaging avoids ionizing agents and contrast agents. It is very effective in distinguishing solid from cystic masses, and is an important tool for evaluating breast abnormalities. It is also helpful in locating and evaluating palpable lesions that are not visible with mammography. MRI with ultrasound can also provide accurate imaging guidance for biopsy procedures and information regarding blood flow intensity and direction in affected vascular structures. Ultrasound images are most widely used for the detection of gynecological, liver, and neck malignancies. Endoscopic ultrasound (EUS), also known as echoendoscopy, combines the techniques of endoscopy with ultrasound imaging technologies and is useful for the diagnosis of esophageal cancer, pancreatic cancer, and rectal cancer. High-intensity focused ultrasound has been utilized as a therapeutic option for ablation of localized breast and prostate cancer.
Computed Tomography
CT scans today have a central role in the diagnosis, staging, and surveillance of cancer because of their ability to offer cross-sectional imaging. This technology has rapidly evolved, with increasing simultaneous imaging slices up to 256, and rotational speeds that allow a whole body scan with a single breath hold. Additional advancements have led to three-dimensional reconstruction and angiography. While CT scans can demonstrate detailed measurements of tumor size and location, intravenous and oral contrast must be used in a coordinated function to obtain optimal images. Some major disadvantages of CT include total radiation dose, renal toxicity and allergic reactions to intravenous contrast, and high financial cost. Triphasic CT scanning (arterial phase, portal venous phase, venous phase after a delay) of a suspicious liver lesion greater than 2 cm and demonstrating classic arterial enhancement is sufficient for making the diagnosis of hepatocellular carcinoma. There has been increasing concern about the carcinogenic potential of multiple diagnostic CT scans. Results from epidemiological studies of medical diagnostic radiation exposure have found that cancer risk from all forms of ionizing radiation is cumulative. The only consistently established link involves exposure to medical radiation during pregnancy and the subsequent risk of pediatric cancer in these children. Thus for the geriatric patient, the risk to the individual patient is minimal, and the benefit/risk balance favors the older patient. The current research evaluating the cancer risk of CT scans when used for symptomatic screening has yet to establish any evidence-based guidelines.
Magnetic Resonance Imaging
MRI scanning offers another form of anatomic imaging without ionizing radiation, and provides superior soft tissue contrast and spatial resolution. MRI is the imaging modality of choice for primary and metastatic tumors of the brain and spinal cord, as well as for musculoskeletal tumors. It also plays an important role in the detection of breast cancer in women with dense breast tissue, and in the diagnosis of soft tissue sarcoma and hepatocellular carcinoma. Today’s MRI machines, at a strength of 1.5 to 3 Tesla units (T), are capable of rapid-pulse sequences and gating of images, allowing the visualization of blood with the use of contrast materials such as gadolinium. As the speed of MRI image acquisition improves and better contrast enhancement is developed, the applications for cancer imaging will only increase. Absolute contraindications for MRI scanning that are especially common in the elderly include cardiac pacemakers, ocular metal, and significantly reduced creatinine clearance. Nephrogenic systemic fibrosis (NSF) has recently been linked to gadolinium-based contrast agents (GBCA). The practitioner should avoid use of these agents in patients whose glomerular filtration rate is less than 30 mL/min/1.73 m unless the diagnostic information is essential and cannot be obtained with noncontrast MRI or other imaging modalities. The technique of diffusion MRI images, used widely for strokes, has showed promise in measuring the response to treatment of brain tumors. This imaging method, which can distinguish between dead and living brain tumor cells, allows assessment of the cancer for therapeutic effectiveness without relying on measurable changes in tumor size.
Nuclear Medicine
Radionuclide bone scans are commonly used to detect bone metastases from such primary malignancies as breast and prostate cancers. The most commonly used isotope for single-photon imaging is technetium-99m, which can be used to image bone (bone scan with 99m Tc -diphosphonate) or thyroid (technetium pertechnetate). In multiple myeloma, the radionuclide bone scan may be falsely negative because of purely osteolytic lesions. Neuroendocrine tumors of the gastrointestinal tract are often located using radiolabeled somatostatin analogues. Metaiodobenzylguanidine (MIBG), which is structurally similar to noradrenaline, can be radiolabeled with radioiodine ( 123 I) and has a sensitivity of approximately 90% for the detection of pheochromocytoma.
The detection of sentinel nodes has an important role in breast cancer and melanoma. Lymphoscintigraphy involves injection of a radiopharmaceutical such as 99m Tc-labeled colloid particles and use of a hand-held gamma probe to localize a focus of increased radioactivity. This technique is highly effective in detecting involved local regional lymph nodes. Therapeutic isotope applications include iodine-131 for the treatment of thyroid cancer, and a CD20 monoclonal antibody linked to the radioactive isotope yttrium-90 (Zevalin) used in refractory B-cell non-Hodgkin lymphoma.
Positron Emission Tomography
Positron emission tomography (PET) allows functional imaging by using intravenous radiolabeled metabolic tracers such as 18-fluorodeoxyglucose (FDG). PET imaging is most sensitive in fast-growing tumors with strong metabolic activity such as head and neck and colon cancers, melanoma, and aggressive lymphoma. When PET scan is performed with concurrent CT scanning, functional and anatomic information can be obtained rapidly, allowing for more accurate decision making. Initial evaluation of both Hodgkin and non-Hodgkin lymphoma is increasingly performed with PET-CT scanning because of its increased sensitivity, with the ability to detect 20% more malignant lesions, including bone marrow and splenic involvement. It also has an important role in determining whether complete response has been achieved for those lymphomas that were PET-avid at the time of diagnosis. There is also substantial evidence that PET-CT is superior to CT alone for colon cancer patients in recurrent cancer is suspected after previous surgical resection. An increasing amount of research supports the use of PET-CT in determining the need to pursue invasive testing for a solitary pulmonary nodule suspected of cancer. In a recent retrospective meta-analysis, PET-CT showed a sensitivity of approximately 96% and a specificity of approximately 80% for detecting cancer in solitary pulmonary nodules (predominantly ≥1 cm in diameter). ( Table 3.1 ).
| Tumor | CT (Contrast) Staging Accuracy | PET-CT Staging Accuracy | PET-CT Staging Sensitivity/Specificity |
|---|---|---|---|
| Lymphoma | 67% | 93% | 93/100 |
| Lung Cancer/ Solitary Lung Nodule | 85% | 93% | 96/88 |
| Head and Neck Cancer | 74% | 94% | 98/92 |
| Colorectal Cancer | 65% | 89% | 86/67 |
| Thyroid Cancer | 75% | 93% | 95/91 |
| Breast Cancer | 77% | 86% | 84/88 |
| Melanoma | 86.3% | 98.4% | 94.9/100 |
Plain X-rays
Traditional plain film x-rays are widely used for the detection of lung cancers and bone cancers. This form of imaging provides high resolution, but with only limited contrast if there are no calcifications located in the tumor. Chest x-ray screening has not been demonstrated to be effective at reducing mortality from lung cancer. A solitary pulmonary nodule 8 mm or larger in diameter requires further evaluation, including repeat chest x-ray, computed tomography, and possibly biopsy. The skeletal survey, which includes plain x-ray films of the skull, axial skeleton, pelvis, and bilateral extremities, has a key role in the evaluation of patients suspected of having osseous involvement from multiple myeloma.
Mammography
Mammography is the main imaging modality used for the early detection of breast cancer. Mammographic screening programs have been shown to save lives when compared with unscreened populations. Mammography has an overall sensitivity of less than 50%, and efforts are underway to improve its effectiveness as a screening tool. Most mammography performed today is based on newer digital imaging systems. A recently completed trial involving over 50,000 women (Digital Mammographic Imaging Screening Trial) found comparable efficacy compared to plain x-ray mammography. Digital mammography is superior for woman with radiodense breasts and those younger than age 50. The sensitivity for digital mammograms is 41%, with 98% specificity and a positive predictive value of 12%. A newer mammographic imaging technique, tomosynthesis, which generates a number of “slices” of the breast for analysis, has shown encouraging results.
Ultrasound
Ultrasound produces high-resolution images from high-frequency sound waves, and its use has many applications in cancer diagnosis. This form of imaging avoids ionizing agents and contrast agents. It is very effective in distinguishing solid from cystic masses, and is an important tool for evaluating breast abnormalities. It is also helpful in locating and evaluating palpable lesions that are not visible with mammography. MRI with ultrasound can also provide accurate imaging guidance for biopsy procedures and information regarding blood flow intensity and direction in affected vascular structures. Ultrasound images are most widely used for the detection of gynecological, liver, and neck malignancies. Endoscopic ultrasound (EUS), also known as echoendoscopy, combines the techniques of endoscopy with ultrasound imaging technologies and is useful for the diagnosis of esophageal cancer, pancreatic cancer, and rectal cancer. High-intensity focused ultrasound has been utilized as a therapeutic option for ablation of localized breast and prostate cancer.
Computed Tomography
CT scans today have a central role in the diagnosis, staging, and surveillance of cancer because of their ability to offer cross-sectional imaging. This technology has rapidly evolved, with increasing simultaneous imaging slices up to 256, and rotational speeds that allow a whole body scan with a single breath hold. Additional advancements have led to three-dimensional reconstruction and angiography. While CT scans can demonstrate detailed measurements of tumor size and location, intravenous and oral contrast must be used in a coordinated function to obtain optimal images. Some major disadvantages of CT include total radiation dose, renal toxicity and allergic reactions to intravenous contrast, and high financial cost. Triphasic CT scanning (arterial phase, portal venous phase, venous phase after a delay) of a suspicious liver lesion greater than 2 cm and demonstrating classic arterial enhancement is sufficient for making the diagnosis of hepatocellular carcinoma. There has been increasing concern about the carcinogenic potential of multiple diagnostic CT scans. Results from epidemiological studies of medical diagnostic radiation exposure have found that cancer risk from all forms of ionizing radiation is cumulative. The only consistently established link involves exposure to medical radiation during pregnancy and the subsequent risk of pediatric cancer in these children. Thus for the geriatric patient, the risk to the individual patient is minimal, and the benefit/risk balance favors the older patient. The current research evaluating the cancer risk of CT scans when used for symptomatic screening has yet to establish any evidence-based guidelines.
Magnetic Resonance Imaging
MRI scanning offers another form of anatomic imaging without ionizing radiation, and provides superior soft tissue contrast and spatial resolution. MRI is the imaging modality of choice for primary and metastatic tumors of the brain and spinal cord, as well as for musculoskeletal tumors. It also plays an important role in the detection of breast cancer in women with dense breast tissue, and in the diagnosis of soft tissue sarcoma and hepatocellular carcinoma. Today’s MRI machines, at a strength of 1.5 to 3 Tesla units (T), are capable of rapid-pulse sequences and gating of images, allowing the visualization of blood with the use of contrast materials such as gadolinium. As the speed of MRI image acquisition improves and better contrast enhancement is developed, the applications for cancer imaging will only increase. Absolute contraindications for MRI scanning that are especially common in the elderly include cardiac pacemakers, ocular metal, and significantly reduced creatinine clearance. Nephrogenic systemic fibrosis (NSF) has recently been linked to gadolinium-based contrast agents (GBCA). The practitioner should avoid use of these agents in patients whose glomerular filtration rate is less than 30 mL/min/1.73 m unless the diagnostic information is essential and cannot be obtained with noncontrast MRI or other imaging modalities. The technique of diffusion MRI images, used widely for strokes, has showed promise in measuring the response to treatment of brain tumors. This imaging method, which can distinguish between dead and living brain tumor cells, allows assessment of the cancer for therapeutic effectiveness without relying on measurable changes in tumor size.
Nuclear Medicine
Radionuclide bone scans are commonly used to detect bone metastases from such primary malignancies as breast and prostate cancers. The most commonly used isotope for single-photon imaging is technetium-99m, which can be used to image bone (bone scan with 99m Tc -diphosphonate) or thyroid (technetium pertechnetate). In multiple myeloma, the radionuclide bone scan may be falsely negative because of purely osteolytic lesions. Neuroendocrine tumors of the gastrointestinal tract are often located using radiolabeled somatostatin analogues. Metaiodobenzylguanidine (MIBG), which is structurally similar to noradrenaline, can be radiolabeled with radioiodine ( 123 I) and has a sensitivity of approximately 90% for the detection of pheochromocytoma.
The detection of sentinel nodes has an important role in breast cancer and melanoma. Lymphoscintigraphy involves injection of a radiopharmaceutical such as 99m Tc-labeled colloid particles and use of a hand-held gamma probe to localize a focus of increased radioactivity. This technique is highly effective in detecting involved local regional lymph nodes. Therapeutic isotope applications include iodine-131 for the treatment of thyroid cancer, and a CD20 monoclonal antibody linked to the radioactive isotope yttrium-90 (Zevalin) used in refractory B-cell non-Hodgkin lymphoma.
Positron Emission Tomography
Positron emission tomography (PET) allows functional imaging by using intravenous radiolabeled metabolic tracers such as 18-fluorodeoxyglucose (FDG). PET imaging is most sensitive in fast-growing tumors with strong metabolic activity such as head and neck and colon cancers, melanoma, and aggressive lymphoma. When PET scan is performed with concurrent CT scanning, functional and anatomic information can be obtained rapidly, allowing for more accurate decision making. Initial evaluation of both Hodgkin and non-Hodgkin lymphoma is increasingly performed with PET-CT scanning because of its increased sensitivity, with the ability to detect 20% more malignant lesions, including bone marrow and splenic involvement. It also has an important role in determining whether complete response has been achieved for those lymphomas that were PET-avid at the time of diagnosis. There is also substantial evidence that PET-CT is superior to CT alone for colon cancer patients in recurrent cancer is suspected after previous surgical resection. An increasing amount of research supports the use of PET-CT in determining the need to pursue invasive testing for a solitary pulmonary nodule suspected of cancer. In a recent retrospective meta-analysis, PET-CT showed a sensitivity of approximately 96% and a specificity of approximately 80% for detecting cancer in solitary pulmonary nodules (predominantly ≥1 cm in diameter). ( Table 3.1 ).
| Tumor | CT (Contrast) Staging Accuracy | PET-CT Staging Accuracy | PET-CT Staging Sensitivity/Specificity |
|---|---|---|---|
| Lymphoma | 67% | 93% | 93/100 |
| Lung Cancer/ Solitary Lung Nodule | 85% | 93% | 96/88 |
| Head and Neck Cancer | 74% | 94% | 98/92 |
| Colorectal Cancer | 65% | 89% | 86/67 |
| Thyroid Cancer | 75% | 93% | 95/91 |
| Breast Cancer | 77% | 86% | 84/88 |
| Melanoma | 86.3% | 98.4% | 94.9/100 |
Cancer Pathology
The treatment of cancer is almost always based on analysis of tissue pathology. With the exception of hepatocellular carcinoma and emergent situations such as acute leukemia with leukostasis, the first step after detection
CT scan of the abdomen with/without intravenous contrast showed dilatation of the gallbladder and the intrahepatic and extrahepatic biliary tree, with a 5 cm mass in the head of the pancreas. A histological diagnosis of adenocarcinoma of the pancreas was made by CT-guided fine needle aspiration (FNA) biopsy.
Pancreatic cancer is the fourth most common cause of cancer-related death for men in the United States. Its peak incidence occurs in the seventh and eight decades of life. When the index of suspicion for pancreatic cancer is high, CT scan should be performed with the “pancreas protocol” (triphasic cross-sectional imaging and thin slices). Endoscopic ultrasound (EUS) is frequently used to further evaluate pancreatic masses and determine the degree of periampullary invasion. Endoscopic ultrasound also provides useful staging information such as the assessment of vascular invasion. Reviews of surgical studies have found that curative pancreaticoduodenectomy (Whipple procedure) can be performed safely in selected patients younger than 80, with morbidity rates, mortality rates, and cost analysis similar to those achieved with younger patients.
K.T. is an 80-year-old married woman, with a past medical history of insulin-dependent diabetes mellitus, chronic renal insufficiency, and atrial fibrillation, who presents to her geriatrician for further evaluation after noticing persistent right cervical adenopathy, which is painless. She reports increased fatigue and a low grade fever. Her hemoglobin level is 11.5 g/µL, with a white blood cell count of 6,500/µL, and a platelet count of 330,000/µL. The serum lactate dehydrogenase level is 720 U/L. Renal and liver function are normal. Her physical examination is unremarkable and her weight has been stable.
Fine Needle Aspiration/Image Guided Biopsy
The technique of fine needle aspiration (FNA), which utilizes a fine-gauge needle to obtain a sample of cells from a suspicious mass, has been a cornerstone of diagnosis for many cancers, such as carcinoma of the thyroid. It
P.M. is a 72-year-old married woman, with a past medical history of insulin-dependent diabetes mellitus, hypertension, gout, and nephrolithiasis, who presents to her geriatrician for further evaluation after a routine complete blood count (CBC) found a significant white blood cell count: leukocytes 35,000/μL with 88% lymphocytes. The hemoglobin level is 12.5 g/dL, and the platelet count is 320,000/μL. She is feeling well and denies weight loss, night sweats, fatigue, shortness of breath, skin changes, or recent infection. Her physical examination is positive for mild splenomegaly (spleen palpable 2 to 3 cm below the costal margin), but is otherwise unremarkable. She has no clinical evidence of lymphadenopathy, or of abnormal bruises.
Immunohistochemistry
Light microscopy utilizing conventional hematoxylin-eosin (HE) staining is central to determining the gross structure of the tumor, such as distinguishing between adenocarcinoma and neuroendocrine solid tumors and evaluating important parameters such as the nuclear/cytoplasmic ratio of lymphoma tumor cells. Immunohistochemical staining (IHC) is a technique for identifying and classifying malignant cells by means of antigen-antibody interactions used in conjunction with standard light microscopy. IHC is widely used to analyze the distribution and localization of biomarkers and differentially expressed proteins in tumor biopsy samples. The site of antibody binding can be identified either by direct labeling of the antibody, or by a secondary labeling method. Its most common use is in immunoperoxidase staining, wherein an antibody is conjugated to the enzyme peroxidase, producing a colored chemical reaction. Although not always able to provide a specific diagnosis, these stains can often aid in the differential diagnosis of carcinomas, lymphomas, melanoma, and certain sarcomas when used in conjunction with routine histological examination. Immunofluorescence is an antigen-antibody reaction in which the antibodies are tagged with a fluorescent dye such as such as fluorescein or rhodamine, and the antigen-antibody complex is visualized using an ultraviolet (fluorescent) microscope. Specific cytokeratin proteins that are components of the cytoskeleton of epithelial cells found on certain cancer cells are often identified this way and play an important role in diagnosis. One example of this is discriminating between the diagnosis of primary lung acinar adenocarcinoma and lung metastasis of colorectal cancer. Positive staining of CK7 was observed in most of the primary lung adenocarcinoma samples and positive staining of CK20 was observed in most lung metastases of colorectal cancer.
Flow Cytometry, Cytogenetics, Molecular Testing, and Cancer Diagnosis
Flow cytometry is a method of measuring the number of cells in a sample, and certain characteristics of cells, such as size, shape, and the presence of tumor markers on the cell surface. The cells are stained with a light-sensitive dye, placed in a fluid, and passed in a stream before a laser or other type of light. The measurements are based on how the light-sensitive dye reacts to the light. Among the most common clinical uses of flow cytometry in cancer diagnosis is the classification of chronic lymphoproliferative disorders and acute hematological malignancies.48 Acute and chronic leukemia display characteristic patterns of surface antigen expression (CD antigens), which facilitate their identification and proper classification and hence play an important role in instituting proper treatment plans. For example, flow cytometry plays a decisive role in distinguishing acute promyelocytic leukemia (APL) from other forms of acute myeloid leukemia (AML), and therefore is critical to determining the initial treatment.49 Cytogenetic testing involves examining the chromosomes in a cell to detect any abnormality characteristic of a malignancy, such as translocation, inversion, deletion, or duplication. The development of a newer cytogenetic process called fluorescence in situ hybridization (FISH) has expanded molecular diagnostic capabilities. FISH uses special fluorescent dyes to recognize specific chromosome changes in certain types of cancer. The DNA from a biopsy sample is combined with a fluorescently-labeled probe, such as the one for HER-2/neu-positive breast cancer, that is visible under fluorescent microscopy.50-51 Another DNA analysis technique, called polymerase chain reaction (PCR), which makes possible the rapid amplification of DNA, is used to detect the bcr-abl oncogene in blood or bone marrow when the myeloproliferative neoplasm (MPN) chronic myeloid leukemia (CML) is suspected.52 ( Tables 3.2 and 3.3 ).
The patient was referred to a head and neck surgeon who performs fine needle aspiration (FNA). Cytology studies demonstrate small cleaved lymphocytes and flow cytometry shows a CD5-negative, CD10-positive, CD20-positive monoclonal population suspicious for non-Hodgkin lymphoma (NHL). However, FNA is not adequate to make a diagnosis of lymphoma. The presence of a monoclonal cell population with a CD10-positive immunophenotype is highly suggestive of follicular lymphoma, but an accurate diagnosis cannot be made without lymph node architecture. Furthermore, FNA cannot determine the histological grade of the follicular lymphoma, which strongly influences treatment choice. NHL is the ninth leading cause of cancer deaths among men and the sixth among women. The incidence of NHL has increased significantly in the past three decades, especially in patients in the sixth and seventh decade of life.
| Genetic Abnormality | Disease | Frequency |
|---|---|---|
| BCR-ABL | Chronic myelogenous leukemia | ≈99% |
| JAK2V617F |
|
|
| JAK2 exon 12 | Polycythemia vera | ≈2% |
| PDGFRA |
| Undetermined |
| PDGFRB | Myeloid neoplasm +eosinophilia | Undetermined |
| KIT (D816V) | Mast cell disease | Undetermined |
| Disorder | Positive | Negative |
|---|---|---|
| Large B-cell lymphoma | CD19, CD20, CD22, CD79a, | CD2, CD3, CD5, CD7 |
| Follicular small cleaved cell lymphoma | CD10, CD19, CD20, CD21, CD22, CD24, | CD2, CD3, CD4, CD5, CD7, CD8, CD11c, CD23, CD25, CD43 |
| Mantle cell lymphoma | CD5, CD19, CD20, CD22, CD24, CD43, | CD11c, CD23, CD5/CD19 or CD5/CD20 |
| Hairy cell leukemia | CD11c, CD19, CD20, CD22, CD25, CD79a, CD103 | CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD23 |
| Acute promyelocytic leukemia, M3 | CD13, CD15, CD33 | CD2, CD3, CD5, CD7, CD11b, CD14, CD41, CD42, CD61, CD71 |
| Acute megakaryoblastic leukemia, M7 | CD33, CD41, CD42, CD61 | CD2, CD3, CD5, CD7, CD11b, CD13, CD14, CD15, CD71 |
| ALL (T-cell precursor) | CD3, CD7 | CD10, CD19, CD20, CD22 |
| ALL (pre-B) | CD10, CD19, CD22, CD79a | CD3, CD4, CD5, CD7, CD8 |
| Sézary syndrome (mycosis fungoides) | CD2, CD3, CD4, CD5 | CD1, CD7, CD8, CD10, CD11c, CD16, CD19, CD20, CD22, CD25, CD56, CD57 |
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