Abeloff's Clinical Oncology, 4th Edition

Part I – Science of Clinical Oncology

Section C – Diagnosing Cancer: Pathology and Laboratory Medicine



The number and types of diagnostic modalities available to characterize cancer has increased dramatically over the past few decades. Although histopathologic diagnosis using techniques that date back over a century remains the gold standard, radiologic techniques are becoming increasingly precise diagnostic instruments, and more and more supplemental laboratory techniques are becoming critical to accurate diagnosis. These latter methods, including cytogenetics and flow cytometry, first introduced in the 1970s and 1980s, and molecular pathology, a more recent addition, greatly expand the armamentarium of tests now available. The past few years has seen an even more rapid evolution in these newer tests. Fluorescence in situ hybridization is a very powerful technique that is changing the way many cytogenetics labs operate. Molecular diagnostics, which originally had a limited test menu largely applicable to hematology, now has a much larger range of tests with applicability to both inherited and sporadic cancers of all types.

Diagnostic radiology is also at a crossroads. The oncologist evaluating a patient can choose among everything from a simple roentgenogram to a complex alphabet of imaging studies—CT, CTA, MRI, MRS, PET, PET/CT and SPECT and SPECT/CT. In the right hands, newer imaging studies have incredible power to improve sensitivity and specificity of diagnosis. In the last several years, PET/CT using the radiotracer 18F-FDG has had a great impact on the management of many common cancers providing staging, treatment planning, and treatment response assessment information more quickly and robustly than by standard anatomic metrics. These technological advances present both opportunity and challenge. The opportunity is to provide better and more accurate methods for detecting and defining the presence of cancer. The challenge is to use the right techniques for the right indications. The overuse of highly sensitive tests results in increased false-positive diagnoses, whereas using highly specific tests inappropriately increases the risk of a false-negative diagnosis. Many newer diagnostic tests are expensive, so that cost is a critically important factor for the clinician to consider, but the cost implications of inappropriate intervention due to inappropriate testing go far beyond the simple expense of the test. Thus, the right algorithm of test use is critical to getting the right diagnosis in the most cost effective and timely manner to optimize patient outcome.

The expertise of the diagnostic pathologist or clinical laboratory scientist is critical in both the selection and interpretation of modern tests for cancer diagnosis. For more subjective tests such as routine histology, flow cytometry, or cytogenetics, experience and skill are well recognized as key determinants for accurate interpretation. More analytically precise tests such as serum tumor marker assays or molecular diagnostics also require a high degree of sophistication by the lab director to ensure the data obtained are accurate and not the result of artifact or sampling error. Experience and skill in both test use and interpretation are critically important in dealing with analytic as well as biologic predictive value. Similarly, for imaging, as in pathology, experience and skill in test use in different modalities such as nuclear medicine, MRI, cross-sectional imaging and ultrasound are critical to optimal use of the technologies to assure that results are robust and technical artifacts are avoided. Given the complexities involved, such expertise may not lie in the hands of a single physician.

The goal of this section is to provide the clinical oncologist with an understanding of the use and interpretation of the current diagnostic modalities available for the evaluation of cancer patients. The goal is not to provide an exhaustive review of tests and details that would be more appropriate for pathologists or radiologists. We have somewhat arbitrarily grouped the many laboratory cancer diagnostics that are now available into five chapters: surgical pathology, flow cytometry, cytogenetics, molecular diagnostics, and clinical chemistry; each chapter outlines the methods, applications, and interpretation of the tests in that area. Following these, there is separate chapter on radiologic diagnosis. This section will provide insight on the best use of tests in different settings and pitfalls in interpretation, so as to be of value to clinical oncologists in interacting both with their patients and with their colleagues in pathology, laboratory medicine, and radiology.