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7.1 The microscopic interpretation of cells can be limited by several factors. Discuss the nature of this problem and suggest ways in which diagnostic reliability can be improved, now and in the future.
Factors affecting the cytological interpretation of cells can be related to the cytologist, the specimen, the disease process being considered, or indeed the external environment. Cytologist-related factors include the scope and depth of training, level of experience, diagnostic reasoning skills, and even fatigue and stress. Specimen-related factors refer to the quality of specimen collection and laboratory processing. Diseases themselves also play a part in the diagnostic process. For instance, a rare cancer will almost certainly be a more difficult diagnosis to make than a more common disease, simply because the cytologist does not encounter it frequently. A wide variety of environmental factors may also influence the ability of the cytologist to make an accurate diagnosis. Factors such as the working environment (e.g. heating, lighting, temperature, ventilation, noise levels, etc.) and the design of the workstation (e.g. microscope ergonomics, seating, and benching) should never be underestimated. Improvements in diagnostic accuracy and reliability therefore require a multipronged approach. Cytologists and laboratory managers must address all of the factors that influence diagnostic reliability in order to maximize the clinical value of cytology. Improvements in adjunctive testing such as immunocytochemistry and molecular diagnostics will no doubt also play their part in the future.
7.2 The most common question asked of the cytopathology department is, ‘are malignant cells present?’ What other questions might the clinician be interested in, and to what extent can cytopathology answer these?
Depending on the nature of the clinical problem clinicians may also be interested to find out whether pre-malignant cells are present (e.g. cervical cytology) or if malignant cells are absent (although of course this can never guarantee a clean bill of health). Even if the cytologist is unable to provide a definitive diagnosis the clinical management of a patient can be improved by a more limited cytological report. For instance, a clinician might decide to perform a fine needle aspirate of a clinically worrying ‘lump in the neck’ in an elderly patient with a long history of heavy smoking. There are several possible explanations for such a clinical presentation, from a simple cyst or abscess, to metastatic lung cancer. Even if the cytologist is uncertain of the diagnosis, by providing the clinician with a complete description of the contents of the aspirate it might be possible to delay or even avoid potentially dangerous or disfiguring facial surgery. For example, the presence in the aspirate of a mixture of white blood cells, macrophages, and cellular debris, whilst in themselves non-diagnostic, suggests the possibility of a cyst and the clinician need not immediately consider surgery. The finding of cancer cells that the cytologist finds otherwise unclassifiable is also very valuable information in that it may guide the clinician towards an investigation for lung cancer. If metastatic lung cancer is confirmed then removal of the neck lump will not benefit the patient, who can therefore be spared unnecessary surgery. To summarize, although cytology can provide a definitive diagnosis of a number of disease processes, it rarely answers all the questions that a clinician might have. However, by providing a complete microscopic description of the nature of the specimen the clinician can be usefully guided towards further investigations.
7.3 Discuss the contribution made by cytologists in screening for and diagnosis of neoplastic conditions.
The contribution of cytology to screening for early neoplastic disease in asymptomatic individuals is currently confined to cervical neoplasia. Although several attempts have been made to validate cytology as a screening test for other neoplastic conditions (e.g. oral cancer, bladder cancer, and oesophageal cancer), these efforts have been largely unsuccessful. However, cytology is of proven benefit in the diagnosis of cancer in symptomatic patients. The reason is that whilst the sensitivity of cytology can be limited, its specificity is often superior to the most sophisticated imaging techniques and other diagnostic modalities currently available. This means that when a cytology laboratory issues a report of malignant cells then this report is highly reliable. In some cases the degree of certainty is sufficient to proceed to treatment without the need for further investigations.
7.4 Sensitivity and specificity are important indicators of the usefulness of diagnostic cytology, but achieving perfection in either of these measures is rarely possible. In the diagnostic setting (i.e. when a patient has symptoms that might indicate a neoplastic condition), explain why the maintenance of high levels of specificity might be considered to be more important than high sensitivity.
Maintaining high diagnostic specificity is often given greater priority than diagnostic sensitivity when cytology is used to investigate symptomatic patients. This is because of the desire to minimise the occurrence of false positives in this group of patients, which could lead to unnecessary further investigations and treatment for a condition that does not exist. The emotional and physical harm that can result from cytological false positives should not be underestimated. Maintaining high sensitivity (i.e. minimising the occurrence of false negatives) is not so important in symptomatic patients, since these patients will continue to be investigated to discover the underlying cause of their symptoms, regardless of a negative cytology result.
7.5 Explain why cytology textbooks go to great lengths to describe non-pathological entities such as metaplasia, atrophy, cell degeneration, and regeneration.
It could be argued that non-pathological entities such metaplasia, inflammation and atrophy should be of no concern to cytologists or patients because such conditions are of no clinical concern. However, the main reason for describing benign processes in cytology text books and atlases is to familiarise the cytologist with the full range of normal cellular features that could be mistaken for neoplasia. As noted in the answer to question 4, false positive reports can cause distress to patients and lead to unnecessary interventions, and should be avoided wherever possible.