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Morphometric and Cell Kinetic Characteristics in The Diagnosis and Prognosis of Neoplasms

The majority of cytologic and histopathologic diagnoses still rely on the basic light microscopy interpretation, based on visual perception and clearly defined diagnostic criteria for each particular disease. Yet, different interpretations and variations in reproducibility (inter- and intra-morphologist) are possible in various neoplasms as well as in inflammatory diseases and other pathologic events. The problem of reproducibility may even increase with the inclusion of prognostic criteria such as grade of differentiation, mitotic activity, etc. Nowadays, optimal treatment demands from the morphologist more than simple distinction between the malignant and the benign. Additional information is necessary to identify patients at an increased risk of recurrence or those with rapid disease progression, and to detect disease recurrence before its clinical manifestation. Furthermore, identification of precancerous lesions in a population at a high risk of malignancy may help in planning the approach of surveillance strategy. In the last years, efforts have been invested to improve diagnostic accuracy and to obtain new, more appropriate and objective information on the process through the introduction of sophisticated computer technologies. Malignant cell alteration leads to changes at the cell, cytoplasm, nucleus and nuclear structure levels, the latter being most numerous. Cell enlargement is most common, resulting in an increased nucleus/cytoplasmic (N/C) ratio and morphologic changes characteristic of particular tumor types. Pronounced pleomorphism and nuclear multinucleation or multilobulation are important nuclear characteristics of malignant growth. Chromatin structure may show hypo- or hyperchromatism as a reflection of abnormal DNA amount due to pathologic mitosis and an increased number of nuclei in the synthetic phase of preparation for mitosis. Both of these parameters, DNA amount and proliferative activity, reflect in abnormal cell function ; abnormal DNA amount characterizes malignant and premalignant cells, whereas considerably increased proliferative activity is associated with neoplasia and biological tumor behavior. Within the nucleus, the number and size of nucleoli increase, along with changes that occur in the nucleolar substructure, the nucleolar organizer region (NOR). Generally, tumor cell nuclear morphology is highly relevant for two reasons. First, the substructure may provide diagnostic help in the identification of specific tumor types. Second, abnormalities of nuclear morphology play a major role in tumor staging. All these alterations can be numerically objectified by computer technologies through analysis of the morphometric characteristics of the cell as a whole, the nucleus and nuclear structures (AgNOR), and by determination of DNA amount using image DNA cytometry.

image analysis; image DNA cytometry; AgNOR

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