Improving diagnostic accuracy into Cytoptahology

Liquid-based cytology (LBC) has been introduced into cytopathology mainly in the field of cervical cytology with the aim of improving diagnostic accuracy. The advantages of thin-layer techniques compared with conventional smears include an optimal viewing of cellular features attributed to the reduction in air-drying artifact and obscuring background elements thus reducing the number of unsatisfactory smears.

Although several disadvantages have been reported with this technique, such as problems related to the reduction or alteration in background and extracellular material, disruption in architectural integrity and altered cellular morphology as well as increased cost of cell preparation, it is now widely accepted that the sensitivity of cervical LBC is similar to the conventional cervical smear, and is superior in high-risk populations.

The clinical utility of LBC has also been explored in non-gynaecological cytology with a relative degree of success. Brandao et al. evaluated the feasibility of grading follicular lymphoma using ThinPrep®(TP) slides and flow cytometry. Counting centroblasts, either in 300 lymphoid cells or per 10 high-power fields in TP slides, represented a statistically significant method to separate different grades of follicular lymphoma in FNA samples. Flow cytometry analysis of cell size was less reliable, especially in differentiating grade 2 from grade 3 tumours.

Similarly, LBC has also been applied to thyroid cytopathology. The cytomorphological features of thyroid FNA on TP preparations have been studied and compared with those obtained and prepared by conventional methods. The sensitivity and specificity levels are higher for conventional smears than for TP (94% versus 81% and 67% versus 60%, respectively).The lower specificity may be related to cytological alterations and reduction in the amount of colloid induced by methanol fixative. In addition, the diagnosis of Hashimoto’s thyroiditis is more difficult on TP slides due to the limited number of lymphocytes.

Automated staining protocols for immunocytochemistry and FISH are now available and, in the context of biomarkers with possible screening value, may become a laboratory tool of choice, provided that rigorous validation studies are carried out beforehand. Similarly, automated scoring of immunohistochemistry and FISH are changing the presumed subjectivity of the qualitative or semi-quantitative analysis of biomarkers with diagnostic or therapeutic implications, and several such systems are available in the market. These methods are beginning to be used for cytology samples as well and, together with strong molecular targets, may provide an automated molecular alternative to conventional screening, as shown recently in the context of sputum cytology.