Final Considerations

Other Situations Presenting Specific Difficulties and Risks

Liquid based cytology

Specific criteria for detection and interpretation using liquid based thin layer preparations are not in the scope of this study. However, these preparations are now widely used and for completeness it should be mentioned that similar diagnostic difficulties and errors occur when using them. Certain aspects of such preparations must be kept in mind when screening and interpreting them. These are as follows:

• Criteria differ slightly as prefixation due to suspension in fluid introduces different artefacts
• Crowded sheets may be under-represented in the sample. 131 Also, nuclear variation may be more subtle in crowded sheets, and chromatin finer than in conventional smears
• Loose cell associations and mucus trails are dispersed
• In AIS some features such as feathering, curved strips and radial polarity, are under represented 132
• Background and diathesis present differently, in small patches rather than throughout the slide
• Abnormal cells may be present in small numbers

Air drying and degeneration

The traditional advice not to diagnose on degenerate material is wise, but as a guide not a prescription. Degenerate material can provide useful diagnostic information, often sufficient to issue a Possible High Grade report. Finding a degenerate high risk pattern will trigger a tuned search that may reveal a few better preserved abnormal cells. Occasionally a confident diagnosis of high grade abnormality is possible, even on degenerate material.
Features of abnormal cell populations that often survive degeneration and air drying:

• Relative nuclear size and local variation

Figure 12

• Local variation in chromasia

Figure 63

• Abnormal nuclear shapes

Figure 109

• N/C ratio

Figure 12

• Tumour diathesis or necrotic debris
• Disturbed polarity

Figure 63

• Crowding

Figure 63

• AIS architecture 79,94 and pinched nuclear moulding

Figure 94

• Variable sticky big bare nuclei

Figure 99

Figure 100

• Pyknotic nuclei are degenerate but their relative corrected size provides reliable and often essential information

Figure 119

Figure 120

Figure 121

• Mitoses and apoptosis

Post Irradiation

Epithelial cellular changes due to radiation therapy may be striking. Radiation changes in squamous cells can
be distinguished from malignancy by the following characteristics: 133

• Enlarged, stretched cytoplasm in some cells
• Hard edged vacuoles, which may be very large
• Engulfment of smaller degenerate cells showing pyknosis or karyorrhexis
• Nuclear enlargement, with some size variation and multinucleation
• Nuclei have smooth borders and fine, bland, pale, evenly distributed chromatin and prominent nucleoli
• When degenerate the enlarged nuclei may be dark, but are smudged
• Moderately reactive parabasal cells, just short of repair, may be present in numerous large sheets

Granulation tissue is common following irradiation. Stromal cells may appear as bizarre dissociated cells but their recognition is aided by:

• Typical stromal features
• Gradation to clearly benign stromal cells
• the context of the typical cell population of granulation, including:
  – Small and giant cell histiocytes
  – Fragments of stroma
  – A range of leukocytes

Epithelial cells may be virtually absent and those present may be reparative.
Persistent and recurrent cancer and post radiation dysplasia exhibit the standard malignant criteria. 38 In any case of doubt, referral for investigation by other means is appropriate. Cytology has little to offer beyond raising suspicion.