9c. Cytological abnormalities

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Criteria for distinguishing normal from abnormal cells

In essence, a cervical screening programme depends on the ability of the cytologist to detect abnormal cells amongst the thousands of normal cells on a Papanicolaou-stained cervical smear or liquid-based cytology preparation using a light microscope. With screening experience and knowledge about the pathological process, the cytologist should be able to predict the histological outcome for the patient.

In cytology, it is very important to strictly apply the morphological criteria to every cell you are questioning. By doing this from the start of your training, you will develop an understanding of the variations between benign, dysplastic/dyskaryotic (pre-neoplastic) and malignant cells.

There are two main components of a cell, the nucleus and the cytoplasm. Generally speaking, the state of nucleus gives information about the health of the cell and the cytoplasm gives clues about the type of cell and its degree of maturation.

A cervical screening programme depends on the ability of the cytology screener to detect dysplastic/dyskaryotic cells
The cytology screener should be able to predict the histological outcome
The state of the nucleus give information about the health of the cell
The cytoplasm gives information about the type of cell and its degree of maturation

Table 9c-1. Criteria for making a diagnosis between benign and neoplastic

Benign criteria	Neoplastic criteria
Chromatin is fine and evenly distributed	Chromatin is course, clumped and unevenly distributed
Nuclear size and shape are within normal physiological limits for the level of maturation of the epithelium	Nuclei showing size and shape variation within the same cell population
Nuclear membranes are even	Nuclear membranes are irregular in outline and show indentation and/or thickening due to chromatin margination and clumping
Nuclei are normochromatic and staining intensity maintained through all cells	Nuclei are usually hyperchromatic and staining varies from one group to the next.
Multinucleation can be seen but rarely (repair, reactive endocervicals)	Multinucleation is common, reflecting rapid cell turnover
Nucleoli are small, even in number and even in size, but may be enlarged but regular in repair/regeneration	If present, nucleoli are large, irregular and vary from nucleus to nucleus; nucleoli are more prominent in cancer than dysplasia/dyskaryosis
Cells are cohesive, architecture is maintained	Loss of cohesiveness (cells coming away from their groups). Nuclei tend to crowd each other in sheets/clusters.
Mitosis normally only occur at the basal layer so are rarely seen in a cervical smear (repair/regeneration)	Mitotic figures may be seen through all the layers of the epithelium

All the variations mentioned in the table above are indicative of the abnormal mitotic activity of dysplastic (pre-cancerous) cells, which have acquired through mutations the ability to evade the physiological controls of cell division.

Invasive squamous cell carcinoma of the cervix is usually preceded by a spectrum of precancerous changes known as cervical intraepithelial neoplasia (CIN), which develops in the metaplastic squamous epithelium at the transformation zone of the cervix. CIN may be present in the cervix for many years before an invasive lesion develops; CIN may regress, persist or progress.

Three grades of CIN are recognised with increasing risk of progression and decreasing likelihood of regression: CIN1, CIN2 and CIN3; CIN3 equates to carcinoma in situ. CIN1 is closely associated with human papillomavirus (HPV) infection from which it cannot reliably be distinguished

Adenocarcinoma of the cervix is rare compared with squamous cell carcinoma and may be preceded by high-grade cervical glandular intraepithelial neoplasia (CGIN), which equates to adenocarcinoma in situ (AIS). Low-grade CGIN is recognised but seldom diagnosed.

The cellular changes of squamous cell carcinoma and adenocarcinoma are also seen in CIN and CGIN and are represented in cytological preparations. The degree of abnormality may be recognised as low-grade or high-grade; invasion may be suggested on cytology but is only diagnosed on histology. The distinction of these abnormalities from benign and reactive changes provides the basis for the Pap [Papanicoloau] test.

The morphological terminology used in this chapter is in accordance with the Bethesda system (TBS) (Nayar & Solomon 2004; Nayar & Wilbur 2015). The EU guidelines recommend that terminologies should be translatable into TBS (Herbert et al. 2007), which allows the use of the term dyskaryosis, as in the UK terminology (Denton et al. 2008), and dysplasia.