High-Grade Squamous Intraepithelial Lesion

Because the Bethesda System combines moderate and severe dysplasia together with carcinoma in situ in the HSIL category, there is wide variation in the cytological appearance of HSIL. When applying the 2001 Bethesda System, many cytopathologists utilize the option of subdividing HSIL into CIN 2 and CIN 3 lesions. As the severity of the lesion increases, the degree of differentiation and the amount of cytoplasm decreases, the nuclear: cytoplasmic ratio increases, and the degree of nuclear atypia also increases. HSIL of the moderate dysplasia type typically contains cells similar to those seen in LSIL, as well as atypical immature cells of the parabasal type (Figure 34).

The nuclei of these cells are more hyperchromatic and irregular than typically seen in LSIL. In severe dysplasia, the overall size of the cells is reduced compared to mild and moderate dysplasia, but because the cells demonstrate minim al differentiation, the nuclear: cytoplasmic ratio is greatly increased. In severe dysplasia, there are usually considerably greater numbers of neoplastic cells that are typically found individually.

Carcinoma in situ can be of the small-cell type, of the large-cell non-keratinizing type or of the large-cell keratinizing (pleomorphic) type. Although separation of carcinoma in situ into these three different cytological types has little clinical significance, all three have quite different cytological appearances. Small-cell lesions consist of small basal-type cells similar to those seen in severe dysplasia but which demonstrate even less cy toplasm and higher nuclear: cytoplasmic ratios (Figure 35).

Because of their small size, these cells can easily be overlooked during routine screening and such cases account for a disproportionate percentage of false negative cytological results. The cells of large-cell non-keratinizing lesions typically form syncytial-like cell sheets in which individual cell membranes are difficult to identify. These cells have enlarged, hyperchromatic nuclei and minimal amounts of cytoplasm. The keratinizing large-cell type of carcinoma in situ is composed of pleomorphic, highly atypical cells, many of which have thick keratinized cytoplasm. These cells are often spindled or tadpole-shaped and have extremely dense nuclear chromatin (Figure 36).