Clinical history: 35 year old woman, follow-up LSIL on last PAP.
What is the diagnosis?
High grade squamous intraepithelial lesion is a precursor lesions to invasive squamous cell carcinoma. Approximately 12% of HSIL lesions will progress to squamous cell carcinoma if left untreated. The vast majority of HSIL lesions (97%) are positive for a high risk HPV subtype (types 16 and 18).
Cytologically, the cells are smaller than the mature squamous epithelial cells with a very high N:C ratio. The nuclei are approximately 3x or more the size of a superficial squamous cell and are hyperchromatic with irregular chromatin distribution and irregular nuclear outlines. The cells may be found in small, cohesive clusters with indistinct cell borders or scattered as single cells. Usually the cells lack evidence of squamous differentiation but if keratinization is present, they may still be classified as HSIL if the nuclear features are consistent.
The cells can be differentiated from LSIL by the increased N:C ratio, more hyperchromasia and more nuclear irregularities. Similarly, the irregular nuclear outline and irregular chromatin distribution are not seen in reactive cells, atrophy or squamous metaplasia. Although endometrial cells may have an increased N:C ratio, they usually appear as three-dimensional balls whereas HSIL is usually in flat sheets. HSIL is distinguished from squamous cell carcinoma by the lack of a tumor diathesis.
A diagnosis of HSIL results in the patient being referred to colposcopy and usually undergoes a LEEP or a cold cone biopsy.