A 36-year-old woman presented for follow-up of a persistently abnormal Papanicolaou (Pap) test. She is a smoker and has had multiple new sexual partners in the last few years. Although she has had several “abnormal Pap tests” in the past, she states she has never needed treatment. She was found to have a dense acetowhite (AW) lesion on colposcopy that was biopsied (Figure 90-1). The pathology returned cervical intraepithelial neoplasia grade 3 (CIN 3) and the patient was treated with loop electrosurgery. She had negative margins on the loop electrosurgical excision procedure specimen and remained recurrence-free at 3 years.
Dense acetowhite (white after application of vinegar) lesions with “rolled” edges in a patient with high-grade disease. Her colposcopically directed biopsies showed cervical intraepithelial neoplasia grade 3. (Courtesy of E.J. Mayeaux, Jr., MD.)
High-grade squamous intraepithelial lesions in adult women are considered true cancer precursors because if left untreated, they have a significant chance of developing into invasive cancer.
Cervical intraepithelial neoplasia (CIN 3 and CIN 2) are high-grade lesions.
- Overall rates of Pap test abnormalities are usually estimated from local or regional studies. For example, in an observational cohort study of routine cervical tests in the Northwest United States, in women of all ages (n = 150,052), high-grade squamous intraepithelial lesion was diagnosed at a rate of 0.8 per 1000 compared to negative routine tests that were diagnosed at a rate of 278.5 per 1000.1
- In high-grade squamous intraepithelial lesions, the abnormalities are immature parabasilar cell types. They have an increased nuclear-to-cytoplasmic ratio, enlarged hyperchromatic nucleoli, few nucleoli, and a reticular or granular appearance.
- On histology, abnormal maturation and nuclear atypia defines CIN. Koilocytosis (perinuclear cytoplasmic vacuolization) is indicative of human papillomavirus (HPV) infection and may be found with high-grade CIN. High-grade CIN is diagnosed when immature basaloid cells with nuclear atypia occupy greater than the lower one third of the epithelium. With increasing lesion severity, there is also increased nuclear crowding, pleomorphism, normal and abnormal mitosis, and loss of polarity.2
- Traditionally, high-grade CIN is thought to arise as a small focus within a larger area of low-grade CIN that expands and eventually replaces much of the low-grade lesion.
- This “monoclonal” theory is supported by the fact that there is a 5-year difference between the peak prevalence of CIN 1 and CIN 2 or 3, and detection of a low-grade squamous intraepithelial lesion. Pap greatly increases the risk that a high-grade CIN will be found on subsequent tests.
- It has been difficult to document the rate of progression because most studies use cervical biopsy to establish an accurate diagnosis, which influences the rate of disease progression.
- With the discovery that most CIN 1 lesions regress or persist, the question has been raised as to whether high-grade CIN might be a process that develops concurrently ...