Definition
• Cytological and architectural atypia of squamous epithelium occurring as single or multiple foci within tracheobronchial epithelium; a precursor of squamous cell carcinoma
Pathogenesis
• Sequential accumulation of molecular and genetic defects as a result of exposure to carcinogens (mainly as a result of smoking) lead to concomitant morphological changes progressing on a spectrum from preneoplastic (squamous dysplasia and CIS) to subsequently neoplastic (invasive squamous cell carcinoma) lesions
• Genetic abnormalities resulting in squamous dysplasia and CIS studied to date include (but are not limited to) loss of 3p, 9p, 17p, and RAR-β; p53 mutation; overexpression of VEGF, Bcl-2, cyclin D1, and cyclin E; and increases in p16INK4A methylation
Clinical features
Epidemiology
• Smoking is the main risk factor
• Incidence of lesions higher in smokers, correlating with the number of cigarettes smoked
Presentation
• Lesions usually found in specimens resected for invasive squamous cell carcinoma
• In centers screening high-risk patients, these lesions are seen on endobronchial biopsy specimens
Prognosis and treatment
• Preinvasive and reversible; do not necessarily progress to invasive carcinoma and may regress with cessation of smoking
• About 25% of dysplastic lesions progress to invasive carcinoma during a mean period of 36 months; more than 50% of patients with CIS progress to invasive carcinoma within 30 months
• Clinical trials are currently evaluating chemoprevention with vitamin D, vitamin A, COX-2 inhibitors, and PGI2; preliminary results suggest chemoprevention is plausible, but no proven clinically effective treatment options are available
Pathology
Histology
• Histological features of mild, moderate, and severe squamous dysplasia leading to CIS represent a continuum of worsening architectural distortion, cell size, N/C ratio, basilar zone expansion, nuclear atypia, and number of mitoses (see Table 7 in the Appendix)
Immunopathology/special stains
• Increased proliferation index; staining with anti-proliferating cell nuclear antigen or Ki-67 reveals immunoreactivity in the proliferating compartment to be between 35% and 40% in dysplasia (vs. 25% in normal epithelium and up to 90% in invasive disease)
• p53: increasing accumulation of nuclear p53 with increasing grade of dysplasia
Main differential diagnoses
• Squamous metaplasia
• Basal cell (reserve cell) hyperplasia
Fig 1 Squamous dysplasia and carcinoma in situ. A, Mild to moderate squamous dysplasia with nuclear enlargement and mitotic figures up to middle one third; B, p53 stain is positive in scattered cells, mostly at the base.
Fig 2 Squamous dysplasia and carcinoma in situ. Moderate dysplasia with nuclear atypia up to middle one third.
Fig 3 Squamous dysplasia and carcinoma in situ. Severe dysplasia with almost full-thickness atypical cells and mitosis in upper one third.
Fig 4 Squamous dysplasia and carcinoma in situ. A, High-grade dysplasia with basaloid-looking cells extending into the upper third; B, p53 stains almost all nuclei, which is very helpful in distinguishing severe dysplasia/CIS from low-grade dysplasia.
Fig 5 Squamous dysplasia and carcinoma in situ. Postradiation nuclear atypia is focal as seen in this endobronchial biopsy specimen from a patient being screened in a high-risk lung cancer clinic because of a prior history of lung carcinoma.