Micronucleus Frequency Test in Epithelial Cells Desquamated From the Oral Mucosa of Patients With Fanconi Anemia

BACKGROUND: Fanconi anemia (FA) is a rare genetic disorder predisposing patients to oral squamous cell carcinoma (OSCC). Hematopoietic stem cell transplantation (HSCT) corrects bone marrow failure but may increase the risk of malignancies. Exfoliative cytology and the micronucleus (MN) test provide noninvasive assessment of genomic instability. OBJECTIVE: To compare relative frequency of micronuclei (RFMN) in intact mucosa and OPMD lesions in FA patients, and to evaluate its correlation with time post-HSCT. METHODS: Forty-six FA patients were included: Group 1 (FA without HSCT, n = 14), Group 2 (FA post-HSCT without OPMD, n = 13), and Group 3 (FA post-HSCT with OPMD, n = 19). Exfoliative cytology samples were collected from buccal mucosa and OPMD lesions. MNs were manually counted to calculate RFMN. Nonparametric tests were applied to compare groups and the Wilcoxon signed-rank test for intraindividual comparisons. Spearman's correlation and linear regression were used to evaluate associations with age and time. RESULTS: RFMN in OPMD lesions (Group 3) was significantly higher than in the integrous mucosa of the same patients (median 8 MN/1000 cells, IQR 4-13; ~3.7-fold increase; p = 0.001). No significant differences were observed between Groups 1 and 2 in integrous mucosa. RFMN in integrous mucosa positively correlated with time post-HSCT (ρ = 0.694, p < 0.001), independent of age and GVHD presence. CONCLUSION: FA patients, particularly post-HSCT with OPMD, exhibited markedly increased genomic instability. RFMN increases over time, including time post-HSCT, emphasizing the need for vigilant long-term oral monitoring in this high-risk population.