Cytologic changes in the conjunctiva mimicking malignancy after topical mitomycin C chemotherapy

Purpose: To describe the epithelial changes observed in the conjunctiva secondary to the use of topical mitomycin C (MMC) for treatment of primary acquired melanosis with atypia. Design: Retrospective comparative case series. Participants and Controls: Conjunctival biopsy specimens (18) were taken during the follow-up of ten patients treated with MMC drops (0.02% or 0.04%) during 14 or 21 days for primary acquired melanosis with atypia. An equal number of age- and sex-matched patients with normal conjunctival biopsy findings were included for control. Conjunctival biopsy specimens from patients treated with MMC were compared with the morphologic changes already described in the urothelium following the use of the same chemotherapeutic agent. Methods: Hematoxylin and eosin-stained biopsy samples were evaluated for recurrent neoplasm and chemotherapeutic effect in the epithelium using the following criteria: nuclear enlargement, nuclear hyperchromasia, smudging of the chromatin, presence of nucleoli, cytoplasmic eosinophilia, and individual cell necrosis. Main Outcome Measures: The presence or absence of morphologic changes in the conjunctival epithelium related to the use of MMC. Results: Morphologic features consistent with chemotherapy effect were seen in the biopsy specimens of nine patients. Nuclear enlargement and chromatin smudging-hyperchromasia localized in the superficial layers of the epithelium were the main features observed (9 patients). Cytoplasmic eosinophilia, single cell necrosis, and occasionally subepithelial chronic inflammation were also seen. Conclusions: Secondary changes with the topical use of MMC are seen in the conjunctival epithelium and are similar to the changes described in the urothelium. These changes are important to recognize and to differentiate from recurrent neoplasm. The localization of the described features in the superficial layers of the conjunctival epithelium is the key feature in the differential diagnosis.