Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia - Clinical experience with histopathologic observations

Objectives: To clinically evaluate topical mitomycin chemotherapy in patien ts with diffuse, multifocal, or recurrent primary acquired melanosis with a typia and/or conjunctival malignant melanoma and to histopathologically stu dy ocular tissue samples obtained before and after treatment. Methods: Chemotherapy with topical mitomycin, 0.04% 4 times daily, was admi nistered fur 28 days as the primary and only treatment in 7 patients (after biopsy) and for 7 days as adjuvant therapy to excision and cryotherapy in 5 patients. Mean follow-up was 38 months. Five patients developed subconjun ctival recurrences, for which 2 underwent orbital exenteration and 3 were t reated conservatively. Histopathologic specimens of conjunctival, adnexal, and ocular tissues obtained before and after chemotherapy were evaluated. Results: Regression of tumor was observed in ii patients with primary or ad juvant topical mitomycin chemotherapy. One patient with nodular melanoma wa s resistant to mitomycin chemotherapy. Histopathologic findings included re gionally variable conjunctival epithelial atrophy and thinning. Dyskeratosi s and focal keratinization in conjunctival epithelium were noted. Epithelia l nuclei were occasionally pyknotic in areas of atrophic epithelium. Subepi thelial inflammation was present and was most intense in areas with severe atrophy and/or keratosis. Two patients with primary treatment and 2 with ad juvant treatment developed subconjunctival recurrence, In patients with rec urrent malignant melanoma, the deeper layers of the lamina propria were inv olved, with sparing of the epithelium and superficial lamina propria. Trans ient keratoconjunctivitis was observed in all patients during treatment. In evaluation of the exenteration specimens, corneal, scleral, episcleral, re tinal, and anterior structures were within normal limits. Conclusions: Topical mitomycin chemotherapy was found to induce regression of conjunctival melanoma and primary; acquired melanosis with atypia. When mitomycin chemotherapy was used as an adjuvant to excision and cryotherapy, 2 (40%) of 5 patients experienced tumor recurrence at a mean of 4.3 years' follow-up. Our histopathologic findings demonstrated a long-term mitomycin chemotherapy-related effect on the conjunctiva. The degree of chronic atro phy and inflammation was not clinically significant. The pattern of effect and location of recurrent disease suggest that this regimen of topical mito mycin chemotherapy was most effective for superficial tumors. No complicati ons that would preclude uses of our dose regimen were: noted. Although subc onjunctival or orbital recurrences were noted, topical mitomycin chemothera py warrants further investigation as an alternative treatment for primary a cquired melanosis with atypia and conjunctival malignant melanoma.