Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia: 12 years’ experience

Clinical Investigation



To report 12-year follow-up experience with topical mitomycin chemotherapy for diffuse and multifocal primary acquired melanosis (PAM) with atypia and conjunctival melanoma.


Interventional case series of 16 patients. Mitomycin was a primary treatment for residual epithelial disease in ten patients (eight with PAM with atypia and two with conjunctival melanoma) and as an adjuvant to excision and cryotherapy in six with conjunctival malignant melanoma. Primary treatments consisted of mitomycin 0.04% qid for 28 days (two 14-day cycles) and for 7 consecutive days as adjuvant therapy. Patients were followed for both local recurrence and metastatic disease.


Sixteen patients were followed for a mean 81 months (range 13–144 months) after treatment. All tumors responded to chemotherapy. Recurrence was noted in eight (three adjuvant and five primary treatment patients). Three underwent orbital exenteration. The remaining five were treated conservatively. The mean time to recurrence was 36.9 months. The short-term mitomycin-related complications included transient keratoconjunctivitis (n=14), severe keratoconjunctivitis (n=1) and one corneal abrasion with scar formation. The long-term complications included pannus (n=2) and corneal haze (n=1). Visual acuity was maintained within two lines in 14 patients (including measurements just prior to exenteration). Three patients died, one of metastatic conjunctival melanoma.


Conjunctival melanoma and PAM responded to mitomycin 0.04% topical chemotherapy; subepithelial nests appeared resistant to treatment. Treatment-related complications were acceptable. In this series, as primary and adjuvant therapy, topical mitomycin yielded an overall recurrence rate of 50%.


Melanoma Mitomycin Pterygium Nodular Melanoma Limbal Stem Cell Deficiency 



This work is supported by The EyeCare Foundation, Inc., and Research to Prevent Blindness, New York City, NY, USA.


  1. 1.
    Billing K, Karagiannis A, Selva D (2003) Punctal-canalicular stenosis associated with mitomycin C for corneal epithelial dysplasia. Am J Ophthalmol 136:746–747CrossRefPubMedGoogle Scholar
  2. 2.
    Crawford JB (1980) Conjunctival melanomas: prognostic factors: a review and analysis of a series. Trans Am Ophthalmol Soc 78:467–502PubMedGoogle Scholar
  3. 3.
    Demirci H, McCormick SA, Finger PT (2000) Topical mitomycin chemotherapy for conjunctival malignant melanoma and primary acquired melanosis with atypia. Clinical experience with histopathologic observations. Arch Ophthalmol 118:885–891PubMedGoogle Scholar
  4. 4.
    De Potter P, Shields CL, Shields JA, Menduke H (1993) Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases. Br J Ophthalmol 77:624–630PubMedCrossRefGoogle Scholar
  5. 5.
    Dogru M, Ertuck H, Shimazaki J, Tsubota K, Gul M (2003) Tear function and ocular surface changes with topical mitomycin treatment for primary corneal intraepithelial neoplasia. Cornea 22:627–639CrossRefPubMedGoogle Scholar
  6. 6.
    Donnenfeld ED, Perry HD, Fromer S, Doshi S, Solomon R, Biser S (2003) Subconjunctival mitomycin C as adjunctive therapy before pterygium excision. Ophthalmology 110:1012–1026Google Scholar
  7. 7.
    Donnenfeld ED, Perry HD, Wallerstein A, Caronia RM, Kanellopoulos AJ, Sforza PD, D’Aversa G (1999) Subconjunctival mitomycin C for the treatment of ocular cicatricial pemphigoid. Ophthalmology 106:72–78Google Scholar
  8. 8.
    Finger PT, Milner MS, McCormick SA (1993) Topical chemotherapy for conjunctival melanoma. Br J Ophthalmol 77:751–753PubMedCrossRefGoogle Scholar
  9. 9.
    Finger PT, Czechonska G, Liarikos S (1998) Topical mitomycin C chemotherapy for conjunctival melanoma and PAM with atypia. Br J Ophthalmol 82:476–479PubMedCrossRefGoogle Scholar
  10. 10.
    Fourman S (1995) Scleritis after glaucoma filtering surgery with mitomycin C. Ophthalmology 102:1569–1571Google Scholar
  11. 11.
    Frucht-Pery J, Pe’er J (1996) Use of mitomycin C in the treatment of conjunctival primary acquired melanosis with atypia. Arch Ophthalmol. 114:1261–1264PubMedGoogle Scholar
  12. 12.
    Frucht-Pery J, Sugar J, Baum J et al (1997) Mitomycin C treatment for conjunctival–corneal intraepithelial neoplasia: a multicenter experience. Ophthalmol 104:2085–2093Google Scholar
  13. 13.
    Gupta S, Basti S (1992) Corneoscleral, ciliary body and vitreoretinal toxicity after excessive installation of mitomycin C. Am J Ophthalmol 104:503–504Google Scholar
  14. 14.
    Jakobiec FA, Brownstein S, Albert W, Schwartz F, Anderson R (1982) The role of cryotherapy in the management of conjunctival melanoma. Ophthalmology 108:502–512Google Scholar
  15. 15.
    Jakobiec FA, Rini JD, Fraunfelder FT, Brownstein S (1988) Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Ophthalmology 95:1058–1070PubMedGoogle Scholar
  16. 16.
    Jakobiec FA, Folberg R, Iwanoto T (1989) Clinicopathologic characteristics for premalignant or malignant lesions of conjunctiva. Ophthalmology 96:147–166PubMedGoogle Scholar
  17. 17.
    Liesegang TJ, Campbell RJ (1980) Mayo Clinic experience with conjunctival melanomas. Arch Ophthalmol 98:1385–1389PubMedGoogle Scholar
  18. 18.
    Lommatzsch PK, Lommatzsch RE, Kirsch I, Fuhrmann P (1990) Therapeutic outcome of patients suffering from malignant melanomas of the conjunctiva. Br J Ophthalmol 74:615–619PubMedCrossRefGoogle Scholar
  19. 19.
    Murphy WM, Soloway MS, Crabtree WN (1981) The morphological effects of mitomycin C in mammalian urinary bladder. Cancer 47:2567–2574PubMedCrossRefGoogle Scholar
  20. 20.
    Norregaard JC, Grener N, Jensen OA, Prause JU (1996) Malignant melanoma of the conjunctiva: occurrence and survival following surgery and radiotherapy in a Danish population. Graefes Arch Clin Exp Ophthalmol 234:569–572CrossRefGoogle Scholar
  21. 21.
    Palmer SS (1991) Mitomycin as adjuvant chemotherapy with trabeculectomy. Ophthalmology 98:317–321PubMedGoogle Scholar
  22. 22.
    Papandroudis AA, Dimitrakos SA, Stangos NT (2002) Mitomycin C therapy for conjunctival–corneal intraepithelial neoplasia. Cornea 21:715–717CrossRefPubMedGoogle Scholar
  23. 23.
    Paridaens ADA, McCartney ACE, Minnassian DC, Hungerford JL (1994) Orbital exenteration in 95 case of primary conjunctival malignant melanoma. Br J Ophthalmol 78:520–528PubMedCrossRefGoogle Scholar
  24. 24.
    Paridaens ADA, Minassian DC, McCartney ACE, Hungerford JL (1994) Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathologic study of 256 cases. Br J Ophthalmol 78:252–259PubMedCrossRefGoogle Scholar
  25. 25.
    Rodriguez-Ares T, Tourino R, Rojas VD, et al (2003) Topical mitomycin C in the treatment of pigmented conjunctival lesions. Cornea 22:114–117CrossRefPubMedGoogle Scholar
  26. 26.
    Rubinfield RS, Pfister RR, Stein RM et al (1992) Serious complications of topical mitomycin C after pterygium surgery. Ophthalmology 99:1647–1654PubMedGoogle Scholar
  27. 27.
    Sacu S, Segur-Eltz N, Horvat R, Lukas JR, Zehetmayer M (2003) Intumescent cataract after topical mitomycin C for conjunctival malignant melanoma. Am J Ophthalmol 136:375–377CrossRefPubMedGoogle Scholar
  28. 28.
    Salamao DR, Mathers WD, Sutphin JE, Cuevas K, Folberg R (1999) Cytologic changes in the conjunctiva mimicking malignancy after topical mitomycin C chemotherapy. Ophthalmology 106:1756–1761CrossRefPubMedGoogle Scholar
  29. 29.
    Schelonka LP, Siegel D, Wilson MW et al (2000) Immunohistochemical localization of NQO1 in epithelial dysplasia and neoplasia and donor eyes. Inv Ophthalmol Vis Sci 4:1617–1622Google Scholar
  30. 30.
    Seregard S (1998) Conjunctival melanoma. Surv Ophthalmol 42:321–350CrossRefPubMedGoogle Scholar
  31. 31.
    Shields JA, Shields CL, DePotter P (1998) Surgical management of circumscribed conjunctival melanomas. Ophthal Plast Reconstr Surg 14:208–215CrossRefGoogle Scholar
  32. 32.
    Shields CL, Naseripour M, Shields JA, Eagle RC (2001) Topical mitomycin C for pagetoid invasion of the conjunctiva by eyelid sebaceous gland carcinoma. Ophthalmology 109: 2129–2133CrossRefGoogle Scholar
  33. 33.
    Shields CL, Demirci H, Shields JA, Spanich C (2002) Dramatic regression of conjunctival and corneal acquired melanosis with topical mitomycin C. Br J Ophthalmol 86:244–245CrossRefPubMedGoogle Scholar
  34. 34.
    Singh G, Wilson MR, Foster CS (1988) Mitomycin eye drops as treatment for pteyrgium. Ophthalmology 95:813–821PubMedGoogle Scholar
  35. 35.
    Wilson MW, Hungerford JL, George SM et al (1997) Topical mitomycin C for the treatment of conjunctival and corneal epithelial dysplasia and neoplasia. Am J Ophthalmol 124:303–311PubMedGoogle Scholar
  36. 36.
    Wilson MW, Czechonska G, Finger PT et al (2001) Chemotherapy for eye cancer. Surv Ophthalmol 45:416–444CrossRefPubMedGoogle Scholar
  37. 37.
    Yu G, Hu D, McCormick SA, Finger PT (2003) Conjunctival melanoma: is it increasing in the United States? Am J Ophthalmol 135:800–806CrossRefPubMedGoogle Scholar
  38. 38.
    Yuen HKL, Yeung EFY, Nongnart R, Chi SCC, Dennis SC (2002) The use of postoperative topical mitomycin C in the treatment of recurrent conjunctival papilloma. Cornea 21:838–839CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.The New York Eye Cancer CenterNew YorkUSA
  2. 2.The New York Eye and Ear InfirmaryNew YorkUSA
  3. 3.New York University School of MedicineNew YorkUSA

Personalised recommendations