Topical chemotherapy an alternative for PAM with atypia

July 15, 2005

Washington, DC—Topical mitomycin-C (MMC) (Mutamycin, Bristol-Myers Oncology) is an effective treatment for conjunctival primary acquired melanosis (PAM) with atypia, and may even be considered a superior alternative to surgical excision and cryotherapy, said Joseph Frucht-Pery, MD, at World Cornea Congress V.

Washington, DC-Topical mitomycin-C (MMC) (Mutamycin, Bristol-Myers Oncology) is an effective treatment for conjunctival primary acquired melanosis (PAM) with atypia, and may even be considered a superior alternative to surgical excision and cryotherapy, said Joseph Frucht-Pery, MD, at World Cornea Congress V.

Dr. Frucht-Pery, associate professor, director of the cornea, external eye diseases, and refractive surgery unit, department of ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, and Jacob Pe'er, MD, chairman of the center's department of ophthalmology, have been using topical MMC to treat conjunctival PAM with atypia since 1995.

Dr. Frucht-Pery presented 10 years of experience from a consecutive series of 12 patients treated with the topical chemotherapy for histologically proven PAM with atypia in one eye.

Dr. Frucht-Pery reported the lesions responded with complete (four eyes) or partial (eight eyes) disappearance of the pigmentation. Regrowth of the lesion occurred in one patient who was successfully treated again. Otherwise, there were no recurrences in patients with complete pigment resolution, and the remnants of pigmentation remained stable in patients who had a partial response.

Safety of topical MMC was acceptable. Although all patients experienced adverse events during treatment, those resolved once MMC therapy ended, and no patients have experienced any reduction in visual acuity at last follow-up.

"PAM with atypia is melanoma in situ, and 50% of these lesions progress to invasive melanoma," Dr. Frucht-Pery said. "Conventional treatment is usually surgical, performed with excision, cryotherapy, or laser therapy. However, some lesions are amelanotic, and there may also be waxing and waning. Therefore, the pigmentation in PAM does not indicate the full extent of the intraepithelial melanocytic lesion.

"Topical chemotherapy has the advantage of covering the entire conjunctiva, and it has a favorable safety profile," Dr. Frucht-Pery continued. "For those reasons it may be a preferred method for treating these lesions."

The 12 patients who made up the series included six males and six females ranging in age from 21 to 78 years (mean, 54 years). PAM was diffused in six cases and localized in six. Pigmentation had been present for 6 months to 10 years (mean, 3.25 years) prior to treatment with topical MMC. In eight patients, treatment with topical MMC was performed as primary intervention while it was secondary treatment in four patients who had been referred for recurrence after incomplete excision.

Among the 12 eyes, the PAM involved various parts of the conjunctiva, but it also had invaded the cornea in four eyes. Aside from presenting with pigmentation, the patients were all asymptomatic and had good visual acuity.

During treatment, conjunctival hyperemia occurred in all patients and some individuals complained of local symptoms including pain, irritation, and tearing. Eyelid swelling developed in two patients and four were affected with corneal adverse events that consisted of superficial punctate keratitis (two eyes), epithelial defect (one eye), and severe keratopathy (one eye).

Pre-treatment histopathology revealed the presence of PAM with atypia in nine eyes whereas there was evidence of early transformation to invasive melanoma in three eyes.

"Topical chemotherapy with MMC should be considered only as a treatment for intraepithelial lesions," Dr. Frucht-Pery said. "It should not be used to treat invasive disease because it does not work very well in those cases."