Topical Interferon Alpha-2b for Diffuse Conjunctival Primary Acquired Melanosis with Atypia

An 80-year-old Caucasian male presented to our office with diffuse primary acquired melanosis (PAM) in the conjunctiva of the right eye (Figure 1; photomontage superior-left). The conjunctival pigmentation had increased progressively during the last 2 years. PAM affected only the bulbar conjunctiva in the four quadrants. The lid conjunctiva was not affected and there were no elevated parts within the lesion. His medical history included cognitive impairment due to dementia and general malaise due to known osseous metastasis, secondary to prostate carcinoma. There were no clinical criteria to differentiate whether this case of PAM was without or with atypia (melanoma in situ). In this case, due to the conjunctival extension, complete resection of the lesion could lead to mutilation of the ocular surface. Therefore, an incisional biopsy of the area (10 × 8 mm) of the superior lesion was performed. Histology confirmed the presence of atypical melanocytes in the basal layers of the epithelium confirming conjunctival PAM with severe atypia. The C-MIN score was >5, similar to a melanoma in situ (Figure 1, right). In this case, the entire lesion was not removed and the presence of atypical melanocytes was suspected in all four quadrants. Further biopsies can only confirm the diagnosis. While complete excision was possible, consequent scarring would have resulted in a compromised outcome. Complete surgical removal and covering with amniotic membrane may be a good technique in extensive corneo-conjunctival lesions. However, in this case most of the bulbar conjunctiva would have had to be removed, resulting in mutilating surgery, and therefore was not considered acceptable. Topical chemotherapy is not employed as a primary treatment in cases of PAM. However, it may be employed in extensive lesions. Topical interferon (IFN) alpha-2b has been used successfully for the treatment of ocular surface squamous neoplasia (OSSN). Topical IFN is well tolerated in the treatment of OSSN. Few reports have described its utility for the treatment of pigmented conjunctival lesions, including PAM and melanoma. After informed consent was obtained, topical treatment with eye drops containing 1 million IU/mL of IFN alpha-2b (4 times a day) was initiated. The lesion was monitored by photographic review every 2 weeks. Topical IFN was well tolerated. The resolution of pigmentation began after 6 weeks of treatment. The pigmentation decreased progressively, and after 12 weeks, the treatment regimen was stopped. The reason was because the pigmentation had diminished considerably and the patient’s family had difficulties with the administration of the eye drops. The duration of treatment was also based on the reported average duration of topical IFN administration in previous publications. The remaining pigmentation continued to diminish for almost a full year after the initiation of treatment (Figure 1; photomontage inferior-left). Histologic confirmation of the resolution was not performed because the patient declined due to the poor general condition of the patient. PAM is an acquired pigmentation that occurs gradually in middle age and may appear as localized, patchy, flat, multifocal, or diffuse pigmentation in the conjunctiva. Abnormal melanocytes near the basal layer of the epithelium are characteristic of PAM. The risk of atypical melanocytes transforming into a malignant melanoma is approximately 50%. Excision with double freeze–thaw cryotherapy is the elective treatment for PAM with atypia. In cases of diffuse disease, topical chemotherapy may be used instead of excision. Mitomycin C (0.02 or 0.04% over several cycles) is the most frequently used drug. However, topical