Management of conjunctival malignant melanoma: a review and update

Abstract

Conjunctival malignant melanoma is a pigmented lesion of the ocular surface. It is an uncommon but potentially devastating tumor that may invade the local tissues of the eye, spread systemically through lymphatic drainage and hematogenous spread, and recur in spite of treatment. Despite its severity, the rarity of available cases has limited the evidence for diagnosis and management. This review will provide an overview of the epidemiology, presentation, diagnosis, management, and surveillance of conjunctival melanoma, with an emphasis on recent advances in biological therapies to treat this disease.

Keywords: BRAF inhibitors; Conjunctival malignant melanoma; dabrafenib; interferon alpha-2b; ipilimumab; melanoma; mitomycin C; ocular neoplasm; vemurafenib.

Figure 1. Various presentations of conjunctival malignant melanoma (CMM)

(A) Discrete, raised, pigmented lesion (B) Multifocal CMM (white arrows) in the setting of diffuse primary acquired melanosis (PAM) (C) Large, raised, pigmented CMM originating from inferior fornix (D) Large, raised, amelanotic/mildly pigmented CMM with surrounding PAM (white arrow), referred as ocular surface squamous neoplasia (OSSN).

Figure 2

Histopathology of a conjunctival melanoma arising in primary acquired melanosis. Low (A) and high (B) magnification images disclose conjunctiva that contains atypical melanocytes located within the basal epithelium as well as within the substantia propria that extends up to full thickness to the deep margin. The atypical melanocytes stain positive for Melan-A (C) and S-100 (D). The Ki-67 stain demonstrates a moderate amount of cells cycling within the tumor (E). (A, Hematoxylin-eosin, original magnification x200; B, Hematoxylin eosin, original magnification x400; C, Melan-A, original magnification x200; D, S-100, original magnification x200; E, Ki-67, original magnification x200)

Figure 3. Ultra high resolution optical coherence tomography (UHR AS-OCT) images of conjunctival malignant melanoma

(a) subepithelial lesion (b) mildly hyperreflective normal-thickness epithelium, (c) shadowing of tissue

Figure 4. Algorithm for management of conjunctival malignant melanoma

After clinical diagnosis is made based on history, slit lamp findings, and imaging, the current standard of care is surgical excision. A trial of mitomycin C (MMC) can be considered prior to excision if there is significant primary acquired melanosis (PAM) for chemoreduction. Surgical excision includes wide margins (~4mm), cryotherapy to the margins, and closure or placement of amniotic membrane transplant (AMT). Sentinel lymph node biopsy (SLNB), if done, is usually done at time of excision but may be done afterwards. Adjuvant therapies include topical MMC or interferon alpha-2b (IFN-α2b), internal radiotherapy (brachytherapy) or external radiotherapy (teletherapy). All cases should be referred to an oncologist for detection of metastasis.

Figure 5. Surgical excision of conjunctival malignant melanoma

(A) 4-mm wide surgical margins are marked, (B) Surgical excision of tumor in no touch technique. Note the dry surgical field. (C) Specimen is carefully oriented for margin control. (D) Swabs soaked in absolute alcohol are placed on involved areas of the cornea for 1 minute for epitheliectomy. (E) Corneal epithelium is debrided and cells sent for evaluation. (F) Cryotherapy is administered to surgical margins, with the conjunctiva raised to avoid damage to the sclera. (G) Amniotic membrane graft placement.