Jakobiec FA, Sandhu H, Bhat P, Colby K. Bilateral conjunctival melanocytic nevi of simultaneous onset simulating conjunctivitis in a child. Cornea. 2010;29(8):937–940.
Shields CL, Fasiuddin AF, Mashayekhi A, Shields JA. Conjunctival nevi: clinical features and natural course in 410 consecutive patients. Arch Ophthalmol. 2004;122(2):167–175.
Preinvasive Pigmented Lesions
Primary acquired melanosis
Primary acquired melanosis (PAM), an acquired pigmentation of the conjunctival epithelium, may be analogous to lentigo maligna of the skin (Hutchinson freckle), a preinvasive intraepidermal lesion of sun-exposed skin. It is usually unilateral and most often seen in light-skinned individuals. The term primary acquired melanosis refers to flat, brown lesions of the conjunctival epithelium (Fig 8-10). By definition, the condition differs from congenital pigmented lesions and from secondary acquired melanosis, such as that caused by Addison disease, radiation, or pregnancy. Table 8-3 compares the various pigmented lesions of the conjunctiva. Most cases of acquired melanosis are benign. The main risk factor for progression to melanoma is the presence of cellular atypia, which, currently, can be determined only by biopsy. PAM with atypia progresses to conjunctival melanoma in 36%–75% of cases. Histopathologic characteristics can help categorize PAM with atypia as low risk or high risk for transformation to melanoma. See BCSC Section 4, Ophthalmic Pathology and Intraocular Tumors.
Folberg R, McLean IW, Zimmerman LE. Primary acquired melanosis of the conjunctiva. Hum Pathol. 1985;16(2):129–135. Sugiura M, Colby KA, Mihm MC Jr, Zembowicz A. Low-risk and high-risk histologic features in conjunctival primary acquired
melanosis with atypia: Clinicopathologic analysis of 29 cases. Am J Surg Pathol. 2007;31(2):185–192.
Figure 8-10 A, Diffuse primary acquired melanosis of the bulbar conjunctiva. B, Primary acquired melanosis of the palpebral
conjunctiva. (Courtesy of Kathryn Colby, MD, PhD.)
PATHOGENESIS Abnormal melanocytes proliferate in the basal conjunctival epithelium of middle-aged, light-skinned individuals for reasons that are unknown. Pigmentation in an individual with dark skin is called benign acquired melanosis rather than PAM, but the 2 conditions may be related.
CLINICAL FINDINGS Multiple flat, brown patches of noncystic pigmentation appear within the superficial conjunctiva of 1 eye. Changes in size may be associated with inflammation or may be the result of hormonal influences. Malignant transformation should be suspected when a lesion shows nodularity, enlargement, or increased vascularity. Pigmented lesions located on the palpebral conjunctiva,
conjunctival fornix, plica, or caruncle should increase clinical suspicion and lead to a biopsy. Complete examination of the ocular surface (including double eversion of the upper eyelid) is essential in any patient with conjunctival pigmentation.
MANAGEMENT Suspicious pigmented lesions of the ocular surface should be removed for histologic diagnosis. Complete excision should be done when possible. If the pigment is diffuse, multiple biopsies should be performed in order to determine the presence or absence of atypia throughout the ocular surface. If the diagnosis of PAM without atypia is made, then the lesion(s) may be followed every 6–12 months. If atypia is present, then every effort should be made to eliminate all conjunctival pigment. If the pigment is diffuse and not amenable to complete excision, adjuvant topical chemotherapy may be useful to treat the entire ocular surface. Care should be exercised in performing intraocular surgery on patients with untreated ocular surface neoplasia, as violation of the Bowman membrane may lead to tumor seeding within the corneal stroma and internal structures of the eye.
Colby K, Bhat P, Novais G, Jakobiec FA. Recurrent primary acquired melanosis with atypia involving a clear corneal phacoemulsification wound. Cornea. 2011;30(1):114–116.
McLean IW, Cameron JD. Melanocytic neoplasms of the conjunctiva. In: Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea. 3rd ed. Vol 1. Philadelphia: Elsevier/Mosby; 2011:477–484.
Malignant Pigmented Lesions
Melanoma
With a prevalence of approximately 1 per 2 million in the population of European ancestry, conjunctival melanomas make up less than 1% of ocular malignancies. Conjunctival melanomas are rare in black and Asian populations. Although malignant melanoma of the conjunctiva has a better prognosis than cutaneous melanoma, the overall mortality rate is 25%. The American Academy of Ophthalmology website contains additional information on this topic, including video.
PATHOGENESIS Conjunctival melanomas may arise from PAM (70%) or nevi (20%) or may arise de novo (10%). Intralymphatic spread increases the risk of metastasis. In rare cases, an underlying ciliary body melanoma can extend through the sclera and mimic a conjunctival melanoma.
CLINICAL FINDINGS Although conjunctival melanomas can arise in palpebral conjunctiva, they are most commonly found in the bulbar conjunctiva or at the limbus (Fig 8-11A). The degree of pigmentation is variable; approximately 25% of conjunctival melanomas are amelanotic. Recurrent melanomas are often amelanotic, even if the primary tumor was pigmented (Fig 8-11B). Because heavy vascularization is common, these tumors may bleed easily. They grow in a nodular fashion and can invade the globe or orbit. Poor prognostic indicators include
location in the palpebral conjunctiva, caruncle, or fornix (Fig 8-11C) invasion into deeper tissues
thickness >1.8 mm
involvement of the eyelid margin
pagetoid or full-thickness intraepithelial spread lymphatic invasion
mixed cell type
Conjunctival melanomas may metastasize to regional lymph nodes, the brain, lungs, liver, and bone.
Figure 8-11 A, Multifocal, partially pigmented malignant melanoma of the limbal conjunctiva. B, Recurrent amelanotic conjunctival melanoma. The primary tumor was pigmented. C, Small conjunctival melanoma in the inferior fornix. (Courtesy of
Kathryn Colby, MD, PhD.)
MANAGEMENT Ocular surface lesions worrisome for melanoma should be treated expeditiously using the paradigm described at the beginning of the chapter. Sentinel lymph node biopsy has been advocated by some authors but has not been widely adopted. Orbital exenteration is occasionally performed for advanced disease when local excision or enucleation cannot completely excise the tumor (when metastases have been excluded) or as palliative treatment for advanced, aggressive tumors that cannot be controlled locally. The role of adjunctive radiotherapy has not been determined.
Conjunctival melanoma has a high rate of recurrence (more than 50%). Patients with a history of conjunctival melanoma need lifelong, close ophthalmic follow-up and should be counseled to contact their physician immediately should they notice any changes in the involved eye. Conjunctival melanomas are potentially deadly tumors. In one study, metastasis was detected in 26% of patients, and death occurred in 13% of patients 10 years after surgical excision. Melanomas arising de novo (ie, not from preexisting nevi or PAM), tumors not involving the limbus, and residual involvement at the surgical margins are factors associated with an especially poor prognosis.
Cancer stem cells may play a role in the high recurrence rate of conjunctival melanoma, which may recur despite appearing to be “cured” both clinically and histologically. The biology of conjunctival melanoma is poorly understood, however. These lesions have more in common with cutaneous melanomas than with uveal melanomas. The use of gene expression profiling for determining prognosis is currently being evaluated. In the future, gene expression profiling may be helpful in determining the response of conjunctival melanoma to targeted chemotherapies that are under development.