Malignant tumor of melanocytes originating in the conjunctiva.Incidence/ Prevalence:
The incidence of conjunctival melanoma is based on 3 epidemiologic studies in Germany, Sweden and the Netherlands with an incidence of .080, .070, and .028 in 100,000 inhabitants, respectively. Conjunctival melanoma is about 1/500 as common as skin melanoma.Etiology:
The cause of conjunctival melanoma is largely debated but is strongly correlated with the presence of PAM
, or acquired conjunctival lesions (manifested as detectable pigmentation), with atypia seen in these lesions. UVR exposure may induce conjunctival melanoma due to its correlation with atypical PAM. A population based study indicated that a focus of PAM with atypia co-existed in 71% of conjunctival melanomas. Several authors have reported conjunctival melanomas have arisen from benign conjunctival nevi
in anywhere from 26-60% of cases (2,3,7,8). The evidence is usually based on co-existence.Clinical Findings:
Age of presentation: Most prevalent in elderly and middle-aged and is equally common to men and women. Pigmented lesions of the conjunctiva above the age of forty should be treated with suspicion; it is promulged that conjunctival nevus is unusual in this age group. However, Jakobiec
reported the mean age of patients with conjunctiva nevi in his series was 40 and almost half the cases were well over 40 yrs!
Conjunctival melanoma occurs in all areas of conjunctiva including the tarsus, fornices, and caruncle. Melanocytic lesions in the palpebral conjunctiva are particular suspicious for PAM or malignant melanoma.
Tumors are usually nodular growths that may involve any portion of the conjunctiva; those not on the bulbar surface appear to behave more aggressively. The precursor to microinvasive melanoma may be a slight thickening of PAM observed through a histopathological examination of the lesionHistopathology:
In general, conjunctival melanomas feature infiltration of the substantia propria by atypical pigmented cells with prominent nucleoli and abundant cytoplasm containing brown granular pigment. The tumor may show pagetoid infiltration of the epithelium and there is often accompanying primary acquired melanosis or a nevus. The neoplasm shows atypical mitotic figures with abnormal forms (tripolar, hyperchromatic, ring forms). However the melanomas may include a variation of cell types such as spindle, epithelioid, and balloon cells. Melanomas may also contain polyhedral cells which are morphologically similar and may be confused with nevus cells or lymphocytes. In the image below and to the right, the epithelium is thin and poorly cohesive nests of tumor cells show atypical cells that vary from a small polygonal shape to a spindle cell shape in the lower portion. The image (high magnification) to the left shows atypical melanocytes that vary in shape and size and contain pigment. The tumor has infiltrated the sclera (low magnification image).
Immunohistochemical stains for S-100 protein, MART1, and HMB-45 may be used to verify Pagetoid spread. Ki67 has been touted as effective for differentiating nevus from melanoma (~19.7% positive cells in 4 high po wer fields versus 9% for junctional nevi).Ref.13
Tumor thickness can be measured objectively using a calibrated microscope; tumors thicker than 0.8 mm carry a greater risk for dissemination and death than thinner ones. However, even lesions less than 0.8 mm thick has resulted in patient mortality. Over history, various thicknesses have been assigned given a poor prognosis ranging from 0.8mm (2) to 4mm (5). Death due to metastatic conjunctival melanoma has been linked with other histologic characteristics as well: (1) invasion of the cornea, episclera, or sclera; (2) over five mitotic figures for every ten high-power fields; (3) involvement of the fornix, caruncle, or palpebral conjunctiva; (4) the presence of acute or moderate atypia; (5) the existence of melanoma cells permeating the entire thickness of the epithelium when PAM is present; (6) an overall absence of inflammation and lack of polyhedral cells exhibited in the invasive component.Treatment:
The primary treatment of conjunctival melanoma is surgical: all traces of invasive melanoma should be removed. Areas of adjacent PAM should also be extirpated by surgical excision, cryotherapy, laser ablation, perhaps topical chemotherapy, or a combination of methods. Cryotherapy is not a primary treatment for conjunctival melanoma and should be used only to treat extensive zones of primary acquired melanosis. Removal of the eye is not indicated unless the tumor invades the eye or the eye is otherwise blind and painful; intraocular invasion by conjunctival melanoma is extremely unusual, especially in the absence of any preexisting wounds such as cataract incisions. Exenteration may be indicated to manage large conjunctival melanomas but has little effect in controlling metastases once the orbit is invaded. It is considered a palliative approach (11). The treatment for conjunctival melanoma is complete surgical removal.Prognosis:
The overall mortality rate from conjunctival melanoma is about 25% (defined over various time periods in several studies showed survival ranging from 69-81% (2-8).
Typically, metastases first develop in parotid or submandibular lymph nodes. Unfavorable prognostic factors, in addition to conjunctival site as mentioned above, include orbital or scleral invasion, histopathologic identification of pagetoid or full-thickness intraepithelial spread, and involvement of the eyelid skin margin.
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3. Jay B. Br J Ophthalmol. 1965 Apr;49:169-204.
4. McGhee CN, Ni C, Albert DM, Chu FR. Int Ophthalmol Clin. 1982 ;22(3):35-56
7. Liesegang TJ, Campbell RJ. Mayo Clinic experience with conjunctival melanomas.Arch Ophthalmol. 1980 Aug;98(8):1385-9.
9. Werschnik C, Am J Clin Oncol. 2002 Jun;25(3):248-55
10. Paridaens AD, Minassian DC, McCartney AC, Hungerford JL.
Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases.Br J Ophthalmol. 1994 Apr;78(4):252-9.
11. Paridaens AD, McCartney AC, Minassian DC, Hungerford JL. Orbital exenteration in 95 cases of primary conjunctival malignant melanoma. Br J Ophthalmol. 1994 Jul;78(7):520-8.
12. Jay B. Br J Ophthalmol. 1968 Jan;52(1):70-3
13. Jakobiec FA et al. Immunohistochemical Studies of Conjunctiva Nevi and Melanomas. Arch. Ophthalmol 128:174-183.