Malignant melanoma of the conjunctiva is a rare tumour with an

unpredictable behaviour, characterised by the high risk of local

recurrence and metastatic spread.

Intraocular extension of a conjunctival melanoma is rare.

Conjunctival melanoma includes three groups:

(i) melanomas derived from primary acquired melanosis,

(ii) those derived from pre-existing nevi, and

(iii) those that develop de novo from apparently normal

conjunctiva.

Survival of the patient depends on the location of the tumour,

tumour size and the histological subtype.

Tumours growing extralimbal especially at the fornix, plica and

caruncle have a significantly poorer prognosis than limbal

tumours.

Most conjunctival malignant melanomas occur in adult, and

two-thirds of these in acquired melanosis.

Any change in a pigmented lesion of the conjunctiva, particularly

growth with increasing elevation, should raise suspicion of a

malignant melanoma.

The definition of a malignant melanoma requires that atypical

melanocytes invade from the epithelium into the substantia

propria of the conjunctiva.

The most easily recognized melanocytes are the large bizarre

epithelioid cells.

Small polyhedral melanoma cells can be difficult to distinguish

from benign nevus cells.

When they are observed, the presence of  mitotic activity, lack

of maturation, and infiltrative growth pattern at the deep

margin are helpful in differential diagnosis.

Spindle-shaped melanoma cells are often amelanotic and they

may induce a desmoplastic stroma.

Extension into the orbit or lacrimal duct occurs in some cases.

Death is usually due to distant metastases.

The management of conjunctival melanoma can be difficult.

In addition to local recurrence and metastases, limbal

melanomas may rarely show intraocular extension, particularly

if surgery to excise the tumour requires the removal of Bowman's

membrane.

Recognition of the precursor lesions at an early stage is

important. Staging of the disease by sentinel lymph node biopsy

is now advocated in some centers. Surgical excision with

adjuvant cryotherapy and alcohol corneal epithelialectomy is

usually effective in eradicating most of these lesions.

Extensive cases of flat primary acquired melanosis with atypia

may be managed with mitomycin C. Multifocal and

advanced melanoma, especially in cases showing intraocular

or orbital invasion, may require exenteration and/or radiotherapy

to adequately extirpate the neoplasm locally.

Regular follow-up of these patients is mandatory.

Visit: Conjunctival Melanocytic Tumours ; Primary Acquired Melanosis ; Conjunctival Nevus .

BACKGROUND: Malignant melanoma of the conjunctiva is a rare tumour with an unpredictable behaviour, characterised by the high risk of local recurrence and metastatic spread. Intraocular extension of a conjunctival melanoma is rare. We present three cases of primary conjunctival melanoma with intraocular extension. METHODS: Three patients presented with primary conjunctival melanomas, which either arose at or later involved the limbus on a background of primary acquired melanosis. Despite adequate primary local excision and adjuvant chemotherapy, all three patients experienced several recurrences, requiring further surgery. Two of the patients had excision of the tumour that required superficial keratectomy. One of these patients then required two further procedures in which the anterior chamber was breached. RESULTS: All three patients ultimately required enucleation or exenteration to control local disease. All three specimens showed intraocular extension. CONCLUSIONS: The management of conjunctival melanoma can be difficult. In addition to local recurrence and metastases, limbal melanomas may rarely show intraocular extension, particularly if surgery to excise the tumour requires the removal of Bowman's membrane. Regular follow-up of these patients is mandatory.

Amelanotic conjunctival melanoma.Cutis. 2006 Jun;77(6):377-81.

Conjunctival melanoma is a rare condition of the eye pigment predominantly affecting white adults. We describe a 32-year-old white man with an amelanotic malignant melanoma of the conjunctiva that is not associated with primary acquired melanosis (PAM) or melanocytic nevus. The patient presented with a 2-year history of nonpigmented vascularized nodules of the right eye. Results of hematoxylin and eosin (H and E) staining of the lesion showed an invasive nodule with vertical spreading, invasion of the substantia propria corneae, and ulceration. S100 protein was expressed in the cells of the invasive nodule. HMB45 protein was highly positive in the melanoma cells. The de novo amelanotic malignant melanoma of the conjunctiva we describe is an extremely uncommon tumor mainly affecting white adults.

Malignant melanoma of the conjunctiva.Cancer Control. 2004 Sep-Oct;11(5):310-6.

BACKGROUND: Conjunctival melanoma is a relatively rare ocular malignancy with substantial associated morbidity and mortality. METHODS: More than 100 articles on conjunctival melanoma were reviewed, including most of the relevant recent publications cited in a current MEDLINE search. The author's experience with conjunctival melanomas is also incorporated in this review. RESULTS: Recognition of their precursor lesions at an early stage is important. Staging of the disease by sentinel lymph node biopsy is now advocated in some centers. Surgical excision with adjuvant cryotherapy and alcohol corneal epithelialectomy is usually effective in eradicating most of these lesions. Extensive cases of flat primary acquired melanosis with atypia may be managed with mitomycin C. Multifocal and advanced melanoma, especially in cases showing intraocular or orbital invasion, may require exenteration and/or radiotherapy to adequately extirpate the neoplasm locally. However, systemic metastases already may have occurred in these patients with advanced disease. CONCLUSIONS: Conjunctival melanoma is a condition of concern because of its rarity and lethal potential. Advances in the understanding and management of this neoplasm have markedly reduced the mortality and possibly the morbidity associated with this malignancy.

Malignant conjunctival melanoma. Clinical review with recommendations for diagnosis, therapy and follow-up.: Klin Monatsbl Augenheilkd. 2002 Oct;219(10):710-21.

BACKGROUND: Malignant conjunctival melanoma is a rare disease with an incidence of 0.03 - 0.08. This tumour is potentially lethal, even after prompt and proper treatment, especially after delayed onset of therapy. Conjunctival melanoma arises from primary acquired melanosis (PAM), from a preexisting nevus or "de novo" without any precursor at all. In contrast to uveal melanomas, conjunctival melanoma metastasizes via the ipsilateral lymph nodes and in rare cases through the lacrimal duct into the nasal cavities. RESULTS: Removing the local tumour with preservation of visual functions and avoidance of metastases is the therapy of choice. Excision alone is followed by a high rate of recurrence. To minimize local recurrence rate surgical excision should be combined with an additional procedure such as cryotherapy, irradiation, or local chemotherapy with MMC. Surgical technique is characterized by a so-called "no-touch" method avoiding any direct manipulation of the tumour to prevent tumour cell seeding into a new area. The behaviour of conjunctival melanomas is individually unpredictable. Prognostic factors are tumour size and tumour location. Tumours growing extralimbal especially at the fornix, plica and caruncle have a significantly poorer prognosis than limbal tumours. In our own patients the 5-year, 10-year, and 15-year cumulative melanoma-specific survival rate was 84.4 %, 77.7 %, and 75.0 %, respectively. Up to now there is no effective treatment of the metastatic disease. CONCLUSION: In all cases with pigmented lesions of the conjunctiva exclusion of a malignant melanoma has to be the first aim. A patient suffering from a conjunctival melanoma should be referred to an ophthalmo-oncological center for proper treatment. An indefinite follow-up including photodocumentation is necessary since the rate of recurrence is high. An international prospective study would be worthwhile to answer open questions and to develop new kinds of treatment of this potentially fatal tumour.

Corneally displaced malignant conjunctival melanomas. Ophthalmology. 2002 May;109(5):914-9.

PURPOSE: To characterize and classify malignant conjunctival melanomas with exclusively corneal invasive growth. DESIGN: Population-based, nationwide retrospective cross-sectional study. PARTICIPANTS: Patients with primary malignant conjunctival melanoma diagnosed between 1967 and 2000 in Finland. METHODS: On the basis of all available clinical and histopathologic data of tumors diagnosed during the study period, malignant conjunctival melanomas that first demonstrated invasive growth on the cornea without evidence of conjunctival tumors other than primary acquired melanosis were identified, their prevalence calculated, and their characteristics reviewed. On the basis of these cases and literature data, a classification for "corneal melanoma" was developed. MAIN OUTCOME MEASURES: Frequency and type of corneal involvement, recurrence, and survival. RESULTS: Patients with exclusively corneal invasive tumor accounted for 5% (95% confidence interval, 1-12) of 85 consecutive primary conjunctival melanomas. Two were separated from the limbus by clear cornea (type I), and two paralleled but did not invade the limbal conjunctiva (type II). Two were associated with clear evidence of primary acquired melanosis. None of the tumors recurred after local excision, and no metastases were observed during a median follow-up of 2 years 5 months (range, 1 year 8 months-7 years 10 months). CONCLUSIONS: Primary malignant conjunctival melanomas can grow on the cornea without conjunctival involvement other than acquired melanosis. They are easily removed and do not cause lymphatic metastases. The term "corneally displaced malignant conjunctival melanoma" would best describe their supposed conjunctival origin and actual corneal location.

Malignant melanoma of the conjunctiva with intraocular extension.Arch Ophthalmol. 2000 Apr;118(4):557-60.

Intraocular extension of a malignant melanoma of the conjunctiva is a rare entity. A 75-year-old woman underwent repeated surgery after receiving the diagnosis of a multilocular recurrent malignant melanoma arising from a primary acquired melanosis. Treatment included 2 lamellar sclerokeratectomies and percutaneous radiotherapy. Five years after initial surgery, intraocular extension of the melanoma was observed, and enucleation was performed. Findings from histopathological examination revealed a malignant melanoma occupying part of the ciliary body, the trabecular meshwork, and the iris. Eyes with recurrent malignant melanoma of the conjunctiva should be carefully monitored for intraocular extension. Deep excision of conjunctival melanoma, including lamellar sclerokeratectomy, may abolish the natural barrier against intraocular extension of malignant melanomas of the conjunctiva.

Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.Ophthalmology. 1998 Jan;105(1):191-4.

BACKGROUND: The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. METHODS: Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. STUDY DESIGN: Case report. RESULTS: Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. CONCLUSIONS: Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases.Br J Ophthalmol. 1994;78(4):252-9.

A series of 256 consecutive cases of invasive primary conjunctival malignant melanomas was examined to identify clinical and histopathological prognostic factors. The follow up period varied between 0.3 and 45.9 years (mean 9 years, median 6.3 years). The 5 year survival rate was estimated at 82.9%, the 10 year survival rate at 69.3%. Multiple regression analysis with the Cox proportional hazards model was used to assess sex, age, and a number of baseline features of conjunctival malignant melanoma as possible prognostic factors influencing melanoma related mortality. In assessing each potential prognostic factor, the effects of all other factors were taken into account in the modelling process. Tumours in unfavourable locations--that is, those involving the palpebral conjunctiva, fornices, plica, caruncle, and lid margins, were associated with 2.2 times higher mortality compared with (epi)bulbar melanomas. Patients with mixed cell type tumours had about three times higher mortality compared with those with pure spindle cell melanomas, and histological evidence of lymphatic invasion by tumour cells was also a prognostic feature, carrying a fourfold increase in the death rate. Multifocal tumours were associated with a fivefold increase in mortality among those with tumours in favourable (epi)bulbar locations, but were not prognostic in patients with melanomas in unfavourable sites. The death rate was significantly higher in those with initial tumour thickness of more than 4 mm, but only among patients with unfavourably located melanomas. Sex, age, and clinical origin of the tumour (primary acquired melanosis, pre-existing naevus, or de novo) were not useful prognostic indicators in this study.

Clinical predictive factors for development of recurrence and metastasis in conjunctival melanoma: a review of 68 cases.Br J Ophthalmol. 1993 Oct;77(10):624-30.

Sixty eight cases of histologically proved conjunctival melanoma were reviewed in order to determine the clinical factors that were predictive of local recurrence and distant metastasis. All patients were treated with surgical excision and most had supplemental cryotherapy. The mean follow up was 7.5 years. Histopathologically, the conjunctival melanoma arose from primary acquired melanosis in 56%, from naevus in 26%, and de novo in 18%. Of the 68 patients, 38 (56%) developed at least one local tumour recurrence and 22 (32%) developed more than one recurrence. The method of initial treatment and the eventual development of metastasis were the two parameters statistically associated with tumour recurrence. Those patients treated initially with tumour excision alone had a statistically significant higher recurrence rate than those treated initially with excision and supplemental cryotherapy (p = 0.001). Fourteen patients (21%) developed metastasis and the mean period between treatment and metastasis was 3.6 years. Twelve (18%) died from metastatic melanoma with a mean interval of 4.4 years from the time of initial surgery until death. The only clinical parameter that was statistically associated with distant metastasis was local tumour recurrence (p = 0.015). Based on these observations, the authors make recommendations regarding the treatment of conjunctival malignant melanoma. It appears that initial complete excision of the tumour with supplemental cryotherapy offers the patient the best chance of remaining free of recurrence and metastasis.

Recurrent conjunctival melanoma with neuroidal spindle cell features.Ophthalmology. 1987 Jan;94(1):56-60.

A 66-year-old white woman had had a 20-year history of flat primary acquired melanosis involving the left inferior forniceal and palpebral conjunctiva. Over the ensuring 12 years, the patient experienced multiple recurrences of invasive malignant melanoma that emerged from the progressive primary acquired melanosis. Two of these recurrences were composed of nonpigmented spindle cells, and in the most florid invasive malignant melanoma that developed, the spindle cells formed a nodule 7.5 mm thick. The spindle cells were organized into fascicles and small bundles, the latter separated by a loose stroma that was devoid of mucopolysaccharides. The fascicular and neuroidal features in this case were sufficiently well developed to suggest the incorrect diagnosis of a neural tumor or a neurofibroma. However, the presence of intraepithelial atypical melanocytes at the edge of the spindle cell lesion, the absence of mucopolysaccharides in the stroma, the mitotic activity, and the absence of intercellular reticulin fibers favored the diagnosis of a spindle cell invasive malignant melanoma. This morphologic variant of conjunctival melanoma is compared with related cutaneous lesions of melanoma featuring a spindle cell population.