Eye Cancer, Retinoblastoma

Introduction

Malignant melanoma of the conjunctiva presents as a raised, pigmented or nonpigmented lesion that appears in adult life. This lesion is uncommon but potentially lethal. It can arise in previously unblemished and unpigmented regions (approximately 10% of cases), from a preexisting nevus (approximately 20% of cases), or from the flat spreading pigmentation of primary acquired melanosis with atypia (60-70% of cases).

Pathophysiology

Primary site: Together with mucus-secreting goblet cells within the stratified epithelium, melanocytic cells exist in the basal layer of the conjunctiva. These melanocytic cells are of neuroectodermal origin, and melanocytic tumors may arise from these cells. Melanomas may arise from junctional and compound nevi. Some uncertainty exists regarding the role of nevi in the histogenesis of malignant melanoma. Previously, compressed cells at the melanoma base have been considered to be nevi, but recent reports suggest that these flattened cells are, in fact, compressed melanoma cells and not nevus cells.

Melanomas also may arise from primary acquired melanosis or de novo. Regional lymph nodes: The regional lymph nodes are parotid, preauricular, submandibular, and cervical.

For pN (see Staging), histologic examination of a regional lymphadenectomy specimen ordinarily includes 6 or more regional lymph nodes. Metastatic sites: In addition to spread by lymphatics and the bloodstream, direct extension to the eyeball and orbit occurs.

Frequency United States

Primary malignant melanoma of the conjunctiva is much less common than intraocular or skin melanomas. Malignant melanoma of the conjunctiva accounts for only 2% of all ocular malignancies.

International

Denmark: Incidence of primary acquired melanosis (PAM) with atypia or with malignant melanoma of the conjunctiva was estimated to be 0.052 cases a year per 100,000. Sweden: Only 2 new cases of primary malignant melanoma of the conjunctiva were diagnosed in 1987.

Mortality/Morbidity

The overall tumor-related mortality rate for conjunctival melanoma is 25-26%. This rate increases to 40-44% if the tumor arose from PAM with an intraepithelial pagetoid growth pattern. This tumor tends to spread first to the parotid or submandibular nodes.

  • Tumor thickness, mixed cell type, and lymphatic invasion on histologic examination were found to increase the death rate (3-4 times).
  • Other poor prognostic features, outlined by Jakobiec and associates, include tumor in unfavorable locations (caruncle, palpebral conjunctiva, or fornical conjunctiva), moderate-to-severe atypia, a paucity of small polyhedral cells in the tumor, invasion of deeper ocular tissues, greater than 5 mitotic figures per 10 high-power fields, and lack of an inflammatory response induced by the tumor.

Race

This condition occurs predominantly in whites and rarely is seen in blacks.

Sex

No clear sex predilection has been established.

Age

Typically, conjunctival melanoma occurs in patients in their early 50s. It rarely is seen in people younger than 20 years. Strempel reported 3 cases of conjunctival malignant melanoma in children.



Clinical History

It is important to elicit a good history of growth characteristics of each lesion. The well-informed patient often is aware of subtle changes that may be crucial in identifying these lesions.

  • Melanomas that arise without a preexisting conjunctival nevus usually are at the limbus and are believed to have, initially, a short horizontal growth phase followed by a rapid vertical growth phase. Melanomas that arise in a preexisting nevus often are characterized by growth of the lesion or by increased vascularity.
  • The onset of malignant degeneration, in the case of PAM, often is heralded by the development of nodular thickening in a previously flat area of pigmentation. Other noteworthy features of malignant degeneration include increased vascularity, fixation of the conjunctiva to the underlying sclera, and hemorrhage.

Physical

The clinical presentation can be variable and is dependent on the antecedent status of the conjunctiva. A melanoma can be distinguished from PAM by its tendency to become fixed to the underlying tissues, which is not a feature of PAM.

  • Conjunctival melanomas may extend onto the peripheral limbus. Most melanomatous nodules at the limbus affect the peripheral cornea; some grow circumferentially around the limbus. Rarely, a melanomatous nodule may be located more centrally in the cornea.
  • Pigmentation of the eyelid margins and skin occasionally accompanies primary conjunctival melanomas, particularly those located on the palpebral conjunctiva and fornix; this combined presentation discloses a poorer prognosis.

Causes

Theoretically, conjunctival melanoma may originate from PAM, from preexisting nevi, and as de novo lesions. It may be difficult to determine the precursor lesion in many cases.

  • Primary acquired melanosis
  • Approximately 50-75% of cases of conjunctival melanoma arise in a setting of PAM. Typically, it is a lesion found in middle-aged whites, and, along with malignant melanomas, it is extremely rare in the younger population.
  • The natural history of PAM begins with the development of superficial epithelial pigmentation, with a typical peppered distribution of pigment. These lesions can evolve slowly over years, waxing and waning, extending in a radial manner over larger areas of conjunctiva and skin.
  • Nevus
  • Approximately 20-25% of patients with conjunctival melanoma had a history or microscopic evidence of a benign conjunctival nevus.
  • Malignant melanomas arising from nevi usually appear as a change (increasing nodularity, variegated pigmentation, bleeding, or inflammation) in known pigmented lesions of the conjunctiva, but it may be impossible to establish a clear clinical history of a preexisting history of nevus.
  • De novo (without any histologic or clinical evidence of a preexisting lesion)
  • Approximately 25% of cases of conjunctival melanoma come from de novo lesions.
  • These lesions can be ulcerative, amelanotic, papillary, or fungating.
  • Occasional reports of cases showing the presence of both acquired melanosis and a nevus have been documented.

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