Conjunctival nevi are not uncommon in the pediatric population. An exact incidence is unknown, but when conjunctival nevi do arise, 43% are apparent by 10 years of age, and another 22% are seen by age 20 [13]. Most appear on the bulbar conjunctiva frequently near the limbus. Approximately 14% are seen on the caruncle or semilunar fold but are unusual to arise in the tarsal or lid margin conjunctiva [2]. The majority are seen in Caucasians with much less frequency in Asians and Blacks.

Three histopathological subtypes classify conjunctival nevi: junctional, compound, and subepithelial. This classification is the same as that used for cutaneous nevi. Melanocytic nevus cells derive from epithelial melanocytes or their neural crest precursors. Collections of these cells are called nevi. Junctional nevus cells are located entirely within the epithelium of the conjunctiva and account for approximately 19% of all pediatric conjunctival nevi. Subepithelial nevi are the largest group accounting for 73% of pediatric nevi [14]. Compound nevi are the least frequent (8%) and have epithelial and subepithelial rests of cells. The clinical appearance of pediatric conjunctival nevi is similar to that in adults – a variable pigmented, isolated, flat lesion usually near the limbus without significant vascularity or inflammatory signs (Fig. 12.3a).

Junctional nevi often have cysts within the pigmented portion of the lesion that purport the benign nature of the nevus (Fig. 12.3b). Clinically scattered pigmentation throughout the epibulbar tissue denotes melanosis rather than nevus. This can be racial pigmentation as seen in very dark-skinned Blacks or melanocytosis if other ocular tissues are involved as previously discussed. Gradually increasing or changing pigmentation or lesion enlargement, especially near puberty, is not unusual and does not typically denote malignant transformation.

The diagnosis of conjunctival melanoma in the pediatric age group is decidedly rare [15]. Review of a large cohort of conjunctival tumors in childhood found melanocytic lesions to have less than a 1% chance of conversion to malignancy [1]. A large study evaluating the clinical appearance of conjunctival nevi and their pathological diagnosis and therapeutic outcome found no clinical features that were consistent with malignant transformation as all specimens were benign on histopathologic examination [16]. Clinical features suspicious for melanomatous transformation in conjunctival nevi have included rapid enlargement, marked pigmentary changes, nodular enlargement within the nevus, and the development of “feeder” vessels. These features were present in multiple specimens in the previously cited reference, but no melanoma was found on pathology. What other clinical features should one use as being suspicious for melanoma resulting in the decision for surgical intervention? The largest series to date evaluating the relationship of conjunctival melanocytic lesions and melanoma did not include data regarding patent age [17]. However, the clinical information regarding the presentation of these reported melanomas features a consistent theme: a pigmented lesion noticed for several years, not evident at birth, which suddenly and rapidly began to change in size and/or pigmentation. This would insinuate that these malignant transformations occurred de novo rather than arising from melanocytic changes in the conjunctiva which is somewhat supported by histopathologic slides lacking signs of nevus cells at the base of these malignancies [17]. Two authors report conjunctival melanomas that presented with ulceration prior to excision and indicate that ulceration was an important prognosticator for local control and survival for these lesions [18, 19]. Tumor thickness was also an important prognosticator as well [18]. Presence of the lesion arising on non-bulbar conjunctiva was considered to be a risk for melanomatous transformation in one case report (Fig. 12.4) [19]. One large observational study of 410 patients with conjunctival nevi found three patients transforming to melanoma (two compound nevi and one blue nevus), but all of these three were adults [20].

It is difficult to arrive at any solid clinical criteria that signal malignant transformation of childhood nevi primarily because so few cases have been reported. A pigmented lesion present for several years, not present at birth, with sudden change in size, pigmentation, thickness, and ulceration or arising from palpebral conjunctiva should alert the clinician to possible transformation.

What should be the next step: biopsy or excision? In children, strong consideration should be given to complete excision with 3 mm margins and submission for fixation and evaluation for tumor type and tumor thickness and whether the margins are free of tumor [13]. Frozen section analysis is fraught with difficulties including obscuration of cells by pigment and distortion of cell morphology. Pathology is very important in establishing the tumor type, marginal involvement, and grade for staging purposes. General agreement among pathologists has emerged regarding the features of atypia in grading conjunctival melanocytic lesions [21, 22].

Still, some lesions defy easy classification resulting in the pursuit of immunohistochemical markers to achieve more definitive diagnostic certainty for the classification of benign, carcinoma in situ and melanomatous lesions of the conjunctiva [23–25]. Here again, the vast majority of these conjunctival melanomas occur in adults, most of which arise from primary acquired melanosis which are exceedingly rare in children and which dominate this research in immunohistochemical analysis as an avenue of better identification for differentiating equivocal melanotic specimens as benign or malignant. Despite the adult predilection, the expression of certain cell antigens could possibly be expected from any melanocytic lesion with the potential of malignant transformation. Jakobiec et al., in a study of immunohistochemical analysis of atypical conjunctival melanocytic lesions (blue nevus, granular cell nevus, epithelioid nevus, and balloon cell nevus), demonstrated that Ki-67 expression was very low (<1%) in these benign variants, whereas this same expression in conjunctival melanomas is usually greater than 10% in nuclear positivity among all cells counted in these specimens [23, 24]. The consideration of immunohistochemical analysis should be utilized in any atypical melanocytic conjunctival lesion where clinical features do not reveal a clear-cut diagnosis.

Faced with these limitations, one must still consider the rate of recurrence after resection and the potential for metastatic spread. Adjuvant treatment with topical mitomycin C, interferon alpha-2b, or 5-fluorouracil may control future recurrence with positive margins seen on pathologic specimens as a secondary treatment based on final pathology findings [18]. As with adult conjunctival melanoma, clinical recurrence may be difficult to assess if pigmentation is not present. Consideration of conjunctival biopsies for any suspicious area of conjunctival erosion, hypervascularity, spotty pigmentation, or amelanotic thickening is warranted. The potential role of topical adjuvant treatment in superficial recurrence or de novo melanomatous change would seem advantageous in these circumstances. It warrants reinforcement that palpebral conjunctiva needs to be adequately visualized in the follow-up of these patients.

Finally, with clear marginal resection, what should be done to monitor for future systemic disease? Only two case reports of metastatic disease in children with conjunctival malignant melanoma have found their way into the literature [15, 26]. Both cases had a history of rapid recurrence after initial and subsequent surgical resection. Folberg et al., with their clinicopathologic review of conjunctival melanosis and melanoma in adults, reported both pathologic and clinical entities that indicate the likelihood of future metastatic or local recurrence: tumor extending to the margin or base of the specimen, orbital extension, a common pagetoid growth pattern, involvement of the caruncle, the full thickness of the epithelium simulating an in situ carcinoma, the absence of an inflammatory response to the invasive component of the lesion, tumor thickness greater than 0.8 mm, and the presence of five or more mitotic figures per ten high-power fields [17]. One could certainly add rapid recurrence after resection to this list which, individually or in multiples, would be a good reason for the involvement of a pediatric oncologist for short-term metastatic assessment and long-term monitoring. The role of the oculoplastic physician will undoubtedly be integral to the original surgical resection and repair of postsurgical defects as well as the possible role of exenteration as a life-sparing technique in hopes of surgical tumor control. The above reference of orbital extension harboring worsening prognosis for survival is based on the clinical findings that approximately 90% of patients at the time of exenteration are already manifesting systemic metastases making exenteration of little use except for pain or mass effect control.

A variety of rare conjunctival tumors have been described in the pediatric population. While most practitioners are unlikely to encounter these entities, an awareness of their presentation is essential when evaluating a suspicious conjunctival mass.

Faced with a child harboring an intraocular mass, the ophthalmologist is obligated to rapidly diagnose the condition such that effective treatment can be undertaken. The diagnosis may require secondary studies such as ultrasonography, CT and/or MR imaging, systemic evaluations by consulting physicians in ophthalmology or pediatrics, and eventual surgical procedures for tissue diagnosis or curative resection. Most ophthalmologists refer these patients to centers in proximity of their practice whom are experienced in the diagnosis and treatments of potentially malignant intraocular lesions.

After establishment of the diagnosis of an intraocular malignancy in a child, oculoplastic surgeons may be called upon to surgically manage this child by performing an enucleation. Many questions will come from the parents regarding the condition, the procedure, the expected healing, prosthesis fitting once healed, and, most importantly, will this save the child’s life. This section reviews the malignant ocular tumors of childhood with emphasis on the oculoplastic surgeon’s role in the care of these special individuals.