A, A 31-year-old white woman had giant pigmented conjunctival nevus measuring 15 mm in basal diameter and 1 mm in thickness. There were numerous clear intralesional cysts. B, A 22-year-old white woman had giant pigmented conjunctival nevus measuring 15 mm in basal diameter and 1 mm in thickness. Note the intralesional cysts. C, A 13-year-old white male had giant amelanotic conjunctival nevus measuring 13 mm in basal diameter and 1.5 mm in thickness. Note the trace pigment and intralesional cysts. D, A 42-year-old white man had giant amelanotic conjunctival nevus of 15 mm in basal diameter and 2 mm in thickness. Note the intralesional cysts.
A, A 16-year-old white male demonstrated a giant conjunctival nevus with slight pigmentation superonasally measuring 20 mm in basal diameter and 4 mm in thickness. B, On anterior segment optical coherence tomography (AS OCT), the intralesional cysts were confirmed. C, A 48-year-old white man showed giant conjunctival nevus superotemporally measuring 18 mm in basal diameter and 2 mm in thickness. D, On AS OCT, the intralesional cysts were confirmed.
A, Giant pigmented conjunctival nevus measuring 23 × 12 × 2 mm, with prominent intralesional cysts. B, Diffuse primary acquired melanosis in an African American woman with dark pigment dusting involving the entire bulbar conjunctiva. C, Pigmented conjunctival melanoma measuring 6 × 5 × 4 mm at the limbus with associated primary acquired melanosis involving inferior bulbar and forniceal conjunctiva. D, Conjunctival lymphangiectasia with associated subconjunctival hemorrhages.
A, A 48-year-old white man had a long-standing giant multicystic amelanotic conjunctival nevus of 20 mm in diameter and 2 mm in thickness. B, Ten years later, slight enlargement of the lesion and expansion of the internal cysts with conservative observation. C, A 40-year-old Hispanic woman with giant conjunctival nevus of 40 mm in diameter and 2 mm in thickness occupying 3 quadrants of bulbar conjunctival surface. D, The lesion was managed with wide surgical excisional biopsy and cryotherapy with reconstruction using amniotic membrane grafting. Histopathology confirmed subepithelial nevus.
Shields CL, Regillo AC, Mellen PL, Kaliki S, Lally SE, Shields JA. Giant Conjunctival NevusClinical Features and Natural Course in 32 Cases. JAMA Ophthalmol. 2013;131(7):857-863. doi:10.1001/jamaophthalmol.2013.160
Copyright 2013 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
Conjunctival nevus is the most common tumor of the ocular surface and we selected the largest nevi to evaluate for clinical features and outcomes.
To describe the clinical features and outcomes of giant (≥10 mm diameter) conjunctival nevus.
Design, Setting, and Patients
Retrospective case series of 618 patients with conjunctival nevus, 32 of which had giant conjunctival nevus, treated at an ocular oncology service between July 1, 1974, and June 30, 2012.
Observation, excisional biopsy, and cryotherapy.
Main Outcomes and Measures
Management, nevus recurrence, and nevus transformation into melanoma.
Of 618 patients with conjunctival nevus, 32 (5%) were classified as having giant conjunctival nevus. The mean patient age at diagnosis was 34 years. Of those with giant conjunctival nevus, a history of an increase in nevus base or thickness was noted in 15 cases (47%) and an increase in color intensity in 2 cases (6%). The giant nevus involved cornea in 11 cases (34%), limbus in 23 (72%), bulbar conjunctiva in 31 (97%), fornix in 9 (28%), tarsus in 3 (9%), semilunar fold in 10 (31%), and caruncle in 7 (22%). The nevi had mean diameter of 16 mm and mean thickness of 2 mm. On slitlamp examination, intrinsic cysts were identified in 25 cases (78%), intrinsic blood vessels in 26 (81%), and feeder vessels in 22 (69%). Management included excisional biopsy with cryotherapy in 23 cases (72%) and observation in 9 cases (28%). Amniotic membrane graft reconstruction was used following excision in 3 cases (13%). Malignant melanoma developed within the giant nevus in 1 case after 23 years of observation. Postexcisional biopsy, nevus recurrence was detected in 4 cases (17%), pseudopterygium in 1 (4%), dry eye in 1 (4%), and eyelid blepharoptosis in 1 (4%).
Conclusions and Relevance
In an ocular oncology practice, giant conjunctival nevus represents 5% of conjunctival nevi. This benign tumor rarely transforms into conjunctival melanoma. Management alternatives include observation or wide excisional biopsy, cryotherapy, and reconstruction, possibly with amniotic membrane graft.
Conjunctival nevus is the most common tumor of the ocular surface.1- 4 In an analysis of 1643 cases of conjunctival tumors in patients of all ages, referred to a clinical ocular oncology service, the most common tumor was the conjunctival nevus, representing 454 cases (28%).3 In that series, other common lesions included melanoma (n = 215, 13%), primary acquired melanosis (PAM) (n = 180, 11%), lymphoid tumors (n = 127, 8%), and squamous cell carcinoma (n = 108, 7%). In an analysis of 2455 cases of conjunctival lesions, including congenital, acquired, inflammatory, degenerative, and neoplastic conditions, in adults from a pathology laboratory, 200 (8%) were nevi.4 Other common lesions in that series included pterygium (n = 444, 18%), epithelial dysplasia (n = 168, 7%), nonspecific nongranulomatous inflammation (n = 177, 7%), and epithelial inclusion cyst (n = 144, 6%).
Further study on the clinical features of conjunctival nevus in 410 consecutive cases revealed that most conjunctival nevi are pigmented as brown (65%) or tan (19%), and most nevi are found on the bulbar conjunctiva (72%) touching the limbus (48%).5 In that large series, the median basal tumor diameter was 3.5 mm (mean, 4.1 mm; ranging up to 30 mm). Lesions greater than 10 mm were identified and the only observation on these large nevi were that they were “diffusely multicystic, poorly circumscribed, and often resembled cystic conjunctival lymphangioma or lymphangiectasia.”5 A conjunctival nevus of 10 mm or greater in basal diameter is arbitrarily termed giant nevus. This is often confused with conjunctival melanoma or lymphangioma/lymphangiectasia, both of which characteristically display similar features of large size, irregular margins, and multinodularity.6 A PubMed search for terms conjunctiva and nevus giant or nevus large revealed 1 case report.7 Herein, we evaluated 32 eyes with giant conjunctival nevus for clinical features, management, and outcomes of transformation into melanoma and melanoma-related metastasis and death.
A computer-based data search for the diagnosis of conjunctival nevus, examined and treated at the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, between July 1, 1974, and June 30, 2012, was conducted. Institutional review board approval was obtained. Those patients with conjunctival nevus at minimum basal diameter of 10 mm or greater were classified as having giant conjunctival nevus and were included in this case series.
The demographic, clinical, and histopathologic data of the patients with giant conjunctival nevus were obtained retrospectively. The demographic data included patient age (years), sex, and race/ethnicity. The referral diagnosis and prior documented change in nevus size or color and prior treatments were recorded. The presence of concurrent cutaneous and/or choroidal nevus or melanoma was noted. The recorded clinical data included affected eye, ocular symptoms, duration of symptoms (months), visual acuity, intraocular pressure (millimeters of mercury), and giant conjunctival nevus features such as basal dimension (millimeters), thickness (millimeters), configuration (flat or elevated), color (brown, pink, yellow, or blue), intrinsic cysts, approximate number of cysts, intrinsic vessels, feeder vessels, tissue involvement (cornea, limbus, bulbar conjunctiva, fornix, tarsal conjunctiva, semilunar fold, or caruncle), clock-hour location (1:00 to 12:00), and distance from the limbus (millimeters).
The imaging features based on anterior segment optical coherence tomography were recorded when available. These features included tumor configuration (flat or dome); tumor basal dimension (millimeters); tumor thickness (millimeters); acoustic characteristics (hollow or solid); presence of cysts; internal pattern (homogenous or heterogenous); visibility of anterior, posterior, and lateral margins; posterior tumor shadowing; and image quality (good, average, or poor).
The details of management of giant conjunctival nevus were listed and included observation, excisional biopsy, and cryotherapy. The use of reconstructive materials, such as amniotic membrane graft, was recorded. When available, histopathology data were recorded regarding features of tissue location (epithelium, stroma, epithelium, and stroma), junctional activity, intrinsic cysts, intrinsic vessels, and final histopathologic diagnosis (junctional nevus, subepithelial nevus, compound cystic nevus, or blue nevus). The outcomes of management, nevus recurrence, and nevus transformation into melanoma were recorded.
Of 618 patients with conjunctival nevus, there were 32 (5%) classified as having giant conjunctival nevus. Patient demographics are listed in Table 1. The mean age at diagnosis was 34 years (median, 33 years; range, 2-75 years). A history of increase in nevus basal dimension and/or thickness prior to referral to our practice was present in 15 cases (47%) and increase in nevus color intensity in 2 (6%).
The nevus features are listed in Table 2. The conjunctival location of nevus epicenter was bulbar (n = 28, 88%), forniceal (n = 1, 3%), tarsal (n = 1, 3%), semilunar fold (n = 1, 3%), and caruncle (n = 1, 3%). The nevus reached the limbus in 23 cases (72%). The mean nevus basal diameter was 16 mm (median, 13 mm; range, 10-40 mm), and the mean thickness was 2 mm (median, 2 mm; range, <1-4 mm) (Figure 1). The lesion displayed features of intrinsic telangiectasia (n = 26, 81%), cysts (n = 25, 78%), and feeder vessels (n = 22, 69%).
The imaging features of anterior segment optical coherence tomography are listed in Table 3 (Figure 2). This was performed in 7 cases and disclosed features of intralesional cysts in 6 (86%) and heterogeneous internal pattern in 6 (86%).
Treatments and histopathology are listed in Table 4. Excisional biopsy, cryotherapy, and reconstruction were performed in 23 cases (72%) and amniotic membrane graft was used in 3 cases. Histopathology revealed subepithelial nevus in 5 cases (22%), compound cystic nevus in 15 (65%), blue nevus in 1 (4%), and blue nevus with a focus of conjunctival melanoma in 1 (4%).
The outcomes are listed in Table 4. Local nevus recurrence postexcision occurred in 4 cases (17%) at a mean interval of 53 months (median, 29 months; range, 10-144 months). Focal melanoma transformation was noted in 1 case (4%) at 280 months of follow-up. This patient had an extensive melanocytic nevus, darkly pigmented, primarily in the inferior fornix and with plical and caruncular involvement. Unlike other cases, there were no cysts and biopsy results showed primarily blue nevus, with a small focus of melanoma. There was no patient requiring enucleation or exenteration, and there was no melanoma-related metastasis or death over a mean follow-up of 36 months (median, 14 months; range, up to 280 months).
The conjunctival nevus is a common benign tumor of the ocular surface of median 3.5 mm in basal dimension.5 Management usually consists of observation vs surgical resection. The main conditions resembling nevus include PAM, melanoma, and lymphangiectasia/lymphangioma, all of which can be small and localized or large and extensive (Figure 3).6,8 Nevus is differentiated clinically from these conditions by several features including nevus detection in young children, at the medial or lateral limbal region, occupying approximately 1 clock hour of the limbus, and with intralesional stromal telangiectasia, cysts, and pigmentation.5 Nevus typically remains stable over time. In contrast, PAM and melanoma generally occur in middle- or older-aged patients, often with enlargement of pigmentation.6,8 In PAM, the pigmentation is flat and within the epithelium, whereas with melanoma, the pigmentation is mostly within the stroma. Lymphangiectasia/lymphangioma resembles nevus because it is a multicystic mass, but it is usually differentiated by the lack of melanocytic pigment and numerous blood-filled lymphatic channels. Standard conjunctival nevus is usually effortlessly differentiated from the previously mentioned conditions. The challenge is the differentiation of giant conjunctival nevus from these conditions because all can display overlapping features of large extent with multinodularity, telangiectasia, and pigmentation.
In this study, we found that giant conjunctival nevus was not necessarily detected during childhood, although we believe it to be a congenital abnormality. In our series, the median age at referral to our practice was 33 years, similar to conjunctival nevus in general (median age, 30 years5) and younger than those with melanoma (median age, 62 years6) and those with PAM (median age, 56 years8). However, it should be noted that melanoma that stems from preexisting conjunctival nevus tends to occur at a younger median age of 44 years.6 The reason for the slightly older age at detection and referral to us is likely related to the hidden location of many conjunctival nevi, particularly those located in the fornix, tarsus, semilunar fold, and caruncle. In our series, the giant nevus location was externally visible at the 3-o’clock or 9-o’clock margins in 14 cases (44%); however, in 18 cases (56%), the nevus was hidden under the upper or lower eyelid within the bulbar, forniceal, or tarsal region. Kim et al9 previously documented the exceptional rarity of conjunctival nevus in the tarsal location.
In this series, the most striking finding of giant nevus was the large extent of this tumor with mean basal diameter of 16 mm. In comparison, typical conjunctival nevus displays a mean basal diameter of 4 mm.5 A comparison of giant conjunctival nevus vs typical conjunctival nevus in a clinic-based population of 410 patients revealed incidence rates by female sex (44% vs 51%), white race (88% vs 89%), right eye involvement (69% vs 51%), brown/tan/yellow color (50% vs 84%), location of nevus epicenter in the nasal or temporal quadrant (75% vs 90%), location of nevus anteroposterior epicenter in bulbar conjunctiva (88% vs 72%), anterior margin at limbus (72% vs 48%), cysts (78% vs 65%), feeder vessels (69% vs 33%), intrinsic vessels (81% vs 38%), compound nevus histopathology (68% vs 70%), and transformation into melanoma (<1% vs <1%).
The feature most suggestive of nevus rather than melanoma was the presence of intrinsic cysts (78%) (Figure 3). The cysts manifested as a minor or a major portion of the nevus. In 2 cases, the entire amelanotic nevus was filled with confluent cysts (Figure 4). Imaging with anterior segment optical coherence tomography can facilitate detection of intrinsic cysts.10,11 Nevertheless, biopsy was performed in several cases to establish the diagnosis of nevus rather than melanoma and for cosmetic reasons.
In the ophthalmology literature, it is well established that conjunctival nevus can evolve into melanoma in less than 1% of cases.5,12 In this cohort, we found 1 case that showed slow transformation over 23 years. Hence, it is important for such lesions to be followed up long-term for transformation into melanoma. Fortunately, there was no case of melanoma-related metastasis or death.
In the dermatology literature, giant congenital melanocytic nevus is defined as that measuring 20 cm or greater and comprising 5% or more of body surface area.13 This pigmented tumor is found in newborn infants and most often involves the posterior trunk (51%), lateral or anterior trunk, legs, buttocks, arms, and scalp, often with satellite nevi (53%).13 Lifetime risk for the development of melanoma has been published at 2% to 9%, often within the first few years of life.13- 16 Additionally, approximately 1% to 5% manifest symptomatic neurocutaneous melanosis that can lead to death in up to 34%.16 Management of the giant nevus consists of observation, multiple incisional biopsies with evaluation for melanoma, or complete resection when possible using tissue expanders for reconstruction.
The management of conjunctival nevus includes observation or excisional biopsy plus cryotherapy (Figure 4).5,17 According to Levecq et al,17 the decision for surgical intervention (for nevus of all sizes) is most often at the request of the patient or family to rule out melanoma, for cosmetic improvement, or to alleviate ocular surface irritation. The extensive size of giant nevus often limits the ability for complete resection and reconstruction with adequate patient comfort, cosmetic appearance, and avoidance of complications. We have found that full resection with amniotic membrane graft reconstruction can alleviate some difficulties in management. In a single case report7 on the management of giant conjunctival nevus, a 54-year-old man had a 23-mm nevus that was surgically resected and successfully reconstructed with amniotic membrane graft, similar to our experience. In this series, complete resection was performed in 23 cases (72%) and amniotic membrane graft was instrumental in reconstruction in 3 cases.
In summary, giant conjunctival nevus represents a small subset of melanocytic conjunctival tumors, but it can lead to diagnostic confusion with conjunctival melanoma, PAM, and lymphangioma/lymphangiectasia (Figure 3). Recognition of intralesional cysts and confirmation by biopsy is suggested to establish the diagnosis and rule out melanoma. Complete resection is preferred when possible. There is a low risk for transformation into melanoma so long-term monitoring is advised.
Submitted for Publication: November 1, 2012; final revision received December 23, 2012; accepted January 14, 2013.
Corresponding Author: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 840 Walnut St, Ste 1440, Philadelphia, PA 19107 (email@example.com).
Published Online: May 23, 2013. doi:10.1001/jamaophthalmol.2013.160.
Author Contributions: Dr C. L. Shields had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (Drs C. L. Shields and J. A. Shields); Mellon Charitable Giving from the Martha W. Rogers Charitable Trust (Dr C. L. Shields); Lift for a Cure, Morrisdale, Pennsylvania (Drs C. L. Shields and J. A. Shields); and the Lucille Wiedman Fund for Pediatric Eye Cancer, Philadelphia, Pennsylvania (Dr C. L. Shields).