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Conjunctival Nevi
Clinical Features and Natural Course in 410 Consecutive Patients
Carol L. Shields, MD;
Airey Fasiudden, MD;
Arman Mashayekhi, MD;
Jerry A. Shields, MD
Arch Ophthalmol. 2004;122:167-175.
ABSTRACT
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Objectives To describe the clinical features of a conjunctival nevus and to evaluate the lesion for changes in color and size over time.
Design Retrospective, observational, noncomparative case series.
Participants Four hundred ten consecutive patients with conjunctival nevi.
Main Outcome Measures The 2 main outcome measures were changes in tumor color and size.
Results Of the 410 patients, 365 (about 89%) were white, 23 (about 6%) were African American, 8 (2%) were Asian, 8 (2%) were Indian, and 6 (1%) were Hispanic. The iris color was brown in 55% (229/418), blue in 20% (85/418), green in 20% (83/418), and not indicated in 5% (21/418). The nevus was brown in 65%, tan in 19%, and completely nonpigmented in 16%. The anatomical location of the nevus was the bulbar conjunctiva (302 eyes, 72%), caruncle (61 eyes, 15%), plica semilunaris (44 eyes, 11%), fornix (6 eyes, 1%), tarsus (3 eyes, 1%), and cornea (2 eyes, <1%). The bulbar conjunctival lesions most commonly abutted the corneoscleral limbus. The nevus quadrant was temporal (190 eyes, 46%), nasal (184 eyes, 44%), superior (23 eyes, 6%), and inferior (21 eyes, 5%). Additional features included intralesional cysts (65%), feeder vessels (33%), and visible intrinsic vessels (38%). Cysts were clinically detected in 70% of histopathologically confirmed compound nevi, 58% of the subepithelial nevi, 40% of the junctional nevi, and 0% of the blue nevi. Of the 149 patients who returned for periodic observation for a mean of 11 years, the lesion color gradually became darker in 5% (7 patients), lighter in 8% (12 patients), and was stable in 87% (130 patients). The lesion size was larger in 7% (10 patients), appeared smaller in 1% (1 patient), and was stable in 92% (137 patients). There were 3 patients who developed malignant melanoma from a preexisting compound nevus (2 cases) or blue nevus (1 case) over a mean interval of 7 years.
Conclusions Conjunctival nevus is a benign tumor most often located at the nasal or temporal limbus and rarely in the fornix, tarsus, or cornea. Over time, a change in tumor color was detected in 13% (20/149) and a change in tumor size was detected in 8% (12/149).
INTRODUCTION
The conjunctival nevus is a common benign ocular tumor. It can manifest with a spectrum of clinical features.1 Recent articles about the conjunctival nevus have primarily focused on the histopathologic features of this entity.2-8 Over the past 2 decades, there have been only 2 relevant studies on the long-term natural history of conjunctival nevi.4, 6 Both studies focused on the pathologic correlation of excised lesions with little information on the varied clinical features. In this article, to our knowledge, we provide for the first time in the recent literature a detailed account of the clinical variations of conjunctival nevi in 410 consecutive patients. We provide information regarding the frequency of change in pigmentation and size of these benign tumors. A comparison of the clinical appearance of conjunctival nevi with conjunctival melanoma is also made.
METHODS
The clinical records of all patients with a conjunctival nevus, examined and treated on the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pa, between July 1, 1974, and May 30, 2002, were reviewed. Clinical data were gathered retrospectively regarding features of the patient and the conjunctival nevus. The clinical data were then analyzed with regard to 2 main outcome measures—color change within the nevus and size change of the nevus.
These data included patient features at the initial examination such as age, race (African American, Hispanic, Asian, or white), and sex (female or male). Data were recorded regarding cutaneous lesions (nevus, dysplastic nevus syndrome, or malignant melanoma), other conjunctival lesions (primary acquired melanosis, pinguecula, pterygium, or squamous cell neoplasia), and choroidal lesions (nevus or melanoma). Data were recorded on iris color (blue, green, brown, or hazel). A history regarding the conjunctival nevus included previous documented growth of the lesion (present or absent), previous treatment of the lesion (none or excisional biopsy), symptoms (spot, inflammation, pain, or none), and the duration of these symptoms.
The ocular data included best-corrected Snellen visual acuity, designation of the eye involved (right or left), and the intraocular pressure. The tumor data included the anatomical location (bulbar conjunctiva, fornix, tarsal conjunctiva, plica semilunaris, caruncle, or cornea), quadrant location of the tumor epicenter (superior, temporal, inferior, or nasal), proximity to the limbus (expressed in millimeters), anterior tumor margin (cornea, limbus, bulbar conjunctiva, or fornix), posterior tumor margin (cornea, limbus, bulbar conjunctiva, or fornix), largest basal dimension (expressed in millimeters), largest thickness (expressed in millimeters), elevation status (flat or elevated), color (amelanotic, tan, or brown), intralesional cysts status (present or absent), and the number of cysts per nevus, feeder vessels (present or absent), and intrinsic vessels (present or absent).
Follow-up examinations were generally made at 6- to 12-month intervals. In this study we included only patients with photographic follow-up for comparison of clinical data. The follow-up data included the type of color change within the nevus (darker, lighter, or no change) and the type of nevus size change (larger, smaller, or no change).
RESULTS
The general information about patient demographics is listed in Table 1. The visual acuity on the initial examination was 20/20 to 20/50 in 403 patients (97%), 20/60 to 20/100 in 5 patients (1%), and 20/200 or worse in 8 patients (2%). Data regarding general ocular findings are listed in Table 2. Data regarding tumor findings are listed in Table 3 and in Figure 1, Figure 2, Figure 3, and Figure 4. There were 180 patients (43%) who reported that the lesion appeared to have enlarged over time before the date of the initial examination. The tumor was most commonly located on the bulbar conjunctiva (72%). Of all 418 lesions, the quadrant location of the tumor was temporal in 46% and nasal in 44%; the anterior margin was immediately at the limbus in 48% and behind the limbus in 25%. The median size was 3.5 mm in basal diameter and 0.5 mm in thickness. The lesion was most commonly pigmented (84%) and had intralesional cysts (65%). Feeder vessels (33%) and intrinsic vessels (38%) were found less often. Tumor treatment is listed in Table 4 and included observation (62%) or excisional biopsy alone or with cryotherapy (38%). The most common reasons for excisional biopsy included our concern for malignant change based on clinical features (16%), recent growth (8%), color change (<1%), or recurrence of previously excised lesion (2%). The clinical features suggestive of possible melanoma include older patient age at recognition of nevus; corneal, forniceal, or palpebral involvement; prominent feeder vessels; lack of intrinsic cysts; and personal or family history of cutaneous melanoma or dysplastic nevus syndrome. Other reasons for excision included patient's concern for melanoma (7%) or cosmetic appearance (4%).
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Table 1. Conjunctival Nevus in 410 Consecutive Patients: Patient Findings at the Initial Examination
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Table 2. Ocular Findings at the Initial Examination of 418 Conjunctival Nevi in 410 Consecutive Patients
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Table 3. Tumor Findings of 418 Conjunctival Nevi in 410 Consecutive Patients
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Figure 1. Variations in pigmentation of conjunctival nevi. A, Heavily pigmented conjunctival nevus. B, Lightly pigmented conjunctival nevus.
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Figure 2. Variations in size of conjunctival nevi. A, Small, pigmented conjunctival nevus measuring approximately 1 mm in basal diameter. B, Giant conjunctival nevus measuring 18 mm in basal diameter.
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Figure 3. Variations in location of conjunctival nevi. A, The most common location of the conjunctival nevus is on the bulbar conjunctiva at the limbus. B, The second most common location of the conjunctival nevus is in the caruncle. C, The least common location of the conjunctival nevus is in the plica semilunaris.
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Figure 4. Variations in associated clinical features of conjunctival nevi. A, Pigmented nevus with prominent clear intralesional cysts. B, Lightly pigmented nevus with pigment-lined intralesional cysts. C, Nonpigmented nevus with clear intralesional cysts and dilated feeder vessel. D, Lightly pigmented nevus with prominent vascularity.
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Table 4. Treatment of 418 Conjunctival Nevi in 410 Consecutive Patients
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The histopathologic diagnoses in the 148 excised lesions are listed in Table 5 and included compound nevus (70%), subepithelial nevus (4%), junctional nevus (3%), and blue nevus (3%) (Figure 5). Of these 148 nevi, tumor pigmentation was found in 82% of those classified as compound, 86% of those classified as subepithelial nevi, 100% of those classified as junctional nevi, and 100% of those classified as blue nevi. Cysts were noted in 70% of the compound nevi, 58% of the subepithelial nevi, 40% of the junctional nevi, and 0% of the blue nevi.
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Table 5. Clinical Features of 148 Histopathologically Confirmed Conjunctival Nevi*
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Figure 5. Variations in the clinical appearance of the 4 histopathologic subtypes of conjunctival nevi. A, Compound nevus of the conjunctiva. B, Subepithelial nevus of the conjunctiva. C, Blue nevus of the conjunctiva.
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Of the 149 conjunctival nevi followed up for a mean of 11 years without being excised, the tumor showed a color change in 13% and a size change in 8% (Table 6 and Figure 6). The clinical features of the 3 patients with nevi that evolved to malignant melanoma (over a mean of 7 years) are listed in Table 7. No patients developed melanoma metastasis.
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Table 6. Natural Course in 149 Conjunctival Nevi That Were Treated by Observation Only*
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Figure 6. Change in nevus appearance over time. A, May 1988. Pigmented conjunctival nevus at the limbus in a 26-year-old woman. B, July 1990. Several years later the conjunctival nevus of the same woman was less pigmented and barely visible.
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Table 7. Initial Clinical Features of the Conjunctival Nevus in 3 Patients Who Eventually Developed Malignant Melanoma
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COMMENT
Epibulbar melanocytic lesions include conditions of the conjunctival epithelium, stroma, and sclera. Some of these conditions include conjunctival racial melanosis, primary acquired melanosis, secondary melanosis, nevus, and melanoma, as well as ocular melanocytosis and extraocular extension of uveal melanoma.1 The clinical features of these pigmented conditions occasionally overlap and cause diagnostic confusion. Moreover, an amelanotic conjunctival nevus can resemble other nonpigmented conditions including inflamed pingueculum, episcleritis, conjunctival cyst, allergic conjunctivitis, foreign body granuloma, lymphangioma, and squamous epithelial neoplasia. The differentiation of these various conditions is important as it implies diverse ocular and systemic prognoses. The diagnosis is usually made based on the clinical features and occasionally confirmed with histopathologic findings. With regard to the conjunctival nevus, the diagnosis is typically made by recognition of the classic clinical features using slitlamp biomicroscopy. In this article, we describe a comprehensive overview of the various presentations of the conjunctival nevi in 410 consecutive patients.
Few articles have focused on the subject of the clinical features of conjunctival nevi. Most previous articles have described the pathological findings with generalizations, but little description of the clinical findings.2-11 In 1965, Jay9 reported the pathological features of benign nevi of the conjunctiva. He gathered basic clinical information only on patient age at diagnosis and noted that the patients most commonly seen by an ophthalmologist were between the ages 10 to 29 years and typically claimed that the lesion was first detected when the patient was younger than 9 years. Other clinical features of the excised tumors were unavailable. Henkind,10 in 1978, provided a comprehensive summary of conjunctival melanocytic lesions with minor generalizations on the clinical findings of conjunctival nevi. Since then, other articles on this condition have concentrated on related histogenesis, light microscopic findings, and ultrastructural features of common and rare subtypes of nevi.2-5,7-8,11
In 1996, a Danish study by Gerner et al6 provided a clinicopathologic study on 343 conjunctival nevi. They described the following tumor locations: the bulbar conjunctiva in 33%, caruncle in 29%, limbal conjunctiva in 27%, and at the eyelid margin in 1%. The patients were seen most commonly between the ages of 10 and 19 years. All but 3 patients were white and only 1 nevus evolved into a malignant melanoma. Further specific clinical information was not reported.
To our knowledge, our report is the first to delineate the specific clinical features of conjunctival nevi. We found the mean patient age at the initial manifestation was 32 years and most commonly, this tumor was found in white subjects (89%) (Table 1). Many patients had cutaneous nevi (19%) and 1% of patients each reported a history of basal cell carcinoma, dysplastic cutaneous nevi,12 and previous cutaneous malignant melanoma. Unlike choroidal melanoma or iris melanoma, which is usually found in patients with blue irides,13-14 conjunctival nevi were most commonly found in patients with brown irides (55%) (Table 2). Additional choroidal nevi were noted in 7% of the white patients, consistent with the expected number in the white population.15
With regard to the symptoms and clinical appearance of the tumor, most patients reported noticing a spot on the eye (88%), 3% noted inflammation, less than 1% experienced related pain, and 10% of patients were unaware of the lesion. The symptoms were present for a mean of 10 years. Enlargement or color change in the lesion over the years prior to our examination was reported by 43% of patients, but such enlargement was rarely supported by photographs. The tumor was most commonly found in the bulbar conjunctiva (72%), caruncle16 (15%), or plica semilunaris (11%) (Table 3). Rarely was the tumor found in the fornix (1%), tarsal conjunctiva (1%), or within the cornea (<1%). We, therefore, suggest that any pigmented lesion in the fornix, tarsus, or cornea might be considered to be a condition other than a nevus.17 This is especially important if the pigmented lesion is circumscribed and extends into the stroma, in which case malignant melanoma might be considered.18-20 In comparison, of 150 consecutive patients with conjunctival melanoma reported by Shields et al,19 the tumor location was the bulbar conjunctiva (92%), caruncle (1%), plica semilunaris (1%), fornix (3%), and tarsal conjunctiva (4%).
Those tumors on the bulbar conjunctiva were a mean of 1 mm (median, 0 mm) from the limbus. In only 2 patients was there corneal involvement and both were unusual cases with small corneal stromal nevi.21 Corneal involvement from a pigmented conjunctival lesion should suggest primary acquired melanosis or racial melanosis if the conjunctival pigmentation is within the epithelium, but, importantly, should raise consideration for conjunctival melanoma if the conjunctival pigmentation has thickness and extends into the stroma.1 Conjunctival nevi generally stop abruptly at the limbus and typically do not involve the corneal epithelium or stroma. Overhang of the cornea from a large conjunctival nevus is possible, but invasion of the cornea by a nevus would be distinctly unusual. On the other hand, conjunctival melanoma often grows beyond the limbus into the cornea.
The tumor involved the temporal (46%) or nasal (44%) quadrants of the conjunctiva more than the superior (6%) or inferior (5%) quadrants. This distribution along the temporal and nasal quadrants is more common with conjunctival nevus compared with conjunctival melanoma, as conjunctival melanoma has been found in the superior (16%), nasal (17%), and inferior (22%) quadrants less commonly than in the temporal (63%) quadrant.19
The conjunctival nevi ranged in basal dimension from 0.2 to 30 mm, with a mean of 4.1 mm. The mean thickness was estimated to be less than 1 mm. In comparison, conjunctival melanoma has been detected at a mean size of 8 mm in basal dimension and 2 mm in thickness.19 All of the patients with large nevi over 10 mm in basal dimension had prominent intralesional cysts to suggest the diagnosis and most had excisional biopsy for histopathologic confirmation. The largest lesions were diffusely multicystic and poorly circumscribed, often resembling a cystic conjunctival lymphangioma or lymphangiectasia.
The biomicroscopic appearance of the nevus was critical to its diagnosis. The tumor was most commonly brown (65%) and less often tan (19%) or completely nonpigmented (16%) appearing as a gelatinous translucent mass. Cysts were recognized in 65% of the nevi, feeder vessels in 33%, and intrinsic vessels in 38%. Interestingly, cysts were most common in compound nevus (70%), decreasingly common in subepithelial nevus (58%) and junctional nevus (40%), and absent in blue nevus (0%). Conjunctival melanoma has been recorded as brown in 68%, tan in 19%, and completely nonpigmented but with prominent intrinsic vessels casting a pink rather than gelatinous color in 11% of these lesions.19 In contrast, however, conjunctival melanoma rarely, if ever, displays intralesional cysts. Feeder vessels are prominent with conjunctival melanoma. Thus, the importance of recognition of tumor cysts is a key point in differentiating conjunctival nevus from malignant melanoma as many other features overlap.
Excision of conjunctival nevi was performed in 38% of the cases, mostly for reasons to rule out melanoma or other tumor, recent growth in the lesion, or cosmetic concern (Table 4). Of the 148 lesions for which histopathologic results were available, the findings revealed the following in descending order: compound nevus (70%), subepithelial nevus (24%), combined nevi (4%) (ie, compound and blue nevi or subepithelial and blue nevi), junctional nevus (3%), and blue nevus (3%) (Table 4). Gerner et al,6 in a clinicopathologic review of 343 conjunctival nevi, found similar distribution of nevi with compound nevi (78%), supepithelial (intrastromal) nevus (15%), junctional nevus (6%), and blue nevus (<1%). Of 57 nevi excised from children and teenagers, McDonnell et al4 identified compound nevi (72%), subepithelial nevus (4%), junctional nevus (21%), blue nevus (2%), and Spitz nevus (2%).4 These results suggest greater junctional activity in children with conjunctival nevi.
In our series, a correlation of the clinical features with the specific histopathologic diagnosis was provided (Table 5). Compound and junctional nevi were found in younger aged groups, whereas subepithelial and blue nevi were in slightly older aged groups. Bulbar conjunctival location was found with all 4 groups, but caruncular or plical tumor locations were seen only with compound or subepithelial nevi. Both compound and subepithelial nevi showed a variation in color types, but junctional and blue nevi were always brown. Cysts and feeder vessels were absent in all 4 patients with a blue nevus, but present in the other types.
The natural history of the 149 observed conjunctival nevi in our series revealed photographically documented change in tumor color in 13% and in size in 8%. Both were gradual and visible only on careful comparison of photographs over years. The change in apparent tumor size could be related to neoplastic growth, but we suspect more commonly it is related to enlargement of the intrinsic cysts, increased pigmentation in previously amelanotic regions of the nevus, or, importantly, inflammation within the nevus. Zamir et al22 found that 75% of the excised conjunctival nevi in children showed some degree of inflammatory infiltrate, some of which showed alarming clinical growth without malignant melanoma formation histopathologically. In our group, 3 patients developed malignant melanoma; all were white; 2 had cutaneous abnormalities including dysplastic nevus syndrome in one patient and a family history of cutaneous malignant melanoma in the other patient. The tumors were dark brown in all cases and lacked cysts in 2 patients. Following excision, evidence for melanoma was confirmed, along with underlying compound nevi in 2 patients and blue nevus in 1 patient. From a reverse perspective, conjunctival melanoma has been found to originate from preexistent nevus in 4% of the patients, primary acquired melanosis in 57%, de novo in 39%, that and not specified in 6%.19 Nooregaard et al20 found melanomas originate from a nevus in 16% of the patients, primary acquired melanosis in 36%, and de novo in 47%.
There are limitations in this study that should be realized. First, the cohort of patients was derived from a tertiary care ocular oncology center and, thus, may represent a biased group with more suggestive features. Thus, the 3 patients who developed conjunctival malignant melanoma likely represent a higher rate than expected in the general population of patients with conjunctival nevi. Second, there was incomplete photographic follow-up on some of the patients in this cohort. This could inflate the worst-case scenario as the stable patient might choose no further follow-up, whereas those with prominent lesions or tumor growth might choose close follow-up. Third, data collection were retrospective and although the collection was extensive, some data were incomplete. Fourth, not all patients had histopathologic confirmation of the nevus because many were followed up conservatively without surgery.
CONCLUSIONS
Conjunctival nevi display a spectrum of clinical features from heavy pigmentation to a complete lack of pigmentation, from diffuse confluence of cysts to a complete lack of cysts, and from a tiny dotlike size lesion to extensive tumors occupying 1 or 2 quadrants of the ocular surface. The natural history of conjunctival nevi is benign with minor gradual changes of pigmentation in 13% of the patients and gradual change in size in 8% of patients.
AUTHOR INFORMATION
Corresponding author and reprints: Carol L. Shields, MD, Ocular Oncology Service, Wills Eye Hospital, 840 Walnut St, Philadelphia, PA 19107.
Submitted for publication May 20, 2003; final revision received September 7, 2003; accepted October 1, 2003.
This study was supported by the Eye Tumor Research Foundation, Philadelphia, Pa (Dr C. L. Shields); the Macula Foundation, New York, NY (Dr C. L. Shields); the Center for Eye Research, Tehran, Iran (Dr Mashaykhi); the Rosenthal Award of the Macula Society, Cleveland, Ohio (Dr C. L. Shields); and the Paul Kayser International Award of Merit in Retina Research, Houston Tex (Dr J. A. Shields).
From the Ocular Oncology Service, Wills Eye Hospital, Thomas Jefferson University, Philadelphia, Pa. The authors have no relevant financial interest in this article.
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