Histopathological analysis of juvenile patients with melanocytic lesions of the conjunctiva :Guilherme Feltrin de Barros, Juliana Portela Passos, Jacqueline Coblentz, Miguel N Burnier, The Pan-American Journal of Ophthalmology

ORIGINAL ARTICLE
Year : 2022 | Volume : 4 | Issue : 1 | Page : 44-

Histopathological analysis of juvenile patients with melanocytic lesions of the conjunctiva

Guilherme Feltrin de Barros¹, Juliana Portela Passos², Jacqueline Coblentz³, Miguel N Burnier⁴,
¹ The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, McGill University, Montréal, Québec, Canada; Department of Ophthalmology, Faculdade de Medicina do ABC, Santo André, SP, Brazil
² The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, McGill University, Montréal, Québec, Canada
³ Department of Ophthalmology, Faculdade de Medicina do ABC, Santo André, SP, Brazil
⁴ The MUHC-McGill University Ocular Pathology and Translational Research Laboratory, McGill University, Montréal; Department of Ophthalmology, McGill University, Montréal, Québec, Canada

Correspondence Address:
Guilherme Feltrin de Barros
Department of Ophthalmology, Faculdade de Medicina do ABC, 2000 Lauro Gomes Avenue, Santo André, SP, 09069-870

Abstract

Objective: This study aimed to examine the frequency of atypical features in conjunctival nevi in pediatric patients referred to the McGill University Health Center-McGill University Ocular Pathology and Translational Research Laboratory and to emphasize the importance of histopathological analysis to rule out malignant lesions, such as melanoma. Methods: Forty-four pediatric patients younger than 20 years of age previously diagnosed with melanocytic lesions of the conjunctiva were included in this study, and the database was analyzed for a 10-year period (2006–2015). Clinical information such as age, gender, location, type, size, and agreement between clinical and pathological diagnosis was also recorded and presented as means and percentages. Results: The mean age was 11.3 years, of which only 9.1% were older than 18 years. Gender predilection was found toward males (52.3%). An agreement was noted between clinical and pathological diagnosis in 77.2% of cases; only 22.72% showed atypia upon histopathological examination. The most common pathological diagnosis was compound nevus with different characteristics. The atypical lesions included conjunctival melanoma, junctional nevi with atypia, compound nevi with atypia, and cystic compound nevi. Moreover, 70% of the patients with atypical lesions were males and 60% of the specimens were from the right eye. Conclusion: An impressive number of 30% of all patients had some type of atypia after histopathological analysis. Therefore, based on these results, it is of extreme importance that all melanocytic lesions are sent for histopathological analysis, so an accurate diagnosis can be established.

How to cite this article:
de Barros GF, Passos JP, Coblentz J, Burnier MN. Histopathological analysis of juvenile patients with melanocytic lesions of the conjunctiva.Pan Am J Ophthalmol 2022;4:44-44

How to cite this URL:
de Barros GF, Passos JP, Coblentz J, Burnier MN. Histopathological analysis of juvenile patients with melanocytic lesions of the conjunctiva. Pan Am J Ophthalmol [serial online] 2022 [cited 2023 Sep 27 ];4:44-44
Available from: https://www.thepajo.org/text.asp?2022/4/1/44/356710

Full Text

Introduction

Melanocytic proliferations are the most common tumors of the conjunctiva, accounting for up to 53% of all conjunctival neoplasms.[1],[2],[3] The most important ones are nevus, racial melanosis, primary acquired melanosis (PAM), and malignant melanoma. Furthermore, ocular melanocytosis should be included in this discussion because its scleral pigmentation can masquerade as conjunctival pigmentation.[1] Out of all of the conjunctival melanocytic lesions, nevus is the most common one.[2],[3],[4],[5] Nevi may be pigmented and can increase their size as well as pigmentation during puberty.[4] However, up to 30% of nevi remain amelanotic. In terms of cutaneous nevus, there are three types of this benign lesion, which are categorized according to their location: junctional, compound, and subepithelial.[3] Histopatologically, nevi are composed of nests of benign melanocytes in the stroma near the basal layers of the epithelium. They remain relatively stationary throughout life and the risk of malignant transformation into melanoma is less than 1%.[2],[6]

Compound nevi are the most common type of conjunctival nevus (70%–78%).[6] They consist of nevi cells at the epithelial-stromal junction and within subepithelial tissue. These nevi have pseudocysts outlined by conjunctival epithelium, and they contain mucus-secreting goblet cells.[7] Junctional nevi are usually found in 5% of all conjunctival nevus and are characterized by nested but potentially lentiginous proliferation of nests of oval cells (type A) or oval-to-cuboidal cells (type B) confined to the epithelium. Mitotic activity may also occur.[6] Subepithelial nevi represent about 9% of all nevi.[6] They consist of nests of type B cells or spindle-like cells in the subepithelium that are located completely within the substantia propria.[6],[7] Racial melanosis is a relatively common (3%) bilateral condition of flat conjunctival pigmentation present at the limbus, found in darkly pigmented individuals. It is extremely rare for conjunctival melanoma to arise from racial melanosis.[1],[2]

PAM is an important benign conjunctival pigmented condition. Approximately 32% of the cases can differentiate into conjunctival melanoma when this lesion has any degree of atypia. PAMs without atypia are usually benign.[2],[8] This lesion is most frequently acquired in middle age and is rarely found in children and young adults.[1],[8]

Melanoma is a rare malignant lesion that usually arises in patients around 60 years.[3],[9] Only 2% of ocular melanomas are localized in the conjunctiva. Most melanomas are situated in the bulbar conjunctiva, but melanocytic lesions may also be located in the caruncle, fornix, or palpebral conjunctiva.[2],[10],[11] Only 1% of all conjunctival melanomas occur in children.[12] Studies that analyzed conjunctival melanoma in adulthood concluded that the estimated mortality rate is 13%–38% in 10 years, making this entity a threat to sight and life.[13],[14] About 25% of conjunctival melanomas will metastasize to tumor-draining lymph nodes via lymphatics; therefore, it is central that systematic investigation for metastasis takes place.[1],[12],[15] Herein, all clinical diagnoses of melanocytic proliferation should be sent to pathology to ensure accurate diagnosis using immunohistochemistry.[2],[10],[11]

This study aimed to examine the frequency of atypical features in conjunctival nevi in pediatric patients referred to the McGill University Health Center (MUHC)-McGill University Ocular Pathology and Translational Research Laboratory and to emphasize the importance of its histopathological analysis to rule out malignant lesions, such as melanoma.

Methods

Forty-four patients referred to the MUHC-McGill University Ocular Pathology Laboratory, Montreal, Canada, diagnosed with melanocytic lesions of the conjunctiva were selected. Database of pediatric patients younger than 20 years of age was analyzed for a 10-year period, from 2006 to 2015. Clinical information such as age, gender, location, type, size, and agreement between clinical and pathological diagnosis was also recorded and presented as means and percentages.

Results

The mean age of the 44 patients was 11.3 years; only 9.1% (n = 4) were older than 18 years. There was a slight gender predilection toward males (52.3%; n = 23). There was an agreement between clinical and pathological diagnosis in 77.2% of cases (n = 34), and less than a quarter of patients showed atypia (22.72%; n = 10) upon histopathological examination. The most common pathological diagnosis was compound nevi with different characteristics, such as congenital features, different degrees of pigmentation, and presence of epithelial cysts. The atypical lesions included conjunctival melanoma (n = 1), junctional nevi with atypia (n = 2), compound nevi with atypia (n = 5), and cystic compound nevi (n = 2). Moreover, 70% (n = 7) of patients with atypical lesions were male, 60% (n = 6) of the specimens were from the right eye, and the mean age of this patient cohort was 10.2 years.

Discussion

The conjunctiva is derived from the surface ectoderm of the optic vesicle as well as the neuro ectoderm. In addition, it contains epithelium and stroma. Conjunctival tumors can arise from any of the component cells, which means that their presentation varies as either benign or malignant.[1] Benign conjunctival tumors include congenital, melanocytic, epithelial, and stromal lesions.

Shields and Shields showed that conjunctival nevus is the most common melanocytic tumor. It becomes clinically apparent in the first or second decade of life as a discrete, variably pigmented, slightly elevated lesion that contains a fine clear cyst.[2] In our case series, the mean age of patients was 11.3 years, in accordance with the literature that shows that nevi are more common in the first or second decade of life.[5]

It is important to determine the histopathological features of a melanocytic lesion to confirm its behavior and the possibility of a surgical approach.[1] Indications for removal vary according to the suspicion of malignancy, mitotic activity, or functional disorders. In this study, from all 44 patients with melanocytic lesions of the conjunctiva, 77.2% were correctly clinically diagnosed, while the misdiagnosed (22.8%) were either malignant or atypical. Therefore, this shows that almost a quarter of all patients were misdiagnosed, which could lead to a life-threatening outcome. Furthermore, although mortality rates in children may seem favorable, such a malignant disease should never be put at risk.[14] Prognosis for this entity involves many factors, such as tumor thickness and diameter; therefore, the longer it takes for the malignancy to be carefully removed, the higher are the chances for a worse prognosis, thus highlighting the importance of early diagnosis.[16]

Conjunctival melanoma may invade local structures including eyelids, orbit, and other nearby structures.[17] In addition, within 10 years, local recurrence and distant metastasis are discovered in 50% and 26% of people, respectively.[17] This study showed that among the atypical lesions, 30% were compound nevi, 30% were compound melanocytic nevi, 20% were junctional nevi, 10% were cystic compound nevi, and 10% were conjunctival melanoma.

A recent study reviewed a case series of 32 patients diagnosed with conjunctival melanoma.[14] All of these patients were children under the age of 18 with a mean age at presentation of 11 years. In accordance with the literature, the patient included in this study was a 9-year-old boy diagnosed with conjunctival melanoma of the left eye. His tumor was confirmed under immunohistochemistry analysis that stained positive for HMB-45, Mart (canceled zzIP), tyrosinase, and CD31.

In this present study, demographic characteristics were also recorded and correlations were noted. Even though there was no gender predilection toward all melanocytic lesions found, among the atypical lesions, a gender predilection was indeed noted, as 70% of all atypical lesions, including conjunctival melanoma, were found in male patients. Furthermore, 60% of the atypical specimens were found in the right eye, which could potentially infer a side predilection.

In conclusion, this cohort of patients shows that the majority of melanocytic proliferation in children is benign. However, we encourage all patients with pigmented conjunctival lesions to be assessed by an ocular oncologist or ocular pathologist, as evaluation once in a specialized center is required, given the need for an accurate no-touch excision biopsy and treatment if needed. Furthermore, an impressive number of 30% of all our patients had some type of atypia after histopathological analysis.

Conclusion

To the best of our knowledge, we strongly suggest that all melanocytic lesions should be sent for histopathological analysis so an accurate diagnosis can be established.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declarations of interest

none.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1	Novais GA, Fernandes BF, Belfort RN, Castiglione E, Cheema DP, Burnier MN Jr. Incidence of melanocytic lesions of the conjunctiva in a review of 10 675 ophthalmic specimens. Int J Surg Pathol 2010;18:60-3.3.
2	Shields CL, Shields JA. Conjunctival tumors in children. Curr Opin Ophthalmol 2007;18:351-60.0.
3	Colarossi C, Milazzo M, Paglierani M, Massi D, Memeo L, Canzonieri V. A juvenile case of conjunctival atypical nevus. Diagn Pathol 2013;8:64.
4	Thiagalingam S, Johnson MM, Colby KA, Zembowicz A. Juvenile conjunctival nevus: Clinicopathologic analysis of 33 cases. Am J Surg Pathol 2008;32:399-406.
5	Strempel I, Kroll P. Conjunctival malignant melanoma in children. Ophthalmologica 1999;213:129-32.
6	Zembowicz A, Mandal RV, Choopong P. Melanocytic lesions of the conjunctiva. Arch Pathol Lab Med 2010;134:1785-92.
7	Liesegang TJ. Pigmented conjunctival and scleral lesions. Mayo Clin Proc 1994;69:151-61.
8	Maly A, Epstein D, Meir K, Pe'er J. Histological criteria for grading of atypia in melanocytic conjunctival lesions. Pathology 2008;40:676-81.
9	Taban M, Traboulsi EI. Malignant melanoma of the conjunctiva in children: A review of the international literature 1965-2006. J Pediatr Ophthalmol Strabismus 2007;44:277-82.
10	Shields CL, Fasiuddin AF, Mashayekhi A, Shields JA. Conjunctival nevi: Clinical features and natural course in 410 consecutive patients. Arch Ophthalmol 2004;122:167-75.
11	Maly A, Epstein D, Meir K, Pe'er J. Histological criteria for grading of atypia in melanocytic conjunctival lesions. Pathology 2008;40:676-81.
12	Al Masaoudi L, Kanaan A, Daniel SJ. Conjunctival melanoma with metastasis to the parotid gland in a 10 year-old boy: A case report and literature review. Int J Pediatr Otorhinolaryngol Extra 2013;8:47-9.
13	Polat A, Yildirim C, Işik Balci Y, Ince T, Bir F, Demirkan N, et al. Conjunctival melanoma in a six-year-old female. Pediatr Blood Cancer 2008;50:384-6.
14	Balzer BWR, Cherepanoff S, Joshua AM, Giblin M, Conway RM, Anazodo AC. Conjunctival melanoma in childhood and adolescence: A systematic review. Ocul Oncol Pathol 2019;5:387-95.
15	Liesegang TJ. Pigmented conjunctival and scleral lesions. Mayo Clin Proc 1994;69:151-61.
16	Kaštelan S, Gverović Antunica A, Beketić Orešković L, Salopek Rabatić J, Kasun B, Bakija I. Conjunctival melanoma-Epidemiological trends and features. Pathol Oncol Res 2018;24:787-96.
17	Grimes JM, Shah NV, Samie FH, Carvajal RD, Marr BP. Conjunctival melanoma: Current treatments and future options. Am J Clin Dermatol 2020;21:371-81.