Congenital Ocular Melanocytosis Research Articles

Congenital Ocular Melanocytosis: Case Report

Aims: To describe Congenital Ocular Melanocytosis.
 Presentation of Case: LPC, 7 years old, male, brown, with no previous comorbidities, was taken to the ophthalmology outpatient clinic of the Hospital Universitário Antônio Pedro, Brazil by parents who alleged the presence of bluish-looking lesions in the sclera of the child's right eye since birth.
 Discussion: Congenital Ocular Melanocytosis is a rare pathology characterized by an increase in the number, size and pigmentation of melanocytes. Its pathophysiological picture is unknown, but it is believed to be due to an alteration in the migration of melanocytes from the neural crest to the epidermis during the embryonic process. This condition can be complicated by glaucoma and uveal melanoma. Gonioscopy is essential in these cases to assess whether there is pigmentation of the trabeculae, so that the propaedeutics of investigation of glaucoma becomes essential in these patients, since 10% of cases can complicate this condition.
 Conclusions: Congenital Ocular Melanocytosis early in life and the importance of monitoring these patients should be emphasized. Comprehensive tests are important for early detection and treatment, in order to improve the prognosis and avoid more severe consequences than what can happen from melanocytosis.

Research progress on primary orbital melanoma

Primary orbital melanoma (POM) is a sort of extremely rare orbital malignancy. It often associates with melanin lesion such as congenital ocular melanocytosis and blue nevus. The most common clinical manifestation of POM is progressive painless proptosis. There are some difficulties in diagnosing this disease. MRI shows characteristic expression of this disease as an important way to diagnose POM, while pathology is the gold standard. Surgery is the mainstay of treatment in patients with POM. In addition, adjuvant radiotherapy and chemotherapy should be considered. This article systematically reviews the research progress of pathogenesis, clinical manifestation, auxiliary examination, differential diagnosis and treatment of POM, in order to provide some thoughts for the future study of the rare malignancy. (Chin J Ophthalmol, 2021, 57: 861-864).

Uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. UMs are usually initiated by a mutation in GNAQ or GNA11, unlike cutaneous melanomas, which usually harbour a BRAF or NRAS mutation. The annual incidence in Europe and the USA is ~6 per million population per year. Risk factors include fair skin, light-coloured eyes, congenital ocular melanocytosis, ocular melanocytoma and the BAP1-tumour predisposition syndrome. Ocular treatment aims at preserving the eye and useful vision and, if possible, preventing metastases. Enucleation has largely been superseded by various forms of radiotherapy, phototherapy and local tumour resection, often administered in combination. Ocular outcomes are best with small tumours not extending close to the optic disc and/or fovea. Almost 50% of patients develop metastatic disease, which usually involves the liver, and is usually fatal within 1 year. Although UM metastases are less responsive than cutaneous melanoma to chemotherapy or immune checkpoint inhibitors, encouraging results have been reported with partial hepatectomy for solitary metastases, with percutaneous hepatic perfusion with melphalan or with tebentafusp. Better insight into tumour immunology and metabolism may lead to new treatments.

Uveal melanoma in Finnish patients with congenital ocular melanocytosis

PurposeTo described the characteristics of uveal melanoma in congenital ocular melanocytosis in Finland.MethodsFor this retrospective observational case series, we identified all 15 of 867 (1.7%; 95% CI 1.0–2.8) uveal melanoma patients (5 male, 10 females) with congenital ocular melanocytosis during January 2000‐May 2015 at the Ocular Oncology Service, Helsinki University Hospital. The patient was followed up at 3 and 6 months, every 6 months for 3 years, and thereafter annually. The diagnosis of uveal melanoma was based on clinical and ultrasonographic features, and metastases were screened with annual abdominal ultrasonography and liver function tests.ResultsThe mean age at diagnosis was 55 years as compared with 64 years for all 867 patients. The mean thickness and basal diameter of the tumours were 6.5 (SD 3.6) and 13.1 (SD 4.4) mm, respectively, as compared to 5.1 (SD 3.9) and 12.5 (SD 4.5) among all patients, respectively. The melanoma involved the ciliary body in 6 patients (40%). The tumours represented TNM stages I in 4 (27%) patients, II in 5 (33%), III in 5 (33%) and IV (metastases at the time of diagnosis) in 1 patient. Enucleation was done in 2 cases, I‐125‐brachytherapy in 7 cases, and 5 patients were treated with Ru‐106. Recurrent tumour growth was observed in 2 patients. Overall 5‐ and 10‐year survival was 68% (95% CI 35–87) and 13% (95% CI 1–43). Survival was associated with TNM stage: 100%, 80%, 33% and 0% at 5 eyars for stages I‐IV, respectively. One patient survived for 10 years without metastasis.ConclusionsIn our data set, uveal melanoma patients with congenital ocular melanocytosis are on average 9 years younger than uveal melanoma patients in general, and have a tendency to die of metastases.

Pigmented Epibulbar Lesions: Overview

Eyes can be affected by a wide variety of epibulbar lesions. The incidence and prevalence of the epibulbar lesions is significantly high, with an incidence of 89.8% of the benign lesions as compared to the malignant lesions that accounted for 10.2% of the lesions. Considering the significance of the knowledge of the different types of epibulbar lesions, there is a need to perform a brief discussion of these lesions to develop the information of these lesions among the general population and the healthcare professionals. This would enable the successful diagnosis of the different types of epibulbar lesions. Epibulbar pigmented lesions include conjunctival epithelial melanosis, conjunctival freckle, primary acquired melanosis, conjunctival nevus, congenital ocular melanocytosis, and malignant melanoma.

Primary uveal melanoma in a 4-year-old black child

Primary uveal melanoma is extremely rare in children and also among blacks. Uveal melanomas may be associated with various preexisting conditions, including congenital ocular melanocytosis and dysplastic nevus syndrome. We report the case of a 4-year-old black girl who presented with pronounced proptosis and no light perception secondary to a massive intraocular tumor with extrascleral extension. Biopsy of the tumor confirmed the diagnosis of primary uveal melanoma, and the patient was treated by enucleation and external beam radiation therapy. Although metastatic disease was ruled out at the time, the patient died approximately 3 months later.

Metastasis from Uveal Melanoma Associated with Congenital Ocular Melanocytosis: A Matched Study

To determine the rate of metastasis resulting from uveal melanoma associated with congenital ocular melanocytosis (COM) and to compare it with the rate of metastasis resulting from uveal melanoma not associated with COM. Matched retrospective study. Fifty-seven patients with uveal melanoma associated with ocular melanocytosis (melanocytosis group). Each patient in the melanocytosis group was matched with 2 patients with uveal melanoma not associated with ocular melanocytosis (no melanocytosis group) for age, gender, location of anterior tumor margin, location of tumor epicenter, tumor basal diameter, and tumor thickness. Review of medical records. Metastasis resulting from uveal melanoma. The mean basal diameter and thickness of tumors in the melanocytosis group were 10 and 4.9 mm, respectively, and most were located between the macula and equator (70%). The melanocytosis and no melanocytosis groups were similar with regard to all patient, ocular, and tumor features studied. Nineteen (33%) of 57 patients in the melanocytosis group and 18 (16%) of 114 patients in the no melanocytosis group demonstrated systemic metastasis during mean follow-up periods of 77 months (range, 1-402) and 64 months (range, 1-252), respectively (P = 0.013). The Kaplan-Meier estimates for systemic metastasis in the melanocytosis group at 5 and 15 years were 27% and 59%, respectively, compared with 15% and 33%, respectively, in the no melanocytosis group (hazard ratio, 1.99; 95% confidence interval, 1.16-3.41). In this matched study, patients with uveal melanoma associated with COM were twice as likely to have systemic metastasis compared with patients with uveal melanoma not associated with COM. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Phacomatosis Pigmentovascularis of Cesioflammea Type in 7 Patients

To describe the features of phacomatosis pigmentovascularis (cesioflammea type). Noninterventional retrospective case series composed of 7 patients. Nevus flammeus combined with ipsilateral ocular melanocytosis or melanosis was seen in all 7 patients. Additional contralateral nevus flammeus was observed in 3 patients. Nevus flammeus (unilateral in 4 patients and bilateral in 3 patients) was distributed in trigeminal nerves V1 (n = 3), V2 (n = 7), and V3 (n = 5). Related findings included diffuse choroidal hemangioma (n = 1) and glaucoma (n = 1), with no patients having brain hemangioma or seizures. Ocular pigmentary abnormalities (unilateral in all 7 patients) included congenital ocular melanocytosis (n = 6) and conjunctival acquired melanosis (n = 1). Pigmentation was sectorial (partial) in 5 patients and complete in 2 patients. Melanocytosis involved the periocular skin in 1 patient, sclera in 2 patients, iris in 2 patients, and choroid in 4 patients. In 3 of 6 patients, melanocytosis was visible in the choroid only on dilated fundus evaluation. Related tumors included choroidal melanoma (n = 3), optic disc melanocytoma (n = 1), and conjunctival melanoma in situ (primary acquired melanosis) (n = 1). Melanoma metastasis developed in 1 patient. Phacomatosis pigmentovascularis shows features of nevus flammeus and more serious ocular pigmentary abnormalities (uveoscleral melanocytosis and conjunctival melanosis). Melanocytosis may be detected only by dilated ocular fundus examination, as found in 3 of 6 patients. Furthermore, choroidal melanoma can develop from melanocytosis, as noted in 3 of our 6 patients (50%). All patients with nevus flammeus should be examined for phacomatosis pigmentovascularis by an ophthalmologist because ocular melanocytosis and uveal melanoma may remain hidden within the eye.

Diffuse choroidal melanocytoma simulating melanoma in a child with ocular melanocytosis.

To report a clinicopathologic correlation of an extensive, diffuse uveal melanocytoma (magnocellular nevus) simulating diffuse choroidal melanoma in a child. Clinicopathologic report. A 14-year-old girl with congenital sector ocular melanocytosis was found to have progressive visual loss and a diffuse choroidal mass measuring 18 mm in basal dimension and 4 mm in thickness. There was overlying orange pigment and secondary retinal detachment. Diffuse choroidal melanoma was suspected, and the eye was enucleated. Histopathologically, the entire uveal tract was diffusely thickened because of a proliferation of benign cells typical of melanocytoma without evidence of melanoma. Diffuse uveal melanocytoma is a rare variant of ocular melanocytosis that can cause reduced vision, overlying orange pigment, and retinal detachment, resembling a diffuse choroidal melanoma.

Iris Melanoma Arising From Sector Congenital Ocular Melanocytosis in a Child

To report a clinicopathologic correlation of a melanoma arising from iris component of ocular melanocytosis in a child. A 13-year-old boy developed a progressive iris nodule arising from sector iris pigmentation that was a component of congenital ocular melanocytosis involving the iris, ciliary body and choroid. The tumor was examined clinically and with ultrasound biomicroscopy (UBM), removed by peripheral iridocyclectomy, and studied histopathologically. Clinically, the pigmented nodule was 3 mm in diameter, located within the sector iris pigmentation, and was 2.4 mm in thickness as measured by UBM. Histopathologically, it was composed predominately of spindle B melanoma cells with adjacent spindle and dendritic melanocytes compatible with iris melanocytosis. Although highly unusual, melanoma can arise in the sector iris pigmentation that is often a component of congenital ocular melanocytosis. Even young patients with ocular melanocytosis should be examined periodically for development of melanoma in the ciliary body and choroid.

Idiopathic intracranial hypertension and congenital ocular melanocytosis: a new association

Congenital ocular melanocytosis is a rare anomaly that requires regular follow-up, since it carries an increased risk of glaucoma and uveal malignant melanoma. Idiopathic intracranial hypertension (IIH) has several identifiable...

Iridociliary melanoma associated with ocular melanocytosis in a 6-year-old boy

A previously healthy 6-year-old boy presented to the ophthalmologist and was found to have congenital ocular melanocytosis associated with uveal melanoma. He was treated with enucleation of the affected eye and has shown no evidence of tumor recurrence or metastasis through over 20 years of postenucleation follow-up. Ocular melanocytosis can be associated with uveal melanoma even in young children.

Pinguecula masquerading as conjunctival melanoma

Dear Editor, Pinguecula is a common degenerative condition of conjunctiva. In atypical cases an erroneous diagnosis of carcinoma may be made. We report an atypical presentation of histopathologically proven pinguecula. A 50-year-old carpenter presented with a dark lesion associated with watering, redness, irritation and itching in right eye since three weeks. He reported no vision loss, pain, trauma or topical use of medication or cosmetics. There was no contributory medical history. On examination, his best corrected visual acuity was 20/40 in both eyes. Ocular movements were normal. The right eye had a vascularized pigmented lesion with surface ulceration, surrounding conjunctival chemosis and vascularization of the surrounding conjunctiva in the temporal bulbar conjunctiva, 3 mm from limbus [Fig. 1]. It measured 8 mm horizontally by 5 mm vertically, with maximal elevation of 2 mm and irregular borders. It was freely mobile over the underlying sclera. There was dellen in the peripheral cornea. Two prominent forniceal vessels extended to the mass. Both eyes had nuclear sclerosis, normal intraocular pressure and normal fundus. Regional lymph nodes were not palpable.Figure 1: Slit lamp photograph of right eye showing vascular pigmented conjunctival lesionIn view of the suspicious nature of the lesion, we performed an excision biopsy with 4mm tumor-free margins using a ‘no touch’ method,1 avoiding direct manipulation of the tumor to preclude tumor cell seeding. The conjunctiva was then re-apposed. Histopathology showed surface epithelium with areas of atrophy and hyperplasia. Sub-epithelial tissue demonstrated hyalinization and calcareous degeneration [Fig. 2]. Areas of granulation tissue with perivascular mononuclear inflammatory cell reaction were seen. Histopathological picture was suggestive of pinguecula.Figure 2: Histopathology of the same lesion showing hyalinization and calcareous degenerationPrimary malignant melanoma may arise from nevi, primary acquired melanosis or de novo. These present as a pigmented vascularized lesions with rapid growth. Histologically, the overlying epithelium is invaded with atypical cells and inflammatory infiltrate.2 Conjunctival nevus and congenital ocular melanocytosis have congenital onset, though conjunctival nevus may present in young adult. Histologically, nevus cells are seen in the sub-epithelial tissue in interlacing fasciculi.23 Primary acquired melanosis has an onset in middle age and has brown diffuse structure.2 Other simulating lesions include nevus of sclera, pseudo pigmentation in blue sclera, ectatic sclera and scleromalacia perforans, endogenous pigmentation (blood, bile), metabolic disorders (Ochronosis, Gaucher's disease), exogenous pigmentations (epinephrine, argyrosis, mascara, dyes, iron and foreign bodies), pigment spots of the sclera2 and aspergilloma.4 Pinguecula is a degenerative process of sub-epithelial connective tissues of bulbar conjunctiva in the inter-palpebral region, over which the epithelium may be ulcerated, atrophic or thickened.5 Histologically, the most characteristic feature is sub-epithelial senile elastosis.5 The control of elastogenesis is seriously defective so that the elastic fibers are abnormal in biochemical composition. P53 mutations in limbal epithelial cells probably caused by ultraviolet radiation, may contribute.6 Secondary hyalinization and calcareous degeneration may be observed.3 Epithelium becomes atrophic or acanthotic and dyskeratotic which can lead to erroneous diagnosis of carcinoma.57 The conjunctival lesion so closely resembled a conjunctival melanoma that an excision biopsy was performed with the ‘no touch’ technique.1 A diagnosis of secondary change in a pinguecula may be made with caution, but must be confirmed by histopathology to facilitate definitive diagnosis and subsequent management.

Isolated choroidal melanocytosis: a distinct clinical entity?

The objective was to describe a distinct, limited form of congenital ocular melanocytosis that involves the choroid only. A retrospective descriptive case series study of 11 patients with similar appearing broad-based but entirely flat melanotic choroidal lesions was carried out. All 11 lesions were homogeneously dark brown in color with at least one striated margin. They were located in various regions of the fundus from the macula and juxtapapillary area to the periphery. They ranged in size from 6 to 23 mm in the largest basal diameter, but all 11 were completely flat. The youngest patient was only 2 months old when the lesion was first detected, but the oldest was 82 years old. None of the 7 lesions that were re-evaluated over a median follow-up of 4 years enlarged or changed appreciably otherwise. The choroidal lesions described in this report may be a distinct, limited form of congenital ocular melanocytosis. We refer to these lesions as "isolated choroidal melanocytosis." Lesions of this type may predispose affected patients to choroidal melanoma.

Malignant melanoma of the choroid associated with misdiagnosed ocular melanocytosis

A 73-year-old white female complained of a darker left eye since childhood, which was interpreted at ophthalmic review some 40 years ago as ‘benign conjunctival melanosis’. Since then, the subject had not consulted an ophthalmologist until this occasion, when she presented with blurry vision OS. On slit-lamp examination, the whole left episclera was seen to show pronounced perivascular melanocytic pigmentation (1, 2). The left iris and choroid also appeared more darkly pigmented. In the periphery, a melanocytic tumour was detected with penetration of the retina and collateral retinal detachment (Fig. 3). The left eye was enucleated. Histological examination revealed an epitheloid cell type melanoma (3, 4) with vitreous invasion and widespread tumour cell seeding 3-5). A dense accumulation of melanocytes as a typical feature of ocular melanocytosis (OM) was found in the uvea, trabecular meshwork, sclera and episclera, especially perivascularly (2, 6). Left eye with brownish subconjunctival pigmentation. Perivascular distribution of episcleral melanocytes. Inset: Masson-trichrome staining: superficial episcleral melanocytes adjacent to blood vessels. The superiorly located choroidal melanoma has penetrated through the retina with strands of malignant cells in the vitreous (arrow). (A) Ultrasonography shows posterior vitreous detachment (arrow). (B) Periodic acid-Shiff staining: epitheloid cell choroidal melanoma penetrates the Bruch's membrane (arrowhead). (C) Masson-trichrome staining: scleral infiltration (arrowheads). Deposits of melanoma cell cover the inferior retina (arrows). Inset: Masson-trichrome staining: melanophages and melanoma cells overlie the retina (arrowhead). Masson-trichrome staining: a typical accumulation of melanocytes in the iris stroma, ciliary body and trabecular meshwork. As a relatively rare condition (with a prevalence of approximately 0.04% among white populations and 0.014% among black populations), congenital OM is often associated with uveal melanomas (Gonder et al. 1982). The lifetime risk of developing uveal melanoma in white OM populations has been estimated to be about 1 : 400, as opposed to 1 : 13 000 for the general white population (Singh et al. 1998). To avoid misdiagnosis as conjunctival melanocytosis (CM), as described in the present report, OM can easily be differentiated from CM. In contrast to OM, CM can be moved over the sclera with a glass rod or cotton tip applicator after topical anaesthesia. Conjunctival melanocytosis is not associated with iris, scleral or choroidal hyperpigmentation. The CM is brownish, whereas episcleral pigment usually has a greyish to bluish tint in OM (Yanoff & Zimmerman 1967; Rummelt & Naumann 1997). Because of an approximately 32-times increased lifetime risk of developing uveal melanomas, patients with OM need to be educated regarding this risk and should be followed with annual lifelong ophthalmoscopic review. This study was supported in part by the Alexander von Humboldt Foundation, Bonn, Germany and the Royal Australian and New Zealand College of Ophthalmologists (RMC).

Iris Melanoma in Ocular Melanocytosis

A pigmented, circumscribed iris lesion thought to be a nevus was noted in the right eye of a 64-year-old man with congenital ocular melanocytosis. Although the patient had excess episcleral and choroidal pigmentation, the iris in the affected eye was blue. Two years later, growth was documented, suggesting that the lesion was malignant. The tumor was resected by a sector iridectomy and studied by light microscopy. Histopathologically, the tumor was shown to be a malignant melanoma of the mixed-cell type. No evidence of congenital melanocytosis was found in the adjoining normal iris. This is a well-documented case of a malignant melanoma of the iris arising in a blue, uninvolved iris in a patient with sectoral congenital ocular melanocytosis. Although this specific association has not been previously reported, we believe that any pigmented uveal tumor occurring in the setting of congenital ocular melanocytosis should be observed closely for growth that can signal malignant transformation.