Isolated choroidal melanocytosis: clinical update on 37 cases

Isolated choroidal melanocytosis is a partial form of congenital ocular melanocytosis in which clinically evident melanotic hyperpigmentation of the eye is limited to the choroid. First described as a distinct clinical entity in 2006 [1], several other cases categorized as this disorder have been reported [2‐8]. Isolated choroidal melanocytosis has the following clinical features: (1) a discrete patch of clinically flat choroidal hyperpigmentation that is indistinguishable from patches of choroidal involvement in persons with partial (sector) ocular melanocytosis [9]; (2) absence of ipsilateral iridic or anterior scleral melanocytosis; and (3) no measurable thickness of the melanotic choroidal lesion by B-scan ocular ultrasonography.

The purposes of this study were to describe an expanded group of patients with this disorder and report three patients who had a choroidal malignant melanoma that appeared to have arisen from the hypermelanotic choroidal patch.

The authors performed a retrospective descriptive study of patients with isolated choroidal melanocytosis encountered in their clinical practice during the period 1986 through 2018. Patients were identified by search of the practice’s patient name—clinical diagnosis database for cases coded as ocular melanocytosis, choroidal melanocytosis, or diffuse choroidal nevus. The medical records of all of these patients were reviewed individually. The inclusion criterion used to identify cases for this study was a patch of confluent melanotic choroidal hyperpigmentation consistent with congenital choroidal melanocytosis in one or both eyes. Exclusion criteria used to eliminate cases were (1) largest arc length basal diameter of the melanotic choroidal lesion less than 5 mm, (2) measurable thickness of the melanotic choroidal lesion greater than that of the surrounding uninvolved choroid by B-scan ultrasonography, (3) presence of ipsilateral anterior scleral or iridic features of ocular melanocytosis [9, 10], (4) acquired bilateral patchy-streaky choroidal melanocytic fundopathy consistent with the fundopathy of cutaneous vitiligo [11, 12] and Waardenburg syndrome [13‐15], and (5) acquired bilateral zonal choroidal melanocytic fundopathy that is age-related or drug-induced [16, 17]. Lesion diameter less than 5 mm was used to exclude typical choroidal nevi, 95% of which have been reported to be smaller than this [18]. Measureable thickness of the lesion greater than the surrounding uninvolved choroid was used to exclude most choroidal nevi larger than 5 mm in basal diameter (most of which are measurably thicker than the surrounding choroid by ultrasonography [19]), choroidal melanocytomas, and small choroidal melanomas. None of the lesions in this series was evaluated by optical coherence tomography.

We abstracted demographic and medical-surgical historical information about each identified patient and eye-specific information (eye involved; best corrected visual acuity; arc length largest and smallest basal diameters of the melanotic choroidal lesion; location of the lesion in the fundus relative to the fovea, optic disc, and ocular equator; shape of the choroidal lesion (coded as either circular-ovoid or irregular-geographic); features of the margins of each lesion (coded as smooth or striated-feathered); absence versus presence of orange pigment (lipofuscin) clumps, drusen, and disruption and/or clumping of the retinal pigment epithelium overlying the lesion; absence versus presence of associated serous subretinal fluid overlying or surrounding the lesion; and absence versus presence of lesions categorized as choroidal nevus, choroidal malignant melanoma, or focal aggregates of normal or near-normal uveal melanocytes (FANNUMs) in the choroid [20]) about each affected and fellow eye from our office records. We created a comprehensive computerized database (SPSS for Windows) of this information and computed conventional descriptive statistics on the study cases.

Thirty-seven patients with isolated choroidal melanocytosis were identified by our records search (Table 1). This series included the 11 cases reported in our 2006 publication on this topic [1]. These cases are identified by their case numbers in the 2006 article in Table 1. Thirty-six of these cases were coded correctly (by either JJA or ZMC) as isolated choroidal melanocytosis at the time of their initial evaluation in the Ocular Oncology Service. One case (case 32 in Table 1) was coded incorrectly initially (by JJA) as diffuse choroidal nevus in 1991. The correct revised diagnosis of isolated choroidal melanocytosis was made during a retrospective chart review in 2018. No case coded as complete generalized or partial (sectoral) ocular or oculodermal melanocytosis underwent recoding as isolated choroidal melanocytosis during retrospective chart review.

Fifteen patients (40.5%) were male and 22 (59.5%) were female. The isolated choroidal melanocytosis involved the right eye in 18 (48.6%) and the left eye in 19 (51.4%). No patient in this series exhibited bilateral isolated choroidal melanocytosis. However, one patient with isolated choroidal melanocytosis in one eye had combined sectoral iridic and choroidal melanocytosis (without any anterior scleral melanocytosis) in the fellow eye (case 24 in Table 1).

The 37 patients in this series ranged in age at initial evaluation in the Ocular Oncology Service from 2 weeks (a child whose melanotic fundus lesion was identified during a retinopathy of prematurity screening evaluation) to 87 years (mean age 31.5 years, median age 18 years). Eleven of the patients (29.7%) were 10 years of age or younger, 8 (21.6%) were between 11 and 21 years of age, 9 (24.3%) were 50 years of age or older, and 3 (8.1%) were 75 years of age or older when they were first evaluated in the Ocular Oncology Service. Twenty-three of these patients were referred to the Ocular Oncology Service shortly after the melanocytic choroidal lesion or other fundus abnormalities were first noted by an eye care professional. However, the melanotic choroidal lesion had been detected at a prior examination by an eye care professional and followed as a large choroidal nevus in 14 cases (cases 6, 11, 16, 17, 19, 20, 21, 23, 24, 26, 28, 29, 36, and 37 in Table 1) from 1 to 22 years (mean 5.7 years, median 3.1 years) prior to the patient’s first evaluation in the Ocular Oncology Service and diagnosis of isolated choroidal melanocytosis.

Best corrected visual acuity in the affected eye at initial evaluation in the Ocular Oncology Service ranged from 20/15 to 20/200 (median 20/20−). Visual acuity was 20/25 or better in 30 of the 37 eyes (81.1%). In contrast, visual acuity was 20/100 or worse in two eyes, one because of dry age-related macular degeneration (case 35 in Table 1) and one because of a choroidal malignant melanoma and associated secondary serous subretinal fluid (case 25 in Table 1).

The melanotic choroidal lesion measured from 5.5 to 37 mm in arc length largest basal diameter (mean 14.6 mm, median 13 mm) and from 4.5 to 23.5 mm in arc length smallest basal diameter (mean 10.7 mm, median 9 mm). The largest lesion in this series (case 6 in Table 1) occupied almost the entire superior hemisphere of the fundus (Fig. 1). The lesion was 10 mm or less in arc length largest basal diameter in 16 cases (43.2%), between 10 and 15 mm in 6 (16.2%), between 15 and 20 mm in 8 (21.6%), and over 20 mm in 7 (18.9%).

Twenty-one of the melanotic choroidal lesions (56.8%) were roughly circular to ovoid in shape, while 16 (43.2%) were irregular or geographic in shape. Thirteen of the lesions (35.1%) had smooth margins, 20 (54.1%) had predominantly smooth margins but at least one striated-feathered margin, and 4 (10.8%) had predominantly striated margins. Large-caliber choroidal blood vessels were visible passing through the lesion (Fig. 2) in 9 cases (24.3%). None of the isolated choroidal melanocytosis lesions in this series exhibited clumps of orange pigment or disruption-clumping of the retinal pigment epithelium overlying the flat lesion or associated serous subretinal fluid attributable to the lesion; however, three patients who were found to have a choroidal malignant melanoma associated with the patch of isolated choroidal melanocytosis (cases 25, 31, and 37 in Table 1) all exhibited clumps of orange pigment and serous subretinal fluid associated with the nodular choroidal tumor. One patient (case 29 in Table 1) exhibited a multitude of drusen on the surface of the lesion both inferonasally and superonasally from the optic disc; however, this patient also had multiple similar-appearing drusen in the corresponding fundus locations in the contralateral eye. Consequently, we did not attribute these drusen to the flat melanocytic choroidal lesion.

The choroidal lesion extended beneath the fovea in 18 cases (48.6%) and to the optic disc in five (13.5%). Four of the lesions that extended to the optic disc surrounded more than half the circumference of the disc. Three patients in this series had a lesion that was both subfoveal and extended to the optic disc. Twelve of the lesions (32.4%) were extrafoveal and extrapapillary but located within one disc-foveal distance (approximately 3 to 3.5 mm) from either the fovea or optic disc or both. Five of the lesions (13.5%) were located more than one disc-foveal distance from both the optic disc and fovea. Twenty-seven of the lesions (73.0%) were located entirely posterior to the ocular equator while ten (27.0%) straddled the equator. Three of these latter lesions extended just anterior to the ora serrata, but none of the lesions extended to the pars plicata. The center point of the isolated choroidal melanocytosis patch was located posterior to the ocular equator in all 37 cases. The center point location of the lesion was categorized as posterior (indicating that it was located within one disc-foveal distance from the optic disc or fovea or both) in 6 cases, superotemporal in 5, temporal in 9, inferotemporal in 9, inferior in 2, inferonasal in 2, nasal in 1, superonasal in 1, and superior in 2.

Associated ocular features in the 37 cases (Table 1) included viable unilateral non-familial retinoblastoma in the fellow eye in one case (case 4 in Table 1 [21]), a classic choroidal nevus contralateral to the isolated choroidal melanocytosis in 2 cases (cases 21, and 34 in Table 1), one or more focal aggregates of normal or near-normal uveal melanocytes (FANNUMs [20]) of the choroid ipsilateral to the isolated choroidal melanocytosis in 4 cases (cases 21, 24, 27, and 36 in Table 1), and one or more FANNUMs of the choroid contralateral to the isolated choroidal melanocytosis in 1 case (case 21 in Table 1).

Four patients in this series were noted to have a choroidal malignant melanoma at initial evaluation in the Ocular Oncology Service. In one of these patients (case 28 in Table 1), the choroidal melanoma (14 mm × 8.5 mm in basal diameters × 5.5 mm in thickness) was contralateral to the isolated choroidal melanocytosis. In the other three patients (cases 25, 31, and 37 in Table 1), the choroidal melanoma was associated with the patch of isolated choroidal melanocytosis and appeared to have arisen from that patch. In case 25, the nodular tumor measured approximately 7 mm × 5.5 mm in basal diameters × 1.8 mm in maximal thickness and was localized to the foveal aspect of the isolated choroidal melanocytosis. In case 31 (Fig. 3), the nodular choroidal tumor measured 8 mm × 7 mm in basal diameters × 2.0 mm in maximal thickness and was just inferior-posterior to the center point of the isolated choroidal melanocytosis. In case 37, the nodular choroidal tumor measured 12.5 mm × 10 mm in basal diameters × 2.0 mm in thickness and was localized to the inferior aspect of the isolated choroidal melanocytosis. As mentioned above, all three of these tumors were associated with prominent clumps of overlying orange pigment and shallow overlying and inferiorly dependent serous subretinal fluid. All four of the choroidal malignant melanomas in this series (i.e., the three associated with the isolated choroidal melanocytosis and the one contralateral to the eye with isolated choroidal melanocytosis) were managed by I-125 plaque radiotherapy. In the three cases of choroidal melanoma associated with isolated choroidal melanocytosis, the location of the tumor margins was confirmed intraoperatively by indirect ophthalmoscopy with scleral depression because ocular transillumination did not distinguish between the tumor and the choroidal melanocytosis. In contrast, the choroidal melanoma not associated with choroidal melanocytosis was localized entirely by intraoperative ocular transillumination. The three choroidal tumors associated with choroidal melanocytosis were all treated with a radioactive plaque that was 4 to 5 mm larger in effective diameter than the preoperatively estimated largest basal diameter of the tumor. The plaque in these cases provided a “safety zone” approximately 2 to 2.5 mm wide or wider around the nodular tumor. No attempt was made to irradiate the entire patch of choroidal melanocytosis to a therapeutic dose in these cases. In contrast, the choroidal melanoma contralateral to the eye with isolated choroidal melanocytosis in our series was treated with a radioactive plaque that was only 2 mm larger in effective diameter than the preoperatively estimated largest basal tumor diameter. This plaque provided a “safety zone” that was only about 1 mm wide around the tumor.

Seven patients in this series were evaluated in the Ocular Oncology Service on one occasion only and advised to follow-up at least annually with their referring ophthalmologist. Four patients were reevaluated within 1 month following initial evaluation in the Ocular Oncology Service to assure us and them that the choroidal lesion was not expanding rapidly. The melanocytic choroidal lesion in these 4 patients appeared unchanged in size, so these patients were also referred back to their primary ophthalmologist for follow-up. The remaining 26 patients in this series were all followed for 3 months or longer (mean 5.0 years, median 2.3 years, minimum 4.9 months, maximum 15.2 years). None of the patches of isolated choroidal melanocytosis in these 26 patients, including those of the three patients with a plaque-irradiated choroidal melanoma associated with the choroidal melanocytosis, showed any appreciable expansion of the flat melanotic choroidal lesion. The four plaque-irradiated cases all showed satisfactory partial post-irradiation flattening of the nodular choroidal melanoma that was sustained through available follow-up. Unfortunately, the patient with choroidal melanoma contralateral to the eye with isolated choroidal melanocytosis (case 28 in Table 1) developed metastasis from his choroidal melanoma and died of that metastasis 3.3 years following treatment. The other three patients with choroidal melanoma remain metastasis-free through follow-up of 25, 28, and 182 months.