Evolving Congenital Hypertrophy of the Retinal Pigment Epithelium in a Pediatric Patient

Abstract

Purpose: To describe the longitudinal evolution of a solitary congenital hypertrophy of the retinal pigment epithelium lesion demonstrating progressive enlargement and increasing border irregularity over time. Methods: A single case was reviewed. Results: A 13-year-old boy presented with an evolving and enlarging congenital hypertrophy of the retinal pigment epithelium lesion over a 7-year period. Fundus images obtained when the patient was 7 years old showed a solitary, circular lesion with a hypopigmented center and mildly irregular, hyperpigmented borders that measured 1.5 mm × 1.5 mm. At age 13, the lesion had increased to 3.1 mm × 3.8 mm. Over the next 1.5 years, it enlarged further to 4.5 mm × 4.3 mm, accompanied by increasing irregularity and scalloping of the lesion borders. Conclusions: Although solitary congenital hypertrophy of the retinal pigment epithelium lesions are generally stable and asymptomatic, this case demonstrates that they may enlarge and become irregular over time. While most lesions remain benign with a good prognosis, regular monitoring is warranted to assess for atypical changes and potential malignant transformation.

Introduction

Congenital hypertrophy of the retinal pigment epithelium was first described by Helmut Buettner in 1975 to characterize a flat, benign, and hyperpigmented fundus lesion previously referred to as a “benign melanoma” or “congenital hyperplasia of the retinal pigment epithelium (RPE).”^1,2 Most patients are asymptomatic, and this condition is often identified incidentally during fundus examination or on widefield fundus photography. ³ Lesions of congenital hypertrophy of the retinal pigment epithelium may appear brown, black, or gray and typically contain well-demarcated areas of atrophy known as lacunae. ⁴ Congenital hypertrophy of the retinal pigment epithelium is most commonly diagnosed in middle-aged adults in their 40s. ³

Over the past 5 decades, understanding of congenital hypertrophy of the retinal pigment epithelium lesions has continued to evolve. These lesions remain typically stable over time; however, infrequent cases of enlargement and nodularity have been documented.^5,6 Although rare, malignant transformation of congenital hypertrophy of the retinal pigment epithelium into adenocarcinoma has been described in a limited number of histopathologic case reports.^7–9

The purpose of this report is to describe a unique pediatric case of congenital hypertrophy of the retinal pigment epithelium lesion that enlarged and evolved over time without evidence of malignant transformation. This case underscores the importance of vigilant longitudinal monitoring, even in pediatric patients.

Case Report

A 13-year-old boy with a history of a pigmented lesion in his right eye was referred to our retina clinic for further evaluation. The patient also had a history of mixed astigmatism corrected with spectacles. The lesion was first noted at 7 years of age, and examination at 13 years demonstrated interval enlargement with increasing border irregularity.

Histologic images obtained 6 years earlier demonstrated a solitary, circular lesion in the right temporal fundus with mildly irregular borders. The lesion initially measured 1.5 mm × 1.5 mm in diameter (Figure 1A). The central area was hypopigmented, consistent with a large solitary lacuna, and was surrounded by a well-defined ring of hyperpigmentation. Retinal vessels coursed over the lesion without disturbance.

Figure 1.

Serial fundus photographs of a lesion arising from congenital hypertrophy of the retinal pigment epithelium. Ultrasonography demonstrated that the lesion was flat and remained flat over time. (A) Fundus photograph obtained at 7 years of age shows a lesion measuring 1.5 mm × 1.5 mm. (B) Fundus photograph at 13 years of age at the initial visit to the retina clinic demonstrates enlargement to 3.1 mm × 3.8 mm. (C) Fundus photograph at 3.5 years of age, 6 months after the initial visit, shows further enlargement to 3.3 mm × 3.9 mm. (D) Fundus photograph at 14.5 years of age demonstrates continued enlargement to 4.5 mm × 4.3 mm.

At presentation to our clinic at age 13, the best-corrected visual acuity (BCVA) of the patient was 20/20 OU. His spectacle prescription was −0.50 + 2.00 × 85 OD and −0.50 +1.50 × 95 OS. No afferent pupillary defect was present. Intraocular pressure in both eyes was 18 mm Hg. Slitlamp examination of both eyes was unremarkable, and fundus examination of the left eye was also normal.

Fundoscopic examination of the right eye revealed an irregular pigmented lesion in the temporal fundus measuring 3.1 mm vertically and 3.8 mm horizontally at its largest dimensions (Figure 1B). It had an irregular, amoeboid shape with sharply demarcated, scalloped borders. The central area was largely hypopigmented and surrounded by a prominent, well-defined ring of dark hyperpigmentation encircling the entire lesion. Retinal vessels coursed over the lesion undisturbed. Ultrasonography demonstrated a flat lesion. No additional lesions were identified. Compared with historical images, the lesion had enlarged and become more irregular, with expansion of both the central hypopigmented area and the surrounding hyperpigmented border.

At the 6-month follow-up, when the patient was 13.5 years of age, BCVA remained 20/20 OU, and the spectacle prescription was unchanged. Fundus examination demonstrated slight interval enlargement of the lesion, measuring 3.3 mm vertically and 3.9 mm horizontally, with an appearance similar to the prior examination (Figure 1C).

The patient returned 1 year later at 14.5 years of age and showed further enlargement of the lesion, measuring 4.5 mm vertically and 4.3 mm horizontally (Figure 1D). BCVA remained 20/20 bilaterally, and the spectacle prescription was unchanged. Compared with the previous examination and imaging, lesion growth occurred predominantly in the vertical dimension, with a mild interval increase in horizontal width and further scalloping of the borders. No increase in lesion thickness was detected, as confirmed by repeat ultrasonography. The lesion continued to demonstrate a hypopigmented center surrounded by a hyperpigmented border, and retinal vessels remained undisturbed as they coursed over the lesion.

Conclusions

Congenital hypertrophy of the retinal pigment epithelium is typically a benign ophthalmic condition that presents as a flat, pigmented fundus lesion with or without lacunae. As these lesions are usually asymptomatic, they are commonly detected incidentally during routine ocular examinations. This condition is regarded as a benign, stable, and nonprogressive condition; however, previous studies have demonstrated that some lesions may undergo subtle, flat enlargement over time. ³ In lesions that exhibited growth, the relative size of lacunae was noted to be the most important factor associated with lesion enlargement. ³ Specifically, increases in the number and/or size of lacunae accounted for much of the growth observed in solitary lesions of congenital hypertrophy of the retinal pigment epithelium. As lacunae represent areas of RPE atrophy and depigmentation, flat enlargement may reflect redistribution of pigmented cells concurrent with expansion of atrophic regions.

The present case describes a pediatric patient with a pigmentary lesion consistent with congenital hypertrophy of the RPE that gradually enlarged over periodic monitoring. After presentation to our clinic for regular follow-up visits, the lesion increased in size from 3.1 mm × 3.8 mm to 4.5 mm × 4.3 mm, reflecting an interval growth of 1.4 mm vertically and 0.5 mm horizontally over 12 months. Compared with a previous study that showed an average growth rate of 10 µm per month, our patient’s lesion underwent a significantly greater rate of growth, measuring approximately 116 µm × 42 µm per month. ³ Over time, the lesion also developed more scalloped and irregular borders compared to historical images. Despite gradual enlargement and morphological changes, no features suggestive of malignant transformation were observed, as the lesion remained flat on ultrasonography and demonstrated consistent pigmentation. Overall, the findings are most consistent with a benign, evolving solitary congenital hypertrophy of the RPE lesion with a large, singular lacuna.

To date, the mechanisms underlying the evolution and enlargement of congenital hypertrophy of the RPE lesions remain unclear. Several factors could have possibly contributed to the progressive changes observed in this patient. Prior studies have proposed that enlargement of congenital hypertrophy of the RPE may reflect age-related changes in the surrounding RPE. ³ As RPE cells lose contact inhibition with surrounding cells, compensatory cellular flattening may occur to offset decreasing cellular density. Consequently, enlargement of congenital hypertrophy of the RPE may correspond to cellular shifts and flattening over time. As mentioned earlier, the relative size of lacunae has been strongly correlated with lesion enlargement. ³ The lesion in our patient is consistent with this observation, demonstrating gradual enlargement of the lacunar area through the years. In addition, pigment migration of the RPE cells may further contribute to the enlargement of lesions of the congenital hypertrophy of the RPE.

Age-related changes in ocular anatomy may have contributed to the enlargement of congenital hypertrophy of the RPE. For instance, myopic progression is associated with several genetic and environmental factors, with higher rates of progression observed during adolescence.^10,11 In pediatric populations, myopia has been associated with a disproportionate elongation of the globe. However, this patient demonstrated mixed astigmatism with only a minor refractive change over 7 years. While axial lengths may increase with no change in prescription, clinically significant axial elongation is more commonly seen in those with high myopia, making it less likely that the evolution of congenital hypertrophy of the RPE in this case was driven primarily by changes in ocular anatomy. ¹²

In addition to growth-related changes in ocular anatomy, other factors to consider include puberty and hormonal influences. Although no studies have specifically evaluated the potential role of puberty or hormonal changes in the enlargement of congenital hypertrophy of the RPE, increases in the size and number of choroidal nevi during puberty have been reported. ¹³ Given the increasing prevalence of choroidal nevi during puberty, it has been speculated that nevus maturation may have a hormonal component. ¹³ As both congenital hypertrophy of the RPE and choroidal nevi contain melanin-producing pigmented cells, future research may help clarify whether puberty-related hormonal changes contribute to the evolution of lesions of congenital hypertrophy of the RPE.

Thorough evaluation is warranted when lesions of congenital hypertrophy of the RPE are identified, particularly when abnormal features are present, as such lesions may be associated with extraocular malignancies. Multiple or atypical lesions observed on fundoscopy examination are associated with conditions such as familial adenomatous polyposis, Gardner syndrome, and Turcot syndrome. ¹⁴ In contrast to benign solitary lesions of congenital hypertrophy of the RPE, pigmented ocular fundus lesions associated with familial adenomatous polyposis are often multiple and bilateral with irregular borders.

The majority of lesions of congenital hypertrophy of the RPE remain benign even if they enlarge; however, rare cases of malignant transformation into adenocarcinoma have been reported. In these cases, malignant lesions typically demonstrate elevation during progression.^7,9 One report described a patient who initially presented with a flat pigmented lesion consistent with congenital hypertrophy of the RPE that subsequently evolved into a solid, dome-shaped mass on ultrasonography and was confirmed as adenocarcinoma on histopathologic examination. ⁷ Such lesions may be mistaken for choroidal melanoma with retinal invasion; therefore, prior recognition of congenital hypertrophy of the RPE may aid in accurate diagnosis of adenocarcinoma. ⁸

In another case report, a patient presented with an RPE tumor associated with exudative maculopathy and cystoid macular edema. ¹⁵ While fundus examination alone was insufficient to characterize the lesion, multimodal imaging suggested that the findings were most consistent with an RPE adenoma rather than neovascularization. Despite advanced imaging, differentiating between RPE adenoma and adenocarcinoma may be difficult. Although adenocarcinomas associated with congenital hypertrophy of the RPE do not seem to have metastatic potential, these neoplasms may cause sight-threatening complications, including retinal detachment, cystoid macular edema, retinopathy, and blindness.^7,9,16 Therefore, careful monitoring and appropriate imaging are essential to distinguish benign from malignant lesions arising from congenital hypertrophy of the RPE.

Solitary lesions arising from congenital hypertrophy of the RPE are generally stable and asymptomatic; however, they may enlarge and become irregular over time. This case demonstrates progressive evolution and enlargement of a lesion arising from congenital hypertrophy of the RPE in a pediatric patient over a 7-year period. Although the majority of these lesions are benign and have a good prognosis, they should be regularly monitored to assess for features suggestive of malignant transformation.