Chapter 157 – Hypertrophy of Retinal Pigment Epithelium
JAMES J. AUGSBURGER
JAMES P. BOLLING
• Benign congenital lesion of retinal pigment epithelium.
• Gray to black, well-defined, thin, circular, oval or geographic lesion deep to sensory retina.
• Unifocal or multifocal, typical and atypical forms.
• Loss of retinal pigment epithelial cells with formation of depigmented lacunae within central regions of larger lesions.
• Marginal pseudoshadowing of many larger lesions.
• Atypical, multifocal, bilateral lesions occur as markers of familial adenomatous polyposis–carcinoma syndrome.
Hypertrophy of the retinal pigment epithelium (RPE) is an uncommon benign fundus lesion that is probably always congenital in nature. Three varieties occur: the typical unifocal unilateral lesion, the typical multifocal unilateral lesion (grouped pigmentation of the retina), and the atypical multifocal bilateral lesion, the last of which is an indicator of familial colonic adenomatous polyposis–carcinoma syndrome.
EPIDEMIOLOGY AND PATHOGENESIS
Unilateral, multifocal clustered lesions of congenital hypertrophy of the RPE (CHRPE) are the most common type, occurring in about 1% of individuals. Unilateral, unifocal CHRPE lesions are slightly less common, occurring in about 0.5% of individuals. The atypical, bilateral, multifocal CHRPE lesions associated with familial adenomatous polyposis (FAP) of the colon are relatively uncommon, occurring in only about 1 in 100,000 persons. Men and women are affected equally. All racial groups appear susceptible to these lesions. No recognized risk factors exist for typical unilateral unifocal and multifocal grouped CHRPE, but autosomal dominant colonic adenomatous polyposis–carcinoma syndrome predisposes individuals to develop multifocal atypical and bilateral lesions (see Systemic Associations ).
CHRPE lesions are usually asymptomatic and detected on routine ophthalmic examination. The typical unifocal CHRPE is a gray to black, well-defined, minimally elevated fundus lesion having a diameter in the range of 2–5?mm ( Fig. 157-1 ). A narrow zone of granular gray pigmentation or depigmentation is frequently
Figure 157-1 Typical unifocal, unilateral hypertrophy of retinal pigment epithelium.
Figure 157-2 Unifocal unilateral hypertrophy of retinal pigment epithelium with prominent depigmented lacunae.
evident around the margins of the lesion. The lesion frequently undergoes at least partial depigmentation with aging, developing discrete intralesional atrophic foci (lacunae, Fig. 157-2 ) that tend to enlarge and coalesce over the years. Slight lesion enlargement has been documented in some patients.
The typical multifocal congenital hypertrophy of the RPE is characterized by multiple flat gray to black retinal pigment epithelial lesions clustered in one region of the fundus ( Fig. 157-3 ). The individual foci within the lesion cluster are usually round to oval and range in size from approximately 0.1–2.0?mm in diameter; however, some larger and smaller lesions and occasional foci that have curvilinear or irregular shapes are frequently present in the clusters. This form of CHRPE is often referred to as congenital grouped pigmentation of the retina or bear tracks of the ocular fundus.
The CHRPE lesions in patients who have familial colonic adenomatous polyposis syndrome (see Systemic Associations ) tend to be oval or irregularly shaped, variable in size (usually between 0.1 and 2.0?mm in maximal diameter), multifocal, widely separated rather than clustered, and usually present in both eyes.
Figure 157-3 Typical multifocal clustered hypertrophy of retinal pigment epithelium (grouped pigmentation of retina).
Differential Diagnosis of Congenital Hypertrophy of Retinal Pigment Epithelium
Reactive hyperplasia of retinal pigment epithelium
Massive gliosis of retina
Combined hamartoma of retina
Melanotic choroidal nevus or melanoma
Syndrome of bilateral diffuse uveal melanocytic proliferation associated with systemic carcinoma
Adenoma or adenocarcinoma of retinal pigment epithelium
Metastatic melanoma to retina
Larger lesions frequently exhibit irregular retinal pigment epithelial disruption adjacent to one or more of the margins and well-defined areas of partial depigmentation of the lesion proper.
DIAGNOSIS AND ANCILLARY TESTING
No diagnostic studies are generally indicated for characterization of these retinal lesions. Fluorescein angiography and indocyanine green angiography show a well-defined blocking defect at the retinal pigment epithelial level. Transmission of choroidal fluorescence takes place through lacunae in the lesion.
The important lesions and disorders in the differential diagnosis of congenital hypertrophy of the RPE are listed in Box 157-1 .
Atypical, multifocal, bilateral CHRPE lesions are strongly associated with several familial colonic adenomatous polyposis–carcinoma syndromes. The most frequently associated disorder, Gardner’s syndrome, is an autosomal dominant cancer syndrome characterized by colonic adenomatous polyposis, bone cysts, hamartomas, and soft tissue tumors (desmoid tumors).    The risk of developing colon cancer during adult life in affected individuals is virtually 100%. When associated with neuroepithelial tumors of the central nervous system, familial colonic adenomatous polyposis–carcinoma syndrome is called Turcot’s syndrome. Autosomal dominant colonic adenomatous polyposis that occurs in the absence of extracolonic features is simply termed familial adenomatous polyposis (FAP). Gardner’s syndrome, Turcot’s syndrome, and FAP are believed to be variable phenotypic expressions of the same genotypic disorder. The gene for familial colonic adenomatous polyposis in these disorders has been localized to chromosome 5q21-q22. The precise site of the mutation in the gene seems to correlate with the presence or absence of CHRPE lesions. In kindreds who have linkage between FAP and atypical CHRPE lesions, almost all at-risk individuals in the family have at least one characteristic fundus lesion as a marker of the disease. Most of the affected individuals have multiple lesions in both eyes, and the total number of such lesions in those patients is frequently as high as 20–30. In contrast, approximately one third of families who have FAP do not have CHRPE lesions as markers of the disease.
Typical unifocal unilateral CHRPE lesions and the lesions of grouped pigmentation are not linked to any of the FAP syndromes.
Baseline Systemic Evaluation
In any individual who has multifocal, bilateral, atypical hypertrophy of the RPE, the ophthalmologist should review the family history for information about colon polyps, colon carcinoma, and colectomy and arrange for comprehensive colonic evaluation.
The lesions of hypertrophy of the RPE consist of well-defined foci of taller than normal retinal pigment epithelial cells that contain an increased number of melanin granules. In classic unifocal unilateral CHRPE, the intracytoplasmic melanin granules tend to be large and oval in shape. In areas of lacunar depigmentation, the hypertrophic retinal pigment epithelial cells are absent. The retinal photoreceptors overlying such lesions typically appear degenerated, at least in adult eyes. Grouped pigmentation of the retina has similar pathology.
No treatment is warranted for these retinal lesions. They are typically photographed and then monitored periodically for enlargement or other changes.
COURSE AND OUTCOMES
Most retinal lesions of this type change minimally if at all over extended periods of follow-up. Malignant change of a classical unifocal hypertrophy of the RPE has been reported  but appears to be rare.
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