Congenital hypertrophy of retinal pigment epithelium: a clinico-pathological case report
- 1Ophthalmic Sciences Unit, University of Sheffield, Sheffield, UK
- 2Department of Ophthalmology and Orthoptics, University of Sheffield, Sheffield, UK
- 3Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield, UK
- 4Department of Histopathology, Royal Hallamshire Hospital, Sheffield, UK
- 5Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
- Correspondence to: Arun D Singh MD, Department of Ophthalmic Oncology, Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA;
- Accepted 29 November 2004
Congenital hypertrophy of retinal pigment epithelium (CHRPE) is a peculiar congenital anomaly of the retinal pigment epithelium (RPE) diagnosed by its characteristic ophthalmoscopic appearance.1 It is now realised that sporadic CHRPE is distinct from the similar appearing retinal lesions described in patients with Gardner’s syndrome.2–4 We recently enucleated an eye with a choroidal melanoma that also had a distinct area of solitary CHRPE with lacunae formation. This provided us with a unique opportunity to correlate clinical and histopathological features of a solitary CHRPE.
A 62 year old woman with a large cilio-choroidal melanoma was observed to have an elliptical retinal pigment epithelial lesion about 1 mm temporal to the foveola (fig 1A). The lesion was about 3 mm×2 mm in basal dimension and appeared flat. The lesion was depigmented in the nasal aspect with scalloped hyperpigmentation temporally. The eye was enucleated and processed routinely for histological examination.
On histopathological evaluation, cilio-choroidal melanoma was confirmed. In areas just outside the CHRPE lesion, the retinal pigment epithelium (RPE) was normal (fig 1B). The pathology of the “CHRPE” lesion varied across the lesion, correlating with the level of pigmentation. Highly pigmented temporal areas showed hypertrophic RPE cells with loss of nuclear basal polarity and variable numbers melanosomes (fig 1C). By contrast, RPE cells were thinned and atrophic in depigmented areas (fig 1D), with a marked reduction in (or loss of) melanosomes and decreased melanosome size. Between these areas, “transitional zones” showed variable changes. Electron microscopy confirmed that, in pigmented areas of CHRPE, hypertrophic RPE cells had dense rounded intact melanosomes, but little or no lipofuscin (fig 1E). In these areas, Bruch’s membrane was normal. Depigmented areas had thin atrophic RPE cells, with cytoplasmic vacuoles and very few, much smaller melanosomes (fig 1F). Here, Bruch’s membrane thickening (of the inner and outer collagenous layers) was most marked, with occasional insertion of RPE cells through the RPE basement membrane into the inner collagenous layer, but not beyond the elastic layer.
Only few reports exist regarding the histopathological findings of CHRPE and its variants (table 1). In solitary CHRPE, hypertrophic RPE cells with hyperpigmention have been reported.5–8 Additional findings have included presence of macromelanosomes7 and absence of lipofuscin.8 In contrast, the grouped CHPRE is composed of normal sized RPE cells with hyperpigmentation.9 The CHRPE-like lesions seen in Gardner’s syndrome show evidence of RPE hyperplasia and even hamartomatous changes in addition to RPE hypertrophy and hyperpigmentation.10
Our case shows many of the features previously described in CHRPE. Pathologically in our case, there appears to be gradation of changes from the pigmented areas to the non-pigmented areas. Depigmentation and atrophy of RPE cells, starting with fragmentation of melanosomes progresses to gradual loss of melanosomes and RPE atrophy. Both the fragmentation of melanosomes and eventual atrophy appear to correlate with increasing changes in Bruch’s membrane—namely, an increased thickness of the inner and outer collagenous layers, by electron lucent material may represent water, lipid or proteinaceous deposit. To our knowledge, this has not been reported previously, although review of an electron micrograph from the 23 year old patient of Buettner suggests that this feature may be present in a depigmented area of CHRPE.5
A close inter-reaction between the functions of RPE cells and Bruch’s membrane is well recognised. It remains possible that the depigmentation of RPE cells caused the changes in the Bruch’s membrane (“ancient” CHRPE). It is also possible that, in our patient, changes affecting Bruch’s membrane are non-specific and are unrelated to CHRPE.
We are grateful to Mr Bart Wagner for assistance with electron microscopy and Mr Robin Farr with the graphics.