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1 Ophthalmic Sciences Unit, University of Sheffield, Sheffield, UK
2 Department of Ophthalmology and Orthoptics, University of Sheffield, Sheffield, UK
3 Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield, UK
4 Department of Histopathology, Royal Hallamshire Hospital, Sheffield, UK
5 Cole 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; singha@ccf.org
Accepted for publication 29 November 2004
Keywords: retinal pigment epithelium; congenital hypertrophy
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.
Case report
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 mmx2 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.
Figure 1 (A) Fundus photograph of the left eye showing an elliptical area of congenital retinal pigment epithelial (RPE) lesion temporal to the foveola. The lesion is depigmented in the nasal aspect with scalloped hyperpigmentation temporally. (B) Normal RPE cells, with prominent apical melanosomes and basal nuclei. Normal Bruch’s membrane and choriocapillaris (haematoxylin and eosin x330). (C) Hypertrophic, thickened retinal pigment epithelial cells from pigmented area of CHRPE. These are thickened, and packed with melanosomes, in both apical and basal areas (haematoxylin and eosin, x500). (D) Atrophic, thinned RPE cells from depigmented areas of CHRPE lesion. Almost no melanosomes remain in these cells (haematoxylin and eosin, x500). (E) Electron micrograph from hypertrophic RPE cells from pigmented areas of CHRPE. Nuclei are both apical and basal. Melanosomes are dense and rounded. Bruch’s membrane is normal (electron microscopy x2000). (F) Electron microscopy from the depigmented area of the CHRPE. RPE cells are atrophic and vacuolated, with very few small melanosomes. Bruch’s membrane consists of the RPE basement membrane (arrow), a lucent thickened inner collagenous layer (below) extending to the elastic layer (middle dark layer). Note the RPE cell (*) within the outer collagenous layer of Bruch’s membrane. The choriocapillaris (C) is separated from this by a thickened lucent outer collagenous layer (right), but choriocapillaris (and endothelial cell basement membrane) are missing from most areas (central and left) (electron microscopyx2000).
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.
Comment
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
Table 1 Summary of previously published histopathological findings in congenital hypertrophy of retinal pigment epithelium (RPE)
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.
ACKNOWLEDGEMENTS
We are grateful to Mr Bart Wagner for assistance with electron microscopy and Mr Robin Farr with the graphics.
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