Table Of ContentCorneal Histopathology in Xeroderma Pigmentosum; Rezaei Kanavi et al
Corneal Involvement in Xeroderma Pigmentosum;
a Histopathologic Report
Mozhgan Rezaei Kanavi, MD; Mohammad-Ali Javadi, MD; Hamid-Reza Zabihi Yeganeh, MD
Shaheed Beheshti Medical University, Tehran, Iran
Purpose: To report the histopathologic features of corneal involvement in a patient with
xeroderma pigmentosum (XP).
Case Report: A 19-year-old man with XP presented with bilateral corneal leukoma and
decreased visual acuity predominatly in his right eye. Penetrating keratoplasty was
performed in the right eye due to severe corneal opacity, vascularization and lipid depo-
sition. The corneal button underwent histopathologic evaluation which disclosed chronic
interstitial lipogranulomatous keratitis.
Conclusion: To our knowledge, this is the first report of corneal involvement in xero-
derma pigmentosum from Iran describing the histopathologic features in this rare con-
dition.
J Ophthalmic Vis Res 2008; 3 (1): 66-69.
Correspondence to: Mohammad-Ali Javadi, MD. Professor of Ophthalmology; Ophthalmic Research Center, No. 5,
Boostan 9 St., Amir Ebrahimi Ave., Pasdaran, Tehran 16666, Iran; Tel: +98 21 22585952, Fax: +98 21 22590607;
e-mail: ma_ [email protected]
INTRODUCTION opacification, development of pterygium-like
growths and epithelial neoplasms.2 Pathologi-
Xeroderma pigmentosum (XP) is a rare pre- cal corneal changes in these patients range from
cancerous autosomal recessive skin disorder disorganized epithelium and Bowman’s layer
which is exacerbated by exposure to ultraviolet destruction to neovascularization and peri-
radiation. The underlying abnormality is defec- vascular infiltration of inflammatory cells in the
tive DNA repair leading to benign lesions and stroma.3 There are few reports describing cor-
malignant transformations.1 Its prevalence is as neal involvement in XP patients; herein we pre-
low as one case per 250,000 worldwide with no sent the clinical presentation and histopatho-
racial predilection. XP presents in the first de- logic features of the cornea in such a patient.
cade of life with hypersensitivity to ultraviolet
radiation resulting in dryness, unusual ery- CASE REPORT
thema and pigmentary changes in sun-exposed
areas of the skin. Additionally, dermal telan- A 19-year-old male subject and a known case of
giectasia and several benign, precancerous and XP was referred to our clinic with bilateral
malignant neoplasms may emerge.2 corneal opacification and loss of vision, more
Ocular complications include severe invol- severe in the right eye, from childhood. There
vement of the eyelids, sclera and cornea. Cor- was no document regarding cutaneous tumor
neal involvement presents as dryness, super- or malignancy. Gross examination revealed
ficial inflammation, angiogenesis, ulceration, widespread hyperpigmentation of the eyelids
66 JOURNAL OF OPHTHALMIC AND VISION RESEARCH 2008; Vol. 3, No. 1
Corneal Histopathology in Xeroderma Pigmentosum; Rezaei Kanavi et al
and slitlamp examination disclosed severe ogenesis, band-like nodular keratopathy, ulcer-
corneal opacification accompanied by stromal ation and even perforation.5 These manifest-
neovascularization and lipid deposits. Due to tations have been reported in 40% of cases.6 Ley
severity of the condition, the right eye under- and Applegate7 believed that DNA destruction
went penetrating keratoplasty. due to ultraviolet radiation is responsible for
The corneal button was sent to the patho- the corneal opacification and neovasculariza-
logy laboratory of the Eye Bank of I.R. of Iran. tion. In our patient, corneal involvement com-
The specimen was approximately 7 mm in dia- prised of severe opacification, stromal neovas-
meter, yellowish-white in color and completely cularization and lipid keratopathy but no sign
opacified. The corneal disc was cut into two of ulceration or acute infection. Haller et al1
halves and fine tissue sections were made after described the histopathological manifestations
histological preparation which then underwent of XP in corneas of a patient which included
hematoxylin and eosin (H&E), Congo red, per- degeneration of basal corneal epithelial cells,
iodic acid Schiff (PAS) and Gram staining. destruction of Bowman’s layer and develop-
Light microscopy of H&E stained sections re- ment of a degenerative pannus extending onto
vealed corneal thickness to about 2 mm (Fig. 1), the underlying stroma. Freedman3 reported
irregular and somehow thinned epithelium irregularity and bullous changes in the epi-
with basal and subepithelial bullous changes thelium and neovascularization of the stroma
(Fig. 2-A). Extensive foci of stromal neovas- as well as perivascular infiltration of inflam-
cularization accompanied by chronic granulo- matory cells and shedding of corneal endo-
matous inflammation (Fig. 2-B) with giant mul- thelial cells in addition to the above-mentioned
tinuclear cells (Fig. 3-A) surrounding intra- changes in Bowman’s layer and superficial
stromal cholesterol clefts (Fig. 3-B) were seen. stroma. Histopathological features in our pa-
The Descemet membrane had apparently nor- tient, likewise, included irregular epithelium
mal thickness, however endothelial cell count with bullous alterations, focal destruction of
was severely reduced (Fig. 1). There was patchy Bowman’s layer replaced by fibrous tissue and
destruction of Bowman’s layer replaced by extensive foci of neovascularization in the
fibrous tissue. Congo red staining was negative stroma together with moderate to severe dec-
for amyloid deposits and no microorganisms rease in endothelial cells. The outstanding fin-
were detected on Gram and PAS staining. The dings in our patient included cholesterol clefts
observed histopathological changes were com- throughout the stroma in addition to chronic
patible with chronic interstitial lipogranulo- lipogranulomatous inflammation and giant
matous keratitis. multinuclear cells, which were not observed in
previous reports.
DISCUSSION Previously defined ultrastructural features
of XP-involved corneas on transmission elec-
Xeroderma pigmentosum is an inherited pre- tron microscopy have included subepithelial
cancerous dermatosis due to defective DNA re- canals located at the basal epithelium, varying
pair after injury induced by ultraviolet expo- amounts of lattice collagen in Descemet mem-
sure. Its clinical course is characterized by pro- brane and the presence of multiple melanin
gressively increasing skin pigmentation and granules in residual endothelial cells.1
atrophy followed by development of dermal To our knowledge, this is the first report
tumors. Ocular complications include eyelid, describing the histopathological features of the
scleral and corneal involvement in up to 80% of cornea in a patient with XP from Iran. The pro-
cases which may be due to greater exposure to minent feature was presence of extensive lipo-
sunlight.4,5 granulomatous inflammatory reaction surr-
Corneal involvement in XP may manifest as ounding severe lipoid infiltration in the corneal
dryness, exposure keratitis, opacification, angi- stroma.
JOURNAL OF OPHTHALMIC AND VISION RESEARCH 2008; Vol. 3, No. 1 67
Corneal Histopathology in Xeroderma Pigmentosum; Rezaei Kanavi et al
Figure 1 Notably increased corneal thickness accompanied
by severe subepithelial and anterior stromal fibrosis (F),
foci of neovascularization with intra-stromal inflammation
and severe loss of corneal endothelial cells (hematoxylin &
eosin staining, ×40).
A B
Figure 2 (A) Bullous changes in the basal epithelial cells (hematoxylin & eosin staining, ×400); (B) Neo-
vascularization foci with chronic granulomatous inflammation and intra-stromal cholesterol clefts (hematoxylin
& eosin staining, ×200).
G
G
G
A B
Figure 3 (A) Multinuclear giant cells (G) in lipogranulomatous reaction of the stroma and foci of neovas-
cularization (hematoxylin & eosin staining, ×400); (B) Intra-stromal cholesterol clefts (C) and lipogranulomatous
reactions (hematoxylin & eosin staining, ×200).
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