Vol.3, No.4, 245-248 (2011) Health
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Massive carcinoma of the cornea in an
immunocompetent patient
Irene Pecorella1, Pierluigi Grenga2, Enzo Maria Vingolo2
1Department of Experimental Medicine, University of Rome “Sapienza” Viale Regina Elena, Rome, Italy;
*Corresponding Author: irene.pecorella@uniroma1.it
2Department of Ophthalmologic Science, University of Rome “Sapienza” Viale Regina Elena, Rome, Italy;
pigig@tiscalinet.it; e.vingolo@rdn.it
Received 11 February 2011; revised 7 March 2011; accepted 29 March 2011.
A case of massive well-differentiated, superfi-
cially invasive, squamous cell carcinoma of the
cornea is described. This patient did not have
any common identifiable risk factors in the de-
velopment of SCC of th e oc ular surfa ce, such as
excessive solar exposure, HPV infection, im-
munocompromised state, or chronic ocular ir-
ritation. A perforating injury in the cornea of the
same eye had occurred 11 years before. The
possible role of trauma in causing subsequent
neoplastic development is discus sed, as well as
the immunohistochemical results for p53 and
Keywords: Squamous Cell Carcinoma; Cornea;
HPV; Trauma; Solar Elastosis
Squamous cell carcinoma (SCC) is the most common
primary malignancy of the ocular surface, making up
14% of all primary ocular and orbital tumors. It pre-
dominantly affects male patients with an average age of
56 years (range: 4 to 91 yrs). SCC most commonly oc-
curs in the limbus (87.8%), where the corneal epithelial
stem cells are located [1], and in the interpalpebral space,
where the ocular tissues are mostly exposed to ultravio-
let irradiation. From this location, the tumour may
spread onto the bulbar conjunctiva and/or the cornea.
SCC of the cornea without involvement of the conjunc-
tiva and limbus is a very rare condition. The corneal
intrastromal infiltration is clinically described as corneal
cystic gelatinous lesion [1]. Intraocular invasion is often
heralded by the onset of low-grade inflammation and
secondary glaucoma. Metastasis is uncommon and,
when present, usually occurs in the preauricular, sub-
mandibular or cervical lymph nodes, the parotid gland,
the lungs or the bones.
Its origin is debated and some investigators believe
that the corneal epithelium may undergo dysplastic and
cancerous changes, whereas the limbal transition zone/
stem cell theory has been proposed for the development
of corneal intraepithelial n eoplasia by Lee and Hirst [1 ].
Recently, Chikama et al demonstrated in transgenic mice
lines that upregulation of FGF-7 signalling pathway(s)
may be common in tumorigenesis derived from limbal
stem cells that undergo oncogenic transformation by
insults, such as lo ng-term ultraviolet B (UVB) exposure,
infection of human papilloma virus (HPV) and human
immune deficiency virus (HIV), and cigarette smoking,
etc. [2].
We present herein a case of massive SCC of the lim-
bus and cornea in an immunocompetent patient and dis-
cuss the possible etiological role of a preceding trau-
matic event to the same eye in causing the occurrence of
the tumor.
A 67-years-old male patient presented with a painful
eye and a massive, protuberant lesion covering the nasal
half of the left co rnea (Figure 1). The lesion had initially
appeared in the nasal limbal area and had been slowly
enlar ging to it s present size for approxim ately 18 m ont hs.
Eleven years before a perforating injury in the left
cornea of the same eye, had caused progression to bulbar
phthisis. His work history did not involve exposure to
radiation, chemicals, or the sun. The patient was other-
wise in good health.
Ophthalmological examination showed a white, fleshy
papillomatous mass, hang ing from the surface of the left
cornea. The neighbouring conjunctiva was markedly hy-
peraemic. A clinical diagnosis of squamous cell carci-
noma of the ocular surface was made. Visual acuity was
of hand motion near to face. Digital tonometry revealed
I. Pecorella et al. / Health 3 (2011) 245-248
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Figure 1. Clinical picture of the large exophitic neo-
plasm covering the nasal half of the left cornea
a hard consistency of the affected painful eye. The ante-
rior chamber structure could not be evaluated due to the
lack of co rneal tran sparency. Ultrasound B-scans did not
reveal any posterior segment neoplastic involvement.
Regional lymph nodes were not palpable.
Visual acuity in the contralateral eye was 10/10 and
no abnormalities were observed at slit-lamp biomicro-
scopic examination. Laboratory examination, including
complete blood count and HIV and HPV tests were nor-
mal and a clinical work-up demonstrated no metastatic
disease. The blind eye was eviscerated for cosmetical
reasons and the cornea and the ocular content were sent
for histological examination.
The postoperative course was uneventful and the pa-
tient is free of local or distant recurrence 14 months
The tumoral mass and the ocular content were forma-
lin fixed and paraffin embedded. The anterior portion of
the eviscerated material consisted of a corneo-scleral
button measuring 1.3 in diameter with an overlying ex-
ophytic mass of 1.5 × 1 × 0.4 and circumferential pe-
ripheral retrocorneal uveal synechiae
Microscopically, the lesion was consistent with a well-
circumscribed, well-differentiated squamous cell carci-
noma (SCC), forming keratin pearls. Invasion of the
superficial corneal stroma was observed (< 1 mm) (Fig-
ure 2). Descemet’s membrane was focally interrupted
and plicated and the endothelial layer attenuated. The
excision margin was clear. At the periphery of the cor-
neal button, a fragment of iris incarcerated in the deep
stroma was observed. Remnants of atrophic iris formed
anterior synechiae and the pupil was obliterated by a
fibro-inflammatory membrane.
Examination of the ocular content revealed a gliotic
retina with overlying fibrovascular epiretinal membrane.
Figure 2. Histological appearance of the corneal mass.
A post-inflammatory fibrous pupillary membrane is
also visible (Haematoxylin-eosin 25 ×).
Foci of chronic choroiditis and areas of subretinal osse-
ous metaplasia were also apparent.
Sections of the tumoral mass were stained immuno-
histochemically for p53, p63 and the proliferation marker
The p53 gene acquires mutations during the develop-
ment of many human malignancies, including SCC of
the ocular surface [3]. Mutations of the p53 gene and
overexpression of p53 protein are closely related events.
p63 is a homologue of the tumour suppressor gene p53,
but acts as an oncogene and is overexpressed in squa-
mous cell dysplasias or neoplasias.
Results showed a positive reaction for p53 in most of
the nuclei of the neoplastic cells. The po sitive cells were
mainly located in the deep infiltratin g tongues and in the
basal layers of the superficial tumoral elements (Figure
3). Positive non tumoral epithelial cells were ob served at
the limbus, as well.
A widespread strong nuclear staining in malignant
cells was observed using antibodies for Ki67 or p63. In
the adjacent non-affected cornea, the positive staining
for p63 was confined to the basal cell layer.
The corneal SCC is a slow growing tumour that re-
mains localized. Massive epithelial carcinomas involv-
ing primarily the cornea are unusual, accounting for
0,76% of cases in one large series of conjunctival SCC
[4]. The tumour size in this case was relatively large.
Large-sized tumours may be related to well differentia-
tion of the neoplasm, and to slow progressive growth.
Alternatively, the difficulty to infiltrate dense structures
I. Pecorella et al. / Health 3 (2011) 245-248
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Figure 3. Immunohistochemical detection of p53 in the
nuclei (brown color) of the malignant cells. Diffuse nu-
clear positivity in the infiltrating tongue of cancer cells in-
vading the anterior corneal stroma (asterisk) (Streptavidin-
biotin- DAB staining 100 ×).
like the cornea and the sclera may favour a superficial
growth for a long time and an exoph ytic pattern in long-
standing lesions.
Our patient did not have any of the several identifiable
risk factors in the development of SCC of the ocular
surface, such as excessive solar exposure, HPV infection,
immunocompromised state such as in HIV, a history of
smoking, or chronic irritation from dust, wind petroleum
Mechanical trauma to the ocular surface, including
thermal burns, is occasionally mentioned among the risk
factors for SCC of the eye. Two of the 17 cases of con-
junctival SCC listed by Auw-Haedrich and coll. had
suffered from ocular injury many years before the oc-
currence of the neoplasm [5]. Three cases were reported
in an orbital socket after long wear ing of ocular pro sthe-
ses [6]. Scars can promote malignant growth of tumour
cells. Thick, dense scars are the type that usually gives
rise to squamous cell carcinoma of the skin and the cica-
trix may be caused by any traumatic event. Surgical in-
cisions have also been claimed to cause skin cancer.
Trauma is considered not to act as initiator, but to act as
promoter of carcinogenesis. There are two theories as for
the induction of scar cancer. One is that the cells com-
posing scar tissues convert themselves directly into tu-
morigenic ones; the other is that scar tissues secrete
soluble factors that stimulate carcinogenic conversion or
proliferation of tumour cells pre-ex isting around the scar
[7]. Whether fibrosis is accompanied with tumour or not
depends on the types of collagen it produces. Tumour-
associated fibrosis is characterized by increased collagen
Type III content [8]. According to Martins-Green and
coll., during the inflammatory response caused by wound-
ing, a plethora of cytokines are released that cause blood
vessel leakage and stimulate cell division which are key
elements in the process leading to possible viral onco-
gene integration and activation and then to tumour de-
velopment. In their experimental work, wounding at 4 or
5 days after inoculation of Rous sarcoma virus resulted
in 100% of the chickens developing wound tumours [7].
Their findings casts a new light on the possible role of
viruses in tumour development and, possibly, on pre-
existing HPV ocular infection and post-traumatic neo-
We believe that the previous injury to the eye may
have played a role in the development of the corneal
neoplasia in this patient. However, we cannot dismiss
the possibility that an actinic damage not related to out-
door working might have contributed to the development
of the corneo/conjunctival neoplasia, as pointed out by
the diffuse immunopositivity to p53. Normally, p53 is
undetectable immunohistochemically and negative in
normal human conjunctiva. Mutations of p53 are char-
acteristic of solar damage and are detected in the major-
ity of SCC of the skin and in around 50% of the con-
junctival SCC. Also Toth and coll. recently repo rted p53
gene overexpression in 78% of conjunctival SCC and
found no relationship with HPV type 16 or 18 infection
within the tumour tissue [4]. In a bilateral SCC of the
conjunctiva, p53 positivity was found in only one of the
eyes [9], perhaps indicating that the presence of mutant
p53 is rather a marker for tumour aggressiveness. Inter-
estingly, also the limbal cells overexpressed this tumour
marker in our specimen. Its detection may be related to
its mutation or, alternatively to its angiogenic activity in
an eye with a previous penetrating injury and ocular
surface remodelling.
Our immunohistochemical results also confirm the
previously reported p63 expression in the neoplastic
cells of the conjunctival SCC and its distribution in all
layers of this invasive carcinoma [6]. Its detection may
prove useful in the differential diagnosis between reac-
tive and malignant neoplastic lesions of the conjunctiva.
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