Download Management and Treatment of Ocular Surface Neoplasia

Case Report
DOI: 10.17354/cr/2016/197
Management and Treatment of Ocular Surface
Neoplasia
Ashjan Y Bamahfouz1, Hanan M Abd El-Moneim2, Mohammed Abdulqadir Bachal3, Khaled Mohammed Bahubaishi4
Assistant Professor, Department of Ophthalmology, Umm al-Qura University, Mecca, Kingdom of Saudi Arabia, 2Professor, Department of Pathology,
Umm al-Qura University, Mecca, Kingdom of Saudi Arabia, 3Assistant Consultant, Ophthalmology Center, King Abdullah Medical City, Mecca,
Kingdom of Saudi Arabia, 4Intern, Department of Medicine, King Abdul Aziz University, Jeddah, Kingdom of Saudi Arabia
1
Conjunctival squamous cell carcinoma (CSCC) is an invasive ocular surface neoplasia ranging from dysplasia to carcinoma in situ to invasive
squamous cell carcinoma, which is identified as premalignant and malignant epithelial lesions. Often, it is seen in males in tropical countries
lying close to the equator where there is excessive exposure to sunlight. Clinical diagnosis requires close examination with a degree of high
suspicion. Appropriate and definitive diagnosis of conjunctival squamous neoplasia by ocular pathologists and the need for future detailed
clinicopathologic studies is recommended. Appropriate and definitive diagnosis requires histopathology. We describe a case of CSCC underlying
dysplasia with intraepithelial squamous cell neoplasia, where the case was confirmed by histopathological examination. The treatment
modality involving surgery and medication and follow-up is described. There was no evidence of recurrence, complication, or metastasis.
Keywords: Cornea, Mitomycin-C, Ocular surface squamous neoplasia, Squamous cell carcinoma of conjunctiva
INTRODUCTION
Ocular carcinomas termed as ocular surface squamous
neoplasia (OSSN) are the most common tumor of
conjunctival epithelium. They carry a high risk of visual
impairment which can be devastating and permanent.
However, 4 conjunctival squamous cell carcinomas
(CSCC) are considered to be rare.1,2 More aggressive course
recognized among patients in tropical/thermal regions
due to environmental factors. All suspicious ocular lesions
should undergo biopsy for early diagnosis.2,3 CSCC in situ
which arises from limbal stem cells of the conjunctival
epithelium is a malignant neoplasm that invades through
epithelial basement membrane into the corneal stroma
through the conjunctiva or rarely to the interior of eye or
orbit.4,5
Over a period of 10-year in Saudi Arabia about conjunctival
SCC were found to have invaded the orbit. Many factors
contribute to the aggressiveness of CSCC in this geographic
location; these factors are continual exposure to ultraviolet
Access this article online
Month of Submission
Month of Peer Review
Month of Acceptance
Month of Publishing
:
:
:
:
01-2016
02-2016
03-2016
03-2016
www.ijsscr.com
rays, genetic factors, and chronic irritation. Often, delay in
presentation and inadequate initial resection are factors
contributing to orbital invasion.6-9
The spectrum in OSSN includes mild dysplasia on one end
and invasive squamous cell carcinoma on the other end.
Diagnosis of CSCC depends on the histopathological
examination.9 Although the clinical diagnosis of in situ
disease is often high (86%), invasive carcinoma is much less
(35%). Preoperatively, correctly diagnosed lesions are much
larger ones and are those with hyperkeratosis.10
It is often difficult to distinguish invasive OSSN from other
common lesions such as pinguecula and pterygium due
to similarities in clinical features.11 The initial therapeutic
approach to this disease is surgery. In addition, cryotherapy
and mitomycin-C (MMC) are also potentially good
therapeutic approaches.12 Orbital invasion and loss of the eye
are usually due to delay in presentation. Successful treatment
of these tumors is often very challenging. It also requires
advanced diagnostic and therapeutic tools for improving
treatment outcomes.13 Superficial excision remains the
important initial step in management, as it is impossible to
exclude invasive disease on clinical grounds. Hence, excision
allows tissue for immediate histopathological diagnosis,
resulting in surgical debulking, and hence removes lifethreatening consequences. The disadvantage of primary
excision alone is the high recurrence rate, which ranges
from 15% to 52%. Therefore, several adjunctive treatments
Corresponding Author:
Dr. Irshad A Subhan, Associate Consultant, King Abdulla Medical City, Mecca, Kingdom of Saudi Arabia. Phone: +91-966543027674.
E-mail: [email protected]
IJSS Case Reports & Reviews | March 2016 | Vol 2 | Issue 10
1
Bamahfouz, et al.: Ocular Surface Neoplasia Management and Outcome
have been described in the literature in an a empt to reduce
the recurrence rate. The efficacy of these various adjunctive
therapies is still debated.14 Surgical excision involving a
wide area and adjuvant chemotherapy may be curative in
some cases. However importantly, high degree of clinical
suspicion leading early diagnosis followed by effective
treatment will minimize the mortality and morbidity related
to the disease.7
CASE REPORT
A 68-year-old male patient presented to the outpatient
clinic, at the King Abdullah Medical City in January 2014
with the chief complaint of reduced vision in his right eye,
and gradually increasing mass in the left eye.
His general physical examination was normal. A complete
ophthalmic examination bilaterally revealed visual acuity
without correction of hand motion in the right eye and 20/40
in the left eye. Intraocular pressures of 14 and 16 mm of Hg
in the right eye and left eye, respectively. Both pupils were
round and equally reacting to light and accommodation.
Ocular movements were normal. Slit lamp examination
showed mature cataract in the right eye and early cataract
in the left eye. There was 3 mm × 4 mm mass minimally
elevated conjunctival lesion in the left eye nasally, with
regular margins and fixed base on the cornea (Figure 1a
and 1b). Clinically, the case was diagnosed as OSSN.
Fundus examination was normal. There was no regional
lymphadenopathy. The patient was subjected for surgical
intervention.
Total excision of the conjunctival mass with a free margin
of 2 mm followed by double freeze-thaw cryo-application.
Amniotic membrane transplant was carried out as shown
in the pictures (Figure 1c). Histopathological examination
revealed moderately differentiated squamous cell
carcinoma with a background of severe squamous dysplasia
and carcinoma in situ (Figure 2a-c) with invasive features
involving superior and temporal margins. Postoperatively,
he was treated with topical MMC 0.02% eye drops 4 times/
day for 14 days for two cycles with refresh tears eye drops
4 times/day for two weeks between the cycles along with
topical steroids and antibiotics. The patient was followed
up every 2 months at the beginning then examined at
6 months intervals. 1-year follow-up showed no recurrence
or complications from treatment.
DISCUSSION
The bulbar conjunctiva and limbal area are the most
frequent sites of conjunctival tumors. Therefore, early
diagnosis and excision were performed. Truly cancerous
lesions are absent. Hence, it is emphasized to perform
early excision of any enlarging limbal lesion in preventing
malignant transformation. Africa has the highest incidence
of OSSN in the world, where males and females are equally
affected.15
Our case highlights the importance of considering CSCC in
refractory cases of conjunctival inflammation with limbal
and corneal epithelial involvement.
OSSN regarded as uncommon disease with a propensity to
affect men in their sixth decade. Histologically, the disease
characterized by changes in basal, supra-basal, superficial,
and full thickness epithelium. Characteristic cellular changes
are increased hyperchromatism, pleomorphism, and loss of
polarity, which when severe, involves with tumor cells
breaching the basement membrane and also invading
into the matrix of the stroma.16 The risk of squamous cell
carcinoma of conjunctiva/dysplasia seemed to be higher
in the presence of multiple than single infections. In the
equatorial Africans, the conjunctiva is the site that is not
protected from ultraviolet light by heavy pigmentation.17
Although complete excision with cryotherapy gives good
results with localized lesions, other newer modalities such
as immunotherapy hold a promise in large unresectable
and recurrent lesions.9 As of now, the best available options
remain early detection and effective treatment. However,
non-invasive diagnostic methods are still not available, and
there is no evidence to guide treatment.15
Herein, we stress the need for early diagnosis and
management of lesions. Routine histopathological diagnosis
a
a
b
c
Figure 1: (a) Slit lamp photograph under diffuse illumination of left eye show
sessile, vascular conjunctival epithelial tumor cover temporal side of limbus of
the left eye. (b) A close-up view of the overhanging conjunctivo-corneal mass with
large intrinsic and feeder vessels. (c) Post-operative excision of the conjunctival
mass was done with free margin of 2 mm and amniotic membrane transplant
covering the conjunctival defect after excision biopsy
2
b
c
Figure 2: (a) Hematoxylin and Eosin stain. The histopathologic appearance of
the tumor showed infiltrating moderately differentiated squamous cell carcinoma.
The infiltrating nests and cords were extending from the basement line into the
underlying connective tissue with lymphocytic infiltrate within the connective
tissue. (b) Background of squamous dysplasia and carcinoma in situ are seen
with the replacement of conjunctival epithelium by dysplastic squamous cells,
thickening, and keratinization of superficial cells. (c) The infiltrating moderately
differentiated squamous cell carcinoma with higher magnification
IJSS Case Reports & Reviews | March 2016 | Vol 2 | Issue 10
Bamahfouz, et al.: Ocular Surface Neoplasia Management and Outcome
of orbital and adnexal tumors uncovered some rare
tumors and varied histological types. This improves the
management of these patients. CSCC, an invasive form
of OSSN that responds well and without any recurrence
on a year follow-up with combined treatment of surgical
excision, cryotherapy, and topical chemotherapy-like
MMC.18 Surgery, chemotherapy, and immunotherapy are
other treatment modalities which in combination show
good results in aggressive, recurrent, and large tumors.9
Surgery often resulted in a low recurrence rate during the
follow-up period with fewer complications.17 For Ca in situ
simple surgical excision associated with cryotherapy was
quiet effective.
2.
3.
4.
5.
6.
Various treatments have been described with good results,
with the use of MMC and topical cyclosporin to prevent
recurrences.19 MMC allows treatment of the entire ocular
surface, including the conjunctival fornices, and may
reach and destroy subclinical disease and prevent new
tumors arising elsewhere on the ocular surface.14 Often,
delay in presentation and previous unsuccessful surgery
leads to invasion of the orbit and loss of the eye.7 Primary
and residual in situ disease can be treated with topical
chemotherapy.20
7.
MMC treatment following surgical excision reduces the
recurrence rate and should be considered as the adjuvant
therapy in the treatment of primary and localized recurrent
disease.21,22 MMC can be used as only therapy in more
diffuse disease, often requiring a close follow-up because
of the significant risk of recurrent disease or persistent.
Clinically, whether the tumor is benign or malignant is of
critical importance. Histopathology is the gold standard
in the diagnoses of various grades and types of CSCC and
gives a fair understanding of disease prognosis.
11.
CONCLUSION
15.
CSCC, an invasive form of OSSN responded well and
without any recurrence on a year follow-up with combined
treatment of surgical excision, cryotherapy, and topical
chemotherapy-like MMC. We recommend the use of such
a combined approach in the management of such cases.
ACKNOWLEDGMENTS
We are grateful to Dr. Tahira Hamid, Associate Consultant
Pathologist from the Department of Pathology of King
Abdullah Medical City.
REFERENCES
1.
Chauhan S, Sen S, Sharma A, Tandon R, Kashyap S, Pushker N, et al.
American joint commi ee on cancer staging and clinicopathological
IJSS Case Reports & Reviews | March 2016 | Vol 2 | Issue 10
8.
9.
10.
12.
13.
14.
16.
17.
18.
19.
20.
21.
high-risk predictors of ocular surface squamous neoplasia: A
study from a tertiary eye center in India. Arch Pathol Lab Med
2014;138:1488-94.
Tiong T, Borooah S, Msosa J, Dean W, Smith C, Kambewa E, et al.
Clinicopathological review of ocular surface squamous neoplasia
in Malawi. Br J Ophthalmol 2013;97:961-4.
Elshazly LH. A clinicopathologic study of excised conjunctival
lesions. Middle East Afr J Ophthalmol 2011;18:48-54.
Gichuhi S, Sagoo MS, Weiss HA, Burton MJ. Epidemiology of
ocular surface squamous neoplasia in Africa. Trop Med Int Health
2013;18:1424-43.
Rishi P, Shields CL, Eagle RC. Conjunctival intraepithelial
neoplasia with corneal furrow degeneration. Indian J Ophthalmol
2014;62:809-11.
Ackuaku-Dogbe E. Histopathological features of tumours of the
orbit and Adnexia seen in Korle-Bu teaching Hospital Ghana. West
Afr J Med 2012;31:58-62.
Johnson TE, Tabbara KF, Weatherhead RG, Kersten RC, Rice C,
Nasr AM. Secondary squamous cell carcinoma of the orbit. Arch
Ophthalmol 1997;115:75-8.
Gökmen Soysal H, Ardiç F. Malignant conjunctival tumors
invading the orbit. Ophthalmologica 2008;222:338-43.
Emmanuel B, Ruder E, Lin SW, Abnet C, Hollenbeck A,
Mbulaiteye S. Incidence of squamous-cell carcinoma of the
conjunctiva and other eye cancers in the NIH-AARP diet and
health study. Ecancermedicalscience 2012;6:254.
Mittal R, Rath S, Vemuganti GK. Ocular surface squamous
neoplasia - Review of etio-pathogenesis and an update
on clinico-pathological diagnosis. Saudi J Ophthalmol
2013;27:177-86.
McKelvie PA, Daniell M, McNab A, Loughnan M, Santamaria JD.
Squamous cell carcinoma of the conjunctiva: A series of 26 cases.
Br J Ophthalmol 2002;86:168-73.
Moshirfar M, Khalifa YM, Kuo A, Davis D, Mamalis N. Ocular
surface squamous neoplasia masquerading as superior limbic
keratoconjunctivitis. Middle East Afr J Ophthalmol 2011;18:74-6.
Nagaiah G, Stotler C, Orem J, Mwanda WO, Remick SC. Ocular
surface squamous neoplasia in patients with HIV infection in
sub-Saharan Africa. Curr Opin Oncol 2010;22:437-42.
Nagata M, Nakamura T, Sotozono C, Inatomi T, Yokoi N,
Kinoshita S. LRIG1 as a potential novel marker for neoplastic
transformation in ocular surface squamous neoplasia. PLoS One
2014;9:e93164.
Chen C, Louis D, Dodd T, Muecke J. Mitomycin C as an adjunct
in the treatment of localised ocular surface squamous neoplasia.
Br J Ophthalmol 2004;88:17-8.
Di Girolamo N. Association of human papilloma virus with
pterygia and ocular-surface squamous neoplasia. Eye (Lond)
2012;26:202-11.
Wa d d e l l K M , D o w n i n g R G , L u c a s S B , N e w t o n R .
Corneo-conjunctival carcinoma in Uganda. Eye (Lond)
2006;20:893-9.
Nigwekar S, Gupta A, Bhosale M, Haldipurkar T, Baviskar B,
Misra S. Combined treatment modality for invasive ocular surface
squamous neoplasia in an HIV positive patient: A case report. Int
J Stud Res 2012;2:25-7.
Crim N, Forniés-Paz ME, Monti R, Espósito E, Maccio JP,
Urrets-Zavalía JA. In situ carcinoma of the conjunctiva: Surgical
excision associated with cryotherapy. Clin Ophthalmol
2013;7:1889-93.
Yin VT, Merri HA, Sniegowski M, Esmaeli B. Eyelid and ocular
surface carcinoma: Diagnosis and management. Clin Dermatol
2015;33:159-69.
Gupta A, Muecke J. Treatment of ocular surface squamous
3
Bamahfouz, et al.: Ocular Surface Neoplasia Management and Outcome
neoplasia with Mitomycin C. Br J Ophthalmol 2010;94:555-8.
22. Prabhasawat P, Tarinvorakup P, Tesavibul N, Uiprasertkul M,
Kosrirukvongs P, Booranapong W, et al. Topical 0.002% mitomycin
C for the treatment of conjunctival-corneal intraepithelial neoplasia
and squamous cell carcinoma. Cornea 2005;24:443-8.
4
How to cite this article: Bamahfouz AY, El-Moneim HM, Bachal MA,
Bahubaishi KM. Management and Treatment of Ocular Surface Neoplasia.
IJSS Case Reports & Reviews. 2016;2(10):1-4.
Source of Support: Nil, Conflict of Interest: None declared.
IJSS Case Reports & Reviews | March 2016 | Vol 2 | Issue 10