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OSSN
Presenter:
DR SHAYRI PILLAI
Liberia Eye Centre
JFK Memorial Medical Centre
August 29,2019
Introduction
 Ocular surface squamous neoplasia (OSSN) includes spectrum of
disease from mild dysplasia to carcinoma in situ to invasive squamous
squamous cell carcinoma
 Involving conjunctiva and cornea
 Usually in the interpalpebral area, mostly at the limbus
Kaliki S, et al. Ocular surface squamous neoplasia with intraocular tumour
extension: A study of 23 patients. Eye (Lond). (2019)
Introduction
 Various intra epithelial lesions of squamous epithelium of conjunctiva
were identified & numerous confusing terminologies such as
 epithelial plaque, intra epithelial epithelioma, dyskeratosis, dysplasia,
precancerous epithelioma, Bowen’s disease of the conjunctiva and
‘Bowenoid epithelioma’ were used to describe this lesion
 Advanced age, male gender, exposure to solar ultraviolet radiation,
infection with human papilloma virus (HPV), immunosuppression and
infection with human immunodeficiency virus (HIV) are the factors
which play an essential role in the development of OSSN
Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and
an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-
186
Epidemiology
 OSSN of conjunctiva and cornea was estimated to be 0.13/100,000 in
tribal groups in Uganda by Templeton in a study published in 1967
 In a recent study published in 2012 an incidence of 37.3 per 106 was
reported for all eye cancers
 OSSN occurs predominantly in adults, average age of 56 years, with
an age range of 4-96 years.
 Younger age of presentation of OSSN was seen in addition to patients
patients suffering from Xeroderma pigmentosum and HIV infection
Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and
an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-
186
Predisposing factors
 dysfunctional limbal stem cells(ultraviolet B radiation, and
infection with human papilloma virus)
 other risk factors include:exposure to petroleum products,
 heavy cigarette smoking, ocular surface injury, vitamin A
deficiency
 light pigmentation of the hair and eye, defective DNA repair in
Xeroderma Pigmentosum
 infection with HIV and other immunocompromised states.
Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and a
n update
on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-186
Clinical Presentation
 Usually as sessile, fleshy,elevated lesion near limbus (inter-
palpebral area)
 Lesions vary in appearance with color from a pearly gray to
reddish brown (if pigmented)
 From papilliform to gelatinous
 Leukoplakia(white plaque) may develop on the surface
 Prominent feeder vessels but their absence does not narrow the
DDX
 Synptoms range from asymptomatic to chronically irritated,red
eye
 Masses initially mobile
 Conjunctiva in late stage becomes fixed to globe with sclera
infiltration
 Rose Bengal staining helps in identifying the extent of lesion
Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and a
n update
on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-186
Various clinical presentation of OSSN
OSSN.ppt
 The gold standard for the diagnosi: histopathological
evaluation of the lesion after an incisional or excisional
biopsy
Impression cytology to diagnose and clinically monitor
patient.It can only assess superficial tissue unable to
dicern depth of involvement
Anterior segment optical coherence tomography ( a
severely thickened hyper-reflective epithelium with an
abrupt transition from abnormal to normal tissue
suggestive of OSSN)
Confocal microscopy helpful in guiding treatment to
reveal cellular details
High frequency ultrasound helpful in determining the
extent of invasion in cases of SCC
Diagnosis
Histopathology
Excisional rather than incisional biopsy should be
performed due to its malignant seeding potential
 Excised lesion mounted on the filter paper in the
operating room should be allowed to dry adequately
(approx. 2–3 min) on the filter paper which causes
adhesion of the tissue on the filter paper.
Margins when not sent separately by the surgeon
should be submitted by the grossing pathologist as
superior/inferior/medial and/or lateral in separate filter
papers submitted in separate cassettes
Main lesion which is seen as a greyish white plaque,
nodule or thickening should be excised into two and
submitted for edge wise processing.
(A)Excised ocular surface squamous lesion placed on the filter
paper. Exact laterality and position of the lesion can be made out
with this pictorial documentation (B). Margins from the excised
tissue are placed on separate filter papers and submitted in different
cassettesmage)
Microscopic examination of the excised lesion with safe margins shows
an abrupt transition of the epithelial lesion from the adjacent uninvolved
conjunctiva
The conjunctival epithelium is markedly thickened with an abrupt transition noted betwe
en the involved conjunctiva and the adjacent normal appearing conjunctival epithelium (
arrow marked). Base of the excision biopsy is free of tumour involvement
Depending on the level and thickness of epithelial involvement varying
grades of dysplasia are classified:
 lower one third and lower two thirds of the epithelium shows
abnormal transformation ; mild and moderate dysplasia
respectively
 abnormality involves more than 2/3rds of the epithelial thickness,
however surface maturation is preserved :severe dysplasia
 Involvement of full thickness of epithelium with retained integrity
of epithelial basement membrane:carcinoma in situ
 Invasive Squamous cell carcinoma-invasion of stroma is seen as
tumour nests and broad expansive tumour masses
A. Moderate dysplasia-squamous intra epithelial lesion
B. Severe dysplasia-there is almost full thickness replacement by abnormal e
pithelia
Histopathology images
(A) Corneal OSSN-slit lamp photograph under diffuse illumination shows minimally elev
ated
lesion involving ¾ of the cornea-scleral limbus
(B) Atypical epithelium of the cornea, infiltration of corneal stroma is limited by intact bo
Differential diagnosis
Pterygium
Pinguecular
Melanoma
Conjunctival nevus
Pyogenic granuloma
Keratoacanthoma
Treatment
Topical chemotherapy alone
Excision alone
Combination of excision and adjuvant
chemotherapy(MMC,5FU, Interferon Alpha 2B)
Rarely radiation, enucleation, or subtotal orbital
exenteration (particularly severe and wide-spread
cases where the extent of the lesion precludes
excision and recurrence)
Medical Treatment
Pros
Helpful in recurrent,annular,or diffuse disease
Minimizes risk of LSCD
Overall well tolerated
IFN>5FU>MMC
Cons
 Prolonged time to resolution compared to sx
Ocular surface pain with MMC,IFN injection can give
malaise
Medical Treatment
Topical MMC 0.02% or 0.04%
 One use for 7 days QID then a week or two off due to
toxicity
May need to tear with steroid and artificial tears for
toxicity
Complication: pain,cornea toxicity,puntal stenosis,
LSCD,
Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and
an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-
186
Medical Treatment
Topical 5FU 1%
 One use for 7 days QID with 30days off
May need to tear with steroid and artificial tears for
toxicity
Overall literature shows clinical resolution with topical
cases around 85% and recurrence rate of 12.5-43%
Complication: pain not as bad as
MMC,hyperemia,puntal stenosis
Prognosis
 Recurrence rate after surgical excision can occur over
in half of cases and may occur years later
Even if surgical margins are negative 1/3 of eyes may
experience recurrence within 10 years
Recurrent can grow rapidlyand more invasive and need
combination therapy
The preferred treatment modality for intraocular tumour
extension extended enucleation including 4 mm wide
tumour-free conjunctival margins by ‘no-touch’
technique and adjunctive cryotherapy to the surgical
margins of the conjunctiva
Kaliki S, et al. Ocular surface squamous neoplasia with intraocular tumour
extension: A study of 23 patients. Eye (Lond). (2019)
Thank you!
Excellence Equity Efficiency
L V Prasad Eye Institute

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OSSN.ppt

  • 1. OSSN Presenter: DR SHAYRI PILLAI Liberia Eye Centre JFK Memorial Medical Centre August 29,2019
  • 2. Introduction  Ocular surface squamous neoplasia (OSSN) includes spectrum of disease from mild dysplasia to carcinoma in situ to invasive squamous squamous cell carcinoma  Involving conjunctiva and cornea  Usually in the interpalpebral area, mostly at the limbus Kaliki S, et al. Ocular surface squamous neoplasia with intraocular tumour extension: A study of 23 patients. Eye (Lond). (2019)
  • 3. Introduction  Various intra epithelial lesions of squamous epithelium of conjunctiva were identified & numerous confusing terminologies such as  epithelial plaque, intra epithelial epithelioma, dyskeratosis, dysplasia, precancerous epithelioma, Bowen’s disease of the conjunctiva and ‘Bowenoid epithelioma’ were used to describe this lesion  Advanced age, male gender, exposure to solar ultraviolet radiation, infection with human papilloma virus (HPV), immunosuppression and infection with human immunodeficiency virus (HIV) are the factors which play an essential role in the development of OSSN Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177- 186
  • 4. Epidemiology  OSSN of conjunctiva and cornea was estimated to be 0.13/100,000 in tribal groups in Uganda by Templeton in a study published in 1967  In a recent study published in 2012 an incidence of 37.3 per 106 was reported for all eye cancers  OSSN occurs predominantly in adults, average age of 56 years, with an age range of 4-96 years.  Younger age of presentation of OSSN was seen in addition to patients patients suffering from Xeroderma pigmentosum and HIV infection Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177- 186
  • 5. Predisposing factors  dysfunctional limbal stem cells(ultraviolet B radiation, and infection with human papilloma virus)  other risk factors include:exposure to petroleum products,  heavy cigarette smoking, ocular surface injury, vitamin A deficiency  light pigmentation of the hair and eye, defective DNA repair in Xeroderma Pigmentosum  infection with HIV and other immunocompromised states. Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and a n update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-186
  • 6. Clinical Presentation  Usually as sessile, fleshy,elevated lesion near limbus (inter- palpebral area)  Lesions vary in appearance with color from a pearly gray to reddish brown (if pigmented)  From papilliform to gelatinous  Leukoplakia(white plaque) may develop on the surface  Prominent feeder vessels but their absence does not narrow the DDX  Synptoms range from asymptomatic to chronically irritated,red eye  Masses initially mobile  Conjunctiva in late stage becomes fixed to globe with sclera infiltration  Rose Bengal staining helps in identifying the extent of lesion Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and a n update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177-186
  • 9.  The gold standard for the diagnosi: histopathological evaluation of the lesion after an incisional or excisional biopsy Impression cytology to diagnose and clinically monitor patient.It can only assess superficial tissue unable to dicern depth of involvement Anterior segment optical coherence tomography ( a severely thickened hyper-reflective epithelium with an abrupt transition from abnormal to normal tissue suggestive of OSSN) Confocal microscopy helpful in guiding treatment to reveal cellular details High frequency ultrasound helpful in determining the extent of invasion in cases of SCC Diagnosis
  • 10. Histopathology Excisional rather than incisional biopsy should be performed due to its malignant seeding potential  Excised lesion mounted on the filter paper in the operating room should be allowed to dry adequately (approx. 2–3 min) on the filter paper which causes adhesion of the tissue on the filter paper. Margins when not sent separately by the surgeon should be submitted by the grossing pathologist as superior/inferior/medial and/or lateral in separate filter papers submitted in separate cassettes Main lesion which is seen as a greyish white plaque, nodule or thickening should be excised into two and submitted for edge wise processing.
  • 11. (A)Excised ocular surface squamous lesion placed on the filter paper. Exact laterality and position of the lesion can be made out with this pictorial documentation (B). Margins from the excised tissue are placed on separate filter papers and submitted in different cassettesmage)
  • 12. Microscopic examination of the excised lesion with safe margins shows an abrupt transition of the epithelial lesion from the adjacent uninvolved conjunctiva The conjunctival epithelium is markedly thickened with an abrupt transition noted betwe en the involved conjunctiva and the adjacent normal appearing conjunctival epithelium ( arrow marked). Base of the excision biopsy is free of tumour involvement
  • 13. Depending on the level and thickness of epithelial involvement varying grades of dysplasia are classified:  lower one third and lower two thirds of the epithelium shows abnormal transformation ; mild and moderate dysplasia respectively  abnormality involves more than 2/3rds of the epithelial thickness, however surface maturation is preserved :severe dysplasia  Involvement of full thickness of epithelium with retained integrity of epithelial basement membrane:carcinoma in situ  Invasive Squamous cell carcinoma-invasion of stroma is seen as tumour nests and broad expansive tumour masses
  • 14. A. Moderate dysplasia-squamous intra epithelial lesion B. Severe dysplasia-there is almost full thickness replacement by abnormal e pithelia Histopathology images
  • 15. (A) Corneal OSSN-slit lamp photograph under diffuse illumination shows minimally elev ated lesion involving ¾ of the cornea-scleral limbus (B) Atypical epithelium of the cornea, infiltration of corneal stroma is limited by intact bo
  • 17. Treatment Topical chemotherapy alone Excision alone Combination of excision and adjuvant chemotherapy(MMC,5FU, Interferon Alpha 2B) Rarely radiation, enucleation, or subtotal orbital exenteration (particularly severe and wide-spread cases where the extent of the lesion precludes excision and recurrence)
  • 18. Medical Treatment Pros Helpful in recurrent,annular,or diffuse disease Minimizes risk of LSCD Overall well tolerated IFN>5FU>MMC Cons  Prolonged time to resolution compared to sx Ocular surface pain with MMC,IFN injection can give malaise
  • 19. Medical Treatment Topical MMC 0.02% or 0.04%  One use for 7 days QID then a week or two off due to toxicity May need to tear with steroid and artificial tears for toxicity Complication: pain,cornea toxicity,puntal stenosis, LSCD, Ruchi M,et al. Ocular surface squamous neoplasia:Review of etio-pathogenesis and an update on clinico-pathological diagnosis.Saudi J Ophthalmo.2013 Jul;27(3):177- 186
  • 20. Medical Treatment Topical 5FU 1%  One use for 7 days QID with 30days off May need to tear with steroid and artificial tears for toxicity Overall literature shows clinical resolution with topical cases around 85% and recurrence rate of 12.5-43% Complication: pain not as bad as MMC,hyperemia,puntal stenosis
  • 21. Prognosis  Recurrence rate after surgical excision can occur over in half of cases and may occur years later Even if surgical margins are negative 1/3 of eyes may experience recurrence within 10 years Recurrent can grow rapidlyand more invasive and need combination therapy The preferred treatment modality for intraocular tumour extension extended enucleation including 4 mm wide tumour-free conjunctival margins by ‘no-touch’ technique and adjunctive cryotherapy to the surgical margins of the conjunctiva Kaliki S, et al. Ocular surface squamous neoplasia with intraocular tumour extension: A study of 23 patients. Eye (Lond). (2019)
  • 22. Thank you! Excellence Equity Efficiency L V Prasad Eye Institute

Editor's Notes

  • #6: It has been speculated that OSSN may arise from dysfunctional limbal stem cells having been altered by various mutagenic agents, such as UV radiation.15 The mutagenic factors which have been best understood include exposure to ultraviolet B radiation, and infection with human papilloma virus. Other reported risk factors include exposure to petroleum products, heavy cigarette smoking, chemicals such as trifluridine, arsenicals, beryllium, ocular surface injury, vitamin A deficiency, light pigmentation of the hair and eye, defective DNA repair in Xeroderma Pigmentosum, family origin in the British Isles, Austria, or Switzerland, infection with HIV16,17 and other immunocompromised states.
  • #7: Clinically OSSN has many presentations Leukoplakia indicate secondary hyperkeratosis, due to squamous cel dysfunction One often finds dilated conjunctival blood vessels feeding and draining the lesion. SCC is locally invasive and metastasis is seen in <2% of cases. It can invade intraocular tissues and orbit. Some lesions can be diffuse, flat, and poorly-demarcated without an obvious tumour making early diagnosis difficult. Massive tumours infiltrating the deeper corneal stroma and covering the entire ocular surface are also seen (Fig. 2A–F). Infiltrative variants of OSSN masquerading as necrotizing scleritis may pose a challenge in early diagnosis (Fig. 3 A–D).33 Rarely pigmented variants of OSSN may be seen making differentiation from conjunctival melanoma difficult (Fig. 1C).34
  • #8:  (A). Slit lamp photograph under diffuse illumination shows papillary ocular surface tumour with prominent feeder (B). Figure shows a globular pink-coloured lesion arising with large feeder vessels. The lesion seems to be overlying a pterygium and was clinically mistaken to be a pyogenic granuloma (C). Figure shows a pigmented OSSN with feeder vessels (D). Slit lamp photograph under diffuse illumination showing large leukoplakic lesions with abnormal vessels
  • #10: The gold standard for the diagnosis of OSSN is the histopathological evaluation of the lesion after an incisional or excisional biopsy However there are several occasions when the clinician may opt to do diagnostic tests to corroborate the clinical suspicion of OSSN. Diagnosis is based on the presence of the universal cytological criteria which included nuclear enlargement, hyperchromasia, irregular nuclear outline, coarse nuclear chromatin, and prominent nucleolcarcinom
  • #11: This includes all smaller tumors (limbal tumors <4 clock hours or <15 mm basal dimension).[8] If the lesion is too large, an incisional biopsy (punch or incisional wedge) to first obtain a histopathologic diagnosis may be necessary before proceeding to more extensive treatment.[8]
  • #12: Nasally wing shaped fibrovascular growth noted encroaching the cornea with stocker’s line seen Linear epithelial iron deposition (Stocker line)
  • #14: When lower one third and lower two thirds of the epithelium shows abnormal transformation the lesion is termed as mild and moderate dysplasia respectively. When the abnormality involves more than 2/3rds of the epithelial thickness, however surface maturation is preserved, the lesion is termed as severe dysplasia. Involvement of full thickness of epithelium, however with retained integrity of epithelial basement membrane is termed as carcinoma in situ (Fig. 6A–D). As the lesion progresses from mild to severe dysplasia, the cells differentiate less and less, gradually losing their squamous features until eventually the full thickness of epithelium is made of undifferentiated/immature atypical cells which can even have basaloid like appearance
  • #15: (A) Moderate dysplasia-squamous intra epithelial lesion, abnormal transformation of epithelium involving more than 2/3rds of epithelial thickness, however the degree of cytological atypia is not sufficient to term this lesion as severe dysplasia (B). Severe dysplasia-there is almost full thickness replacement by abnormal epithelium, surface maturation is noted with keratinisation. Basement membrane is intact. (C). Carcinoma- in-situ- there is full thickness replacement by abnormal epithelium with marked nuclear pleomorphism. Basement membrane is intact, (arrow marked) (Haematoxylin-eosin, X 400) (D). Invasive Squamous cell carcinoma-invasion of stroma is seen as tumour nests and broad expansive tumour masses
  • #16: (A) Corneal OSSN-slit lamp photograph under diffuse illumination shows minimally elevated lesion involving ¾ of the cornea-scleral limbus. The corneal surface is covered by a greyish membrane with abnormal vessels (B). Atypical epithelium of the cornea, infiltration of corneal stroma is limited by intact bowmans membrane (arrow marked). An inflamed fibrovascular membrane is seen above the corneal stroma