Lumps, Bumps and Lid Lesions Know When to Hold Them & Know When to Fold Them Disclosures Cancer Cancer Cancer Cancer

8/1/2016

Lumps, Bumps and Lid Lesions Disclosures

Know when to hold them & ò Financial disclosures: The content of this COPE accredited CE activity was prepared independently by Dr. Robert E. Prouty without input from members of know when to fold them the ophthalmic community. COPE #47629-SD ò Dr. Robert E. Prouty is affiliated with the following companies as a member or their Speaker’s Bureau or as a Consultant but has no direct financial or proprietary Robert E. Prouty, O.D., FAAO interest in any companies, products or services Specialty Eye Care mentioned in this presentation: VAlcon – Allergan – Optovue – Zeiss Meditec - VSP - Parker, Co B&L – Ivantis [email protected] ò The content and format of this course is presented without commercial bias and doesn’t claim superiority of any commercial product or service.

Cancer Cancer

ò Definitions: ò Characteristics: – A group of diseases characterized by – Can affect any tissue or organ at any age uncontrolled growth and spread of ò ~77% of all cancers occur in patients > 55 yo abnormal cells – American Cancer Society. Cancer Facts & Figures 2008 . Atlanta: American – All cancers begin with a defect in a single Cancer Society; 2008 cell (monoclonal) – Any of various malignant neoplasms characterized by the proliferation of – This is followed by unrestrained growth anaplastic cells that tend to invade ò Benign tumors may damage localized tissue surrounding tissue and metastasize to by occupying space but they do not spread new body sites – www.dictionary.com

Cancer Cancer

ò Characteristics: ò Characteristics: – Malignant tumors invade surrounding – Malignant tumors invade surrounding tissue and may metastasize tissue and may metastasize ò A one cm tumor contains one billion cells ò A one cm tumor contains one billion cells ò One trillion cells usually means a lethal tumor ò One trillion cells usually means a lethal tumor – Cell division is controlled by genes that – Cell division is controlled by genes that promote it and genes that suppress it promote it and genes that suppress it ò Cancer is the result of some combination of ò Cancer is the result of some combination of defects in this genetic functioning defects in this genetic functioning

1 8/1/2016

History Cancer

ò Risk factors: ò Duration – Only ~5% of cancers are strongly hereditary ò Bleeding – Environmental factors account for 75%-80% ò Discharge ò Tobacco ò Change in size ò Poor nutrition ò Obesity ò Change in color ò Infectious agents ò History of skin cancer ò Sunlight/Radiation ò Carcinogens

Cancer Cancer

ò Risk factors: ò Risk factors: – Sunlight/Radiation – Sunlight/Radiation ò Lindqvist PG, Epstein E, et al. J Intern Med. 2016 ò Lindqvist PG, Epstein E, et al. J Intern Med. 2016 Mar 16 Mar 16 – Nonsmokers who stayed out of the sun had a life expectancy – Nonsmokers who stayed out of the sun had a life expectancy similar to smokers. similar to smokers. – “We find an increased risk of…skin cancer. However, the skin – “We find an increased risk of…skin cancer. However, the skin cancers that occurred in those exposing themselves to the sun cancers that occurred in those exposing themselves to the sun had a better prognosis.” had a better prognosis.” – Smokers exposed to the sun lived ~2 yrs longer than – Smokers exposed to the sun lived ~2 yrs longer than non-sun exposed nonsmokers non-sun exposed nonsmokers

Cancer Cancer

ò The 5 leading non-skin cancers in the U.S. ò The 5 leading non-skin cancers in the U.S. – Prostate – Prostate – Lung (90% in tobacco use) – Lung (90% in tobacco use) – Breast – Breast – Colo-rectal – Colo-rectal – Urinary/bladder – Urinary/bladder ò Cancer accounts for 25% of the deaths in ò Cancer accounts for 25% of the deaths in the U.S. the U.S. – 25% of people will be personally – 25% of people will be personally affected in their lifetime affected in their lifetime

2 8/1/2016

Cancer Cancer

ò Basal Cell Carcinoma (BCC) ò Basal Cell Carcinoma (BCC) – The most common malignancy in humans – 80% of BCC cases are on the head & neck – 50% of all U.S. cancer, is skin cancer ò 15% on the trunk ò 80% of that is BCC! – Greater risk of recurrence of BCC on – Greater risks exist for BCC & SCC in eyelids (lower), nose & ears patients: – There is no precursor to BCC ò White – 19X greater whites:blacks ò Light colored eyes & hair ò Freckle easily and tan poorly ò Increases with UV exposure – Tanning beds = 1.5X relative risk

Cancer Cancer

ò Basal Cell Carcinoma (BCC) ò Basal Cell Carcinoma (BCC) – 80% of BCC cases are on the head & neck – 20% of all eyelid neoplasms ò 15% on the trunk ò 90% of all malignant eyelid neoplasms – Greater risk of recurrence of BCC on – Spread is by local invasion (almost exclusively) eyelids (lower), nose & ears Nodular Superficial

• Morpheaform

Cancer Cancer

ò Basal Cell Carcinoma (BCC) ò Basal Cell Carcinoma (BCC) – 20% of all eyelid neoplasms – 20% of all eyelid neoplasms ò 90% of all malignant eyelid neoplasms ò 90% of all malignant eyelid neoplasms – Spread is by local invasion (almost exclusively) – Spread is by local invasion (almost exclusively)

3 8/1/2016

16 weeks of Erivedge ® 16 weeks of Tarceva ® (Erlotinib) (Vismodegib)

Basal Cell Nevus Syndrome (Gorlin-Goltz Syndrome) Source: Yin VT, Pfeiffer ML, Esmaeli B: Targeted therapy for orbtial and periocular basal cell carcinoma and squamous cell carcinoma. Source: Yin VT, Pfeiffer ML, Esmaeli B: Targeted therapy for orbtial and periocular basal cell carcinoma and squamous cell carcinoma. Ophthalmic Plastic and Reconstructive Surgery 2013;29(2):87-92 Ophthalmic Plastic and Reconstructive Surgery 2013;29(2):87-92

Cancer Cancer

ò Squamous Cell Carcinoma (SCC): ò Squamous Cell Carcinoma (SCC): – SCC is increasing in incidence – 2 nd most common eyelid malignancy ò Greater rate of increase for SCC vs BCC ò 10% of all eyelid malignancy – 200% for SCC vs 80% for BCC – Demographics

– Estimated BCC:SCC = 4:1 ò Older population

ò SCC is most common skin cancer in blacks (30%) ò Fair complexion, sun damage – 60% of cutaneous SCC occurs on the head & – Intraepithelial spread or deep invasion with neck (sun-exposed) potential rare regional lymph node metastasis ò 90% of head & neck cancer = SCC

Cancer Cancer

ò Squamous Cell Carcinoma (SCC): ò SCC vs BCC: – Risks: – SCC grows faster, ulcerates, bleeds & ò Cumulative UV-B exposure is the primary risk scabs more than BCC factor – SCC recurs more frequently that BCC – UV-A is less indicated but data is unclear ò Since SCC extends deeper (not local), more ò Smoking = 2X risk severe ò Tanning beds = 2.5X risk ò Lesions on the ear & lips are at greater risk for ò Born in high UV exposure area = 3X risk recurrence ò Light skin & hair = 2-5X risk – Scalp, forehead, temple, eyelid, nose and hands are close behind ò Outdoor occupation = 5X risk

4 8/1/2016

Cancer Cancer

ò SCC vs BCC: ò SCC vs BCC: – SCC grows faster, ulcerates, bleeds & – SCC grows faster, ulcerates, bleeds & scabs more than BCC scabs more than BCC – SCC recurs more frequently that BCC – SCC recurs more frequently that BCC ò Since SCC extends deeper (not local), more ò Since SCC extends deeper (not local), more severe severe ò Lesions on the ear & lips are at greater risk for ò Lesions on the ear & lips are at greater risk for recurrence recurrence – Scalp, forehead, temple, eyelid, nose and hands are – Scalp, forehead, temple, eyelid, nose and hands are close behind close behind

SCC- Conjunctival

• Unrelated to sun exposure • Commonly misdiagnosed as conjunctivitis • Higher incidence of metastatic disease if lesion extends into fornix

Cancer Cancer

ò Solar lentigo ò Seborrheic keratosis – Benign sun-induced area of darkening – Common benign skin lesion in older adults pigmentation – Proliferation of epidermal cells occurring ò Commonly referred to as “Liver Spot” on sun exposed areas of skin ò Easily mistaken for melanoma

5 8/1/2016

Cancer Cancer

ò Seborrheic keratosis ò Malignant Melanoma (MM): – Common benign skin lesion in older adults – Increasing incidence (~6% per year) – Proliferation of epidermal cells occurring ò Greatest incidence increase amongst neoplasms on sun exposed areas of skin ò ½ the incidence of MM is between 35-65 ages – 80% of cases occurring between 20-74 ages ò Variable pigmentation – Pink – brown – dark brown – black ò Survivability has improved – 60% in 1960’s ò Can transition to solar lentigo – >89% in 1990’s – Usually begin as flat, brown, circumscribed ò Median age of diagnosis is 57 areas that can increase in size and thickness ò Causes suspicion for melanoma

Cancer Cancer

ò Malignant Melanoma (MM): ò Malignant Melanoma (MM): – Increasing incidence (~6% per year) – Increasing incidence (~6% per year) ò Greatest incidence increase amongst neoplasms ò Greatest incidence increase amongst neoplasms ò ½ the incidence of MM is between 35-65 ages ò ½ the incidence of MM is between 35-65 ages – 80% of cases occurring between 20-74 ages – 80% of cases occurring between 20-74 ages ò Survivability has improved ò Survivability has improved – Stage IA: The 5-year survival rate is around 97%. The 10- – Stage IIA: The 5-year survival rate is around 81%. The 10- year survival is around 95%. year survival is around 67%. – Stage IB: The 5-year survival rate is around 92%. The 10- – Stage IIB: The 5-year survival rate is around 70%. The 10- year survival is around 86%. year survival is around 57%. – Stage IIC: The 5-year survival rate is around 53%. The 10- year survival is around 40%.

Cancer Cancer

ò Malignant Melanoma (MM): ò Malignant Melanoma (MM): – Increasing incidence (~6% per year) – Increasing incidence (~6% per year) ò Greatest incidence increase amongst neoplasms ò Greatest incidence increase amongst neoplasms ò ½ the incidence of MM is between 35-65 ages ò ½ the incidence of MM is between 35-65 ages – 80% of cases occurring between 20-74 ages – 80% of cases occurring between 20-74 ages ò Survivability has improved ò Survivability has improved – Stage IIIA: The 5-year survival rate is around 78%. The – Stage IV: The 5-year survival rate is about 15% to 20%. 10-year survival is around 68%. The 10-year survival is about 10% to 15%. – Stage IIIB: The 5-year survival rate is around 59%. The 10-year survival is around 43%. – Stage IIIC: The 5-year survival rate is around 40%. The 10-year survival is around 24%.

6 8/1/2016

Cancer Cancer

ò Malignant Melanoma (MM): ò Malignant Melanoma (MM): – Risks: – Risks: ò FHx offer 10% increase risk ò Sunlight exposure is primary risk factor ò Dysplastic nevus syndrome can increase risk – Past sunburn at ANY age = 2X risk 100-500X • Childhood sunburns increase risk – ~25% of nevi develop to MM – Tanning beds = 1.25X risk – Living near equator increases risk ò Blondes = 2X risk ò Red heads = 4X risk ò Sun sensitive or inability to tan = 2X risk ò Freckling = 2X risk ò Whites = 10X risk vs blacks/Asians/Hispanics

Cancer Cancer

ò Malignant Melanoma (MM): ò Dermal Melanoma – ABCDE rule: ò Asymmetry, Border irregularity, Color abnormality & Diameter (>6mm) ò E has now been added: – Evolving = change in size, shape, surface (bleeding) or symptoms (itching or tenderness)

Tissues of the conjunctiva

ò Epithelium Now to the tour….. – Stratified layers ò Basal ÏWing ÏSurface ò Melanocytes ò Langerhahn’s cells ò The sentry cells – Signal the immune system ò NOT in the cornea! – They stimulate the system to cause scarring

7 8/1/2016

Tissues of the conjunctiva Tissues of the conjunctiva

ò Epithelium ò Epithelium – Stratified layers – Stratified layer ò Melanocytes ò Langerhahn's cells ò Melanocytes ò Goblet cells ò Langerhahn's cells ò Fibroblasts ò Nerve cells ò Goblet cells ò Lymphatics – Not IN the eye but in the conj & lids – This allows for lymphatic related spread of disorders

Early Phase Allergy Nerves Tissues of the conjunctiva Sensitized Mast Cell

Antigen Other Mediators: Tryptase ò Blood vessels Heparin Prostaglandins ò Mast Cells H1 nerve stimulation – At BV wall @ 3-5 min = Itching! Histamine – Degranulate in allergy Endothelial Gaping ÙÙÙ fluid leakage = Swelling! ò Itch ò Erythema Vasodilation @ 5-10 min = Redness! Fluid ò Edema Blood Vessel Blood Vessel

Tissues of the conjunctiva Tissues of the conjunctiva

ò Limbal stem cells Palpebral conjunctiva ò Goblet cells – Thickened area of – Mucus producing cells conjunctiva – Distribution of goblet ò Source of cells in the conj is not replenishment of uniform corneal epith ò Greater density away – A highly mitotic & from the limbus immunologic area toward fornix – Explains why the limbal area can be ò Greater nasally then the source of so temporally many disorders Limbal stem cells

8 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Limbal Dermoids – Limbal Dermoids ò Congenital choristoma ò Congenital choristoma – Definition: – White – solid lesion • Choristoma is a congenital lesion composed of types of normal tissue that would not normally be – Usually seen in children (rarely seen by ODs as a new found at that location of the body lesion) • Hamartoma is a congenital lesion of an abnormal – Can consist of fat tissue-hair follicles-teeth density of normal tissue that would be found at that location - Freckle/nevus = hamartoma of pigment - Hemangioma = hamartoma of blood vessels

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Limbal Dermoids – Limbal phlectenule ò Differentiate for Goldenhar’s Syndrome ò Located at the limbus – Oculoauriculovertebral syndrome ò Similar to marginal • Facial asymmetry (FLK): Usually unilateral infiltrate (staph) but no • Scoliosis clear zone at the limbus ò Possible association with So to differentiate, TB (if regionally at risk) look at the ear as well ò Very responsive to topical as the eye! steroids

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Salzman’s nodular – Bitot’s spot degeneration ò Squamous Metaplasia ò May develop from any – Mucosal tissue change in chronic surface disease response to chronic – Common after chronic dryness as protection phlectenulosis – HSK – etc. • Keratinization ò Bluish-gray color to – Reversible! avascular lesion ò – Epith intact but thinned Leukoplakia – = White plaque ò Not overly inflamed ò Vitamin-A deficiency ò Often needs graft – ERG to r/o night blind

9 8/1/2016

Ocular Surface Squamous Clinical Identification tips Neoplasia

ò Conjunctival lesions – Conjunctival Intraepithelial Neoplasia (CIN) *Melanosis ò Was Carcinoma in situ *Melanocytic *Malignant Melanomas ò Collective term for ALL Ocular Surface *Ocular Surface Squamous Neoplasms (OSSN) Squamous Neoplasia *Non-Melanocytic *Papillomas *Corneal Intraepithelial Neoplasia (CIN) *Squamous Cell Carcinoma

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Conjunctival Intraepithelial Neoplasia (CIN) – Conjunctival Intraepithelial Neoplasia (CIN)

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Conjunctival Intraepithelial Neoplasia (CIN) – Conjunctival Intraepithelial Neoplasia (CIN) ò Once the lesion reaches the limbus, it likes the ò Once the lesion reaches the limbus, it likes the high mitotic area so it works around the limbus high mitotic area so it works around the limbus instead of marching across (like a pterygium) instead of marching across (like a pterygium) ò Once the lesion breaks through to the underlying conjunctival stroma (invasive), it is termed a Squamous Cell Carcinoma (SCC) – One step beyond CIN ò Basal Cell Carcinoma (BCC) is unheard of in the conjunctiva! – On skin think BCC 1 st but conj think SCC !

10 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Conjunctival lesions ò Conjunctival lesions – Conjunctival Intraepithelial Neoplasia (CIN) – Conjunctival Intraepithelial Neoplasia (CIN) ò Conjunctival Gelatinous Polypoid Squamous Cell ò Upcoming diagnostic aids: Carcinoma – High Resolution OCT – Will cross the cornea! • Normal areas of tissue are thin & dark – HPV-16 often found but NOT considered the cause • OSSN is thickened & hyper-reflexive with a smooth transition at borders • Imaging may show shadowing due to leukoplakia • Can use HR-OCT to monitor resolution while Tx

Treatment options Clinical Identification tips

ò Conjunctival lesions ò Cystic lesions – Conjunctival Intraepithelial Neoplasia (CIN) – Epithelial Inclusion Cyst (EIC) ò Existing Tx options (ALL are used off-label): ò Use optic-section beam to “light up’ the lesion – MMC 0.2% (QID X 1week then 2-3 week off for 3-4 – Formation: cycles, 85%-100% success, $$$, with toxicity) – 5-FU (QID X 1 w then 3 week off for 4 cycles, 82%- ò Epithelial cells are driven below the surface 100% success, $35/month, with toxicity) – Interferon--2b (QID X 4 months, high success rate yet $240/month, little toxicity) ò If lesion is <3-4 clock hrs, excision works well ò If lesion is large and annular, use medical chemo

Clinical Identification tips Clinical Identification tips

ò Cystic lesions ò Cystic lesions – EIC Formation Sequence – EIC Formation Sequence ò Epith. Cells are designed to separate 2 ò Epith. Cells are designed to separate 2 environments from each other environments from each other – Base toward stroma and top should be away from stroma – Since it can only divide, they make a wall/chain until a new space is inside and the base is to stroma – Once they achieve a separated space, they go back to their function and secret fluid = cyst

11 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Cystic lesions ò Cystic lesions – EIC – Lymphangiectasis ò Fornix lesions are cloudy due to mast or goblet ò May be linear or multi-lobular cell secretions

Clinical Identification tips Clinical Identification tips

ò Cystic lesions ò Lid lesions – What is it? – Transition Areas ò Generally, in areas where one epithelium transitions from one type to another, is prone to viral induced lesions – Lid conj to palpebral conj (Lid Margin) – Bulbar conj to cornea (Limbus)

Clinical Identification tips Clinical Identification tips

ò Lid lesions ò Lid lesions – Molluscum Contagiosum – Molluscum Contagiosum ò Characteristics: ò Characteristics: – Sessile papillomatous lesion – Sessile papillomatous lesion – Highly contagious – Highly contagious – Viral induced – Viral induced • Chronic follicular conjunctivitis Molluscum bodies

12 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Lid lesions ò Lid lesions – Molluscum Contagiosum BCC – Differentiate lesions ò Characteristics: ò History – Sessile papillomatous lesion ò Onset timing – Viral induced ò Biopsy? ò A small “prick” of the surface to draw a bit of Melanoma SCC blood may involute the lesion ò Curettage, Cryo, Cantharidin & Salicylic acid

Masquerade Clinical Identification tips Presentations ò Differentiate from HSK lid lesions ò Many eyelid tumors spread in a manner that involves different tissue planes at a microscopic level ò As a result, the process does not present as a discrete lesion and is often misdiagnosed as a benign inflammatory lesion

Clinical Identification tips Clinical Identification tips

ò Lid lesions ò Lid lesions – Sebaceous Cell Carcinoma – Sebaceous Cell Carcinoma ò Often masks as persistent/recurrent chalazia ò Often masks as persistent/recurrent chalazia or unresponsive blepharitis or unresponsive blepharitis ò Note lash line alteration! ò Note lash line alteration!

13 8/1/2016

Chronic Conjunctivitis Chalazion

ò “The patient is non-compliant” ò Recurrent chalazion, same/multiple ò “I haven’t found the right drop yet” locations

Dermatitis Ectropion

ò Allergic dermatitis, chronic eczema, ò Cicatricial LL ectropion, LL retraction scleroderma

Entropion Blepharitis

ò Trachoma, OCP ò Non-compliant patient, poor hygiene

14 8/1/2016

Facial numbness or Clinical Identification tips paralysis ò “It’s just a Bells palsy” ò Lid lesions – Sebaceous Cell Carcinoma ò Often masks as persistent/recurrent chalazia or unresponsive blepharitis

Clinical Identification tips Clinical Identification tips

ò Lid lesions ò Lid lesions – Sebaceous Cell Carcinoma – Sebaceous Cell Carcinoma ò Pagetoid spread ò Lash Margin could be best clinical clue – Can significantly complicate the surgical – Very rare but VERY bad cancer: management of this disease ò 8%-25% die from this cancer (even at this early stage)

Clinical Identification tips Clinical Identification tips

ò Pink-colored lesions ò Pink-colored lesions – Pyogenic granulomas – Pyogenic granulomas ò Neither pyogenic nor granulomatous! ò Ocular causes: – Complication of tissue malpositioning – May also occur in response to a retained foreign material – May occur if a chalazion/hordeloum ruptures through the tarsus to the conjunctival surface and spontaneously drains

Retained suture

15 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Pink-colored lesions ò Pink-colored lesions – Pedunculated papillomas – Sessile papillomas ò Viral induced ò Difficult to differentiate! – Note “feeder” vessel(s) ò Pox virus induced – HPV 6 & 11 have been associated

Clinical Identification tips Clinical Identification tips

Viral Neoplastic ò Pink-colored lesions Children/Adolescents Adults – Lymphoma Often Bilateral Unilateral ò Mucosa Associated Lymphoid Tissue (MALT) Often Multiple Solitary – Less aggressive Pedunculated in fornix Sessile, at limbus – Most common No inflammation Inflammation ò Mantle Resolve in 2 yrs Do not resolve – Malignant-behaving

MALT Mantle

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Iris Nevus – Iris Nevus ò Melanoma transition & metastasis is rare ò Melanoma transition & metastasis is rare ò Management of nevi is photos and monitor for: ò Management of nevi is photos and monitor for: – Growth – Growth – TM invasion – TM invasion – Watch for – Watch for sentinel vessel sentinel vessel

July ‘07

16 8/1/2016

Clinical Identification tips Clinical Identification tips

July ‘07 March ‘08 March ‘08

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Iris Nevus – Nevus at the caruncle ò Melanoma transition & metastasis is rare ò Caruncle is usually very quiet ò Management of nevi is photos and monitor for: ò More suspicious for development of melanoma – Growth – TM invasion – Watch for sentinel vessel

July ‘07 March ‘08

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Nevus at the caruncle – Conjunctival Nevus ò Caruncle is usually very quiet ò Focal, movable, congenital hamartoma ò More suspicious for development of melanoma ò May darken in puberty ò Always sample/biopsy if inflamed

17 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Conjunctival Nevus – Ocular Melanosis ò Focal, movable, congenital hamartoma ò Blue, gray or brown pigmentation ò May darken in puberty ò Does NOT move ò Always sample/biopsy if inflamed

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Ocular Melanosis – Primary Acquired Melanosis (PAM) ò Associated with Nevus of Ota (Hori’s Nevus) ò 35% develop melanoma – Most frequently in Asians – Male:Female = 1:4.8 – 50% present at birth – Second peak at adolescence – Rare ocular melanoma but incr uveal melanoma

Classification of Conjunctival Papillomas Clinical Identification tips Conjunctival Congenital Ocular Primary Acquired Nevus Melanosis Melanosis (PAM) Onset Congenital-may Congenital Acquired-middle age ò Pigmented lesions darken Structure Discrete Diffuse Diffuse – Primary Acquired Melanosis (PAM) Color Brown Blue/slate gray Brown ò 35% develop melanoma Cysts 50% of None None compound nevi Pigmentation Variable Always Always With conj Lesion moves Lesion does NOT Lesion moves movement move Growth Stationary Stationary Waxes and wanes Uvea Not involved Heterochromia Not involved Skin Not involved May be involved Not involved (Nevus of Ota) Malignant Conjunctival Skin or uveal, rarely Conjunctival Potential melanoma conjunctival melanoma Adapted from Thomas Freddo, O.D., Ph.D, FAAO, Univ of Waterloo

18 8/1/2016

Clinical Identification tips Clinical Identification tips

ò Pigmented lesions ò Pigmented lesions – Conjunctival Melanoma – Conjunctival Melanoma ò 10% develop de-novo ò 20% from pre-existing nevus ò 60%-70% from spreading PAM ò Mortality = 25% – 40%-44% if from PAM – Spreads to PA node or Sub-mandibular nodes

Clinical Identification tips

ò Pigmented lesions – Lid Melanoma Case: Ah… those suspicious lumps & bumps

HG HG

ò 67 yowf ò Pupils: PERRL - APD ò CC: Raised limbal lesion OS ò EOM: full range of motion ò MHx: Neg (Smoker!) ò Tapp: 15 OU ò OHx: Neg ò SLE: - OD: WNL ò Meds: None - OS: Temporal raised gelatinous ò FHx: Neg vascularized lesion X 6+ months ò DFE: c/d 0.3 OU Mac/vessels/periph WNL ò VA SC : 20/20 OU

19 8/1/2016

HG HG

ò Diagnosis: – Pterygium – Pinguecula – Corneal intraepithelial neoplasm (CIN) – Squamous cell carcinoma (SCC) – I don’t know, that is why I called YOU!

HG HG

ò Management: ò Lesion was biopsy positive SCC – Topical antibiotics and referred to us for a second opinion: – Mitomycin-C 0.002% (MMC) – Enucleate – Surgery – Other options – No treatment necessary ò No association with HPV – Monitor ò No evidence of AC invasion, TM involvement or cataract.

HG HG

ò What is the most identifying ò What is the most identifying characteristic of these lesions? characteristic of these lesions? – Gelatinous appearance – Gelatinous appearance – Location on the cornea – Location on the cornea – Vascularization – Vascularization – Raised lesion – Raised lesion – Persistence &/or changes over time – Persistence &/or changes over time

20 8/1/2016

HG MMC Tx example

ò Management: – Option #1: ò Lamellar keratectomy with conjunctivectomy and sclerectomy ò Cryo of the margins 6/21/00 6/28/00 – Option #2: ò Topical Mitomycin-C 0.002% (MMC) ò Head and Neck oncologists start systemic chemo of Fluoruracil and Cisplatin (X two cycles) 7/17/00 12/13/00

A newer biopsy technique Is it reasonable to monitor CIN? ò Impression Cytology – Non-invasive technique that allows ID of cell types to classify a lesion

Not all will need MMC! Cases should be managed based specific components

Impression Cytology Impression Cytology Procedure Procedure

ò Instructions for patient specimen collection: – The Biopore membrane device (Millicell-CM 0.4 [m PICM ò Instructions for patient specimen 02550, Millipore Corp, Bedford, MA, USA) comes in a sealed sterile package collection: ò The filter disc is 8 mm in diameter and is attached to a small plastic tube which is held during collection of the specimen – We use the Univ. of Colorado Denver Dept. – Before collecting a sample, three protruding plastic legs must be snapped off from the base of the tube with a pair of Spencer– of Anatomic Pathology/Cytology Lab at The Wells forceps Anschutz Center – Topical proparacaine 0.5% eye drops are then instilled onto the ocular surface/lower fornix ò There are national labs that accept overnight – Cytology specimens are obtained from the conjunctiva or cornea delivery for assessment – The membrane device is firmly pressed against the area to be sampled for 10-20 seconds (until the membrane becomes translucent) – Lastly, the device is immediately transferred into a 10 ml container of 95% ethanol without air drying ò Be sure to fully immerse the membrane in the solution

21 8/1/2016

Impression Cytology Limitations & Disadvantages Procedure

ò Codes: ò Tissue Biopsy and Surgical Excision – Can cause disorganization of the specimen during – Benign Neoplasm of eye NOS = D31.90 – Can often miss tumor margins in the tissue collection (224.90) – Longer recovery time – More invasive procedure for the patient ò Unspecified Conjunctiva = D31.00 (224.30) – Recurrence rate near 52% ò Unspecified Cornea = D31.10 (224.40) – Can cause scarring ò Unspecified Eye lid = D23.10 (216.10) – Removes limbal stem cells with each surgical procedure – Carcinomas (in situ) ò Impression Cytology – Sample depth is only first few superficial layers ò General code for unspecified eye = D09.20 – Inconsistent reliably to distinguish invasive SCC or (234.00) epithelium carcinoma in situ from minimally invasive disease – Keratinizing dysplasias may yield no or few atypical cells on ò Unspecified Eye lid = D04.10 (232.10) impression cytology

Impression Cytology What is that bump?

ò OSSN lesions have been routinely ID’ed by surgical biopsy – P/op stem cell deficiency concerns ò Impression cytology is a less invasive diagnostic option

References

ò 1. Yanoff M, Duker J. Ophthalmology. 2nd ed. St. Louis, MO Mosby; 535-541 ò 2. McKelvie P. Ocular Surface Impression Cytology. Adv Anat Pathol 10;6:328-337 ò 3. Nolan G, Hirst L, Bancroft B. The Cytomorphology of Ocular Surface Squamous Neoplasia by Using Impression Cytology. Cancer (Cancer Cytopathol) 2001;93:60–67 ò 4. Tananuvat N, Lertprasertsuk N, Mahanupap P, et al. Role of impression cytology in diagnosis of ocular surface neoplasia. Cornea . 2008;3:269-274 ò 5. Tole D, McKelvie P, Daniell M. Reliability of impression cytology for the diagnosis of ocular surface squamous neoplasia employing the Biopore membrane. Br J Ophthalmol 2001;85:154-15 ò 6. Chen C, Louis D, Dodd T, et al . Mitomycin C as an adjunct in the treatment of localized ocular surface squamous neoplasia. Br. J. Ophthalmol. 2004;88;17-18 ò 7. McKelvie P, Daniell M. Impression cytology following mitomycin C therapy for ocular surface squamous neoplasia. Br J Ophthalmol 2001;85:1115–1119 ò 8. Thatcher R, Darougar S, Jones B. Conjunctival impression cytology. Arch Ophthalmol. 1977;95:678– 681 ò 9. Egbert P, Lauber S, Maurice D. A simple conjunctival biopsy. Am J Ophthalmol. 1977;84:798–801 ò 10. Singh R, Joseph A, Umapathy T, et al. Impression cytology of the ocular surface. British Journal of Ophthalmology 2005;89:1655-1659 ò 11. Mathew A, Stumpf T, McGhee C. Impression cytology: implications for ocular surface squamous neoplasias. British Journal of Ophthalmology 2008;92:157-158 ò 12. Sun E, Fears T, Goedert J. Epidemiology of squamous cell conjunctival cancer. Cancer Epidemiol Bio Prevent 1997; 6: 73–77 ò 13. Yamamoto N, Ohmura T, Suzuki H, et al. Successful Treatment with 5-Fluorouracil of Conjunctival Intraepithelial Neoplasia Refractive to Mitomycin-C. Ophthalmology 2002;109:249–252 ò 14. Mahar P, Nwokora G. Role of mitomycin C in pterygium surgery. British Journal ò of Ophthalmology 1993;77:433-435 ò 15. Hirst L, Randomized Controlled Trial of Topical Mitomycin C for Ocular Surface Squamous Neoplasia. Ophthalmology 2007;114:976–982