Essential Pathology

Molluscum contagiosum
 Molluscum contagiosum

Definition / general
• Infectious disorder caused by molluscum contagiosum
poxvirus
• Multiple nodules on skin, trunk or anogenital region, due
to skin to skin contact or sexual transmission
• Exuberant lesions appear in adults with AIDS
 Gross description

• Multiple firm, pruritic, pink-tan nodules, up to 4 mm,

with central cores containing white keratinous
material

• Dome shape, waxy epidermal nodules

• skin nodules with umbilicated centers (crateriform)
• Secondary follicular conjunctivitis
 Microscopic (histologic) description

• Lobules epithelium that surround intracytoplasmic

eosinophilic inclusion bodies (molluscum bodies) which
become larger as they reach superficial epithelium
(Hendeson- Patterson corpuscles)

• Lobulated endophytic hyperplasia that produces a

circumscribed intradermal pseudotumor

• Eosinophillic inclusion near the base of the epithelium---

becomes denser and more basophilic as they reach and
migrate up
Standard histology slides
 Treatment

• Observation
• Oral cimetidine
• Excision if on eyelid margin to prevent
infection of ocular surface
• Controlled cryotherapy
• Curretage
Basal Cell Carcinoma of eyelid
• Most common eyelid malignancy
• 90-95% of malignant eyelid tumours

• Risk factors
– Fair skinned, blue eyed, red-haired/ blond
– Middle aged/older persons
– Irish, Scottish, Scandinavian ancestry
– Cigarette smoking
– Prolonged sun exposure within first 2 decades

• Systemic associations
– Basal cell nevus syndrome (Gorlin syndrome): AD
• Multiple nevoid basal cell CA
• Skeletal anomally (mandible, maxilla, vertebrae)
– Xeroderma pigmentosum :AR
• Extreme sun sensitivity
• Defective repair mechanism for UV light induced DNA damage
 Clinical features
• Location
– Lower eyelid (50-60%)
– Medial canthus (25-30%)- deeply invasive
– Upperlid
– Lateral canthus

• Origin
– Stratum basale or stratum germinativum of the epidermis
and the outer root sheath of the hair follicle
– Occur only in hair bearing tissue
Nodular basal cell CA
– Firm, raised, pearly nodule
– Telangiectatic vessels
– Central ulceration
– Histology-
• nests of basal cells originate from basal layer
• Peripheral palisading
• Nest of atypical cells break through to the surface
epithelium
Morpheaform type
– less common
– Aggressive
– Firm and slightly elevated
– Margins may be indeterminate
– Chronic inflammation of lid margin with madarosis
– May be mistaken for blepharitis
– Histology :
• no peripheral palisading
• Thin chords and strands of tumour cells in fibrotic stroma
 Histology

• Tumour cells are characterized by

– Bland, monomorphus nuclei
– Higher nuclear : cytoplasmic ratio
– Form cohesive islands with nuclear pallisading of
peripheral cell layer

• Variety of histologic patterns

– keratotic(hair follicle)/ squamous/ sebeceous/ adenoid and
eccrine differentiation
 From pathology class

• Low power ( blue lesion, beneath the epithelial plane)

– Lower lid lesion
– Irregular chords and islands of basophilic cells
– Keratinized cells
– Green stain- margin of the sample
– Irregular infiltrative lesion up to the margin
– Stroma
• Desmoplastic reaction ( host tissue reaction)
• Tumour invading the stroma
• Fibrosis- fibroblasts and necrotic tissue
• Inflammation-infiltration of lymphocytes
Low power
Low power
High power
– Chords of irregularly proliferating basal cells
– Abundant mitoses
– Highly invasive
• High dense fibrous stroma
• Increase desmoplastic reaction
• Leads to tumour clefting
– Peripheral palisading (peripheral nuclei
arrangement perpendicular to the margin of the
tumour lobule
• This fibrosis leads to tumour clefting during
fixation/preparation- artifactual (but represent highly fibrous
nature)
• DDs
– Sebeceous cell CA
• sebeceous differentiation
• No tumour clefting
– Squamous cell CA
• Superficial keratinization
• upper layers are not basaloid, if mixed presence of cleft
makes the diagnosis of basal cell CA
High power
Cystic spaces with central necrosis
Management
– Biopsy and histological confirmation
– Surgical resection + eyelid reconstruction
– Radiotherapy
– Other treatment modalities
• Incisional biopsy
– To confirm
– Area should be photographed

• Excisional biopsy
– When lesions are small
– Do not involve eyelid margin
– Eyelid margin lesions are centrally located away from lateral canthus
and puncum
– In incomplete removal, borders should be marked
– Should be oriented vertically to minimize vertical traction
Surgical resection – Intraoperative histologic
confirmation
– Treatment of choice • Frozen section
– Surgeon excise tumour with
– Recurrent rate is lower 1-2 mm margins, oriented on
– BCC involving medial canthal a drawing
region • Mohs micrographic surgery
• Need removal of lacrimal – for recurrent,
drainage system – deeply infiltrated
• Reconstruction should not – Morpheaform type/ SCC
be done until it is confirmed – Tumour in medial canthal
to be tumour free region
– Ensures complete cancer
– Orbital invasion removal with preserving
• Orbital exentertion maximal healthy tissues
• Mortality rate is 3% – Difficult to identify the
tumour margins when the
tumour has invaded the
orbital fat
 Reconstruction of the eyelid

• Should be done expeditiously

• If immediate reconstruction is not possible, the cornea should
be protected by patching/ temporary suturing
• Cryotherapy • Radiation therapy
– Reserved for patients who are poor
candidates for surgery – Considered only as a palliative
– Disadvantages treatment
• Higher recurrence – Disadvantages
• Cannot evaluate histologic margins • Higher recurrence
• Depigmentation and tissue atrophy- • Difficult to assess histologic margins
not good for cosmesis
• Difficult to detect recurrence
– Avoided in • Recurrences occur long time after
• Canthal lesions treatment
• Recurrent lesions • Surgical treatment of recurrences is
• Lesions >1 cm difficult due to poor healing
• Morpheaform lesion
– Avoided in
• Oral Vismodegib (block hedgehog • Avoided in canthal lesions
signalling pathway)
– Complications
– For advanced orbital infiltrative BCC • Cicatricial eyelid changes
not amenable for surgical resection • NLD scarring and obstruction
• Keratitis sicca
– Need to monitor for SCC at involved
• Radiation induced malignancy
sites
• Radition induced globe injury
Conjunctival melanocytic lesion
 Histology
• Low power
– Epithelium covered hyperpigmented polypoidal lesion
– Conjunctival epithelium- non keratinized stratified squamous cells with
Goblet cells

• High power
– Cohesive collection of epitheliod cells -Ovoid
– Cytoplasm- Brown pigmented-melanocytic lesion (normal cells pink in
colour)
– Bleeched sample to see features of nucei/mitoses
– Nuclei
• Pleomorphism/ hyperchromatism/ mitoses
– Some show apoptotic bodies
• Shrunken cells
• Pyknotic nuclei ( round ball like)
Low power- raw sample
Conjunctival melanoma- high power (from web source)
 Differential diagnosis

• Conjunctival nevus
• Conjunctival melanoma or secondary
melanocytic deposit

• Why?.... Pigmentation involves the stroma as

well
– Congenital, benign and primary acquired
melanosis occurs in conjunctival epithelium and
they are flat lesions
• Is it a primary or secondary deposit
– In secondary
• no junctional cellular reaction
• May have necrotic background

• IHC on a bleached sample

– S-100
• most specific for melanocytic differentiation
– HMB45
• common marker to confirm melanoma
• But activated naevi may confuse the diagnosis
– Melan-A
• both naevi and melanoma
– Ki67- proliferative marker
• Melanoma (+)
• Naevi (this should be 0)
• More differentiating power
Conjunctival pigmentary lesions
 Conjunctival melanoma
• <1% ocular malignancies
• Rare among black and Asians
• Overall mortality 25%
• Better prognosis than cutaneous melanoma
Pathogenesis
– Arise from
• PAM-70%
• Nevi-20%
• De novo 10%
• Clinical findings
– Most commonly on bulbar conjunctiva/ at limbus
– 25% - amelanotic
– Recurrent melanoma mostly amelanotic
– Grow in a nodular fasion and can invade the globe
Poor prognostic factors

• Location in the palpebral conjunctiva, curuncle or fornix

• Deep tissue invasion
• Thickness >1.8 mm
• Involvement of the eyelid margin
• Pagetoid or full thickness intraepithelial spread
• Lymphatic spread
• Mixed cell type
Metastasize to
– Regional LN
– Distal- brain, lung, liver, bone
Management

• Thorough SLE including double eversion or eyelids

• Dilated funduscopy with indirect
• Palpate regional LNs
• Systemic evaluation (chest/ abdomen/ bones..)
• Consider dermatology referral to assess skin melanotic lesion
• Metastatic work up
• Lacalized lesion
– Surgical excision (excisional biopsy)
• Corneal- alcohol corneal epithelialectomy+ beaver blade scraping
• Conjunctiva
– excision with 3-4 mm margin
– Cryotherapy at limbus and excisional margins
• Stromal bed
– Lamellar sclerectomy+ cryo
– Adjuvant topical chemotherapy with MMC
• 0.02% qid for 2 weeks, off cycle 2 weeks ( continue until
resolution)
• Punctal occlusion and steroids to reduce toxic effects

• Large infiltrating lesion

– Exclude mets ( if present chemo with palliative tumour debulking)
– Enucleation/ exenteration +/- radiotherapy ( if no mets)
Management
Sebeceous gland carcinoma
• 1-3% of eyelid malignancies
• Highly malignant and potentially lethal
• Arise from
– Meibomian glands of tarsal plate
– Gland of Zeis associated with eyelashes
– Sebaceous glands of the curuncle, eyebrow, facial skin

• F>M (common after 50 yrs) (75%- women)

• Upper lid: lower lid=2:1
• Multicentric origin (10%)
• Appear yellow (lipid collection)

• Masquerade as benign eyelid disease

– Chalazia/Chronic blepharitis
– Ocular cicatricial phemphigoid
– Superior limbic kerato-conjunctivitis
– Pannus with inclusion conjunctivitis
– BCC /SCC
Spread

– Tumour arise within tarsal plate

– Progress to an intraepidermal growth phase
– Extend over palpebral and bulbar conjunctiva
– Pappilary elevation of tarsal conjunctiva indicates pagetoid
spread
– Intraepithelial growth replace corneal epithelium
– Metastazise to regional LNs (parotid/ submandibular)
– Lacally- nasopharynx/ lacrimal drainage system
– Rarely spread hematogenously

• 1/3 recur, 25% die of metastasis

When to suspect/ warrant biopsy

– Nodule that simulates a chalazion-later causing madarosis

and destruction of meibomian gland orifices
– Solid material from a recurrent chalazion (need special
stains)
– Chronic unilateral blepharitis

 Needs full thickness biopsy with permanent sections ( shave

Bx may reveal only chronic inflamation.
Poor prognostic factors
– Orbital or vascular invasion
– Bilateral involvement of eyelids
– Poorly differentiated or multicentric tumors
– Large size
– Infiltrative pattern
– Pagetoid spread
Microscopic (histologic) description

– Epithelium- stratified squamous

– Subepithelial nesting, comedonecrosis ( larger lobules have
central necrosis) or papillary patterns
– Morphology varies from well differentiated to anaplastic
– Often pagetoid spread ( extending in to overlying epithelium or
carcinoma in situ

– Well differentiated:
• Contain ovoid to sauamous cells with foamy, finely vacuolated
cytoplasm and distinct cell borders
• Better differentiated cells are usually in center of nests, often near
tarsus and meibomian glands
• Lobules lack peripheral palisading
• More pleomorphic, hyperchromatic and atypical than BCC
• Abundant mitoses ( Differentiate from sebeceous hyperplasia)
• Lympho-plasmocytic infiltration
 – Anaplastic:
• Often scant cytoplasm with indistinct vacuoles
• Central necrosis, pagetoid involvement of overlying skin

Vacuolation
 Fat- dissolves in Xylene
 Glycogen- dissolves in alcohol
Normal sebeceous glands
High power
• Treatment options

– Wide surgical excision is mandatory

– Mohs micrographic surgery is advocated
– Can have skip lesions, pagetoid spread and polycentricity

– Map Bx of the conjunctiva- to eliminate the potential of pagetoid spread

• If presents- need adjunctive cryotherapy

– Orbital exenteration for

• Recurrent or large tumours invading through orbital septum

– Sentinal LN Bx for high risk category

• Recurrent lesions
• Extensive involvement of lid and orbit
• (Conj/ cutaneous melanoma with a Breslow thickness > 1mm)
• (Merckel cell CA of the eyelid)

– Sebeaceous CA is relatively radioresistant

Pleomorphic adenoma of
lacrimal gland
• Most common epithelial tumour in lacrimal
gland
• Arise from ducts, secretory elements,
myoepithelial cells
• Common in 4th-5th decade
• M>F
• Symptoms
– Painless
– Slowly progressive proptosis
– Swelling in superolateral eye lid
– > 1 yr duration

• Signs

– Orbital lobe tumours

• Smooth, firm, non tender mass in lacrimal fossa
• Inferonasal dystopia
• Proptosis, ophthalmoplegia, choroidal folds ( in posterior extention)

– Palpebral lobe tumours

• Upper lid swelling, no dystopia
• Visible on inspection
Histology
– Has a fibrous pseudocapsule (well circumscribed)
– Hypo and hypercellular areas
– Comprises a mixture of ductal derived epithelial and fibromyxoid
stroma)
– Well differentiated glandular structures
– Uniform pattern in chords of cells
– No necrotic areas

– Immunohistochemistry
• Keratin (in ductal areas)
• Actin, myosin, fibronectin and S-100 ( in myoepithelial areas)
• High power
– Myxoid appearance of cell cytoplasm
– Ground glass apprearance ( GAGs)
– Basaloid cells arrenged in regular chords
– Ductal structures ( can show metaplasia)
• Epithelial components form nests or tubules lined by 2 layers of
cells
– Outermost layer (myoepithelial cells)
» Blending with stroma
» Myxoid stroma- Contain heterogenous elements( Cartilage and
bone)
– Inner layer
» Epithelial and myoepithelial components derived from
epithelium
Management

• En bloc excision
Complete removal of tumour (with pseudo
capsule,margin of orbital tissue)

• No incisional biopsy/ FNAC- increases tumour

recurence.. Tumour seeding.

• Complete excision- excellent prognosis

• In recurrence higher rate of malignancy (10% per
decade.)
Tumours of palpebral lobe
through anterior (trans-septal) orbitotomy

Orbital lobe tumours.

• Through lateral orbitotomy
• Temporalis is excised
• Bone drilled
• Lateral orbital wall removed
• Tumour excision with a margin
• Repair of lateral orbital wall
Adenoid cystic carcinoma of
lacrimal gland
• Gross morphology
– Tends to be rounded or globular in imaging studies
like pleomorphic adenoma
– But margin of tumour is often irregular and
serrated
– May extend into the medial or posterior orbit
– Bone destruction is seen in 80%
• Five histologic patterns
– Cribriform (Swiss cheese)-commonest (70%)
– Basaloid or solid (worst prognosis)
– Sclerosing
– Tubular with true duct formation
– Comedocarcinoma ( lobules with central necrosis)

• Perineural invasion- thus painful

 Microscopic description

• Low power
– Areas of irregular basaloid growth with cribriform change
– Peripheral areas with normal glandular architecture with
acni
– Multiple pools of mucin impart a swiss-cheese appearance
to the basophilic lobules
– (Perineural invasion, focal tumor necrosis may be seen)
Under high power
• Normal acini
– Lined by regularly arranged basaloid epithelial cells
– Lumens are filled with mucin
– Cellular polarity is present.
• Abnormal acini
– Basaloid ovoid cell clusters
– Mitotic figures
– Abundant Nuclear:cytoplasm ratio
– Loss of aciniform structure/polarity
– Comedonecrosis
– Fibrous desmoplastic stroma

• Tumour cells are relatively uniform and bland cytology.

 Differential diagnosis

• Basaloid variant of adenoid cystic CA

• Basal cell CA infiltrate
• Secondaries from breast CA
Normal glandular areas
 Management
• Incisional biopsy should be performed if the diagnosis is
suspected on clinical grounds
• Orbital exenteration once the diagnosis is confirmed ( should
never be based on frozen section diagnosis)
– +/- en bloc resection of tumour and contiguous bone or
radical orbitectomy including roof and lateral walls

• Alternative
– Globe sparing intra-arterial chemotherapy
Retinoblastoma
• Most common malignant ocular tumour in childhood
• Neuroblastic tumour
• Occurs due to somatic and germline mutation of RB-
tumour suppressor gene located at Q14-Ch13
• M=F
• 60% unilateral (somatic)
• 40% bilateral (germline)
 How do they present?
• Most common –leucocoria
– Strabismus
– Hyphema
– Periocular inflammation
– Proptosis
– Pseudohypopyon
– Nystagmus…..
 Diagnosis
A. It’s mainly a clinical diagnosis
• By identifying the ocular features
• Characteristic calcification
• 03 patterns of growth
• Endophytic (towards vitreous)
• Exophytic
– Grows subretinally
– Exudative RD
– Overlying vessels are large and tortuous
• Diffuse infiltrative
– Mimics pan-uveitis
– Diffuse retinal infiltration without a distinct mass
– pseudohypopyon
B.) Imaging
• MRI orbits and brain (CT is not recommended)
– Confirm diagnosis
– Evaluate extension
• USS- intraocular calcification
C.) FNAB ( in situations where clinical diagnosis
is difficult
• Vitreous sampling ( risk of seeding)
 How do RBs spread?
 Vitreous seeding-CB/Iris/AC

 Through TM-
 Conj. Lymphatics-> preauricular and cervical lymphnodes

 Through invasion of choroid(Hematogenous spread )

 Bone marrow
 Abdominal viscera

 Through optic nerve

 SAS-brain and spinal chord

 Through sclera
 To orbit
 Genetic basis

• RB1-tumour suppressor gene (Ch13-Q14 band)

• Need mutation in both allels

• Somatic (60%)
– Non hereditory
– Mutations occur in a retinal cell
– Unilateral/unifocal

• Germline (40%)
– Mutation in one of the 02 allels
• Inherited by parents (10%)
• Occurs spontaneously (90%)
– Requires a 2nd hit ( Knudson theory)

• If B/L RB- 98% chance of a germline mutation

• Sporadic cases accounts for 95%
 Genetic counseling

• 50% from inheritance/ 90% penetrance= 45%

International Classification for intraocular RB
 Histopathological features

Under low power

– Notice ocular structures
• Iris, ciliary body. Lens (pink)..
– Highly necrotic extensive pink areas
– Notice the detached retina and continuation of tumour
from retina
– Endophytic tumour growth
– Notice ( prognosticate factors)
• vitreous seeding
• Optic nerve head involvement (peripapillary area/ lamina cribrosa
• Choroidal (thickness matters)/ scleral penetration
Under high power
• Ovoid to rounded basophilic cells filled with hyperchromatic
nuclei and fine granular chromatin
• Twice the size of lymphocytes ( looks like lymphocytic
infiltration)
• Abundant mitoses
• Scanty cytoplasm
• Flower petal like arrangements ; “rosettes”( indicates some
degree of differentiation)
– >50% rosettes- well differentiated
– <5% - poorly differentiated
• Flexner wintersteiner rosettes
– Characteristic to RB
– Central lumen lined by refractile structure surrounded by radially
arranged single columnar cells with eosinophilic cytoplasm
• Homer wright rosettes
– Rosettes without retinal differentiation
– Found in other neuroblastic tumours as well
– Center is filled with a tangle of eosinophilic cytoplasmic processes
• Flurettes
– Shows evidence of photoreceptor differentiation
– Clusters of cells composed of rod and cone inner segments attached to
abortive outer segments

In a retinoblastoma, undifferentiated tumour cells outnumber the flurettes

and Flexner wintersteiner resottes
 How to differentiate lymphocytic infiltration from
retinoblastoma?..

IHC
– LCA ( leucocyte common antigen; CD45)
• + in lymphocytes/ - in RB
– Synaptophysin ( neuro-endocrine marker)
• + in RB/ - in lymphocytes
Flexner Wintersteiner rosettes
 High risk histologic features associated with
metastasis

• Optic nerve invasion ( laminar, retrolaminar or cut margin)

• Massive choroidal invasion
– Invasive focus of a tumour with a maximum diameter at least 3mm
– Tumour reaching at least the inner fibers of the sclera
• Extraocular extention
• Extensive tumour necrosis
 Treatment
• Multidisciplinary approach
• Options
– Enucleation
– Chemotherapy
• Intravenous
• Intra-arterial
– Cryotherapy
– Laser
– TTT
– Plaque radiotherapy
– Intravitreal chemotherapy
• For large RB with poor visual prognosis (category E)
– Primary enucleation

• For small RB confined to retina (category A)

– Anterior lesion- cryo
– Posterior lesion- laser (diode laser)

• For B/L RBs/ Spare vision in large tumours ( A/B/C)

– Iry chemoreduction ( varios combinations with carboplatin/
vincristin/ etoposide +/- cyclosporin)
– Secondary consolidation
• Cryo/laser/TTT
• For U/L RBs
– Chemoreduction with intra-arterial melphalan
Orbital lympho-proliferative
disorders
Classification of lymphoproliferative lesions
• Reactive lymphoid hyperplasia ( RLH)
• Atypical lymphoid hyperplasia ( ALH)
• Ocular adnexal lymphoma (OAL)
 Reactive lymphoid hyperplasia

Composed of well differentiated lymphocytes

with occasional plasma cells, macrophages,
eosinophils and follicels with germinal centers
 Atypical lymphoid hyperplasia

• Diffuse lymphoid proliferation

• Generally with out reactive germinal centres
• Composed of admixture of
• Small mature appearing lymphocytes
• Larger lymphoid cells of unknown maturity
 Lymphomas of the orbit
•Accounts for more than 20% of all orbital
tumors
•Most orbital lympho-proliferative lesions are
non– Hodgkin lymphomas
•Most are derived from B cells ( T cells are rare
and lethal)
• 90% are monoclonal
 Classification
• REAL classification ( Revised European – American
Lymphoma)
• 4 most common types of orbital lymphomas
1. MALT – Mucosa Associated Lymphoid Tissue
lymphomas – commonest
2. Chronic lymphocytic lymphoma ( CLL) – low grade
3. Follicular center lymphoma – low grade
4. High grade lymphomas
– Large cell lymphoma
– Lymphoblastic lymphoma
– Burkitt lymphoma
 Clinical features
• Painless , gradual onset , progressive proptosis
• Can be bilateral (17%) – if so suspect fro systemic
disease
• Usually located anteriorly in the orbit (50% in lacrimal fossa)or
conjunctiva
• Risk for systemic disease
• Lowest – conjunctiva
• Greater – orbit
• Highest – lids
• Salmon patch appearencce
• Mold to surrounding orbital structures
 Biopsy
• Open biopsy
• For retrieval of adequate tissue specieman
• Diagnosis based in lesion’s
• Morphologic – light microscopic examination
• Immunologic
• Cytogenetic
• Molecular properties
 Histology
• Low power
– Fibrous stroma
– Basophilic cells- diffuse infiltrate
– Cells are separated and scattered; not cohesive
– Round cells with hyperchromatic nuclei
– Features in favour of lymphocytic infitration
• Lymphocytes are normally seen in the eye at two
sites
– Conjunctiva
– Few in lacrimal gland
– Any other site is abnormal
 Is it a benign or malignant infiltration?
Benign malignant

Plasma cell differentiation No plasma cell differentiation

polymorphism monomorphic

Reactive follicles with pale centres ?no or less reactive follicles

Pleomorphism of nuclei

Mitoses- high in high grade lymphoma

Less in low grade
Plasma cells
 IHC in diagnosis
• Lymphocyte cluster differentiation
– T cells- (CD <10)– CD 3/5
– B cells – CD>10 – CD20
– Common is CD10
– (Leucocyte common antigen- CD45)
• Reactive lymphocytic infiltration
– IHC + for CD3 and CD20 ( mixed)
IHC with a proliferative marker Ki-67

– In a T cell population if high Ki67- T cell Lymphoma

– In a B cell population if high Ki67
• <60%- reactive
• >60% - B cell lymphoma
• Thus requires B cell maturity marker- CD 40
– If maturity is high- reactive
– If maturity is low- neoplastic
Choroidal melanoma
 How to differentiate
• Light microscopy
– Can not differentiate reactive hyperplasia from malignant
• Immunologic identification
– Malignant lymphomas represent clonal expansions of
abnormal precursor cells
– B or T cells – identification of cell surface markers
– Monoclonal (malignant) or polyclonal
– By specific monoclonal antibodies directed against surface light
chain immunoglobulins ( k or l)
• Molecular analysis
– Precise identification of tumor clonality by extracting ,
amplifying and hybridizing tumor DNA with radioactively labled
nucleotide probes
– DNA genetics – monoclonal ( 90%) and polyclonal (10%)
 Management

Oncologist involvement
Investigations – depending on the histological type
– CBC
– Liver spleen USS
– CXR
– Serum immunoprotein electrophoresis
– CT thorax and abdomen – mediastinal and retroperitoneal nodal involvement
– Bone marrow biopsy
• Treatment
• Radiotherapy – for localized disease – mainstay
• 2000 – 3000 cGY
• Surgical cure – can not achieve due to infiltrative nature
• Chemotherapy
Choroidal melanoma
 HISTOLOGY
Low power
– General appearance
• Darkly stained discoid lesion of choroid
• Visible scleral rim
• Overlying thin sheet like retina with underlying SRF
High power
– fascicular arrangement of spindle shaped cells
– Nuclei are elongated/ cigar shaped
– Features of dysplasia
• Condensed hyperchromatic appearance
• Mitotic figures
– Mitotic count is very low comparatively
– Detection of even a single mitotic figure is significant
 Modified Callendar Classification
• Spindle cell nevus- spindle cell A ( cigar shaped,
no nucleolus)
• Spindle cell melanoma- spindle cell B (larger, oval
shaped, prominent nucleolus)
• Epitheliod melanoma ( large, oval or round,
prominent nucleolus,polymorphsm)
– worst prognosis
• Mixed- epitheliod/spindle cell B
 Clinical risk factors of melanoma related
mortality
• Large tumour size
• CB extension
• Extra scleral extension
• Older age
• Faster tumour growth
• Tumour regrowth after globe conservative
therapy
 Histologic and molecular features affecting survival

Histological
• Tumour cell type
– Epithelioid- worse prognosis
– Mixed- intermediate
– Spindle B- best prognosis
• The mean of the 10 largest melanoma cell nucleoli
• Intrinsic tumour extravascular matrix pattern ( closed loops and
networks- increase risk of mets)
• High mitotic or cell proliferative indexMicrovascular density
• Large number of tumour infiltrating lymphocytes and macrophages
Molecular
– Monosomy 03
– BAP-1 mutation
 Clinical evaluation

• History
• Slit lamp+ gonioscopy
• Post. segment with indirect oph.
• Fundal photograph
• B- scan
• OCT
• FAF
• Evaluation for metastasis
– Liver imaging
– LFT
– Chest X –Ray
– If any of above are abnormal
• Triphasic liver CT/ MRI abdomen
• If a metastatic lesion is found- biopsy
 Treatment

Options
– Enucleation
– Conservative
• Ionizing radiation
• Adioactive plaque brachytherapy
• External beam radiation
• Charged particle therapy
• Steriotactic radiation therapy
• PDT
• TTT
• Local excision of tumour
Choice of treatment depend on 04 factors
– Size, location and extent of tumour
– Vision status of affected eye and fellow eye
– Age and general health
– Patient and physician preference
• Enucleation (COMS large tumour trial; Iry enucleation Vs pre-
enucleation EBR))
– Large tumour size
– Optic disc invasion
– Extensive involvement of the CB or angle
– Irreversible loss of useful vision
– Poor motivation to keep the eye
• Brachytherapy (COMS medium size tumour trial; enucleation Vs I125
Brachytherapy)
– Small to medium size tumours (< 20mm base diameter and up to
10mm thickness)
– Presence of useful vision.
• Charge particle radiation
– When brachytherapy is unsuitable ( large tumour size, posterior
location)
 Metastatic disease

• Surgical resection of metastatic nodules

• Hepatic intra arterial chemotherapy/ chemoembolization
• Systemic chemotherapy
• immunotherapy