Ocular Pathology Case
Kari Eisley, M.D.
PGY3
Pathological images © Charleen T. Chu, 2010
Clinical History
• 66 yo white female
• Presents to ED with right eye redness,
drainage and decreased vision x 2 weeks
• Has a history of mental retardation
• Eye enucleated (PHS10-11472)
Mass in Anterior Chamber
Extrascleral
Mass
Cornea
Pathological images © Charleen T. Chu, 2010
Pathological images © Charleen T. Chu, 2010
Intraocular Mass
under
transillumination
Pathological images © Charleen T. Chu, 2010
Extrascleral
extension
Intraocular
tumor
Subretinal
Gel
Dislocated
Retina
Detachment
lens
Pathological images © Charleen T. Chu, 2010
Under transillumination
Pathological images © Charleen T. Chu, 2010
Ciliary Body Tumor
Sclera
Extrascleral
extension
Pathological images © Charleen T. Chu, 2010
Dislocated Lens
Anterior Subcapsular
Cataract
Detached
Retina
with
Subretinal
Gel
Tumor
Posterior Polar Cataract
Pathological images © Charleen T. Chu, 2010
Tumor Invasion of Iris
Sclera
Pathological images © Charleen T. Chu, 2010
Lens
Cornea
Tumor extension along
posterior surface of cornea
Pathological images © Charleen T. Chu, 2010
Pathological images © Charleen T. Chu, 2010
Rubeosis Iridis of fine thin-walled vessels barely larger than the RBCs inside
Pathological images © Charleen T. Chu, 2010
Tumor behind the Cornea
Cornea Neovascularization
Pathological images © Charleen T. Chu, 2010
Pathological images © Charleen T. Chu, 2010
Immunostain for Ki-67 Proliferation Antigen
(Tumor Nuclei are staining red)
Pathological images © Charleen T. Chu, 2010
Background staining of macrophage cytoplasm for Ki-67 stain (due to
unquenched macrophage peroxidases) as opposed to prior slide where the
nuclei are staining.
Pathological images © Charleen T. Chu, 2010
Tumor Invasion of Subconjunctival Tissue
Immunohistochemical stain for the melanocyte marker Melan A
Pathological images © Charleen T. Chu, 2010
Melan A Melanocyte Immunostain
Pathological images © Charleen T. Chu, 2010
Immunohistochemical Stain HMB-45
Tumor cells
with positive
HMB-45
Melanophages
Pathological images © Charleen T. Chu, 2010
Uveal Melanoma
• Incidence: 6 per million per year in adult
Caucasians
• Most common primary intraocular malignancy in
adults
• Peak incidence: 55 years old
• 94% arise in the choroid, 3% arise on ciliary
body, 3% arise in iris
• Can present with blurred vision, visual field
defect, photopsia, or metamorphopsia (but most
often are asymptomatic)
Risk Factors
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Uveal nevus
Congenital ocular melanocytosis
Dysplastic nevus syndrome
Family history of uveal melanoma
Xeroderma pigmentosa
97.8% of uveal melanomas are in whites
Signs of Ciliary Body Melanoma on
Ocular Exam
• Sentinel Vessel (dilated episcleral vessel)
• Low intraocular pressure (>5mmHg difference between
eyes)
• High intraocular pressure from pigment dispersion,
melanin-laden macrophages (melanomalytic glaucoma),
tumor cells, rubeosis iridis, angle closure
• Darkly pigmented mass posterior to the pupil
– usually are solid but can be cystic
• Can extend around the circumference of the ciliary body;
known as ring melanomas
• Unilateral Cataract
Differential Diagnosis
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Choroidal Nevus
Conjunctival Melanoma
Primary Acquired Melanosis (PAM)
Melanocytoma
Juvenile Xanthogranuloma
Iris Leiomyoma
Medulloepithelioma (Diktyoma)
Sarcoid nodules (Granuloma)
Adenocarcinoma
Fuchs adenoma (senile hyperplasia of the ciliary body)
Lymphoid Tumor
Iridociliary epithelial cysts
Other Metastatic Tumor
Classification of Uveal Melanoma
• Spindle Cell Nevus (benign)
• Spindle Cell Melanoma
– Spindle A (stripe down nucleus)
– Spindle B (granular chromatin, larger nucleous)
• Epithelioid Melanoma
– Abundant eiosinophilic cytoplasm, enlarged oval
nuclei with prominent nucleolus, cells lack
cohesiveness
• Mixed-Cell Type (Spindle & Epithelioid)
Methods of Spread/Metastasis
• Distant Spread: Hematogenously
– most commonly to liver
– Also to lung, bone, skin and CNS
• Extrascleral extension:
– through aqueous channels, ciliary arteries, vortex
veins, ciliary nerves, and the optic nerve
– can metastasize locally into the orbit and conjunctiva
– Axenfeld’s nerve loops (normal posterior cilliary nerve
loops visible in the sclera) can be pigmented and
confused with extrascleral extension of melanoma
• Remember – the eye has NO lymph vessels so
no lymphatic spread!!
Prognosis
• Mortality of Ciliary Body Melanoma is 30-50%
within 10 years from diagnosis
• Ciliary Body Melanoma has a worse prognosis
than posterior choroidal melanomas, likely due
to delayed diagnosis
• Spindle Cell – Best
• Epithelioid – Worst
• Mixed-cell Type – Intermediate
• With Metastatic disease : < 6 months
Work-Up
• A-Scan and B-Scan
– In tumors more than 3 mm thick, ultrasound has a diagnostic
accuracy of over 95%
– Ultrasound features
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Low-to-medium reflectivity
Excavation of underlying uveal tissue
Shadowing of subjacent soft tissues
Internal vascularity
An acoustic quiet zone at the base of the tumor (acoustic hollowing)
• Ultrasound biomicroscopy (UBM)
• Consider CT orbits for extraocular extension and to help
differentiate between detachment and a solid tumor
Metastatic Work-Up
• Importance:
– To determine medical risk of surgery
– If metastatic disease is present, enucleation is
inappropriate unless the eye is painful
• Thorough physical, especially to hepatic
abdominal region & skin/subcutaneous
tissues
• LFTs, CT/Ultrasound of liver
• Chest X-Ray
Conjunctival Melanoma vs Ciliary
Body Melanoma
• Clinical exam of conjunctival melanoma
– Known history of PAM (esp with atypia) or a nevus
– Pigmented area becomes anchored to underlying
sclera
– No intraocular extension evident
• Pathologically
– No extension through sclera to intraocular tissue
• Can consider radiologic testing if necessary
Ciliary Body Melanoma Treatment
• Many factors considered in treatment
approach:
– Visual acuity of the affected eye
– visual acuity of the contralateral eye
– intraocular pressure
– ocular structures involved
– size of the tumor
– age and general health of the patient
– presence of metastases
Ciliary Body Melanoma Treatment
1. Enucleation has been the preferred treatment for advanced and
complicated tumors, especially when other treatment has failed
2. External beam irradiation with either protons or helium ions is a frequently
used alternative method to treat medium-size tumors (<10 mm in height and
15 mm in diameter).
– Complications include cataract, dry eyes, radiation retinopathy, and rubeosis
iridis
3. Plaque brachytherapy is a widely accepted alternative to enucleation for
medium-size posterior uveal melanomas
– Local recurrence rate of about 12%
– Can still get radiation retinopathy but less frequently than external beam
4. Block excision, or sclerouvectomy, is an alternative treatment method for
ciliary body melanomas covering less than 4 clock hours of the
circumference.
5. If there is extensive orbital extension, consider orbital exenteration
• Overall, remains controversial
• adjuvant systemic treatment is not currently advocated without metastases
Metastatic Ciliary Body Melanoma
Treatment
• Systemic chemotherapy is the primary
treatment
• Enucleation is only offered as palliative
treatment if the eye is painful