08 Retinal Oncology (Malignant Tumors)

What is the most common primary malignant intraocular tumor in adults?

malignant uveal melanoma

What is the appearance of a malignant uveal melanoma?

-Unilateral

-Solitary

-Elevated

-Dark brown or gray with orange pigment on surface

-Variably pigmented

-Dome-shaped mass

-Associated RD

-Low internal reflectivity on A-scan

What are symptoms of malignant uveal melanomas? (4)

-May be asymptomatic

-Blurred vision (if macula involved)

-Blind spot (where lesion is)

-Flashes (if associated RD)

How does a malignant uveal melanoma evolve?

-Not known to be hereditary

-Originates from pigmented cells in the uvea (iris, choroid, ciliary body)

-May transform from a choroidal nevus

-Originates in 5th or 6th decade of life

-Enlarges with time

What are complications of malignant uveal melanomas? (2)

-Loss of vision

-Metastatic death

Metastasis occurs in about ___% of malignant uveal melanomas.

50%

Where do malignant uveal melanomas metastasize to? (4)

-Liver (90%)

-Lungs

-Bone

-Skin

What are treatment options for malignant uveal melanomas? (3)

-Surgical resection

-Chemoembolization

-Clinical trials

What is the risk of malignant uveal melanoma metastasis associated with? (2)

-Tumor size

-Molecular markers (Monosomy 3)

What can be done to look at the genetic makeup of the tumor to determine molecular markers?

fine needle aspiration biopsy

What are risk factors for developing malignant uveal melanomas? (3)

-Light skin

-Blue or green eyes

-UV radiation exposure

What are differential diagnoses for malignant uveal melanomas? (8)

-Choroidal Nevus*

-Choroidal Hemangioma

-Choroidal Metastasis

-Choroidal Osteoma

-CHRPE

-Choroidal Detachment

-Hemorrhagic Retinal Detachment

-Retinoschisis with hemorrhage

How can we distinguish between a small malignant melanoma and a benign choroidal nevus?

To Find Small Ocular Melanoma Using Helpful Hints Daily:

-Thickness over 2mm

-subretinal Fluid

-Symptoms

-Orange pigment

-tumor Margin near the optic disc

-Ultrasonigraphic Hollowness

-lack of surrounding Halo

-lack of chronic Drusen

*If 3 or more characteristics are present, think malignant melanoma and refer out!

What are the priorities of treating malignant tumors of the eye? (3)

-Save a life

-Save the eye

-Save the vision

How can we "save a life" when treating a malignant uveal melanoma? (5)

-Monitor suspicious lesions for transformation carefully

-Educate patients on their condition

-Treat small melanomas early

-Refer patients early to ocular oncologist

-Enucleation

How can we "save the eye" when treating a malignant uveal melanoma? (2)

Radiation:

-Iodine-124 plaque brachythreapy (invasive)

-Gamma knife radiotherapy (non-invasive)

How can we "save the vision" when treating a malignant uveal melanoma? (2)

-Silicone oil in the vitreous during plaque brachytherapy can attenuate the radiation that occurs to the healthy parts of the eye

-Treatment with virus nanoparticles are being studied

What were the results of the COMS Trials on medium sized ocular melanomas?

no clinically significant difference between I-125 brachytherapy vs. enucleation for up to 12 years after treatment of medium tumors

What were the results of the COMS Trials on large sized ocular melanomas?

no significant difference between pre-enucleation radiation vs. enucleation alone for treatment of large tumors

What is the most common intraocular malignancy in infants and children?

retinoblastoma

What is retinoblastoma?

a congenital malignant intraocular tumor derived from neurosensory elements of the evolving fetal retina

What is the appearance of retinoblastoma?

-Bilateral

-Leukocoria

-Strabismus

-Cellulitis-like appearance

-Flat-diffuse or dome-shaped tumor

-White pink

-Associated RD

-Cottage cheese-like calcifications

-High reflectivity on ultrasound

What are the 3 primary clinical patterns of retinoblastoma growth?

1. Endophytic: tumors grows from the retina into the vitreous cavity; may cause vitreous seeding (parts of tumor breaks off and float in vitreous)

2. Exophytic: tumors expands into subretinal space (out of globe)

3. Diffuse Infiltrating: do not have a discrete mass, rather infiltrates throughout the retina

What are symptoms of retinoblastoma?

no pain or complaints

What is the average age of diagnosis for retinoblastoma?

18 months

almost all are diagnosed by age 5

True or False: Retinoblastoma can be inherited.

True, and genetic mutation indicates a more aggressive form

Inherited retinoblastoma tends to occur _____ in life and is more likely to be _____.

Sporadic retinoblastoma tends to occur _____ in life and is more likely to be ______.

earlier (6 months), bilateral

later (2-3 years), unilateral

How does retinoblastoma evolve?

-Can be sporadic in occurrence

-May spread into orbit

-Will eventually metastasize

What are complications of retinoblastoma? (2)

-Blindness

-Metastatic death (100% without treatment)

What are differential diagnoses for retinoblastoma? (9)

-Cataracts

-Coats disease

-Persistent Fetal Vasculature

-Retinopathy of Prematurity

-Retinal Detachment

-Choroidal Coloboma

-Vitreous Hemorrhage

-Myelinated NFL

-Astrocytic Hamartoma

How can we "save a life" when treating retinoblastoma?

enucleation (especially for advanced tumors with little vision to salvage)

How can we "save the eye" when treating retinoblastoma? (3)

-Intraarterial or intravitreal chemotherapy in conjunction with focal consolidation therapy (to localize chemotherapy and avoid systemic symptoms)

-Systemic chemotherapy (if subclinical metastasis)

-External beam radiation (for recurrent tumors)

What is the follow-up routine for retinoblastoma?

-After eye salvaging treatment: frequent follow-up required to monitor for recurrence

-For hereditary retinoblastoma: long-term follow-up with systemic oncologists

What is retinocytoma?

rare and relatively benign retinal tumor that can convert into retinoblastoma

What is the appearance of retinocytoma?

-Leukocoria

-Strabismus

-Translucent retinal mass

-Associated retinal calcification

-Alternation of surrounding RPE

-Well-defined margins

-Closely resembles a successfully treated retinoblastoma

What are symptoms of retinocytoma?

blurred vision (if macula involved)

What is the inheritance pattern of retinocytoma?

autosomal dominant

What are the demographics of retinocytoma?

young Caucasian patients

What is the risk of a retinocytoma transforming into a retinoblastoma?

4%

What are differential diagnoses for retinocytoma? (3)

-Retinoblastoma

-Toxoplasmosis

-Trauma

How can we differentiate between retinocytoma and retinoblastoma?

Use FA to distinguish; retinoblastoma is highly vascularized.

How is retinocytoma managed if we are uncertain of the diagnosis (suspecting retinoblastoma)?

referral to retinal specialist

How is retinocytoma managed if it is confirmed to be a retinocytoma (and not retinoblastoma)? (4)

-Annual examination

-Photodocumentation

-Ultrasound to monitor size/depth

-FA for any vascularization

What is the most common adult intraocular malignancy (metastasis occurs TO the eye)?

metastatic uveal carcinoma

What is the appearance of a metastatic uveal carcinoma?

-Unilateral or Bilateral

-Subretinal mass

-Yellow (96%), Orange (3%), or Brown (3%)

-Usually posterior to equator

-Unifocal or multifocal

-Associated serous RD possible

-Moderate to high internal reflectivity with ultrasound

What are symptoms of metastatic uveal carcinoma? (4)

-Asymptomatic

-Blurred vision (if macula involved)

-Flashes/floaters (if RD)

-Eye pain

The primary tumor that metastatic uveal carcinoma derives from is most often from the _____ in women and from the _____ in men.

breast, lungs

True or False: Choroidal metastases tend to become apparent LATE in the course of malignancy.

True, the disease if already advanced and probably metastasized to other parts of the body.

In 34% of cases, the choroidal metastasis precedes the diagnosis of _____.

systemic cancer

True or False: Incidence of metastatic uveal carcinoma will likely decrease.

False, will likely increase due to longer survival rates of cancer patients.

What is a complication of metastatic uveal carcinoma?

metastatic death

What are differential diagnoses for metastatic uveal carcinoma? (4)

-Choroidal melanoma

-Hemangioma

-Granuloma

-Osteoma

How is metastatic uveal carcinoma managed?

immediate referral to ocular oncology

What is the most common malignant orbital tumor in childhood?

rhabdomyosarcoma

What is rhabdomyosarcoma?

a rare tumor of the soft tissue

What are signs of rhabdomyosarcoma?

-Rapid and progressive unilateral proptosis

-Eyelid edema

-Ptosis

-EOM restriction

-CT shows irregular, yet well-defined soft tissue mass

What are symptoms of rhabdomyosarcoma if the sinuses are involved? (3)

-Headache

-Sinusitis

-Nosebleeds

90% of rhabdomyosarcomas occur before age ___, with a median onset age of ___ years old.

16, 5-7

True or False: Rhabdomyosarcoma is more common in males than females.

True

What are rhabdomyosarcomas associated with?

coexisting medulloepitheliomas

What are differential diagnoses for rhabdomyosarcoma? (4)

-Orbital cellulitis

-Metastatic neuroblastoma

-Lymphangioma

-Ruptured dermoid cyst

How is rhabdomyosarcoma managed?

-Refer for immediate incisional biopsy

-Radiation and chemotherapy if confirmed to be rhabdomyosarcoma

-Oncology referral for complete systemic work-up

What is a metastatic lesion of the optic nerve head?

metastasis of another tumor TO the optic nerve head

What is the appearance of a metastatic lesion of the optic nerve head?

-Chalky white to creamy yellow in color

-Infiltrate with sharply circumscribed border

-Scalloped nodules

-Associated hemes possible

-Optic nerve edema

-Associated choroidal metastasis possible

What are symptoms of a metastatic lesion of the optic nerve head?

loss of vision

What do metastatic lesions of the optic nerve head typically occur secondary to?

lung or breast carcinoma

What is the mean survival time after metastasis to the optic nerve head?

10 months

What are differential diagnoses for metastatic lesions of the optic nerve head? (5)

-Papilledema

-Papillitis

-Optic disc granuloma

-Optic nerve drusen

-Retinal capillary hemangioma

How are metastatic lesions of the optic nerve head managed? (2)

-Immediate referral to ocular oncology

-Radiation and chemotherapy

What are lymphoproliferative tumors?

intraocular infiltration of malignant lymphoid cells, associated with systemic lymphoma

What is the appearance of vitreoretinal lymphoproliferative tumors? (5)

-White diffuse retinal infiltrates

-Associated vitritis

-Associated anterior uveitis

-KP's

-Optic neuropahty

What is the appearance of uveal lymphoproliferative tumors?

-Creamy white-yellow

-Single or multiple

-At the level of uvea

What are symptoms of lymphoproliferative tumors?

-Asymptomatic

-Blurred vision

What are complications of lymphoproliferative tumors?

metastatic death

What are differential diagnoses for lymphoproliferative tumors? (2)

-Posterior uveitis

-White dot syndromes

How are lymphoproliferative tumors managed?

Immediate referral to ocular oncology and systemic oncoology

What is the prognosis of lymphoproliferative tumors?

poor prognosis

average life expectancy is 2 years after diagnosis

What is radiation retinopathy?

a predictable complication following exposure to any source of radiation, occurring after treatment for nasopharyngeal, paranasal sinus, or orbital tumors where there is limited protection for the eye

What is the appearance of radiation retinopathy?

-Retinal microaneurysms

-Retinal hemorrhages

-Retinal telangiectatic vessels

-Retinal hard exudates

-Macular edema

-Cotton-wool spots

-Retinal neovascularization

-Vitreous hemorrhage

-Tractional RD

-Optic disc edema

-Neovascularization of the iris

-Neovascularization of the angle or neovascular glaucoma

-Cataract

(looks like diabetic retinopathy!)

What are symptoms of radiation retinopathy? (3)

-Asymptomatic

-Decreased vision

-Floaters

Radiation retinopathy can develop anywhere from ___ to ___ following radiation.

Most commonly occurs between ___ and ___ following radiation.

1 month to 15 years

6 months and 3 years

What are complications of radiation retinopathy?

tractional RD

What are differential diagnoses for radiation retinopathy? (6)

-Diabetic retinopathy

-Branch retinal vein occlusion (BRVO)

-Central retinal vein occlusion (CRVO)

-Hypertensive retinopathy

-Coats' disease

-Perifoveal telangiectasia

How is radiation retinopathy managed? (4)

-Anti-VEGF

-Focal/Grid laser

-Panretinal photocoagulation

-Vitrectomy

(similar to treatment for diabetic retinopathy!)

What is radiation optic neuropathy?

optic neuropathy that occurs following radiation to the head

What is the appearance of radiation optic neuropathy?

-Normal, pale, or edematous disc

-Pallor develops after 4-6 weeks

-(+)APD

What are symptoms of radiation optic neuropathy?

sudden and irreversible unilateral or bilateral vision loss

Radiation optic neuropathy most commonly manifests within ____ following treatment.

8-16 months

What are risk factors for developing radiation optic neuropathy? (3)

-Radiation dose

-Systemic chemotherapy

-Diabetes

What are differential diagnoses for radiation optic neuropathy?

-Ischemic optic neuropathy (ION)

-Glaucoma

How is radiation optic neuropathy managed?

monitor

(no treatment available)