Retinal Tumors and RPE Abnormalities

• Most lesions are asymptomatic, patients present for routine eye care
• Macular lesions are uncommon, vision is affected
• Symptoms include metamorphopsia, scotoma, and loss of vision

Cellular Changes

• Atrophy is missing cells
• Hypertrophy is increased cell size, increased pigment granules and pigmented granule increases
• Hyperplasia: normal cell size, cell proliferation occurs with too many cells present
• Migration is the movement of cells from one place to another
• Metaplasia is a change of one cell type to another cell type
• Hamartoma is exaggerated hypertrophy and hyperplasia of cells/tissue in a normal location
• Choristoma is excessive cells in a location that is not supposed to be there
• Increased pigmented cells in the retina are hamartoma

Carcinoma

• Accumulation of cancerous epithelial cells

Lesion Appearance

• Dictated by cellular appearance
• Examine features of patient and examination
• Ocular and medical history is important
• If a parent especially a father had tumor in eye, make a note
• Examination techniques are important to monitor lesions that are followed and/or referred out
• Recognition of clinical features differentiates benign from malignant RPE change
• Initiate management as appropriate
• Malignant lesion misdiagnosis can result in patient death
• Differentiate from choroid lesions that can be dangerous
• The choroid has the most malignant lesions
• Choroid lesions like melanoma can be life-threatening
• OCT, US, FAF, FA can be used

Congenital Hypertrophy of the RPE (CHRPE)

• Benign and asymptomatic lesions found in 1.2% of the population
• Association to systemic diseases or other ocular diseases
• No association to systemic disease
• Unilateral, singular, round, flat, heavily pigmented lesions (light brown or black sometimes) in the mid-peripheral fundus with sharply demarcated edges
• Malignant lesions are elevated; benign are flat
• Over time, CHRPE can change in size
• Rare if the time is too long, but it can happen
• CHRPE does not change in size most of the time
• Minimum size in typical CHRPE is ½-1 disc diameter, but goes up to 14 disc diameter
• Typical CHRPE is big round plate, big lesions

CHRPE Components

• Lacunae are openings within and missing spots
• Marginal halo
• Overlying retinal vasculature abnormalities
• Underlying CM and overlying photoreceptors
• Photoreceptors are missing above the RPE
• Thickened Underlying Bruch's membrane and photoreceptor layer degeneration occurs w/ increasing age

CHRPE Histopathology

• RPE cells are 1.5 to 2.0 times larger than normal in height, maintaining monolayer arrangement (hypertrophy)
• Within these large cells, there are increased number and size of pigment granules
• Potential for malignant transformation is rare

CHRPE & Filters

• Color CHRPE, Red-free, Green- free
• Red-free: green 540 nanometer:
• Green penetrates more and shows more of the choroid rather than the green
• Green-free: red 600-620 nanometers
• Shows more retina & is sharper
• Retinal lesions are seen w/ both filters*
• Using the green filter, lesion disappears which means the lesion is in the choroid

CHRPE Signs and Diagnosis

• Choroidal nevus
• Red-free (green filter)
• Green-free (Red filter)
• VA: Does not affect vision unless it hits the macula
• VF: Absolute scotoma can be created in that area
• Red/green separation: will see on both red free and green free
• First white line is the RPE & the photoreceptors line is the second white line
• RPE is brighter/hyper, line of the photoreceptors disappears
• Outer retina layers can be minimized sometimes
• Inner retina has a dip due to inner retina layer concavity
• More shadow looking in the choroid area is thickening of the Bruch's membrane
• OCT Findings: Hyperreflectance of the RPE, missing photoreceptors, shadowing in the choroid, and inner retina concavity
• Hypofluorescence

CHRPE Differences

• Lacunae (looks white)
• Always rule out the choroidal ones
• Choroidal nevi
• Choroidal melanoma and other choroidal malignant lesions

Congenital Grouped Pigmentation of the RPE (CGP-RPE)/ Grouped CHRPE/ Bear Tracks

• Multiple, small, brown-black, well-circumscribed flat lesions that cluster in a specific location
• Varies in size, but much smaller than CHRPE
• Ranges 200-400 microns, otherwise less than one-quarter of disc diameter
• Unilateral, always in one quadrant (mono quadratic)
• Multiple, clustered, small lesions
• Nonpigmented variants are also referred as “polar bear tracks" or "congenital grouped albinotic spots (look white)
• Not associated with heritable or systemic disease or visual symptoms

Bear Tracks Histopathology

• Imaging suggests increased concentration of pigment granules within otherwise normal SIZE RPE cells, that is, "hypertrophy type" change
• multiple, clustered, small lesions
• unilateral, quadrantic
• size is normal, increased pigment granules only
• Location of pigment has changed in cells, but not the cell size
• Hyperreflectance of the RPE (appears v. white), photoreceptors are present

Grouped Congenital Albinotic Spots of the RPE (Polar Bear Tracks)

• Congenital albinotic spots of the retinal pigmented epithelium (CASRPE) can be configured in solitary or grouped configurations
• Congenital albinotic spots of the retinal pigmented epithelium (CASRPE) are bilateral
• "polar bear tracks" due to their milky color and resemblance of animal footprints
• WHITE is caused by loss of melanin
• These spots develop secondary to deposition of a white material (lipocytic material) that gives off appearance of a white lesion in RPE cells instead of darkly pigmented melanin
• Focal thickening of the retinal pigment epithelium is filled with a white material that may be diffusely distributed or more concentrated in the periphery of the lesion
• Flat, sharply circumscribed, placoid, chalky white, and lie at the level of the RPE
• Spots are close in size, but may appear a little smaller

Management

• F/U
• Important to note family history, especially if patient has a family history of polyps or colon cancer
• Educate patient

DDx for Bear Tracks

• Differentiate from Pigmented Ocular Fundus Lesions or Atypical CHRPE result of Familial Adenomatous Polyposis(FAP)
• No relationship between classic CHRPE or Grouped Pigmentation of the Retina and Familial Adenomatous Polyposis (FAP
• Bear tracks are NOT associated to the polyposis, only atypical

Pigmented Ocular Fundus Lesion of Familial Adenomatous Polyposis (FAP)/ Atypical CHRPE

• Familial Adenomatous Polyposis (FAP) is associated with with Congenital Hypertrophy of the Retinal Epithelium (CHRPE)/Atypical CHRPE lesions
• FAP is an autosomal dominant syndrome that causes colonic polyps resulting in colorectal cancer by age 35 in 95% of cases
• FAP can be associated with Gardner Syndrome
• About one-third of patients with FAP will have no RPE lesions

Gardner Syndrome

• Familial colorectal polyposis
• Clinical variant of FAP with systemic manifestations

Extra Colonic Signs Of Gardner Syndrome

• epidermoid cysts, fibromas of the scalp, shoulders, arms, and back
• dental abnormalities (supernumerary, impacted teeth,)
• osteomas of the skull and mandible are prominent
• Benign tumor of bone cells
• FAP-associated CHRPE lesions are histologically like grouped CHRPE lesions
• Can be distinguished based on ocular exam

Exam Findings of FAP-associated CHRPE Lesions

• All findings must be assessed in this group
• BILATERAL
• Location: multiple quadrants
• Pisiform (fishlike shape) featuring a posterior tapered tail
• Irregular borders with halo around the border
• Size similar to bear-tracks, can be 200-300 micro
• Can see in red-green filters in Red free (green) or red filters
• Typical hamartomas in Histopathology
• Characteristic association: may demonstrate choroidal elevation, excavation or both and have overlying shallow serous detachments
• Presentations in OCT: some elevation in RPE & Serous detachment (separation of the retina from RPE)

What To Do If All Signs Are Inconclusive For FAPS

• Elongated w/ halo, more than in one quadrant, bilateral presentation, send out for screening tests

CHRPE'S: Differential Diagnoses

• Choroidal Nevus
• Choroidal Melanoma
• Chorioretinal atrophy
• Hyperplasia of the RPE
• Old chorioretinal scar (toxoplasmic retinochoroiditis)
• Metastasis, malignancy

CHRPE'S: Management

• Refer to gastroenterology for colonoscopy
• Retina consultation for retina lesions: RPE lesions themselves do not require tx but must refer patients to a gastrointestinal specialist
• Carefully Follow up, tell patient, “prevent cancer through the eyes"

Reactive Hyperplasia of the RPE/Single or Multiple

• Common, stable condition of the RPE
• Arises idiopathically or due to intraocular inflammation, trauma, hemorrhage, or retinal detachment
• Classically presents as small irregularly shaped, relatively flat, well-demarcated areas of pigment clumping
• Benign proliferation of RPE cells appears as a flat sheet or cellular mass, minimal to no changes over time
• One can be Single, or have Multiple- reactive hyperplasia of the RPE
• Pigment granules (any tiny pigment)
• Proliferation of RPE cells appearing as a cellular mass
• Seen in both filters
• Dark are in area In OCT causes a dark area underneath in the choroid or shadowing
• R/G in both, OCT: migration and shadows
• Same differential diagnosis as CHRPE
• F/U annually, monitor patient

Congenital Simple Hamartome of the RPE (CSHRPE)

• mostly asymptomatic non-progressive benign lesion
• Appears clinically a small (but can vary) nodular, darkly pigmented lesion as in reactive hyperplasia
• Normal cell size, but mainly increased RPE cells
• Congenital proliferation and migration of RPE cells
• Locations- a little bigger in size versus typical hyperplasia
• Happens On the macula or very close to peri macula region
• A pseudonym or another name is congenital hyperplasia
• May show vitreous traction and be rare and show macular edema
• Vitreous traction on the bottom vs. top is just flat and has shadow
• Management is, like the other conditions discussed, the Same DDx as CHRPE
• Monitor annually patient

Combined hamartoma of the retina and RPE

• Relatively uncommon, benign, hamartomatous malformation -Typically appears as a unilateral, nonuniform, charcoal gray-white, fibroglial mass involving the neurosensory retina with pigment accumulation
• Shiny and translucent, this involves RPE and retina
• In young children, associated with strabismus and loss of vision
• Combined hamartoma involves more than one layer (RPE and sensory retina)
• Non progressive
• Epiretinal membrane is always found
• The mass may be obscured by a gliotic semitranslucent mass
• Lesions often feature prominent, overlying tractional changes, affecting vessels and neurosensory retina
• Can explain present reductions in VA, in the setting
• Associated retinal changes commonly display retinal folds
• These lesions are associated with neurofibromatosis type 2

Diagnostic Findings For Combined Hamartoma

• Highly reflective elevated macular lesion and hyporeflective shadowing
• ERM is visible in OCT
• VA is variable
• FA shows early HYPOfluorencense with late leakage
• Rare, but possible complications include:
• Vitreous hemorrhage
• Pre-Retinal or Choroidal Neovascularization
• Macular or Peripheral Hole formation
• retinal detachment (RD)
• To DDx for a more accurate diagnosis, do the following studies
• OCT, then FA & B Scan to rule out Choroidal melanoma or Nevus
• Consider an RPE adenoma/adenocarcinoma, or even a Melanocytoma

Management for Combined Hamartoma

• Rule out bilateral combined hamartomas should especially prompt consideration of neurofibromatosis type 2*****
• When diagnosed as a young age Amblyopia prevention is very important
• Treatment for neurofibromatomas
• Vitrectomy and membrane peel
• Follow up with a retinologist in 3-6 months to avoid retinal detachment due to ERM worsening

RPE adenoma/Adenocarcinoma

• RPE adenomas can be both benign and malignant
• Adenoma, is more or so benign, where and adenocarcinoma, is malignant
• Note, that Rare intraocular tumors that are extremely are uncommon in the RPE
• Difficult to differentiate an adenoma and Adenocarcinoma of the RPE from malignant choroidal melanoma
• Adenocarcinomas manifest as Abruptly elevated masses
• Can induce retinal exudation
• Black in 85% of cases
• They are a full thickness retinal mass, , often has.................................. (62%), surrounding exudative retinopathy
• These can be diagnosed when Chorioretinal scars are present
• An Adenomas is often suspected only once clinical diagnoses are confirmed
• Often they may be associated with the presence of a visible halo

Differential Diagnosis For Adenomas and Adenocarcinomas of the RPE

• Usually an Adenoma's lesion are generally flatter when compared to that of a adenocarcinoma
• Furthermore, tumour samples show nuclear pleomorphism, this indicates that the mass is infact, a RPE adenocarcinoma Other signs include:
• The change in colour
• General, the size shows that of the cells
• Adenocarcinomas are also a lot rarer

Primary Malignant Signs of RPE Melanoma and how to differentiate them

• Rule out a malignant epithelioma, or to see if the mass, has spread into the choroid or retina
• If the Tumor contains a blood vessel that supplies and drains the tumor, this is an indicator of primary cancer
• Lipoprotienaceous retinal or sub retinal exudation are also indicators
• You might notice BLURRY VITREOUS* (Cells in vitreous!)- RPE adenocarcinoma
• Adenocarcarcinoma typically will manifest with a feeder vessel, cells in vitreous and is,overall, more elevated NOTE: EDI-OCT can show the tumour's surface irregularities
• Remote macular findings of epiretinal membrane and cistold noncystoid is always a consideration

Management

• Review ultrasonography, which will moderately show internal relectivitiy with no choroidial excavation
• This is as opposed to a melanoma, where is this will be a very obvious sign that should be considered
• With Atrophy of the RPE can cause defects in the RPE layer continuity
• The conditions we look at can be caused or affected when the retina begins to atrophy
• A common sign that is usually present is the so geographic atropy that is secondary to
• This also be can due to -Retinal scarring -Chorioretinal
• Myotic Degeneration
• As a result of a scar
• Or from geographic atropy
• Often with the presence of RPR atrophy we find 3 distinctive signs
• A lack of any phororeceptors in the retina layer
• Highly relective lighting is cast toward the choroid
• The condition will thin due to atrophy

This lesson covers remote macular findings, differentiating retinal tumors from choroidal melanoma using ultrasonography, and appropriate management steps for suspected retinal tumors. It also reviews the appearance and key findings associated with RPE atrophy and features of RPE adenoma.