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Ocular Pathology
Manual of
Ocular Pathology
Jyotirmay Biswas MS, SNAMS
Director of Uveitis and Head
The Larsen and Toubro Ocular Pathology Department
Medical and Vision Research Foundation
Sankara Nethralaya, 18, College Road
Chennai 600 006, India
E-mail: drjb@snmail.org
S Krishnakumar MD
Larsen and Toubro Ocular Pathology
Medical and Vision Research Foundations
Sankara Nethralaya, 18, College Road
Chennai 600 006, India
E-mail: histopath@snmail.org
Shweta Ahuja MD
Larsen and Toubro Ocular Pathology
Medical and Vision Research Foundations
Sankara Nethralaya, 18 College Road
Chennai 600 006, India
E-mail: histopath@snmail.org
Foreword
Narsing A Rao
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Narsing A Rao MD
Professor, Department of Ophthalmology and Pathology
Director of the A Ray Irvine, Jr., MD, Ophthalmic Pathology Laboratory
Doheny Eye Institute, University of Southern California
Los Angeles, California, USA
PREFACE
Jyotirmay Biswas
CONTENTS
PART I
1. Introduction ............................................................................................... 1
2. Pathology of the Eyelid ........................................................................ 13
3. Pathology of the Conjunctiva .............................................................. 25
4. Pathology of the Cornea ....................................................................... 35
5. Pathology of the Lens ........................................................................... 45
6. Pathology of the Uvea ........................................................................... 51
7. Intraocular Tumors ................................................................................. 55
PART II
PART III
PATHOLOGIC STUDY
Some aspects of pathologic study of ophthalmic specimens are different from
other branches of pathology and are highlighted here.
Figure 1.1: Gross photograph of the posterior surface of globe showing posterior ciliary
vein by the side of the optic nerve (arrow)
d. Transillumination
The transilluminator is used for transillumination of the globe. The globe is
transilluminated with a bright, point source of light in a dark room
6 MANUAL OF OCULAR PATHOLOGY
f. Internal Description
The section of the globe called a calotte is then examined from anterior to
posterior as follows: (Figure 1.4).
INTRODUCTION 7
Figures 1.3A and B: A. Showing an eyeball specimen with the forceps holding inferior oblique
muscle which indicates temporal side of the globe; B. Taking section of the globe through the
horizontal meridian cutting the superior calotte
Figures 1.3C and D: C. Taking section of the globe to obtain central calotte;
D. Showing the central calotte containing pupil and optic nerve
Cornea: Thickness
Anterior chamber: Normal or abnormal depth, any material inside
Vitreous cavity: Contents are examined
Retina: Peripheral cystoid degeneration is seen at the periphery close to ora
serrata in many eyes. Macula appears as a dark area on the temporal side
of the optic disk.
8 MANUAL OF OCULAR PATHOLOGY
Optic disk head: Any obvious pathology, e.g. color, swelling, cupping, etc. is
noted.
Choroid and sclera: Examined for any gross pathology, e.g. thickening, etc.
In case of any interesting findings, gross photography can be taken of the
calotte at this stage (Figure 1.3).
After the interior of the globe is examined, a second plane of section parallel
to the first is made again passing from back to front.
The other two calottes are examined for any gross pathology. The P-O
section is submitted for paraffin processing, the other two calottes are stored
and if needed can be studied later, on the basis of examination of the section
(Figure 1.5).
Figure 1.5: Gross photograph of the cut section of a globe showing thickening of a
choroid (arrow) in a case of sympathetic ophthalmia
Special Procedures
1. Retinoblastoma suspect: Optic nerve cross-section is taken at the end of the
surgical cut section prior to opening of the globe and submitted in a separate
cassette for processing. The patient’s prognosis, average life expectancy
and need for chemotherapy correlates with the extent of the tumor spread
into the optic nerve. Globe with long section of the optic nerve should be
taken during enucleation (Figure 1.6).
Figure 1.6: Showing gross photograph of the eyeball with long optic nerve
INTRODUCTION 9
2. Malignant melanoma: The vortex vein is identified and a section is made
and submitted for processing to search for possible extrascleral extension
via vortex vein (Figure 1.7).
Figure 1.7: Gross photograph showing vortex vein in an eyeball with suspected malignant
melanoma of the choroid (arrow)
3. Intraocular foreign body: Prior X-ray of the globe should be done and after
sectioning, the foreign body should be looked for in the cut section. If found,
it should be removed, measured and preserved carefully in the file for
medico-legal reference.
4. In suspected calcification: Decalcification is necessary before sectioning.
Cornea
1. Measure the diameter in any meridian.
2. Examine both surfaces of the cornea under a dissecting microscope.
10 MANUAL OF OCULAR PATHOLOGY
Lens
1. Measurement of diameter
2. Description of the gross characteristics
3. Cut into two halves, one half can be submitted while the other half can
be saved.
IOL
1. Measurement of diameter
2. Make a note of pigmentation, deposits, etc.
3. Stain directly placing it in a concavity slide
HISTOLOGIC SECTIONS
Following fixation the tissue is processed through a series of dehydration and
clearing steps and is embedded in paraffin in the desired direction so that
histological sections can be obtained through a plane that contains all tissue
layers, including the pathologic process. Care should be taken to orient the
block properly to prevent tears, folds and cellular distortion. Sections should
be of adequate thickness. Most ocular biopsy specimens are cut at 5-8 µm but
in suspected lymphoma cases thinner sections (3-4 µm) are preferred to make
the nuclear details clearer. Exenteration specimens or globes are usually
sectioned at 8-10 µm.
Ribbons of serial sections are taken and placed on cleaned glass slides lightly
coated with a tissue adhesive, such as chrome alum gelatin. Two or three
sections should be mounted and placed for staining on each slide. Routinely
two or three slides of hematoxylin and eosin (HE) and one of periodic acid-
Schiff (PAS) stain are prepared. Several histochemical or immunohistochemical
stains may be performed when necessary, but if several unstained slides can
be prepared at the time of sectioning for later special staining (e.g.
immunohistochemistry, fungi or bacteria), the tissue is used most effectively.
IMMUNOHISTOCHEMICAL STAINING
Examination of tissue sections with the conventional hematoxylin and eosin
stain and histochemical characterization with special stains may not be
sufficient to arrive at precise diagnosis. Immunohistochemical methods will
help in some of these instances by providing additional information. For
example, poorly differentiated or undifferentiated tumors can be identified
for the origin of tumor cell type by their specific cytoplasmic or surface
antigens, utilizing monoclonal or polyclonal antibodies directed to these
antigens. The conjugation of the antibody with the tissue antigens is then
detected by a fluorescent secondary antibody, by peroxidase or by other labeled
antibodies.
In the first of these methods, immunofluorescence, a fluorescence
microscope is needed to visualize the complex and the technique usually does
not allow for prolonged storage. Moreover, formalin-fixed tissue may not be
ideal for this technique because such tissue emits autofluorescence. Lens and
retinal pigment epithelium may also emit autofluorescence. The
immunoperoxidase technique is much more convenient for use with
ophthalmic specimens because it can be performed on formalin-fixed and
paraffin embedded tissue. This technique does not require a fluorescence
microscope and the stained sections can be stored for a long time. Modifications
of this method include the peroxidase-antiperoxidase (PAP) method or the
avidin-biotin complex (ABC) method, both of which have higher sensitivity
and specificity than the immunoperoxidase method.
14 MANUAL OF OCULAR PATHOLOGY
Histology
It has two parts:
• Epidermis
• Dermis.
a. Epidermis
Keratinized stratified squamous epithelium, composed of four layers of cells:
1. Keratin layer (stratum corneum)
2. Granular cell layer (stratum granulosum)
3. Squamous or prickle cell (stratum spinosum) layer
4. Basal cell layer (stratum germinativum).
b. Dermis
Important structures:
- Hair
- Glands
PATHOLOGY OF THE EYELID 15
- Nerves
- Vessels.
Neoplasms may arise from any of these structures.
Pathological changes in lid lesions are as follows:
A. Hyperkeratosis: Thickening of the keratin layer.
B. Parakeratosis: Retention of nuclei within the keratin layer.
C. Dyskeratosis: Abnormal intraepithelial keratinization (Normally
keratinization occurs only at the surface of the epithelium).
D. Acanthosis: Thickening of prickle cell layer—A feature of hyperplasia of
epidermis.
E. Acantholysis: Separation of squamous cells by lysis leading to the formation
of an intraepidermal vesicle like a herpetic bulla.
Lid Lesions
Pathologic classification:
- Nonneoplastic
- Neoplastic
Nonneoplastic Lesions
I. Inflammation:
a. Infectious
– Bacterial—Hordeolum (stye), tuberculosis, syphilis, leprosy
– Viral—Molluscum contagiosum, human papilloma virus
– Fungal—Blastomycosis, coccidioidomycosis, aspergillosis, rhinospori-
diosis.
b. Non Infectious:
– Chalazion.
II. Degeneration:
– Xanthelasma
– Amyloidosis.
III. Cyst:
– Epidermoid inclusion cyst
– Dermoid cyst
– Sebaceous cyst
– Eccrine hidrocystoma
– Apocrine hidrocystoma (cyst of the gland of Moll).
Chalazion
It is a sterile foreign body lipogranulomatous inflammation caused by
extravasations of lipid material from either the meibomian gland of the tarsus
or glands of Zeis. Within the granuloma, clear spaces corresponding to lipid
material are seen along with multinucleated giant cells intermixed with
epithelioid cells, neutrophils and lymphocytes (Figures 2.2A and B).
16 MANUAL OF OCULAR PATHOLOGY
Viral Infections
a. Molluscum Contagiosum
It is caused by molluscum virus of the pox virus group. These are seen as
multiple, small, raised umbilicated pearly nodules along the lid margin (Figure
2.3A). On microscopic examination, the lesion consists of a lobulated collection
of acanthotic epithelial islands opening into a central crater. The squamous
cells contain characteristic eosinophilic cytoplasmic inclusion called
molluscum bodies (Figure 2.3B). Almost the entire cytoplasm is filled with
molluscum bodies and the nucleus is compressed at the periphery.
Figures 2.3A and B: Patient having multiple waxy dome-shaped umbilicated lesions of molluscum
contagiosum on eyelid as well as on face; B. Photomicrograph showing lobulated collection
of acanthotic epithelium opening into a central crater with multiple eosinophilic cytoplasmic
inclusions (Molluscum bodies) within the thickened epidermis (arrow)
b. Verruca Vulgaris
Viral warts are common in children and show acanthosis, papillomatosis,
hyperkeratosis and elongated peripheral rete ridges curve involved towards
the base of the lesion (Figure 2.4A). These lesions characteristically show
PATHOLOGY OF THE EYELID 17
ground glass intranuclear inclusions, perinuclear vacuolation and
keratohyaline globules (Figure 2.4B).
Figure 2.5: Showing apple green birefringence in a case of amyloidosis of the lid
Neoplastic Lesions
1. Tumors of the surface epithelium.
2. Tumors of the glands of the eyelid.
3. Vascular tumors
4. Neurogenic tumors
5. Melanotic tumors.
Tumors of the surface epithelium of the lid:
18 MANUAL OF OCULAR PATHOLOGY
Benign
1. Squamous papilloma (Figure 2.6)
2. Pseudoepitheliomatous hyperplasia
3. Inverted follicular keratosis
4. Keratoacanthoma
5. Seborrheic keratosis.
Keratoacanthoma
This is a self-involuting lesion simulating squamous cell carcinoma clinically
as well as histopathologically.
Clinical
- Common in middle age or elderly people
- Solitary lesion
- Rapidly progressive lesion
- Involution occurs within a year leaving a depressed scar
Histopathology
It shows a cup-shaped invagination of well-differentiated squamous cells
forming irregular nests and strands inciting lymphocytic host response.
Seborrheic keratosis
- Common in middle age.
- Well circumscribed, oval to dome shaped lesion.
Histopathology: The epidermis show hyperkeratosis, acanthosis and
papillomatosis along with characteristic pseudohorn cysts which are
concentrically laminated collections of surface keratin within the acanthotic
epithelium (Figure 2.7).
PATHOLOGY OF THE EYELID 19
Malignant:
1. Basal cell carcinoma
2. Squamous cell carcinoma.
Basal cell carcinoma:
This is the most common eyelid tumor (39 times more common than squamous
cell carcinoma).
Location (according to frequency) — Lower lid, upper lid, medial canthus,
lateral canthus.
Clinical presentations:
- Nodular
- Noduloulcerative (Figure 2.8)
- Cystic
- Sclerotic (morphea form)
- Pigmented (can be confused with melanoma).
Figure 2.8: Clinical photograph of a case of basal cell carcinoma (rodent ulcer)
20 MANUAL OF OCULAR PATHOLOGY
Histopathology:
Nodular—Nests and cords of proliferating epidermal basilar cells (Figures 2.9A
and B).
Noduloulcerative type - Peripheral palisading of tumor cells.
- Collagen deposition in the dermis.
- Separation of nests of tumor and dermal tumor
stroma (retraction space or cracking artefact).
- Central necrosis.
Cystic type - Sometimes cysts are filled with blood or
degenerating blood products such as hemosiderin.
Morphea type - Tumor tends to penetrate in the dermis, diffusely
branching cords of cells.
Spread—Mainly local into periorbital and orbital structures.
Metastasis - Extremely rare.
- Directly invasion of the cranial cavity can lead to
secondary metastasis.
Figures 2.9A and B: A. Showing multiple islands of basaloid cells within the dermis;
B. High power review showing peripheral palisading and cracking arteacts (arrow) in a case
of basal cell carcinoma
Pathology
Progress through phases:
i. Intraepithelial squamous dysplasia:
- Partial thickness replacement of epithelium by atypical cells.
ii. Intraepidermal squamous cell carcinoma (carcinoma in situ):
PATHOLOGY OF THE EYELID 21
- Full thickness replacement of epithelium by malignant epithelial cells
without invasion beyond basement membrane of epithelium (Figure
2.10B).
iii. Invasive squamous cell carcinoma:
- These atypical squamous cells forms nests and strands, break the
epithelial basement membrane, infiltrate into dermis and incite a
desmoplastic fibrous tissue reaction (Figure 2.10C).
Figures 2.10A to C: A. Patient showing cauliflower likes growth from the lower eyelid;
B. Full thickness replacement of epithelium with malignant squamous cells with intact basement
membrane, suggestive of severe conjunctival dysplasia (carcinoma in situ); C. Showing multiple
nest of malignant squamous cells invading into the dermis in a case of squamous cell carcinoma
Occurrence:
- Elderly (rare before 40 years)
- More common in females
- More in Asians (Chinese).
- Predilection for eyelids (extremely rare elsewhere in the body).
Types of Presentation
1. Solitary nodule – mimics chalazion
2. Diffuse spread to surface skin or conjunctiva.
- Chronic blepharitis or chronic blepharoconjunctivitis.
- Loss of cilia
- Yellow secretions (masquerade syndrome).
Site: Upper eyelid is involved in 2/3rd of cases. It may be multicentric –
involving both lower and upper eyelid.
Microscopic examination:
• Lesion is extensive infiltrative and has lobular pattern (Figure 2.11A)
• Tumor cells have abundant finely vacuolated, foamy cytoplasm showing
sebaceous differentiation (Figure 2.11B).
Figures 2.11A and B: A. Clinical photograph showing case of sebaceous gland carcinoma
presenting as a single yellow nodule from lower eyelid; B. Photomicrograph of the tumor showing
nuclear pleomorphism with cytoplasmic lipid droplets indicating sebaceous differentiation
Figures 2.12A and B: A. Sebaceous gland carcinoma with pagetoid spread; B. Photomicrograph
of the tumor cells containing lipid droplets in the frozen section stained with Oil Red O
Neurogenic Tumors
1. Neurofibroma
2. Schwannoma.
Malignant Melanoma
- 1% of all eyelid malignancies.
- Associated with preexisting nevus or may develop de novo.
- Clinically appears as a flat to nodular lesion with a variable degree of
pigmentation.
There are 4 main histopathological subtypes:
1. Superficial spreading
2. Lentigo maligna
3. Nodular
4. Acral lentiginous.
24 MANUAL OF OCULAR PATHOLOGY
HISTOLOGY
Epithelium
- Stratified columnar—general
- Stratified squamous—limbus, lid margin
- Goblet cells—secrete mucin, an essential component of tear film, stains
positive with PAS stain.
Stroma
- Fibrovascular connective tissue
- Fibroblasts, melanocytes
- Chronic inflammatory cells
- Lymphoid follicles and accessory lacrimal gland.
Pathology
- Congenital
- Inflammation
- Degeneration
- Cysts
- Neoplasm
- Changes in systemic diseases.
Congenital
- Dermoid
- Dermolipoma
- Ataxia telangiectasia.
Dermoid
Choristomatous mound of coarsely thickened collagen fibers covered by skin-
like epithelium, containing epidermal appendages (hair, sebaceous and sweat
glands).
The following types of dermoid are seen in the conjunctiva:
i. Isolated dermoid: Choristoma is seen alone.
ii. In association with Goldenhar syndrome: Epibulbar solid dermoids,
preauricular appendages, aural fistulas.
iii. Dermolipoma: Dermoid choristoma composed primarily of fatty tissue.
Inflammation
i. Acute conjunctivitis
True Membrane
- Inflammatory exudates firmly adherent to epithelium.
- Bleeding occurs when membrane is peeled, e.g. Diphtheria, Gonococcus.
PATHOLOGY OF THE CONJUNCTIVA 27
- Stevens-Johnson syndrome.
Pseudomembrane
- Less adherent, can be peeled without bleeding.
Causes:
- Viral (HSV, Adenovirus 8, Adenovirus).
- Bacterial (Staphylococcus, Pneumococcus, Meningococcus, Pseudomo-
nas, Coli forms).
- Chemical burns, ocular pemphigoid, foreign body, ligneous
conjunctivitis.
ii. Chronic conjunctivitis:
Ligneous conjunctivitis:
- Bilateral, chronic pseudomembranous conjunctivitis is seen in children.
- Massive, woody accumulation of fibrin with chronic inflammatory cells.
Similar lesions may be seen in the vagina and other mucosal structures.
Pathological Classification
Follicular conjunctivitis Develops insidiously.
The inflammatory response consists of
lymphocytes and plasma cells.
Follicles are composed of aggregates of
lymphocytes and plasma cells. Lymphocytes
may form germinal centers within the follicles.
It is seen in bacterial, viral and chlamydial
infections as well as with toxins.
Papillary conjunctivitis It shows a cobblestone arrangement of flattened
nodules with a central vascular core. It is
commonly associated with allergic or vernal
conjunctivitis and part of a foreign-body
reaction.
iii. Vernal conjunctivitis—Bilateral, recurrent conjunctivitis in adolescents
with history of atopy.
Pathology
- Worsens in spring, marked itching–chronic papillary hypertrophy.
- Epithelial hypertrophy, then atrophy.
- Fibrovascular papillary core which contains perivascular and diffuse
infiltration of lymphocytes, plasma cells and numerous eosinophils.
iv. Giant papillary conjunctivitis - Seen in soft contact lens wearers. When
the papillae become large sized, it’s
called giant papillary conjunctivitis.
v. Conjunctival tuberculoma— Very rare. It can be seen in HIV positive
patients as a conjunctival mass lesion
28 MANUAL OF OCULAR PATHOLOGY
Pathology
- Solar elastosis, acellular homogenous deposit, basophilia, thickened
vermiform collagen fibers (Figure 3.3B).
- Stains positive with Verhoeff-Van Gieson elastic stain.
Cysts
i. Inclusion cyst: It is an empty or mucus-filled lumen lined by conjunctival
epithelium and caused by trauma or surgical implantation.
ii. Ductal cyst: This is an analogue of sudoriferous cysts in the skin. It is
lined by a dual layer and has a clear lumen. It arises from the accessory
lacrimal glands.
Tumors
There are three basic categories:
i. Squamous lesions—proliferation of epithelium
ii. Lymphoid lesions—proliferation of normal resident population of
lymphocytes
iii. Melanocytic tumors.
Squamous Lesions
Types
i. Squamous papilloma
ii. Conjunctival dysplasia
30 MANUAL OF OCULAR PATHOLOGY
i. Squamous papilloma
• Bulbar or palpebral conjunctival swelling (Figure 3.4)
• Can be multiple and recurrent, especially in children
• Many are viral lesions (papilloma virus)
• Vascular ‘Hairpin’ loops are seen clinically.
Figure 3.4: Conjunctival papilloma, multiple red dots correspond to fibrovascular core
Pathology
- Benign proliferation of conjunctival epithelium as multiple fronds with
central fibrovascular cores (Figure 3.5).
Figure 3.5: Photomicrograph showing multiple fronds of acanthotic epithelium with central
fibrovascular core in a case of conjunctival papilloma
Lymphoid Tumors
- These arise from the conjunctiva’s resident population of lymphocytes
(Figure 3.8).
Melanocytic Tumors
Nevi: Congenital lesion – may enlarge or become more pigmented during
pregnancy or puberty, these being cosmetic indications for excision (Figs 3.10
A and B).
There are 3 main variants:
- Junctional: Nevus cells confined to epithelial subepithelial junction (can be
impossible to distinguish from acquired melanosis in small biopsy without
good history).
- Subepithelial: Nevoid nests confined to substantia propria.
- Compound: Nevus cells in both epithelium and substantia propria.
Malignant Melanoma
- Relatively rare (Uveal: Conjunctival melanoma ratio is 10:1)
- 25% mortality and unpredictable behavior.
- Can arise from:
- Acquired melanosis (most)
- Preexisting nevus
- De novo (nodular melanoma).
- Acquired melanosis found in 75%, Nevi 25%.
- Behave like skin, not uveal melanomas (Calendar classification not
applicable to conjunctival melanomas).
- Malignant tumor cells with melanin pigments in the stroma.
- Lymphatic spread common (preauricular and intraparotid nodes).
36 MANUAL OF OCULAR PATHOLOGY
HISTOLOGY
Normal cornea is composed of laminated collagenous tissue lined on both
sides by a membrane and a cellular layer. There are five layers of cornea (Figure
4.1).
1. Epithelium
2. Bowman’s membrane
3. Stroma
4. Descemet’s membrane
5. Endothelium.
Epithelium: It is composed of five cell layers of nonkeratinized stratified
squamous epithelium which is continuous with the conjunctival epithelium.
Beneath the epithelium, a thin basement membrane is present which can be
easily seen by PAS stain.
Bowman’s membrane: It is a homogenous layer of 10 mm thickness. It is not
a true membrane but an acellular condensation of the anterior corneal stroma.
Stroma: It constitutes the major portion of the cornea and is composed of very
regularly arranged lamellae, of collagen fibers. Between the lamellae, spindle-
shaped fibroblast-like cells are seen, known as keratocytes.
Descemet’s membrane: It is a true basement membrane about 10 mm thick, best
seen with PAS stain.
Endothelium: It is a single layer of cuboidal cells derived from the neural crest.
PATHOLOGY OF THE CORNEA 37
Pathology of cornea can be studied systematically looking from above
downwards as described below:
Epithelium
1. Arrangement:
a. Regular or irregular.
b. Loss of epithelium—partial or total (one should keep in mind that it
could be artifactual during initial cutting or during microtome
sectioning). Partial or full thickness loss with underlying stromal tissue
shrinkage is seen in Dellen.
2. Thickening and epidermadization: Vitamin A deficiency.
3. Exposure keratitis: Intraepithelial cyst formation.
4. Elevation: Epithelium raised from underlying structures, e.g. bullae
formation, seen typically in bullous keratopathy.
5. Pannus: Fibrous or fibrovascular tissue underneath the epithelium can occur
due to chronic inflammation along with concurrent destruction of
Bowman’s membrane or in noninflammatory conditions without
destruction of Bowman’s membrane e.g. advanced bullous keratopathy.
6. Band keratopathy: Deposition of calcium in epithelial basement membrane,
Bowman layer and anterior stroma which is characteristically seen as sub
epithelial basophilic granular degeneration in band-shaped distribution
with hematoxylin and eosin stain (Figure 4.2) and confirmed by the use
of special stains such as Alizarin Red or Von-Kossa satin. It occurs in chronic
inflammation and glaucoma.
Figure 4.3: Bullous keratopathy showing swelling of the corneal epithelial cells (epithelial
edema), a large bullae is present between the epithelium and Bowman layer
8. Pigment deposit: Iron is found in the basal epithelial cells and can be
demonstrated by using the Prussian blue stain.
Stroma
Look for staining character, e.g. pale staining is observed in corneal edema.
Normal cornea will show multiple areas of separation of stromal lamellae
due to dehydration during processing. This is a meaningful artifact.
1. Edema: Lack of lamellar separation indicates corneal edema. In advanced
cases, the keratocyte density is diminished. Epithelial edema is accompanied
in most cases.
2. Vascularization: Vascular lakes are seen with RBCs inside. The location of
vessels is noted, e.g. superficial or deep, in the central or peripheral portions.
3. Inflammation:
i. Ulcerative: There is destruction of epithelium and Bowman’s membrane
with invasion of acute and chronic inflammatory cells.
ii. Non-ulcerative: Interstitial keratitis: non-ulcerative keratitis accompanied
by vascularization, e.g. syphilis.
1. Infections
A. Bacterial
Modified Grams stain (Brown-Brenn or Brown-Hopps) can be used for
identification. Gram-negative organisms will stain red and gram-positive
organisms will stain blue. Common bacteria which cause keratitis are
Staphylococcus aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa.
Atypical mycobacteria may rarely cause keratitis and can be stained by Ziehl-
Neelsen stain.
B. Fungal
Organisms can be identified with Gomori’s methenamine silver stain (Figure
4.4), calcoflour or lectin staining. The most common organisms are Aspergillus,
Candida and Fusarium.
PATHOLOGY OF THE CORNEA 39
C. Viral
Herpes simplex and herpes zoster. Herpes simplex keratitis occurs in three
distinct clinical forms:
i. Dendritic
ii. Disciform
iii. Necrotizing interstitial.
I. Dendritic: Self-limited epithelial disease characterized by linear arborizing
pattern of opacification and swelling of epithelium (dendrite). Corneal
scraping from dendrite reveals the presence of intranucelar viral
inclusion by Giemsa stain.
II. Disciform: It is thought to be caused by cell-mediated immune response
to viral antigens, although sometimes viral particles are seen. It can also
be due to herpes zoster, varicella, vaccinia, etc.
III. Necrotizing interstitial: Sometimes full thickness stromal involvement and
granulomatous reaction in the region of Descemet’s membrane is seen.
D. Protozoal (Acanthamoeba)
A free living, nonparasitic protozoan is found in fresh and salt water, soil
and air. Direct corneal contact with contaminated contact lens solution or
water results in such infection. The organism has trophozoite and cyst forms.
The cyst has a characteristic appearance with a double wall. The outer being
wrinkled and the inner round. The cyst can be seen with the H&E, PAS and
calcoflour stains, KOH preparation and by immunohistochemical methods.
It causes a chronic progressive keratitis, that often mimicks viral, fungal or
bacterial keratitis.
40 MANUAL OF OCULAR PATHOLOGY
2. Dystrophies
Corneal dystrophies are a group of disorders that are primary, bilateral,
symmetrical, avascular and often hereditary. They are classified according
to the principal layers involved.
i. Epithelial (e.g. map dot-finger print): Primary epithelial adhesion, epithelial
reduplication, bullae, folding and excessive sub or intraepithelial
basement membrane production.
ii. Stromal: Stromal dystrophies have characteristic clinical presentation and
specific type of histochemical characteristics as outlined below:
Figures 4.5A and B: A. Lattice corneal dystrophy; B. Lattice dystrophy showing apple green
birefringence of stromal deposits in a Congo red stained section viewed with polarized light
Figures 4.6A and B: A. Granular corneal dystrophy; B. Granular deposits (stained red)
are present in the stroma and beneath the epithelium (Masson trichrome stain)
PATHOLOGY OF THE CORNEA 41
3. Degeneration
May be actinic keratopathy, spheroidal degeneration or labrador keratopathy.
It is seen as basophilic globules in the superficial stroma (Figure 4.8). It is
due to damage to the corneal collagen.
Figures 4.9A and B: A. Blood staining of cornea; B. Blood staining of the cornea.
Numerous small orange red particles are scattered within the stromal lamellae of the cornea
42 MANUAL OF OCULAR PATHOLOGY
Descemet’s Membrane
1. Thickening: It is thickened in various diseases, e.g. Bullous keratopathy
and endothelial dystrophy.
2. Pigment deposition, e.g. Kayser-Fleischer ring—The brown ring seen in
the periphery of the cornea in Wilsons disease, which corresponds to copper
deposition in the Descemet’s membrane.
Endothelium
During processing endothelial cells may be lost. Examination of the other
layers of the cornea will help to distinguish artificial from actual endothelial
cell loss. Endothelial cell loss can occur in the following conditions.
1. Intraocular surgical procedure:
a. Cataract extraction – more often with intracapsular than extracapsular.
b. Cataract with IOL implantation – more after anterior chamber lens
implantation.
c. Penetrating keratoplasty.
2. Trauma.
3. Glaucoma.
4. Inflammations involving the anterior chamber, e.g. iridocyclitis.
5. Dystrophy:
i. Fuch’s endothelial dystrophy (Figure 4.10): Abnormal basement
membrane material, secreted on Descemet’s membrane (guttae).
Figure 4.11: Keratoconus: Low magnification showing central stromal thinning and scarring
The crystalline lens is a soft elastic, avascular structure that measures 9-10
mm in diameter and 3.5 mm in anterior posterior thickness.
HISTOLOGY OF LENS
- Unique tissue in the body.
- It is a derivative of a single primitive tissue (surface ectoderm).
- The surface epithelium grows inwards at the equator—so it sheds its
epithelium inwards and forms lens fibers.
- It becomes compact with age—following which yellow pigments are
deposited on it to form cataracts.
- The lens capsule is the thickest basement membrane in the human body.
PATHOLOGY
It is of 4 types:
I. Zonular alterations.
II. Capsular alterations.
III. Epithelial changes.
IV. Lens substance alterations.
I. Zonular Alterations
- Subluxation.
- Dislocation.
Marfan’s Syndrome
An autosomal dominant condition, it is disorder of connective tissue in which
there is spontaneous subluxation of lens in a superotemporal direction. Other
phenotypical features include, long slender extremities, musculoskeletal
deformities and cardiovascular changes.
Pathology
- Hypoplasia of dilator muscles.
- Ciliary processes are often elongated and extending from the anterior to
the posterior surface of the iris.
Homocystinuria
Inferonasal displacement of the lens.
Weill-Marchesani Syndrome
Superotemporal or temporal displacement of a spherophakic lens.
PATHOLOGY OF THE LENS 47
II. Capsular Alterations
Exfoliation can be true or pseudo
True:Steel workers
Glass blowers.
- The most anterior layer of the anterior capsule splits into several layers.
- These split layers are seen as scrolls.
Histology
- Amorphous eosinophilic floccular deposits
- Stains with acid mucopolysaccharide stain.
Coronary cataract: Consist of wart-like excrescences on the capsule, which with
time are replaced by clumps of epithelium, resulting in granular debris in
the peripheral cortex.
Figure 5.2: Iron deposits are seen in the subcapsular region in siderotic cataract
(Prussian blue stain)
d. Soemmering’s ring cataract (Figure 5.3): Dense opaque lens cortex forms
a ring behind the iris.
Cortical Cataract
- Fragmentation of lens fibers.
- Morgagnian globules—Small round globules caused by fragmentation of
lens fibers.
- Liquefaction of lens fibers (Figure 5.4).
Figure 5.4: Lens fibers showing extensive cortical degeneration in cortical cataract
Hypermature Cataract
It is of two types:
1. Morgagnian—Lens capsule contained liquefied cortex–nucleus resting on
dependent portion of the lens.
2. Sclerotic—Fluid leaked out.
52 MANUAL OF OCULAR PATHOLOGY
GRANULOMATOUS
Three pathological types of granulomatous inflammation are encountered
in uveitis and are given below:
Pathologic type Diagnosis
1. Zonal Lens induced uveitis, tuberculosis
2. Diffuse Sympathetic ophthalmia
3. Discrete Sarcoidosis
Figure 6.1: Microphotograph showing Dalen Fuchs nodule with diffuse inflammation of the choroid
in a case of sympathetic ophthalmia (arrow) (Courtesy: Dr Deepak Edward, USA)
PATHOLOGY OF THE UVEA 53
The following histopathologic characteristics are seen in these two uveitic
entities:
i. Diffuse lymphocytic infiltration of the choroid with epithelioid cells and
occasional giant cells.
ii. Focal chorioretinal scar.
iii. Pigment migration in the disorganized retina.
iv. Pigment phagocytosis of epithelioid cells.
v. Dalen-Fuchs nodule: Focal collections of epithelioid cells, macrophages
and lymphocytes between the retinal pigment epithelium and Bruch’s
membrane.
vi. Neutrophils, plasma cells and eosinophils occasionally.
vii. Sparing of choriocapillaries was earlier thought to be specific for
sympathetic ophthalmia and not for VKH. As eyes with sympathetic
ophthalmia are removed earlier than VKH cases, such a difference can
be seen histopathologically and the finding should not be considered
to be a differentiating feature.
56 MANUAL OF OCULAR PATHOLOGY
RETINOBLASTOMA
Retinoblastoma is the most common pediatric intraocular malignancy. It is
the third most common intraocular malignancy in any age group.
The tumor is unique as it exists in both familial and nonfamilial forms.
It is also one of the highly malignant tumors of the eye.
- It occurs in 1 in 14,000-34,000 live births. The tumor is seen commonly
below 3 years of age and presents clinically as a white reflex in the pupil,
squint, spontaneous hyphema, pseudohypopyon (tumor seeding of anterior
chamber) and proptosis (advanced stage).
- Complete spontaneous regression is also possible. Enucleation is the
treatment of choice in advanced stages of retinoblastoma.
- Enucleated eyes are subjected to histopathological study for confirmation
of the clinical diagnosis and to rule out tumor cell invasion at the surgical
margin of the optic nerve.
Gross Examination
On sectioning, the retinoblastoma shows several characteristic findings.
Findings
1. Chalky white mass, often friable (Figure 7.5A).
2. Can present with different growth patterns exophytic, endophytic, mixed
and diffuse.
3. Extension to the uvea, epibulbar structures and optic nerve is grossly visible
in advanced cases.
4. Choroidal invasion may also be grossly visible (Figure 7.1).
MICROSCOPIC EXAMINATION
Findings
Low Power
- Basophilic mass (e.g.) with lightly eosinophilic areas (necrosis of tumor).
- Multiple dense basophilic foci (calcification).
- Tumor can be endophytic, exophytic, mixed (endophytic and exophytic)
or diffuse infiltrating (Figures 7.2 to 7.4).
INTRAOCULAR TUMORS 57
Figures 7.3A and B: Showing tumor arising from the inner layer of the retina
58 MANUAL OF OCULAR PATHOLOGY
Figures 7.4A and B: Showing tumor arising from the outer layer of the retina (arrow)
High Power
Tumors show two different types of cellular characteristics (Figures 7.5A
and B):
a. Poorly differentiated
b. Well-differentiated.
Figures 7.5A and B: A. Cut section of the globe in retinoblastoma showing a chalky white
mass filling whole of the vitreous cavity; B. Microphotograph showing basophilic tumor mass
in a case of retinoblastoma
a. Poorly Differentiated
- Small to medium sized round cells with hyperchromatic nuclei and
scanty cytoplasm (Figure 7.6).
a. Rosettes
Rosettes are of two types:
i. Homer-Wright
ii. Flexner-Wintersteiner.
Figures 7.7A and B: A. Homer-Wright rosettes—Tumor cells are arranged radially around a
central core of neural fibrilin in contrast to the clear lumen in Flexner-Wintersteiner type; B.
Photomicrograph showing Flexner–Wintersteiner rosettes consisting of tumor cells arranged
around a central lumen
b. Fleurettes
- Highly specific for retinoblastoma.
- Flower boquet like aggregates of tumor cells with bulbous eosinophilic
processes projecting through the fenestrated membrane (Figure 7.8).
Figure 7.8: Showing “Fleurettes” which are flower bouquet like aggregates of tumor cells
with bulbous eosinophilic processes projecting through the fenestrated membrane
- Extension of tumor cells into the anterior chamber, iris, choroid, optic nerve
and orbital tissue (Figs 7.9 A and B).
Figures 7.9A and B: Cross section of the optic nerve showing invasion of retinoblastoma
into the optic nerve
Pathology
- The tumor can arise from choroid, ciliary body or both (Figure 7.10C).
- Ciliary body tumors have a poorer prognosis.
Pigmentation
- Variable pigment content (amelanotic to deeply pigmented) and multiple
variably pigmented clones are often seen.
Growth Pattern
This is of two types: (i) Focal, (ii) Diffuse.
i. Focal
- Common.
- Early tumors confined to the uvea.
- Oval in shape.
- As the tumor grows, it can rupture through the Bruch’s membrane and
produce a collar button or mushroom-shaped mass (Figures 7.10A and B).
Figures 7.10A to C: A. Fundus photograph showing a pigmented mass breaking through Bruch’s
membrane in a case of malignant melanoma of the choroid; B. Showing gross photograph of
the malignant melanoma of the choroid with mushroom-shaped pigmented tumor mass; C.
Showing low power photograph showing collar stud appearance of a case of malignant melanoma
of the choroid rupturing through Bruch’s membrane
62 MANUAL OF OCULAR PATHOLOGY
ii. Diffuse
- Rare.
- Involves a larger area of the uvea.
- Known to be more aggressive, resulting frequently in extrascleral extension.
- Associated with secondary retinal detachment commonly.
- Macrophages laden with lipofuscin pigments correspond with the orange
pigmentation seen clinically.
Histologic characteristics of uveal melanoma cells (Tables 7.1 and 7.2):
Five histologic types of uveal melanoma cells are recognized and are used
for the classification of melanomas of the uveal tract (Callender’s cytologic
classification).
Table 7.1: Cell type
Cell Type Approximate no. of choroidal melanomas (%)
Spindle A 5
Spindle B 39
Epithelioid 3
Mixed 45
Necrotic 8
Different cell types correlate with the mortality of the patient and are given
in Table 7.3:
Table 7.3: Cell type and mortality
Tumor Cell type and mortality 5-year mortality
Spindle A Predominantly spindle A 5
Spindle B Predominantly spindle B 14
Mixed Spindle B and epithelioid 51
Epithelioid Predominantly epithelioid 69
Necrotic Majority of cells are necrosed 51
Extension of Melanoma
1. Vortex veins
2. Scleral emissary canals
3. Vitreous infiltration
4. Optic nerve and orbital invasion—more in peripapillary melanoma.
5. Melanomalytic glaucoma—macrophages with engulfed melanin pigment
blocking the angle.
INTRAOCULAR TUMORS 65
Novel Prognostic Parameters in Uveal Melanoma
Uveal melanoma is the most common primary cancer of the eye and the second
most common form of melanoma. Uveal melanoma has a strong predilection
for hematogenous metastasis, particularly to the liver. Several prognostic
factors based on clinical and histological features were identified but none
of these prognostic factors were specific enough for identification of patients
at risk for metastatic disease (Table 7.4). Chromosomal aberrations were
studied by cytogenetic analysis, spectral karyotyping and fluorescent insitu
hybridization.
Microscopic Features
- Most iris melanomas are of the spindle cell type.
- Slow growing and relatively benign.
- Better prognosis.
66 MANUAL OF OCULAR PATHOLOGY
Metastatic Tumors
Metastatic tumors are rare intraocular malignancies encountered in
ophthalmic practice. It has been found that 10% of the patients who die of
cancer have intraocular metastasis.
Medulloepithelioma
It is also known as “Diktyoma”. They originate from nonpigmented ciliary
epithelium. Most common in children around 5 years of age.
Histopathology
It can be benign or malignant which are further subclassified into teratoid
or nonteratoid medulloepithelioma (Figure 7.13).
INTRAOCULAR TUMORS 67
Benign
a. Nonteratoid—Contains multilayered sheets and cords of neuroepithelial cells
similar to that of ciliary epithelium.
b. Teratoid—It also contains heteroplastic tissue-like hyaline cartilage or
rhabdomyoblasts.
Malignant
a. Nonteratoid—Tumor consists of poorly differentiated neuroepithelial cells
with areas resembling retinoblastoma. However, the lumen of the rosettes
is surrounded by more than a single layer of cells.
b. Teratoid—Shows areas of undifferentiated cartilaginous tissue and
rhabdomyoblasts with carcinomatous or sarcomatous change.
Intraocular Lymphoma
Primary lymphoma: Large B-cell Non-Hodgkin’s lymphoma, previously known
as reticulum cell sarcoma, often presenting clinically as an intermediate uveitis
with or without involvement of the retina, retinal pigment epithelium and
choroid. On clinical evaluation, cellular infiltration of the vitreous may suggest
an inflammatory process. In most cases a vitreous biopsy alone is adequate
for diagnosis; sometimes, however, a more aggressive approach, with
choroidal or retinal biopsy, may be required. Vitreous biopsy of this lymphoma
generally reveals large pleomorphic cells wih prominent round or oval nuclei
and scanty cytoplasm. The nuclear membrane may show indentations. Often
one or more prominent nucleoli are present. Necrotic or ‘ghost’ cells often
serve as a marker for this tumor (Figures 7.14A to C)
However, interpretation of the vitreous biopsy may still be difficult due
to the presence of a number of inflammatory cells. The cytologic picture and
the presence of ghost or necrotic cells may help in this differentiation. A
monomorphic population of normal-appearing lymphocytes does not rule
68 MANUAL OF OCULAR PATHOLOGY
Figures 7.14A and B: A. Montage photograph showing multifocal creamy yellow subretinal
plaque lesion in a patient; B. Magnetic resonance image showing lesion in the brain in a case
of intraocular lymphoma (arrow)
The retina is the neural layer which lines the inner eye and it is composed
of ten layers from outside inwards (Figure 8.1).
Layers of Retina
1. Retinal pigment epithelium
2. Photoreceptor layer (layer of rods and cones)
3. External limiting membrane
4. Outer nuclear layer
5. Outer plexiform layer
6. Inner nuclear layer
7. Inner plexiform layer
8. Ganglion cell layer
9. Nerve fiber layer
10. Internal limiting membrane.
Diabetic Retinopathy
- Diabetic retinopathy is one of the major worldwide causes of blindness
in adults.
- Clinically diabetic retinopathy is divided into two stages:
1. Nonproliferative or background diabetic retinopathy.
2. Proliferative diabetic retinopathy.
Pathologically however, changes can be divided into four stages:
1. Preretinopathy
2. Nonproliferative
3. Preproliferative
4. Proliferative.
The following basic pathological changes are seen in diabetic retinopathy:
a. Breakdown of blood-retinal barrier
b. Capillary basement membrane thickening.
DISEASES OF THE RETINA 71
c. Loss of microvascular intramural pericytes
d. Microaneurysms
e. Capillary acellularity.
Preretinopathy
A. Breakdown of blood-retinal barrier
B. Increase in retinal blood flow
C. Impaired autoregulation of retinal vasculature.
Site of Damage
Intercellular tight junction is the primary site.
Leakage occurs from:
- Retinal vessels.
- Choriocapillaries with malfunctioning RPE.
- Both.
Nonproliferative Retinopathy
I. Vascular changes
II. Exudative changes
III. Hemorrhagic changes.
The earliest histological change is the selective loss of intramural pericytes
in retinal capillaries.
I. Vascular Changes
1. Loss of capillary pericytes.
Pericyte/endothelial cell ratio.
Normal 1:1
Diabetic retinopathy <1:1
2. Capillary microaneurysms: Pathologically, these microaneurysms can be
seen in retinal digest preparations as grape-like or spindle-shaped
dilatations of the retinal capillaries.
3. Thickening of capillary basement membrane: Thickening of the microvascular
basement membrane has been observed in retinal capillaries and
choriocapillaries (diabetic choroidopathy).
4. Capillary acellularity: With the advancement of microvascular lesion in
diabetic retinopathy, there occurs complete loss of all cellular elements
from retinal micorvessels.
Figures 8.2A and B: A. Clinical photographs of the patient with hard exudates;
B. Showing serum and glial neuronal breakdown products in outer plexiform layer (arrow)
Figures 8.3A and B: A. Clinical photographs of the patient with soft exudates; B. Showing
eosinophilic acellular globular deposits in the nerve fiber layer of the retina in a case of soft
exudates (arrow)
Clinical Histopathology
Dot and blot hemorrhages Hemorrhages in inner nuclear layer and
outer plexiform layer.
Flame-shaped hemorrhages Small hemorrhages in nerve fiber layer.
Globular hemorrhages Hemorrhages in middle retinal layers.
Confluent hemorrhages Hemorrhages in all retinal layers.
Preretinal hemorrhages Hemorrhages just below the internal
limiting membrane.
Clinical Histopathology
1. Retinal neovascularization (NVE) New vessels proliferate in front of the
retina and optic nerve. They usually
emanate from the venous circulation,
after breaking through the internal
limiting membrane of the retina.
2. Optic disk neovascularization New vessels arise from the optic head.
(NVD)
Diabetic Maculopathy
Clinical Histopathology
Edema in the macular region Multiple cystoid spaces in the outer plexiform
and inner layer of retina in the macular region,
probably containing extracellular fluid.
76 MANUAL OF OCULAR PATHOLOGY
Figures 9.1A and B: A. Slit lamp photograph showing leukokoria in a case of Coats’
disease; B. Low power microphotograph showing bullous exudative retinal detachment
Figures 9.2A and B: A. Showing multiple cholesterol clefts in the eosinophilic exudates;
B. Showing extensive retinal edema with cystic spaces within the retinal layers
The vitreous is a transparent jelly like structure situated behind the lens and
surrounded by the inner surface of the retina, ciliary body and optic nerve
head. It is about 4ml in volume and weighs about 4 gm. Its index of refraction
is equal to that of the aqueous. It transmits light to the retina. It assists in
supporting surrounding structures in maintaining intraocular pressure and
the contour of the eye.
The attachment of the vitreous to adjacent structures varies in firmness.
It is strongest at the vitreous base and at the margin of the optic disk. The
vitreous base straddles the ora serrata as a circular band varying in width
from 2 to 6 mm. The vitreous is loosely attached to the macular region over
a zone of 3 to 4 mm in diameter.
The vitreous gel is composed of a liquid phase and a solid phase. The solid
component of the vitreous constitutes only 1% of its weight. These include
collagen fibrils, hyalocytes and fibroblasts, and minute amount of protein.
The liquid phase is 99% water with some inorganic salts, sugar, ascorbic acid,
soluble proteins and hyaluronic acid.
Light microscopic study of fixed and stained vitreous shows a series of
net-like fibrous membrane extending centrally from the vitreous base and
parallel to the retina. Vitreous collagen is predominantly type II collagen.
Vitreous is intimately attached in the young adults. This attachment
weakens with increasing age. Vitreous may get separated from the retina in
adults (posterior vitreous detachment). The space between the detached
vitreous and the retina is filled up with nonviscous fluid (liquefied vitreous).
ASTEROID HYALOSIS
It is usually found in more elderly patients and is unilateral in 75% of these
cases. This is a benign degenerative process occurring in the vitreous which
is otherwise normal. Clinically, multiple minute, spherical or disk-shaped
opacities are seen in the vitreous. They have a glistening polychromatic
appearance (Figure 10.1A). Microscopically they are spherical, 0.01 to 0.1 mm
in diameter and are weakly basophilic in hematoxylin and eosin stain. They
are stained by lipid stains like oil red O or Sudan black. They stain intensely
positive blue with stains for acid mucopolysaccharide like alcian blue or
colloidal iron (Figure 10.1B). This stain reaction is not affected by
hyaluronidase.
VITREOUS AMYLOIDOSIS
Bilateral amyloid deposition may occur in the retina and vitreous either as
a part of a primary systemic heredofamilial process or in individuals. with
primary systemic nonfamilial amyloidosis. It may also occur without systemic
or familial involvement as reported by us.
DISEASES OF THE VITREOUS 79
Figures 10.1A and B: A. Showing fundus photograph of a patient with multiple round opacities
in the vitreous of a case of asteroid hyalosis; B. Showing multiple globular bodies stained positive
with alcian blue in a vitrectomy specimen from asteroid hyalosis
Figures 10.2A and B: A. Showing fundus photograph of a case of vitreous amyloidosis showing
multiple vitreous strands; B. Showing positive Congo red stain in vitrectomy specimen of vitreous
amyloidosis
82 MANUAL OF OCULAR PATHOLOGY
ORBITAL INFLAMMATION
Orbital inflammatory diseases and ‘pseudotumors’ are more common than
neoplasms.
A. Acute
a. Suppurative
b. Non-suppurative.
B. Chronic
a. Granulomatous
b. Nongranulomatous.
Orbital Cellulites
- Usually invades from sinuses
- Orbital inflammation.
PATHOLOGY OF THE ORBIT 83
Causes
1. Fungi
- Aspergillus
- Mucormycosis
i. Debilitated patients.
ii. Cancer, diabetic ketoacidosis, patient on immunosuppressive
treatment.
iii. Large, nonseptate fungus visible on H&E stain.
2. Bacteria – pyogenic.
3. Tuberculosis – chronic granulomatous inflammation.
4. Parasites – hydatid cyst.
5. Sarcoidosis.
6. Vasculitis.
- Wegener’s granulomatosis.
- Polyarteritis nodosa.
7. Immunogenic – thyroid ophthalmopathy.
8. Idiopathic – pseudotumor.
PSEUDOTUMOR
Microscopic Examination
A. Polymorphs, lymphocytes, plasma cells, lymphoid follicles, eosinophils:
- Infiltration of orbital fat, muscle, tendon.
- Heals by progressive fibrosis.
B. Reactive lymphoid hyperplasia:
- Mature lymphocytic infiltrate.
- Look for lymphoid follicle, plasma cells, etc.
- Immunohistochemistry to differentiate from lymphoma.
- Lymphoma – monoclonal.
- Reactive lymphoid hyperplasia – polyclonal.
THYROID OPHTHALMOPATHY
Microscopic Examination
- Orbital tissue edema.
- Lymphocytic infiltration.
- Increase in mucin.
- Fibrosis, degeneration and inflammation of extraocular muscles.
- Optic atrophy, corneal changes in late stages.
Vasculitis
- Polyarteritis.
- Temporal arteritis.
84 MANUAL OF OCULAR PATHOLOGY
- Wegener’s granulomatosis:
Generalized
Limited.
Wegener’s Granulomatosis
- Necrotizing vasculitis of upper respiratory tract, lungs and kidney
- Limited form – no renal involvement
- Ocular involvement (28.5%)
- Proptosis 40%
- Scleritis 25%
- Peripheral corneal ulcer.
Micro: Granulomatous vasculitis with fibrinoid necrosis.
Orbital Tumors
- Primary
- Secondary from adjacent structures
- Metastatic.
Congenital Tumors
- Choristoma
- Hamartoma.
Choristoma
Congenital tumors composed of tissues which are not normally found in the
area.
PATHOLOGY OF THE ORBIT 85
4 types have been described:
- Dermoid
- Epidermoid
- Teratoma
- Ectopic lacrimal gland.
Dermoid
Site—Upper and outer aspect of orbit
Gross—Usually solid, occasionally cystic
Micro—The cyst is lined by keratinized stratified squamous epithelium and
the cyst wall contains epidermal appendages (sweat glands, hair follicles,
sebaceous glands). The lumen contains keratin or hair.
Epidermal Cyst
The cyst wall is lined by keratinized stratified squamous epithelium, but the
cyst wall does not bear adnexal structures.
Hamartoma
It is a congenital benign tumor composed of hypertrophy and hyperplasia
of mature tissue at a normal location.
Types
- Phakomatosis
- Hemangioma
- Lymphangioma
- Hemangiopericytoma.
Vasculogenic Tumors
1. Cavernous hemangioma
2. Capillary hemangioma
3. Hemangiopericytoma
4. Lymphangioma
5. Kaposi’s sarcoma.
Cavernous Hemangioma
- Most common adult vascular tumor
- Common in middle aged females
- Low grade proptosis.
Gross: Round encapsulated vascular lesion (Figure 11.1A).
86 MANUAL OF OCULAR PATHOLOGY
Micro: They are composed of large, dilated blood cells (Figure 11.1B). The
stroma contains fibroblasts, smooth muscle and fat and may show hyaline
or myxoid changes.
Capillary Hemangioma
- Infants
- Smaller in size
- Solitary
- Proptosis within 1-2 weeks of birth.
Micro
- Composed predominantly of capillaries
- Lined by benign plump endothelial cells.
Hemangiopericytoma
- Common in adults
- Manifests with proptosis, pain and diplopia.
Micro
- Densely packed oval to spindle-shaped cells with Staghorn vascular pattern
(branching vascular pattern).
- Reticulin stain is helpful in demonstrating tumor cells.
Lymphangioma
- Common in children.
- Characteristically there is fluctuation in proptosis.
Gross
- Uncapsulated lesion.
Micro
- Lymphatic vascular spaces
- Well-formed lymphoid aggregates in fibrotic interstitium.
PATHOLOGY OF THE ORBIT 87
Peripheral Nerve Tumors
Neurofibroma
- Solitary
- Plexiform.
Neurilemmoma (Schwannoma)
- Encapsulated round tumor.
- Usually benign but may also be malignant.
- Composed of proliferating Schwannoma cells in a collagen matrix arranged
in two histologic patterns (Figure 11.2).
i. Antoni A
ii. Antoni B.
Micro
- Fusiform swelling of nerve
- Proliferation of benign spindle-shaped pilocytic astrocytes (Figure 11.3B)
- Eosinophilic clump of glial filaments
- Mucinous degeneration.
Figures 11.3A and B: A. Patient with optic nerve glioma; B. Showing elongated tumor cells
to resemble hair (Pilocytic) along with degenerative eosinophilic substance (Rosenthal fibers)
(arrow)
Types
• Primary Arises from optic nerve meninges
• Secondary Invades from orbit
• Ectopic From ectopic nests.
Micro
- Clusters and whorls of meningothelial cells.
- Intranuclear vacuoles of herniated cytoplasm.
- Psammoma bodies (Figure 11.4).
Rhabdomyosarcoma
- Most common malignant orbital tumor in childhood
- Average age – 7 years.
- Fulminant and rapidly develops proptosis
- Superior orbit most commonly involved.
PATHOLOGY OF THE ORBIT 89
Micro
It is of 4 types:
- Embryonal
- Botryoid
- Alveolar
- Pleomorphic.
Embryonal
- Most common
- Fasicles of tumor cells
- Loose myxomatous stroma
- Spindle cells and strap cells
- Cross-striations.
Botryoid
Embryonal type present beneath the mucous membrane.
Alveolar
- Worst prognosis
- Large polygonal cells with abundant eosinophilic cytoplasm
- Loosely cohesive cells enclosed by connective tissue trabeculae.
Pleomorphic
- Rarest
- Older patients
- Striated muscle differentiation
90 MANUAL OF OCULAR PATHOLOGY
- Cross-striation.
- Strap cells with abundant eosinophilic cytoplasm.
Treatment
- Radiotherapy and chemotherapy (70% survival)
- Exenteration (40% survival).
Malignant Lymphoma
- Malignant lymphoma of the orbit may be primary or orbital manifestation
of systemic lymphoma. Hodgkin lymphoma is rare in the orbit and the
majority of primary orbital lymphomas are non-Hodgkin’s lymphoma
which are immunophenotypically B cell type.
- Clinical:
• Usually older patients except Burkitt’s lymphoma which is more
common in children.
• Proptosis or upper lid ptosis.
- Microscopic examination:
• Low-grade lymphomas—Revised European American Lymphoma (REAL)
classification includes marginal zone lymphomas, chronic lymphocytic
lymphoma/small lymphocytic lymphoma, follicular lymphomas.
• High-grade lymphomas—Large cell lymphoma, lymphoblastic, Burkitt’s
lymphoma.
Follicular Lymphoma
Follicles are well-formed and dominated by cleaved (centrocytes) and few
non-cleaved cells (centroblasts).
Burkitt’s Lymphoma
- Endemic type—Common in children in equator Africa.
- Sporadic type—Common in young adults and older and is present
worldwide.
PATHOLOGY OF THE ORBIT 91
Microscopic Examination
A diffuse population of monomorphic lymphoid cells, interspersed with
tingible body macrophages is a characteristic feature (Starry sky pattern).
Large Cell Lymphoma
- Large cells with vesicular nuclei and distinct nucleoli with numerous mitotic
figures.
Tumors of the Lacrimal Gland
A. Epithelial tumors.
B. Non-epithelial tumors.
- Lymphoma
- Lymphoid hyperplasia
- Inflammation
- Inflammatory pseudotumor.
A. Epithelial Tumors
- Benign mixed tumour
- Malignant mixed tumour
- Adenoid cystic carcinoma
- Ductal adenocarcinoma
- Miscellaneous, e.g. mucoepidermoid.
Epithelial Lacrimal Gland Tumors
a. Benign mixed tumor (Pleomorphic adenoma) –50%
Most common epithelial tumor.
Gross: Encapsulated and expansile
Micro:
- Mixture of epithelial and mesenchymal elements (Figure 11.5).
- Double layer of epithelial cells (epithelial ductules)
- Stroma may appear myxoid
Figure 11.5: Pleomorphic adenoma of the lacrimal gland showing epithelial cells as well
as mesenchymal component
92 MANUAL OF OCULAR PATHOLOGY
- Good prognosis.
b. Malignant mixed-13%
- Malignant transformation of benign mixed tumor
- Poor prognosis.
c. Adenoid cystic- 25-30%
- 2nd most common epithelial tumor of the lacrimal gland
- Pain is a common symptom and occurs due to perineural invasion
- Tightly packed, benign appearing basal cells are found arranged in
masses of variable sizes.
Figures 11.6A and B: A. Adenoid cystic carcinoma of the lacrimal gland showing cystic spaces
within aggregates of basaloid tumor cells giving rise to “Swiss-Cheese” pattern; B. Showing
typical perineural invasion in a case of adenoid cystic carcinoma
Orbital Metastasis
Tumors from distant sites spreading to the orbit by metastasis.
I. IMPRESSION CYTOLOGY
It is a noninvasive technique for obtaining a representative sample of
superficial epithelial cells from the ocular surface.
Indications
• Dry eye disorders
• Ocular surface disorders
• Mucopolysaccharides
• Neural chlamydial conjunctivitis
• Herpes simplex keratitis
• Herpes zoster ophthalmicus
• Allergic eye disease
• Alkali burns.
Procedure
The ocular surface is anesthetized with 1 to 2 drops of proparacaine
hydrochloride 0.5%. A 6 mm disk of cellulose acetate filter membrane with
one side cut off obliquely is placed, dull side down on the bulbar
conjunctiva; the cut edge of the disk faces the limbus. Uniform pressure
of 40 to 45 grams is applied for 10-15 seconds. The cellulose acetate filter
membrane is gently peeled from the ocular surface and placed specimen
side up on a glass slide.
Processing
Generally 1-3 layers are obtained on a filter membrane. Alcohol fixed smears
are stained with hematoxylin and eosin whereas air dried smears are stained
with Giemsa (Figure 12.1).
CYTOPATHOLOGY OF THE EYE 97
Figure 12.1: Photomicrograph showing basophilic inclusion bodies capping the nucleus in
a case of trachoma (Giemsa stain, x 200)
Interpretation
Imprint cytology has utility in ocular surface disorders like ocular surface
squamous neoplasia and dry eye disorders. Dry eye cellular sample shows
increased keratinized cells with pyknotic nuclei (Figures 12.2A and B). In
keratoconjunctivitis sicca, the main feature is squamous metaplasia of
epithelial cells and altered goblet cell density.
Figures 12.2A and B: A. Imprint smear showing a sheet of normal epithelial cells with multiple
goblet cells (hematoxylin and eosin x 100); B. Photomicrograph showing multiple keratinized
epithelial cells and absence of goblet cells (hematoxylin and eosin x 400)
Indications
a. Infectious conditions: Trachoma, viral conjunctivitis, bacterial, fungal and
protozoal infections
b. Non-infectious conditions: Vernal conjunctivitis, pemphigoid, Hay fever
c. Degenerative changes: Keratoconjunctivitis sicca, vitamin A deficiency
d. Neoplastic conditions: Epithelial tumors.
98 MANUAL OF OCULAR PATHOLOGY
Procedure
Topical anesthesia (proparacaine hydrochloride 0.5%) is required.
A sterile kimura spatula is used for scarping or a No.15 blade may be used
as an alternative.
a. Corneal scraping: To obtain a corneal sample, the blade is held at an angle
of 30 degrees to the corneal surface and pressure is applied as the blade
is moved across the lesion. Great care has to be taken to avoid perforation.
Processing
After the scraping, the material is sent to the pathology and microbiology
department. The slide are stained with hematoxylin and eosin as well as with
special stains like Grams, Periodic Acid Schiff and Gomari’s Methanamine
Silver Stain.
Cytopathological correlation
Conjunctiva
Neutrophils Acute infection
Plasma cells, inclusion bodies Trachoma
Eosinophils Allergic response, vernal conjunctivitis, Hay
fever, pemphigoid
Keratinized epithelium Keratoconjunctivitis sicca/vitamin A
deficiency
Atypical epithelial cells Malignancy
CYTOPATHOLOGY OF THE EYE 99
Cornea
Bacteria, fungi (Figure 12.5) and protozoa (acanthamoeba) (Figure 12.6) can
be demonstrated in the material from the corneal scraping.
Figure 12.5: PAS showing septate fungi in corneal scraping (PAS x 200)
Figure 12.6: Corneal scraping showing acanthamoeba (hematoxylin and eosin x 200)
100 MANUAL OF OCULAR PATHOLOGY
Indications
• Endophthalmitis
• Lens-induced uveitis
• Masquerade syndrome
• Parasitic uveitis
• Necrotizing retinitis.
Procedure
Prior instillation of broad spectrum antibiotic drops and local anesthesia is
required. A tuberculin or 2cc syringe with a 27 to 30 gauge needle is used.
In case of fibrin or granulomatous uveitis a large bore 25-26 gauge needle
is used. The needle is passed through the anterior chamber, obliquely through
the stroma, via the lower limbus with the beveled end facing upwards
throughout the procedure. Obtain a 0.1 to 0.3 ml yield of aqueous and on
withdrawal, external pressure is applied to the entrance with a sterile cotton
tipped applicator (Figures 12.7A and B).
Figures 12.7A and B: A. A clinical photograph showing collection of aqueous aspirate sample
by anterior chamber tap; B. Microphotograph showing collection of malignant tumor cells in
the aqueous aspirate sample in a case of metastatic tumor
Processing
As the amount of material is small, it should be handled carefully. In case
of infected uveitis and endophthalmitis, a portion of the material should be
sent to microbiology for direct smear culture and PCR. The remaining fluid
should undergo cytospin to obtain better cell recovery.
Figures 12.8A and B: A. Uveitic eye with hypopyon; B. Photomicrograph showing a microfilaria
surrounded by polymorphonuclear leukocytes (hematoxylin and eosin x 200) from a case of
hypopyon uveitis
Figure 12.9: Slit lamp photograph of a HIV positive patient with hemorrhagic hypopyon
Figures 12.11A and B: A. Slit lamp photograph showing granulomatous uveitis following finger
nail injury; B. Photomicrograph of the same patient showing multiple macrophages engulfing
lens particles (hematoxylin and eosin x 200)
Figures 12.12A and B: A. Slit lamp photograph showing an exudative mass in anterior chamber
of a patient following cataract extraction; B. Photomicrograph showing multiple septate fungi
in KOH calcoflour preparation (KOH calcoflour x 200) from the same patient
Indications
• Endophthalmitis
• Infective posterior uveitis
• Recalcitrant posterior uveitis
• Suspected large cell lymphoma
• Acute retinal necrosis.
Procedure
The procedure is usually done in the operation theater using a surgical
microscope with a subconjunctival or retrobulbar injection. It can also be
performed in the outpatient department under sterile precautions.
Vitreous sampling is done using 25 to 23 gauge needles. Most eyes with
long-standing intraocular inflammation have liquefied vitreous or fluid pockets
within the vitreous. In such a situation, a fine bored 25-guage needle can be
used. When organization of vitreous is seen, a 23-gauge needle is preferred.
The vitreous sample is obtained with the use of a three-way stopcock. One
CYTOPATHOLOGY OF THE EYE 103
end is attached to the needle and the other two openings are attached to a
tuberculin syringes. The globe is immobilized with conjunctival forceps and the
needle is inserted in the vitreous cavity under direct visualization with a slit lamp
microscope. The empty syringe withdraws the vitreous and manipulating the
stopcock, a similar quantity of antibiotic is injected into the vitreous cavity. After
the injection, the needle is slowly withdrawn from the eye.
Processing
The volume of sampled vitreous is relatively large compared to the aqueous
specimen. One half of the specimen is sent to microbiology for culture and
PCR and the other half of the sample is centrifuged by cytospin to prepare
a smear and for immunohistochemistry study.
Indications
• Epithelial malignancies
• Metastatic tumors
• Infection
• Fibrous tumor
• Pseudotumor of orbit.
The Limbal route is used to approach anterior uveal lesions, e.g. iris lesions
or in aphakic patients for posterior ciliary body lesions.
In the posterior segment lesions, the possible approaches are:
gel. For some of the eyes with tumors located posteriorly; a vitrectomy needs
to be performed before aspiration. The purpose of vitrectomy is as follows:
1. To maintain clear visualization of the lesions and the needle path.
2. To remove the vitreous that could potentially adhere to the needle, hence
reducing unnecessary retinal traction.
3. To eliminate adherence of tumor cells in the needle to the vitreous as the
needle is withdrawn (mitigate potential of tumor cells tracking in the
wound).
4. To control bleeding after aspiration.
Corneolimbal Approach
This approach through the zonules prevents dissemination of the tumor mass
through the needle track. This approach is used in patients with
retinoblastoma, a highly friable tumor, as the chance of needle track
dissemination is extremely high. Through a corneolimbal approach the needle
passes through multiple planes, thus wiping out the tumor cells as the needle
is removed from the eye. In addition the absence of blood vessels theoretically
decreases the chances of dissemination.
Subretinal FNAB
This can be done in cases of subretinal abscesses, tuberculomas and large
cell lymphoma (Figures 12.13A and B and 12.14) considering the site is
approachable.
Most surgeons prefer to use a 25-gauge needle with a flexible connector
to a 2-ml syringe to minimize the movement and surgical trauma during
biopsy. Others prefer a spinal needle with a trochar and cannula, although
the excess movement caused by removing the trochar and attaching the syringe
and flexible connector may lead to increased complications.
Figures 12.13A and B: A. Montage photograph showing multifocal creamy yellow subretinal
plaque lesion in a patient; B. Photomicrograph showing necrotic cellular material within which
large lymphoma cells (hematoxylin and eosin x 200) from the same patient
CYTOPATHOLOGY OF THE EYE 105
Figure 12.14: Photomicrograph of FNAB material from the orbit showing monomorphic
lymphoid cells suggestive of lymphoma (hematoxylin and eosin x 100)
Complications
1. The most common complication of FNAB is bleeding from the site of the
needle track. Virtually all intraocular FNABs are associated with a small
degree of hemorrhage, which can be subretinal, retinal or in the vitreous
cavity.
2. Orbital dissemination of tumor cells and distant metastatic spread caused
by tumour implantation along the needle track has been reported. These
are greatly reduced with the use of smaller 25-gauge needles. Theoretically
this procedure can also disseminate a subretinal focus of infection.
3. Iatrogenic retinal perforations are unavoidable by the indirect needle
approach to the choroidal lesions and can theoretically cause a retinal
detachment after FNAB. The numbers of cases developing these retinal
detachments following FNAB are few, possibly because the blood clot
usually closes the site of perforation.
Processing
The sample is taken and processed to form smears and a cell block and stained
with hematoxylin and eosin and special stains like Gomori’s methenamine
silver, Warthin starry stain and Acid-Fast stains, as well as
immunohistochemical stains using antibodies.
Orbital FNAB
FNAB has been used successfully for lymphoid lesions of the orbit and for
detecting metastatic tumor. It provides a definite diagnosis whether the lesion
is primary or metastatic. However in cases of hemorrhagic cystic lesions and
desmoplastic tumors, it is not useful as it may not yield cellular material for
cytological studies.
106 MANUAL OF OCULAR PATHOLOGY
Summary
Cytopathology is a very useful diagnostic technique in ophthalmology.
However, it requires a pathologist experienced in ophthalmic pathology. A
portion of the specimen should be submitted to microbiology in cases of
suspected infective etiology.
Applications
1. Anterior segment:
a. Conjunctiva
b. Cornea
c. Anterior chamber aspirate.
2. Posterior segment:
- Vitreous.
- Needle biopsy of intraocular tumors in selective cases.
3. Orbit: Fine needle aspiration biopsy.
Anterior Segment
Conjunctiva
A. Infectious conditions:
- Trachoma
- Viral conjunctivitis
- Bacterial and fungal infection.
B. Non-infectious conditions:
- Vernal conjunctivitis
- Hay fever conjunctivitis
- Pemphigoid.
C. Degenerative changes:
- Keratoconjunctivitis sicca
- Vitamin A deficiency.
D. Neoplastic conditions:
- Epithelial tumor (biopsy to confirm).
Cytopathologic Correlation
Neutrophils Acute infection
? bacteria
? fungal
Plasma cells Trachoma
Eosinophils Allergic response
Vernal conjunctivitis
Hay fever
Pemphigoid
CYTOPATHOLOGY OF THE EYE 107
Atypical epithelial cells
- ? basal cell carcinoma
- ? squamous cell carcinoma (biopsy to confirm).
Keratinized epithelium
- Keratoconjunctivitis sicca
- Vitamin A deficiency.
Special Techniques
Indirect immunofluorescent staining
- Pemphigoid
- Trachoma.
Imprint smear
- Vitamin A deficiency
- Ocular surface eye disorder.
Imprint smear is taken by pressing Millipore filter paper strips on the surface
of the conjunctiva and is stained with PAS stain. Goblet cells of the conjunctiva
are PAS-positive. The deficiency of these cells, if noted microscopically,
indicates mucin-deficiency and dry eye state.
Inflammatory Conditions
- Endophthalmitis
- Lens-induced uveitis
- Recalcitrant uveitis.
Neoplasms
- Reticulum cell sarcoma
- Juvenile xanthogranuloma
- Metastatic carcinoma.
108 MANUAL OF OCULAR PATHOLOGY
Secondary Glaucoma
- Phacoanaphylactic
- Blood induced
- Melanomalytic.
Others
- Amyloidosis
- Acute retinal necrosis
Intraocular fluid Specimen was submitted in one piece to pathology.
Collection:
- Sterile technique, mandatory
- Immediately in the operation theatre.
Approach
i. Smear for direct examination
ii. Culture for infective organisms
iii. Freeze if immunological study is anticipated.
Figure 13.2: Showing frozen section of squamous cell carcinoma with keratin pearl (arrow)
114 MANUAL OF OCULAR PATHOLOGY
Orbital Involvement
- Burkitt’s lymphoma
- Kaposi’s sarcoma.
118 MANUAL OF OCULAR PATHOLOGY
FURTHER READING
1. Apple DJ, Naumann GOH. General Anatomy and Development of the
Eye: Techniques of Investigation. Human Pathol 1982;13:1-18.
2. Apple DJ, Rabb MF. 1985. Ocular Pathology: Clinical Applications and
Self-assessment 3rd edn 1985.
3. Biswas J, Subramaniam N. Frozen section diagnosis in ophthalmic
pathology. Ind J Ophthalmol 1993;41:114-16.
4. Green WR Diagnostic cytopathology of ocular fluid specimens:
Ophthalmology 1984;91(6): 726-48.
5. Grossniklans HE, Green WR: Conjunctival lesions in adults — A clinical
and histopathologic review Cornea 1987;6(2):78-116.
6. Mclean IW, Foster WD, Zimmerman LE. Uveal melanoma: Location size,
cell type and enucleation as risk factors in metastasis, Human Pathol
1982; 13:123-32.
7. Naumann GOH, Apple DJ. Pathology of the Eye, 1986.
8. Rao NA, and Biswas J , Ocular pathology in AIDS: Ophthalmology clinics
of North America 1988;1:63-72.
9. Sang DN, Albert Dm. Retinoblastoma: Clinical and histopathologic
features. Human Pathol 1982;13:133-46.
10. Spencer WH (Ed) Ophthalmic Pathology: An Atlas and Textbook rd edn
1985.
11. Yanoff M. Fine BS Ocular Pathology: A Text and Atlas, 2nd edn. 1982.
INDEX
I O
Identification of side of globe 4 Ocular pathology in AIDS 113
Immunohistochemical staining 12 Ophthalmic pathology specimens 3
Impression cytology 96 Opportunistic infections of retina 114
Infections 38 Optic nerve
Inflammation 26 glioma 87
Inflammatory conditions 107 meningeal tumors 87
Internal description 6 meningioma 88
Interpretation 97,100,103 Orbit 108
Intraocular lymphoma 67 Orbital tissue 10
Intraocular tumors 55 Orbital cellulites 82
Invasive squamous cell carcinoma 31 Orbital FNAB 105
Orbital inflammation 82
K Orbital involvement 115
Keratoacanthoma 18 Orbital metastasis 92
Orbital tumors 84
L Other histologic features related to
Large cell lymphoma 91 prognosis 63
Layers of retina 70 Other pathologic features 59
Lens 10
P
Lens substance alterations 48
Pars plana transvitreal approach 103
Lid 10
Pathologic study 3
Lid lesions 15
Pathological classification 27
Low power 56
Pathology of
Lymphangioma 86
conjunctiva 25
Lymphoid tumors 32
cornea 35
eyelid 13
M
hair and glands of eyelid 21
Malignant lesions 32
lens 45
Malignant lymphoma 32,90 orbit 81
Malignant melanoma 23,34, 60,65 uvea 51
Marfan’s syndrome 46 Peripheral nerve tumors 87
Marginal zone lymphoma 90 Pigmentation 61
Measurement of globe 5 Pleomorphic 89
Medulloepithelioma 66 Poorly differentiated 58
Melanocytic tumors 33 Posterior segment lesions in aids 114
Melanomas of ciliary body 66 Preproliferative diabetic retinopathy 72
Melanotic tumors of eyelid 23 Preretinopathy 71
Metastatic tumors 66 Primary acquired melanosis (PAM) 33
Microscopic features 65 Primary orbital tumors 84
Molluscum contagiosum 16 Primary site of choroidal metastasis 66
Processing of biopsy specimen 3
N Processing of tissues includes 3
Neoplasms 107 Proliferative diabetic retinopathy 73
Neoplastic lesions 17 Protozoal (Acanthamoeba) 39
Neurogenic tumors 23 Protozoal infections of retina 115
New AFIP classification 62 Pseudo exfoliation syndrome 47
Noninfective vascular disorders 114 Pseudotumor 83
Nonneoplastic lesions 15 Pterygium and pinguecula 29
Nonproliferative retinopathy 71
Novel prognostic parameters R
in uveal melanoma 65 Reactive lymphoid hyperplasia 32
Nuclear sclerosis 48 Retina 114
INDEX 131
Retinoblastoma 56 Treatment 90
Rhabdomyosarcoma 88 Tumor sample collection for molecular
Rosettes 59 biological studies 9
Tumors of lacrimal gland 91
S Types of presentation 22
Secondary glaucoma 108
Secondary orbital tumors 93 U
Sectioning of globe 6 Uveal tissue 10
Site of damage 71
Size of tumor vs prognosis 63 V
Small lymphocytic lymphoma 90 Vascular changes 71
Special procedures 8 Vascular tumors of eyelid 23
Special techniques 107 Vasculitis 83
Squamous cell carcinoma 20 Vasculogenic tumors 85
Squamous lesions 29 Verruca vulgaris 16
Squamous papilloma 30 Viral infections 16
Stains used in ocular pathology lab 10 Vitreous amyloidosis 78
Stevens-Johnson syndrome 27 Vitreous tap 102
Stroma 26,38 Vogt-Koyanagi-Harada (VKH)
Structures adherent to corneal surface 43 syndrome 52
Subretinal fnab 104
Sympathetic ophthalmia 52 W
Wegener’s granulomatosis 84
T Weill-Marchesani syndrome 46
Telepathology 117
Thyroid ophthalmopathy 83 Z
Transillumination 5 Zonular alterations 46