Last revised 23 August 2010
Copyright (c) 2004-2010, PathologyOutlines.com, Inc.
Bold and underlined topics are hypertext links and may open a new window
Links in green are to free full text-no registration journals
Eye (Ophthalmic) Pathology Books
Advertisement
Eye-general
Normal anatomy, autopsy findings, trisomy 13, trisomy 21, congenital rubella syndrome, cyclopia
Conjunctiva
Grossing, normal anatomy/histology, actinic keratosis, ataxia-telangiectasia, benign melanosis, caruncle tumors, conjunctival intraepithelial neoplasia, cystinosis, cysts, dermoid, dysplasia, ephelides, fibrous histiocytoma, graft versus host disease, hereditary benign intraepithelial dyskeratosis, keratoacanthoma, leukoplakia, lymphoid hyperplasia, myxoma, nevi, ocular cicatricial pemphigoid, oncocytoma, pinguecula, plasmacytoma, primary acquired melanosis, pseudoepitheliomatous hyperplasia, pterygium, pyogenic granuloma, sarcoidosis, squamous papilloma, steatocystoma simplex, Sturge-Weber syndrome
Conjunctivitis: general, acute hemorrhagic, allergic, arsenic, chronic, cicatrizing, giant papillary, granulomatous, infectious, ligneous, trachoma
Carcinoma: adenoid squamous carcinoma, basal cell carcinoma, carcinoma in situ, lymphoepithelioma-like carcinoma, metastases, mucoepidermoid carcinoma, sebaceous carcinoma, spindle cell carcinoma, squamous cell carcinoma
Other malignancies: Kaposi’s sarcoma, lymphoma, malignant fibrous histiocytoma, melanoma, rhabdomyosarcoma
Miscellaneous: tumor features to report, TNM staging for carcinoma, TNM staging for melanoma
Cornea
Normal anatomy/histology, grossing, acanthamoeba, actinic band keratopathy, aphakic bullous keratopathy, blood staining, bullous keratopathy, calcific band keratopathy, chronic active keratopathy, collagen-rich crystalloids, corneal dystrophy, epithelial ingrowth, Fuchs dystrophy, graft failure, herpes simplex keratitis, infectious keratitis, keratoconus, keratomalacia, limbus, nonspecific responses, pannus, pseudoexfoliation syndrome, rheumatoid arthritis, transplant, ulceration, tumor features to report
Eyelid
Inflammatory disorders: chalazion, mites, molluscum contagiosum, necrobiotic xanthogranuloma, Prototheca, pseudorheumatoid nodules, pyogenic granuloma, silica granuloma, stye
Tumors: general
Adnexal tumors: adenocarcinoma, eccrine acrospiroma, eccrine carcinoma, pleomorphic adenoma, sebaceous gland adenoma, sebaceous gland carcinoma, sweat gland carcinoma, syringoma, trichilemmal cell tumor, trichilemmoma, trichoepithelioma, trichofolliculoma
Melanocytic tumors: melanoma, melanosis oculi, nevi, nevus of Ota
Other tumors: actinic keratosis, amyloidosis, basal cell carcinoma, cysts, dermoid cyst, hemangioma, Kaposi sarcoma, keratoacanthoma, Merkel cell carcinoma, metastases to eyelid, myxoma, neurofibroma, phakomatous choristoma, pilomatrixoma, pleomorphic adenoma, port wine stain, seborrheic keratosis, squamous papilloma, squamous cell carcinoma, xanthelasma
Miscellaneous: tumor features to report, TNM staging for carcinoma
Glaucoma
General, congenital glaucoma, primary glaucoma, secondary glaucoma, degenerative changes
Globe
General, grossing, inflammation, leukemia, lymphoma, metastases, phthisis bulbi, trauma
Lacrimal duct/gland
General, adenocarcinoma, adenoid cystic carcinoma, dacryoadenitis, dacrocystitis/canaliculitis, dacryoliathiasis, ectopic, malignant mixed tumor, melanoma, Mikulicz’s disease, mucocele, oncocytoma, papilloma, pleomorphic adenoma, squamous cell carcinoma, transitional cell carcinoma, TNM staging for carcinoma of lacrimal gland
Lens and vitreous humor
General, Alport’s syndrome, cataract, dislocation, persistent hyperplastic primary vitreous, phacoanaphylactic endophthalmitis, prosthetic intraocular lens, pseudoexfoliation, vitreous pathology
Orbit and optic nerve
General, alveolar soft parts sarcoma, anterior ischemic optic neuropathy, coloboma, dermoid cyst, drusen, dysthyroid ophthalmopathy, epithelial cyst, Erdheim-Chester, fibrous dysplasia, fibrous histiocytoma, giant cell angiofibroma, glioma of optic nerve, glioma of orbit, granulocytic sarcoma, Grave’s disease, hemangioblastoma, hemangioma, hemangiopericytoma, idiopathic sclerosing inflammation, inflammatory processes, inflammatory pseudotumor, Kimura’s disease, Langerhans cell histiocytosis, lymphangioma, lymphoid hyperplasia, lymphoma, melanocytoma, meningioma, metastases to orbit, mucocele, neurofibroma, nevus, optic atrophy, papilledema, plasmacytoma, rhabdomyosarcoma, Schnabel cavernous degeneration of optic nerve, schwannoma, shaken baby syndrome, sinus histiocytosis, solitary fibrous tumor, subconjunctival herniated orbital fat, temporal arteritis, teratoma, Wegener’s granulomatosis, TNM staging for sarcoma of orbit, TNM staging for ocular adnexal lymphoma
Retina
General, adenocarcinoma, astrocytic tumor, Behcet’s disease, central retinal artery occlusion, central retinal vein occlusion, CMV, Coats’ disease, cystic macular edema, detachment, diabetes, hemangioblastoma, hypertension, lattice degeneration, macular degeneration, massive retinal gliosis, myxopapillary ependymoma, peripheral cystoid degeneration, pleomorphic xanthoastrocytoma, retinal dysplasia, retinitis pigmentosa, retinoblastoma, retinocytoma, retrolental fibroplasia, sickle cell retinopathy, toxoplasmosis, tuberous sclerosis, visceral larva migrans, von Hippel-Lindau disease, Wyburn-Mason syndrome
Miscellaneous: tumor features to report-retinoblastoma, TNM for retinoblastoma
Uvea (iris, choroid and ciliary body), limbus and sclera
Choroid-general, ciliary body-general, iris-general, sclera-general, adenocarcinoma of ciliary epithelium, adenoma of pigmented ciliary epithelium, aniridia, anterior chamber cleavage syndrome, blue sclera, coloboma, diffuse uveal melanocytic proliferation, Fuchs’ adenoma, glioneuroma, hemangioma, herpes zoster, hypertensive changes, idiopathic solitary granuloma, iris pigment epithelial cyst, juvenile xanthogranuloma, leiomyoma, Lisch nodules, medulloepithelioma, melanocytoma, melanoma, mesenchymoma, nevi, osteoma, post-traumatic uveitis, rubeosis iridis, sarcoidosis, scleritis, senile scleral plaques, sympathetic uveitis, uveitis, uveomeningoencephalitic syndrome
Miscellaneous: tumor features to report, TNM for uveal melanoma
Primary references for eye chapter
AJCC Cancer Staging Manual (7th ed)
American Journal of Clinical Pathology, (AJCP), January 1975 to October 2007
American Journal of Surgical Pathology (AJSP), March 1977 to September 2007
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to September 2007
Human Pathology (Hum Path), March 1970 to September 2007
Modern Pathology (Mod Path), January 1988 to October 2007
Font: Tumors of the Eye and Ocular Adnexa (AFIP Atlas of Tumor Pathology, Series 4, Vol 5); 2006
McLean: Tumors of the Eye and Ocular Adnexa (Atlas of Tumor Pathology, Series 3, Vol 12)
Mills: Histology for Pathologists (3rd Ed); Lippincott Williams & Wilkins, 2006
Mills: Sternberg’s Diagnostic Surgical Pathology (4th Ed); Lippincott Williams & Wilkins, 2004
Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004
Websites: University of Utah, University of Illinois at Chicago
Journal search terms: eye, conjunctiva, choroid, ciliary body, cornea, eyelid, globe, iris, lacrimal, lens, orbit, retina, uvea, vitreous and each disease entity listed
Please refer to these primary references for more detailed discussions and additional images
Eye-General
Anterior chamber: between iris and corneal endothelium; contains Schlemm’s canal, trabecular meshwork and aqueous humor
Micro images: anterior chamber; anterior and posterior chambers
Bowman’s layer: see cornea
Bruch’s membrane: see uvea (choroid)
Canaliculi: see lacrimal duct / gland
Caruncle: see conjunctiva
Choriocapillaris: see uvea (choroid)
Choroid: see below
Ciliary body: see below
Conjunctiva: see below
Cornea: see below
Descemet’s membrane: see cornea
Episclera: see sclera
Eyelid: see below
Fornix: see conjunctiva
Fovea centralis: see retina
Globe: see below
Intraocular tissues: uveal tract (iris, choroid and ciliary body), retina, lens and vitreous
Iris: see below
Lacrimal duct / gland: see below
Lacrimal sac: see lacrimal duct / gland
Lamina cribrosa: see orbit and optic nerve
Lamina fusca: see sclera
Lens: see below
Limbus: see below
Macula: see retina
Macula lutea: see retina
Nasolacrimal duct: see lacrimal duct / gland
Optic nerve: see below
Ora serrata: see retina
Orbit: see below
Normal anatomy of eye (continued)
Palpebral fissure: longitudinal opening for the eyes between the eyelids
Pars plicata: see uvea (ciliary body)
Plica semilunaris: see conjunctiva
Posterior chamber: space in the eye between the iris and the suspensory ligament of the lens and the ciliary processes; contains aqueous humor
Micro images: anterior and posterior chambers
Puncta: see lacrimal duct / gland
Pupil: see uvea (iris)
Retina: see below
Schlemm’s canal: see uvea (limbus)
Sclera: see below
Trabecular meshwork: see uvea (limbus)
Trochlea: see orbit and optic nerve
Uvea: see below
Vitreous humor: see below
Zonule: see uvea (ciliary body)
Drawings: schematic of eye #1; #2; section of eyeball; anterior half of eye; posterior half of eye
Virtual slides: whole mount of eye
Most common findings are diabetic retinopathy (14%), age related macular degeneration (5%), melanoma of uvea or choroid, metastatic carcinoma (Archives 2001;125:1193)
Rare findings are retinitis pigmentosa
May be useful for forensic cases (Leg Med (Tokyo) 2003;5 Suppl 1:S288)
Trisomy 13 (Patau syndrome) and eye
Almost all patients have severe ocular abnormalities
80% have microphthalmos (abnormally small eyes), cyclopean synophthalmus (fused eyes), colobomas, cataracts (Am J Ophthalmol 2006;141:1057), or persistent hyperplastic primary vitreous
75% have retinal dysplasia (tubular and rosette-like structures)
65% have cartilage within coloboma
60% have anterior chamber dysgenesis (defective development of cornea, iris or anterior chamber angle), often associated with congenital glaucoma
Case reports: tarsal kink (Ophthal Plast Reconstr Surg 2003;19:408)
Clinical images: cyclopia with proboscis #1; #2
References: Oftalmol Zh 1990;7:423, Wikipedia, Orpha.net
Less severe than trisomy 13
Hypertelorism (widely spaced eyes), lid abnormalities (oblique, arched palpebral fissures), epicanthus (vertical fold of skin on either side of nose), ectropion and eversion of upper eyelid; also keratoconus (may be due to knuckle rubbing) and retinal dysplasia
Also esotropia, significant refractive errors (43% at school age, Dev Med Child Neurol 2007;49:513), hyperemic optic disc, retinal pigment epithelial atrophy, prominent whitened choroidal vessels, chronic blepharoconjunctivitis, nasolacrimal duct obstruction (Ophthalmology 2003;110:1437)
Iris is speckled due to Brushfield spots (ringlike foci of iris hypoplasia surrounded by normal stroma), present in 85% with blue or hazel eyes (Indian Pediatr 2002;39:97), uncommon in Asian children with Down’s syndrome (Eye 2002;16:710)
Cataracts develop at age 15+ years
Recommended that Down’s patients have initial eye exam at 6 months of age, then annually
Clinical images: Brushfield spots
Molecular images: karyotype #1; #2
References: eMedicine
Congenital rubella syndrome and eye
Associated with cataracts (90%), iris abnormalities, retinopathy, congenital glaucoma, microphthalmos (Indian J Ophthalmol 2002;50:307)
Cataracts are due to retention of cell nucleus in lens cells
Rubella virus can survive within these cells for years; surgery on these infants may cause uveitis or endophthalmitis, due to release of virus; cataract surgery has less than optimal results (J AAPOS 2003;7:91)
Iris abnormalities include poorly developed dilator muscle and necrotic appearing epithelium; granulomatous inflammation is common; iris looks leathery since it doesn't dilate normally
Rubella retinopathy consists of alternating atrophy and hypertrophy of retinal pigment epithelium (salt and pepper appearance); may have subretinal neovascularization
Incidence of 0.6 per 1000 live births in Oman (Arch Ophthalmol 2004;122:541)
Disease persists in industrialized countries in those infected prior to 1969 vaccine (Optometry 2002;73:418)
Clinical images: bilateral cataracts
_PHIL_4284_lores.jpg/250px-Cataracts_due_to_Congenital_Rubella_Syndrome_(CRS)_PHIL_4284_lores.jpg){kind=link}
Congenital facial abnormality with one medial eye (either single eye or 2 fused eyeballs) and proboscis (tubular appendage) superior to the orbit
Usually associated with holoprosencephaly, due to impaired midline cleavage of embryonic forebrain
Incidence of 1 per 100K births
Incompatible with life
Associated with trisomy 13, trisomy 18, triploidy; also other chromosomal abnormalities
May be due to malfunction of sonic hedgehog protein
Case reports: Archives 2005;129:e19
Clinical images: various images; trisomy 13 - cyclopia with proboscis #1; #2
Conjunctiva
Grossing of conjunctiva
Specimens are thin and tend to fold when placed in fixative
Surgeon should spread lesion onto filter paper, allow to dry for a few seconds, then place in specimen container (see University of Illinois at Chicago protocol)
Relevant landmarks should be labeled
For lesions that extend to limbus, cut so sections are perpendicular to limbus
Don’t use methylene blue or toluidine blue ink for margins, as they bleed into sample
Don’t place specimens on sponges, which expand in fixative and distort specimen
Normal anatomy / histology of conjunctiva
Thin mucous membrane that lines inner eyelid (tarsal or palpebral portion) and anterior surface of ocular globe (bulbar portion)
Has protective function and also allows eyelids to move smoothly over globe
Has rich lymphatic channels connecting to parotid and submandibular nodes
Bulbar conjunctiva: covers anterior surface of sclera and surface epithelium of cornea; cuboidal and columnar epithelium; goblet cells more common in inferior and nasal parts, particularly near fornix; substantia propria has loose connective tissue with scattered inflammatory cells and deep dense collagen
Caruncle: small (5 x 3 mm) fleshy nodular prominence in nasal portion of interpalpebral fissure (inner angle of eye) between skin and conjunctiva; lined by conjunctival epithelium and nonkeratinized squamous epithelium; contains cutaneous adnexal structures, accessory lacrimal gland tissue
Fornix: portion of conjunctiva that forms a cul de sac where it reflects onto surface of the globe; pseudostratified columnar epithelium rich in goblet cells (may mimic dysplasia); contains accessory lacrimal tissue, ductules of main lacrimal gland and lymphoid follicles; site of sarcoid granulomas
Limbal conjunctiva: annular rim of conjunctiva extending from cornea to 3 cm on bulbar surface; contains corneal epithelial stem cells in its basal layers; also branching dendritic melanocytes
Palpebral (tarsal) conjunctiva: lines interior of eyelid; has pseudoglands of Henle (invaginations of surface epithelium that form tubular and cystic structures), hair follicles (Cornea 2006;25:781); substantia propria is more uniform than in bulbar conjunctiva and is more closely attached to tarsus (so invasive lesions appear clinically flat), has arterioles, veins and complex capillary network, myelinated and nonmyelinated branches of trigeminal nerve, lymphoid aggregates near fornices, acini and ducts of accessory lacrimal glands of Wolfring and Kraus; conjunctiva becomes papillary with allergic or bacterial conjunctivitis
Plica semilunaris (semilunar fold): arc shaped fold of conjunctiva just lateral to caruncle; may be vestigial nictitating membrane of lower species; contains abundant goblet cells and rarely cartilage or smooth muscle
Regional lymph nodes: preauricular/parotid (drains temporal lymphatics), submandibular (drains nasal and caruncle lymphatics)
Micro: mucous membrane with epithelium and substantia propria; has 2-5 layers of columnar or cuboidal cells resting on continuous basal lamina; epithelial cells may have eosinophilic cytoplasm and apical snouts; also goblet cells that secrete mucin, melanocytes (more prominent in dark skinned patients), Langerhans cells and intraepithelial lymphocytes (conjunctival associated lymphoid tissue-Invest Ophthalmol Vis Sci 2000;41:1270)
Micro images: bulbar conjunctiva #1; #2-stratified nonkeratinizing squamous epithelium with goblet cells covers a vascular lamina propria; conjunctival goblet cells (right) facing pigmented corneal epithelium (left) near junction; palpebral conjunctiva rests upon tarsal plate
Positive stains: CK19, MUC1 and MUC4 (Invest Ophthalmol Vis Sci 2000;41:398), MUC7 (Cornea 2003;22:41); very low levels of MUC2 and MUC5AC (Invest Ophthalmol Vis Sci 2000;41:703),
Negative stains: CK3
References: Hum Path 1997;28:1348 (cytokeratin)
Actinic keratosis of conjunctiva
Also called leukoplakic lesions, ultraviolet light related lesions
Usually limbal conjunctiva at advancing head of pterygium
Case reports: 73 year old man (J Fr Ophtalmol 1998;21:458), bilateral limbus lesions (J Fr Ophtalmol 1992;15:65), 42 year old man with conjunctival mass (Indian J Ophthalmol 2004;52:154)
Clinical images: elevated white limbal tumor
Gross: thickened conjunctiva with leukoplakia
Micro: sharply demarcated; mild atypia of epithelium, acanthosis, parakeratosis, hyperkeratosis but normal polarity, normal maturation; elastotic degeneration and lymphocytes in substantia propria
Micro images: mild epithelial atypia, degenerative changes in substantia propria #1; #2; sharply demarcated intraepithelial lesion with acanthosis, moderate atypia, parakeratosis and subepithelial actinic elastosis; intraepithelial corneal lesion with severe atypia and parakeratosis #1; #2; acantholytic lesion with subepithelial lymphocytes; atrophic lesion with atypia
DD: dysplasia (more diffuse and gelatinous, Can J Ophthalmol 1995;30:312), carcinoma in situ
Ataxia-telangiectasia and conjunctiva
Autosomal recessive disease; previously called Louis-Bar syndrome
Characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia and recurrent respiratory and sinus infections
Telangiectatic blood vessels in bulbar conjunctiva in >90% (Am J Ophthalmol 2002;134:891)
Mostly visible by age 4-5 years, primarily within palpebral fissure (Acta Ophthalmol Scand 2007;85:557)
References: eMedicine #1; #2; Atlas of Genetics and Cytogenetics
Benign melanosis of conjunctiva
See also primary acquired melanosis
May be normal finding in dark skinned individuals - bilateral, continues throughout life
Present in 92% of blacks, 36% of Asians, 28% of Hispanics, 5% of whites
Uncommon finding in Laugier-Hunziker syndrome (Arch Dermatol 2007;143:631)
Clinical images: racial melanosis
Micro: dense pigmentation at basal layer of epithelium, but normal number of melanocytes
Micro images: dendritic melanocytes are present in racial melanosis
Negative stains: HMB45 in racial melanosis (Histopathology 2001;39:426)
DD: melanocyte migration associated with inflammation or trauma, medications (epinephrine, tetracycline, silver-containing products), ochronosis, iron containing foreign bodies, early primary acquired melanosis (melanocytic proliferation is present), ocular melanocytosis (pigmentation of ocular structures due to abnormal migration of melanocytes during development)
4% of conjunctival tumors
May include any tumor type that occurs in conjunctiva, skin or lacrimal gland
Usually papilloma or nevus (Am J Ophthalmol 2006;142:448)
5% are malignant - melanoma, squamous cell carcinoma, sebaceous gland carcinoma, lymphoma
May be due to spread from other conjunctival, eyelid or lacrimal tumors
Case reports: basal cell carcinoma #1 in 80 year old man (J Cutan Pathol 2005;32:502), #2 in 82 year old man (Ophthal Plast Reconstr Surg 2006;22:313), inflammatory pseudotumor (J Fr Ophtalmol 2003;26:204), sebaceous gland carcinoma in 68 year old woman (Cornea 2006;25:858); metastasis from pulmonary large cell neuroendocrine carcinoma (Am J Ophthalmol 2002;134:438)
Conjunctival intraepithelial neoplasia
Precursor to squamous cell carcinoma
Dysplastic changes of conjunctiva ranging from dysplasia to carcinoma in situ
Incidence of 1.9 cases per 100K per year
Associated with ocular pigmentation, tobacco use, sun exposure (Br J Ophthalmol 2003;87:396), exposure to petroleum products, chronic cyclosporine for transplants
HIV is associated with aggressive tumors presenting at younger ages
HPV 6/11 in 38%, HPV 16 in 30-58%, HPV 18 in 50-57% (Ophthalmology 2002;109:542)
Treatment: excision, but often recurs; topical interferon-alpha-2b (Ophthalmologe 2006;103:124), mitomycin (Arch Soc Esp Oftalmol 2004;79:375) or adjuvant cryotherapy reduces recurrence rate; usually does not become invasive with recurrence; amniotic membrane grafts may be useful (Chang Gung Med J 2003;26:737)
Gross: sharply circumscribed limbus lesion; annular and gelatinous; may see delicate epithelial proliferation of cornea with indirect illumination
Micro: sharply circumscribed atypia; dysplasia begins in basal layers and extends towards surface; large or small squamous cells, may be spindled; often atypical mitotic figures at all levels of epithelium; fronds of proliferating blood vessels and connective tissue resemble papilloma; rarely HPV related changes (koilocytes); usually NO keratinization or dyskeratosis; no invasion of epithelial basal membrane
Positive stains: p53, Ki-67, HPV
DD: UV related lesions (without dysplasia), sebaceous gland carcinoma, adenocarcinoma from eyelid glands of Moll, melanosis
Must fix tissue in absolute alcohol, not formalin, or crystals will be dissolved
Micro images: cystinosis in conjunctiva of child
DD: gout, hypergammaglobulinemia
See also steatocystoma simplex
Most are acquired due to surgery (Ophthalmology 2006;113:1049), trauma (Br J Anaesth 2005;95), foreign bodies or chronic inflammation; also parasitic cysts
Usually on nasal conjunctiva and lower fornix
Most (65%) conjunctival nevi are also cystic (Curr Opin Ophthalmol 2007;18:351)
Cyst may be injected with Healon V and trypan blue to facilitate visualization and excision (Cornea 2005;24:759)
Dermoid cysts: lined by stratified squamous epithelium, contains cutaneous adnexae (Ophthal Plast Reconstr Surg 2006;22:137); see also dermoid tumor below
Inclusion cysts: one or two cell lining of non-keratinized epithelium containing goblet cells; may have apocrine snouts resembling apocrine glands; may be associated with Stevens-Johnson syndrome (Ophthal Plast Reconstr Surg 2006;22:475)
Clinical images: multiloculated cyst post-anesthetic injection; large cyst
Gross: usually translucent to light blue
Dermoid tumor and other congenital lesions of conjunctiva
A type of choristoma (congenital, non-neoplastic lesion composed of cytologically normal tissue not normally found at that location), often at limbus
Mainly children
No malignant potential
May be associated with colobomas of iris and ciliary body, Goldenhar’s syndrome (ocular dermoid tumors, extra-auricular appendages, vertebral anomalies, East Afr Med J 2002;79:502), organoid nevus syndrome (also called linear nevus sebaceous of Jadassohn, Br J Ophthalmol 1987;71:268)
Gross: bulbar tumors are firm, localized, elevated, opaque, yellow-white masses at limbus
Micro:
Dermoid: solid (not cystic) choristoma mass with surface epithelium resembling epidermis and dermis and containing a few hairs, overlying thick bundles of collagen, which make up bulk of mass (eMedicine)
Complex choristoma: cartilage, lacrimal tissue, smooth muscle, adipose tissue, neural tissue (Ophthalmology 1987;94:1249); may be confused with prolapsed lacrimal gland (Acta Ophthalmol Scand 2005;83:100)
Osseous choristoma: small, solid, circumscribed, red-white bony lesion behind limbus and between superior and lateral rectus muscles; composed of compact lamellar bone surrounded by dense, collagenous bone (Br J Ophthalmol 1979;63:173, Ophthalmic Surg Lasers 2002;33:410)
Dermolipoma: abundant adipose tissue but minimal skin adnexae, usually in upper outer fornix; only superficial portion is excised as deep portion is attached to rectus muscles and fascia (The Internet Journal of Ophthalmology and Visual Science 2006;4:Number 1, Arch Ophthalmol 1994;112:1114); resembles subconjunctival herniated orbital fat (Aust N Z J Ophthalmol 1999;27:33)
Smooth muscle hamartoma: gray, cyst-like appearance; spindled smooth muscle, fibrous stroma, lobules of adipose tissue (Am J Ophthalmol 1999;128:643)
Clinical images: epibulbar dermoid
Micro images: limbal dermoid - subepithelial fibrous tissue resembling reticular dermis with skin appendages #1; #2
complex choristoma - lacrimal gland tissue within a limbal dermoid; island of cartilage within a limbal dermoid
osseous choristoma - bone within connective tissue capsule; bone contains marrow
dermolipoma - abundant adipose tissue
Lesions intermediate between squamous papilloma and carcinoma in situ
Also called conjunctival intraepithelial neoplasia
Associated with HPV 16/18 (AJCP 2004;122:938)
Scape cytology may be useful for diagnosis after toxin exposure (Acta Cytol 2001;45:909)
Tends to recur (Can J Ophthalmol 1995;30:312)
Gross: diffuse and gelatinous
Micro: acanthotic lesions with atypia but no/minimal parakeratosis or hyperkeratosis; surface maturation (i.e. changes are NOT full thickness)
Micro images: acanthotic lesion with moderate atypia involves half the epithelial thickness; less than full thickness epithelial atypia #1; #2
Positive stains: PAS in surface epithelium (evidence of maturation)
Ephelides or freckle of conjunctiva
Congenital pigmentation, does not evolve into melanoma
Surrounding conjunctiva is normal
Associated with fair skin, red hair, and Carney syndrome
Gross: flat pigmented foci
Micro: well circumscribed area of hyperpigmented basal cells
Micro images: increased melanocytic activity in basal layer
Fibrous histiocytoma of conjunctiva
Occasionally occurs in conjunctiva
See also fibrous histiocytoma of orbit
Case reports: corneoscleral tumor (Br J Ophthalmol 2002;86:477)
Treatment: excision is curative (Am J Ophthalmol 2006;142:1036)
Gross: fleshy, yellow, nodular
Micro: elongated fibroblasts, plump histiocytes with occasional vacuolated cytoplasm, some multinucleated giant cells, scattered lymphocytes.
Micro images: various images
References: Am J Ophthalmol 1988;106:579
Graft versus host disease of conjunctiva
Occurs in up to 80% of chronic graft versus host disease patients with allogeneic hematopoietic transplants
Most commonly affects conjunctiva and lacrimal gland, also cornea, choroid
Bulbar conjunctiva is biopsied for diagnosis
Micro: reduced goblet cells (Eur J Ophthalmol 2006;16:17); pseudomembrane due to loss of conjunctival epithelium; may have keratinization
References: Graefes Arch Clin Exp Ophthalmol 2007;245:1001
Hereditary benign intraepithelial dyskeratosis of conjunctiva
Also called Witkop von Sallman syndrome
Rare, autosomal dominant disease with incomplete penetrance
Originally described in Haliwa Indians in North Carolina (USA), also elsewhere in US and Europe
Bilateral lesions of conjunctiva; also oral lesions (J Am Acad Dermatol 2001;45:634)
Treatment: excision, but lesions commonly recur; no malignant transformation
Gross: gray-white, inflamed, horseshoe shaped elevated lesions of conjunctiva and oral mucosa
Micro: acanthotic and dyskeratotic epithelium of conjunctiva and oral mucosa; middle and superficial layers have large squamous cells and dyskeratotic cells, but no atypia; subepithelial lymphoid infiltrate
EM: numerous vesicular bodies in immature dyskeratotic cells; densely packed tonofilaments fill mature dyskeratotic cells, which lack cellular interdigitations and desmosomes (Oral Surg Oral Med Oral Pathol 1977;44:567)
Molecular: associated with 4q35 telomeric region (Am J Hum Genet 2001;68:491)
DD: conjunctival dysplasia (atypia, no family history, not bilateral, no oral mucosal involvement)
Keratoacanthoma of conjunctiva
Uncommon, rapidly growing, squamous cell proliferation
Sun exposed bulbar conjunctiva
Grows for weeks and then regresses or stays unchanged
Case reports: 39 year old Japanese man (Arch Ophthalmol 2003;121:118); 34 year old woman (Rev Hosp Clin Fac Med Sao Paulo 2004;59:135), with xeroderma pigmentosum (Indian J Dermatol Venereol Leprol 2005;71:430)
Treatment: excision; may need cryotherapy of margins due to possibility of malignant diagnosis; only rarely recurs
Clinical images: white, dome-shaped mass with a central crater filled with white material; 1.2 cm lesion at nasal bulbar conjunctiva; nodular white conjunctival mass; mobile conjunctival mass with central hyperkeratotic area
Gross: crater like
Micro: lobules of proliferating squamous epithelium, often mitotic figures; deep edges are well circumscribed and regular appearing; epithelial cells are glassy with vesicular nuclei and prominent eosinophilic nucleoli; no/rare parakeratosis; often acute and chronic inflammatory cells which extend into adjacent epithelium
Micro images: central crater containing keratin plug (arrowheads), surrounded by acanthotic conjunctival epithelium including horn pearls (arrow); crater like lesion with central keratin and acanthotic epithelium; eosinophilic, glassy cytoplasm and mitotic figures
DD: squamous cell carcinoma (infiltrative margins, often cannot be definitively excluded), pseudoepitheliomatous hyperplasia
A clinical term referring to a white mass, usually on bulbar conjunctiva; may be benign or malignant
Not a diagnostic term
Benign lesions are often due to ultraviolet light damage or associated with advancing edge of pterygium
Bitot spot: sharply defined, bubbly, white focus of keratinization near limbus; due to squamous metaplasia, epidermalization, hyperkeratosis and loss of goblet cells; associated with early vitamin A deficiency; more common in children under age 3
Xerosis (drying of conjunctiva): associated with acanthosis, keratinization, loss of goblet cells; due to keratoconjunctivitis sicca, Sjogren’s syndrome, radiotherapy, other conjunctival drying disorders
Case reports: due to hyperplasia post-limbal epithelium transplant (Clin Experiment Ophthalmol 2006;34:889)
Clinical images: corneal xerosis; irregular white lesion of superior limbus
Gross: nodular, irregular, gray-white lesion due to parakeratosis and keratinization
Micro images: xerosis
Lymphoid hyperplasia of conjunctiva
May be response to infection by various pathogens or toxins/irritants (DNA Cell Biol 2002;21:421)
Rare in children; low apparent risk of subsequent malignancy (Arch Ophthalmol 1999;117:832)
Case reports: post LASIK surgery (Graefes Arch Clin Exp Ophthalmol 2006;244:529), 14 year old boy with bilateral lesions (Clin Experiment Ophthalmol 2005;33:285), myopic scleral thinning (Clin Experiment Ophthalmol 2005;33:73)
Treatment: excision; may recur (Can J Ophthalmol 2006;41:753)
Clinical images: lymphoid hyperplasia
Gross: red thickenings, may be nodular; may appear as small bumps with pale centers giving a cobblestone appearance, usually in inferior tarsal conjunctiva
Micro: well differentiated, somewhat pleomorphic lymphocytes with occasional plasma cells, macrophages, eosinophils and follicles with germinal centers; follicles usually contain tingible body macrophages (containing apoptotic debris) and mitotic activity; often hyperplastic vessels
DD: MALT lymphoma
Rare benign tumor
May be associated with Carney’s complex
Median age 50 years, range 18-76 years (Am J Ophthalmol 1986;102:80)
Case reports: 18 year old woman (Br J Ophthalmol 1984;68:618), 80 year old woman (Jpn J Ophthalmol 1995;39:77)
Treatment: local excision; does not recur (Arch Ophthalmol 1983;101:1416)
Clinical images: glistening cystic mass of nasal conjunctiva with overlying blood vessels
Gross: smooth, fleshy, gelatinous, pale yellow
Gross images: well circumscribed cystic mass with connective tissue tail
Micro: hypocellular with stellate/spindled cells in myxoid stroma; cells have delicate cytoplasmic processes and intranuclear vacuoles; minimal vessels
Micro images: loose connective tissue covered by conjunctival epithelium; stellate and spindle cells in myxoid stroma
Positive stains: cells - vimentin, smooth muscle actin; stroma - Alcian blue (hyaluronidase sensitive )
DD: myxoid neurofibroma, nerve sheath myxoma, spindle cell lipoma, lymphangioma
See also Nevus of Ota in eyelid below
Common in conjunctiva; only rarely invades cornea or appears in fornix or over palpebral conjunctiva
May be observed at birth or later
May enlarge and become more pigmented at puberty or during pregnancy
About half of excised pigmented lesions are nevi, remainder are melanomas or primary acquired melanosis
Treatment: excision or watchful waiting, only rarely transforms (1 per 150K); excise if newly acquired in adults, clinical growth, change in pigmentation, cosmetic reasons
Case reports: bilateral nevi of caruncle (Klin Monatsbl Augenheilkd 2002;219:380), 70 year old with growing peripunctal nevus (Ophthalmologe 2003;100:476), balloon cell nevus (Arch Pediatr Adolesc Med 2001;155:93)
Clinical images: various images #1; #2; anterior to plica; balloon cell nevus
.+They+do+not+usually+extend+onto+the+cornea+or+develop+large+feeder+blood+vessels.){kind=link}
Gross: discrete, flat or slightly elevated; circumscribed, pink, yellow-tan, brown or nonpigmented, in interpalpebral zone near limbus; 1/3 are amelanotic
Micro: small round nevus cells with junctional or compound features; often with solid and prominent cystic inclusions of conjunctival epithelium and chronic inflammatory infiltrate; may have atypical features and mitotic figures during growth periods
compound - common, nevi cells in epithelium and subepithelial connective tissue; cells have cysts lined by cuboidal and goblet cells and intranuclear inclusions; may have large pigmented cells with prominent basophilic nucleoli; usually mixed inflammatory cells
junctional - contiguous nests of round/spindle melanocytes near basal cell region with oval nuclei, small nucleoli; nucleoli may be basophilic and prominent, but no atypia; uncommon except in young children; resembles primary acquired melanosis with atypia
subepithelial - nevus cells only in subepithelial connective tissue, no pigment, bland nuclei; may have clear cytoplasm due to lipid and central round nucleus (balloon cell nevus)
Micro images: nevi #1; #2; #3; compound nevus-variability in cytology; atypical compound nevus-melanocytes in junctional area mature into smaller and less hyperchromatic cells as they extend deeper into lamina propria
balloon cell - balloon cell compound nevus composed of large clear cells; various images
cystic compound nevus - multiple large cysts; nevoid cells in junctional area around cystic spaces; sheets of melanocytes with variable-sized cysts; diffuse proliferation of melanocytes, with cysts lined by conjunctival epithelium with goblet cells
DD: melanoma (atypical intraepithelial component, atypical mitotic figures, necrosis)
References: Arch Ophthalmol 2004;122:167
Blue nevus (cellular blue nevus) of conjunctiva
Combined nevus: combination of nevocytic and blue nevus (Trans Am Ophthalmol Soc 1999;97:170)
Case reports: 54 year old man with multifocal pigmentations (Klin Monatsbl Augenheilkd 1994;205:242), 71 year old woman with slow growing lesion (Ophthalmology. 1992;99:1714), giving rise to melanoma (Arch Ophthalmol 2000;118:1581)
Gross: blue-brown due to superficial location, lack of dermal collagen and numerous pigmented nevus cells
Micro: spindled and dendritic melanocytes in epithelium and collagenous stroma; melanocytes have coarsely clumped melanin granules
Micro images: combined nevus - pigmented dendritic and spindled blue nevus cells in area adjacent to nevocytic foci #1; #2; #3; #4; #5
Inflammatory juvenile conjunctival nevus
Benign, inflammatory juxtalimbal lesion characterized by marked eosinophils
Children and teenagers
May grow rapidly and cause congestion, and clinically resemble melanoma
Associated with systemic allergies and bilateral papillary conjunctivitis (Br J Ophthalmol 2002;86:28)
Treatment: excision and close follow up
Micro: epithelial cysts and solid islands composed of benign nevus cells; also prominent eosinophils and mast cells (some degranulated); often lymphocytes and lymphoid follicles (Invest Ophthalmol Vis Sci 2002;43:1850) and plasma cells
Micro images: various clinical and micro images
DD: melanoma (Klin Monatsbl Augenheilkd 2007;224:422)
Spitz nevus of conjunctiva
Also called spindle and epithelioid cell nevus
Rare; usually children
Case reports: 28 year old man with rapidly growing mass (Bull Soc Belge Ophtalmol 2007:63)
Gross: nonpigmented, pink-yellow, nodular
Micro: large, uniform, epithelioid cells and lightly pigmented spindle cells; rarely has more pigmented nevus cells; no/rare mitotic figures
Micro images: lesion of eyelid
Positive stains: HMB45, S100, Ki-67
DD: melanoma
Ocular cicatricial pemphigoid of conjunctiva
Also called mucus membrane pemphigoid of conjunctiva
Mucocutaneous autoimmune disorder
Usually age 50+ years, more common in women
50% of cases involve conjunctiva, usually 10 years or more after onset of cutaneous or other mucosal disease; may occasionally demonstrate purely ocular disease (Ophthalmology 1999;106:355)
Uncontrolled cases are associated with infection (Cornea 2004;23:819)
Rarely presents with corneal ulceration (Eur J Ophthalmol 2007;17:121)
Divide sample in two - one for formalin, one in transport media for immunofluorescent studies
Impression cytology may be useful for diagnosis (Arch Soc Esp Oftalmol 2004;79:67)
Diagnosis: compatible clinical picture plus linear deposition of IgA and IgG along conjunctival basal lamina or circulating anti-basement membrane antibodies (Ophthalmology 2004;111:45)
Case reports: associated with anti-laminin 5 antibodies (Clin Exp Dermatol 2005;30:679)
Clinical images: various images; subepithelial fibrosis and fornix foreshortening
Micro: early - epithelial erosions and bullae; late - epithelial and stromal scarring, perivascular lymphocytes and plasma cells
Micro images: bullous separation of epithelium from inflamed and scarred substantia propria; IgG staining shows linear pattern #1; #2; IgA deposition (figs 1, 3)
EM: EM has limited usefulness in diagnosis (Ophthalmology 2006;113:1651)
DD: epidermolysis bullosa acquisita (Arch Ophthalmol 2006;124:1615), paraneoplastic syndrome from nonocular carcinoma (Br J Ophthalmol 2007;91:1562)
References: Curr Opin Allergy Clin Immunol 2004;4:435, eMedicine #1; #2
Usually caruncle (Arch Ophthalmol 1977;95:474)
Often elderly (mean age 73), more common in women
Case reports: tumor of caruncle #1 (Int Ophthalmol 2004;25:321), #2 (Klin Monatsbl Augenheilkd 2005;222:733); #3 (Indian J Ophthalmol. 2002;50:60); tumor of bulbar conjunctiva (Klin Monatsbl Augenheilkd 1996;209:176)
Clinical images: red subconjunctival lesion at plica semilunaris
Gross: red-orange or yellow-tan mass
Micro: solid nests and cords of polyhedral cells with abundant, finely granular acidophilic cytoplasm and round/oval paracentral nuclei, usually with one prominent nucleolus; may have microcystic areas with occasional goblet cells (Am J Dermatopathol 2007;29:279), may have malignant histology and behavior
Micro images: well circumscribed, subepithelial, multiloculated cystadenomatous lesion; tall columnar acidophilic cells lining glandular spaces; subepithelial glandular tumor #1; #2-glandular spaces are lined by oncocytes and goblet cells; well circumscribed lesion; large polyhedral cells with abundant eosinophilic granular cytoplasm and small nuclei with single prominent nucleoli; cystic areas contain eosinophilic secretions; light and dark cells with acinar formation on left side
Positive stains: alpha-1-antitrypsin, GCDFP-15, CEA, lysozyme, MUC1; CK 5/6 and p63 in some cells
Negative stains: smooth muscle actin, muscle-specific actin, S100,. ER, PR
EM: large numbers of mitochondria (Br J Ophthalmol 1980;64:935)
Common bilateral degenerative process associated with sun damage and age; also advanced glycation end products (Graefes Arch Clin Exp Ophthalmol 2006;244:104)
Not progressive
Usually not biopsied
May cause uneven distribution of tear film, leading to focal dehydration and saucer like depression in corneal tissue (“dellen”)
Treatment: excision for cosmetic reasons or to remove mild irritation; otherwise no treatment
Gross: elevated yellow lesion (due to solar elastosis) in bulbar conjunctiva in interpalpebral region near nasal limbus; conjunctiva is atrophic or thickened
Micro: band of subepithelial actinic elastosis with variable hyalinization and calcification; may have acanthosis or dyskeratosis resembling carcinoma; may have foreign body giant cell reaction around elastotic material (actinic granuloma)
Very rare
Due to multiple myeloma or rarely solitary disease
Solitary disease is usually indolent
Case reports: 70 year old woman with solitary tumor (Klin Monatsbl Augenheilkd 1997;211:128)
Gross: red, circumscribed, resembles inflammatory or vascular lesions
Micro images: plasmacytic differentiation with occasional mitotic figures (arrow); kappa light chain restriction
unknown site; skin - figure 1: atypical plasma cells, 2: plasmablastic, 3: plasmablastic kappa staining, 4: plasmablastic with some kappa staining; figure 1: plasmablastic, 2: CD117+
DD: plasmacytic conjunctivitis, MALT lymphoma
Primary acquired melanosis of conjunctiva
See also benign melanosis
Called melanoma in situ by some, although cases without atypia don’t progress (Mod Path 1991;4:253)
Variable biologic behavior from benign to locally spreading to malignant
Usually ages 40+ years, whites
Presents as gradual appearance of golden brown pigmented lesion of bulbar conjunctiva
May be associated with Addison’s disease
May be contiguous with lentigo maligna (similar histology but with rete pegs) of adjacent eyelid skin
May involve pseudoglands of Henle in palpebral conjunctiva and resemble invasive melanoma
Prognosis: cases without atypia have no/minimal risk of progression to melanoma; 46% with atypia do progress to melanoma (Hum Path 1985;16:129); extent in clock hours is significant factor for recurrence and progression (Ophthalmology 2007 Sep 18; [Epub ahead of print])
Case reports: associated benign pigmented nodule (Orbit 2007;26:57), 30 year old black woman (Cornea 2005;24:352)
Treatment: excision or cryotherapy; also topical mitomycin C (Clin Experiment Ophthalmol 2006;34:708, Graefes Arch Clin Exp Ophthalmol 2005;243:1108) or 5-FU; cases with atypia usually recur or develop new foci
Clinical: unilateral, flat, acquired, brown pigmentation, fair skinned individual
Clinical images: diffuse involvement; flat diffuse pigmentation of the fornix and palpebral conjunctiva; multifocal involvement #1; #2
Gross: diffuse granular conjunctival pigmentation, usually in bulbar conjunctiva, also cornea, palpebral conjunctiva, eyelid skin
Micro: intraepithelial proliferation of abnormal melanocytes with variable atypia; early - pigmentation of basilar epithelium only; later - basilar melanocytic hyperplasia with nests, resembling Paget’s disease; cells have retracted cytoplasm, larger nuclei than neighboring cells, clumped chromatin and prominent basophilic nucleoli; cells may be small with scant cytoplasm and small round nuclei
Primary acquired melanosis of conjunctiva (continued)
Micro:
classification: with or without atypia
high risk of progression: atypia plus epithelioid features including abundant cytoplasm, vesicular nuclei, prominent nucleoli, may be mixed with low risk areas (almost all are associated with invasion, AJSP 2007;31:185)
low risk of progression: atypia plus primarily single cell lentinginous growth, small/medium size, high N/C ratio, small/medium hyperchromatic nuclei, no nucleoli, 15% risk of invasion
pitfalls: don’t interpret melanophages as invasive tumor cells
sine pigmento: melanocytes without pigment
post-topical chemotherapy changes: epithelial atrophy, dyskeratosis, pyknosis, focal keratinization
Micro images:
without atypia - melanocytic hyperplasia is confined to basilar layer #1; #2; #3
with atypia - minimal atypia due to mildly atypical melanocytes in basilar layer; moderate atypia due to nests of atypical melanocytes extending throughout epithelial thickness; severe atypia with nests and individual epithelioid melanocytes extending throughout epithelial thickness in pagetoid fashion; severe atypia due to spindled malignant melanocytes that completely replace the conjunctival epithelium, with minimal invasion of the inflamed substantial propria; cellular atypia, nesting and discohesion
Positive stains: HMB45, S100, MelanA, vimentin
Negative stains: keratin, EMA
EM: grade 1 - melanocytes with dendritic processes and transferred melanin in epithelial cells
grade 2 - melanocytes have short dendritic processes, incomplete melanin transfer and immature melanosomes, irregular nuclei with clumped chromatin and large nucleoli
grade 3 - epithelioid cells, no cytoplasmic processes, large irregular nuclei with large prominent nucleoli and abnormal melanin transfer
DD: junctional nevus (children, no irregular epithelial involvement, no melanocytic nests, no polygonal cells, no atypia), melanoma (invasion)
Pseudoepitheliomatous hyperplasia of conjunctiva
Response to chronic conjunctival irritation or inflammation
Develops rapidly, may ulcerate
Case reports: associated with granular cell tumor (Am J Ophthalmol 1981;91:234), post-limbal epithelium transplant (Clin Experiment Ophthalmol 2006;34:889)
Treatment: remove cause of inflammation
Gross: pink mass with leukoplakia
Micro: reactive epithelial proliferation with irregular lobules containing variable acanthosis and keratinization, reactive epithelial changes, inflammation and mitotic activity; may have ill defined border with subepithelial connective tissue due to inflammation; no nuclear atypia
Micro images: resembles squamous cell carcinoma; infiltrating squamous cells are benign
DD: fungi (multinucleated giant cells), pseudoadenomatous hyperplasia (reactive gland-like proliferation resembling mucoepidermoid carcinoma), squamous cell carcinoma (atypical cells, individual cell keratinization)
Bilateral, asymmetric fibrovascular lesion of bulbar conjunctiva similar to pinguecula but which extends onto nasal cornea; usually doesn’t cross pupil and so doesn’t pose significant threat to vision
Recurs but doesn’t undergo malignant transformation
Thought to be UV light associated; not associated with HPV (Br J Ophthalmol 2007;91:1016)
High prevalence (18%) in population age 40+ years living at high altitude in Mongolia (Eye 2007 Oct 19; [Epub ahead of print])
Causes significant changes in corneal refractive status, which increase with the grade of pterygia (Indian J Ophthalmol 2007;55:383)
Clinically may resemble melanoma or dysplasia
Not related to multiple pterygium (webbing) syndrome (Am J Hum Genet 2006;79:390)
Treatment: excision for cosmetic reasons, visual impairment, recurrent inflammation, mild irritation
Clinical images: pterygium #1; #2; #3
Gross: fleshy
Micro: fibrovascular connective tissue that migrates onto cornea, dissecting into plane of Bowman’s layer; similar to pinguecula but with corkscrew configuration / basophilic fibrillar degeneration of individual collagen fibers; also variable acute and chronic inflammatory infiltrate and vascular congestion; may cause atrophy, thickening or dysplasia of adjacent corneal epithelium
Micro images: left side-dilated vessels beneath epithelium, right side-severe solar elastosis beneath epithelium; pterygium #1; #2; with stromal elastosis
References: eMedicine
Pyogenic granuloma of conjunctiva
Also called lobular capillary hemangioma
Hyperplastic vascular lesion that occurs after trauma or inflammation
Rapid growth followed by stabilization or regression
Name is inaccurate, since not pyogenic (pus-forming) and not granulomatous
Case reports: with chalazion (J Fr Ophtalmol 2003;26:1085)
Clinical images: polypoid protrusion from conjunctiva #1; #2
Treatment: excision, may recur
Gross: flashy, polypoid, red-yellow
Micro: lobulated capillary vessels with edema, collagen and inflammatory cells; surface is often ulcerated and covered by fibrinous exudate
Micro images: polypoid lesion with prominent blood vessels; prominent vessels with inflammatory cells; low power-circumscribed vascular lesion; abundant vasculature and mononuclear inflammation; mononuclear inflammation in edematous background
Conjunctival involvement occurs in 25-50% with systemic disease; also eyelid, lacrimal gland, uvea
Conjunctival biopsy (blind, bilateral, J Chin Med Assoc 2006;69:472) is often performed for diagnosis
Noninvasive confocal microscopy for multinucleated giant cells may be diagnostic (Ocul Immunol Inflamm 2006;14:203)
Clinical features include increased angiotensin-converting enzyme and bilateral hilar lymphadenopathy
Grossing recommendations of University of Illinois at Chicago: breadloaf to take n-1 cross sections for a specimen that is n mm long (i.e. 9 cross sections for a 10 mm specimen), embed on edge, place all on one slide
Cut levels through entire specimen (one level of all cross sections will appear on each slide)
Make 3 slides of each level for H&E, future AFB and fungi (if necessary), UIC website
Case reports: bilateral large conjunctival tumors (Klin Monatsbl Augenheilkd 2006;223:326), 10 year old girl with bilateral 0.5 to 2 mm pale yellow deposits in bulbar conjunctiva (Eur J Ophthalmol 2006;16:168)
Clinical images: bulbar conjunctival involvement
Micro: noncaseating granulomas without microorganisms
Micro images: noncaseating granuloma in fornix; noncaseating granulomas #1; #2; #3
DD: tuberculosis, cat scratch fever and tularemia (all have extensive necrosis); syphilis, foreign body
References: eMedicine
Squamous papilloma of conjunctiva
Common, benign acquired papillary lesion
In children, often near caruncle and semilunar fold, often bilateral, recurs after excision
In adults, often near limbus, usually solitary, may grow over cornea; may clinically resemble squamous cell carcinoma
Probably lacks malignant potential, even if dysplasia present
Treatment: excision with cryotherapy but often recurs; also topical interferon, topical mitomycin C (Cornea 2002;21:838) or oral cimetidine (Cornea 2006;25:687)
Clinical images: pedunculated red-orange mass of caruncle; pedunculated vascular lesion of conjunctiva with smooth surface; sessile lesion
Gross: pedunculated, papillary, sessile or mulberry surface on conjunctiva with prominent surface vessels
Micro: exophytic growth of papillary, well differentiated, acanthotic nonkeratinized squamous epithelial cells with variable goblet cells supported by prominent, branching fibrovascular core; also inflammation; occasionally koilocytosis, mild dysplastic changes
inverted mucoepidermoid papilloma - endophytic, invaginated lobules of nonkeratinized squamous epithelium with goblet cells; may resemble low grade mucoepidermoid carcinoma
Micro images: acanthotic squamous epithelium overlies fibrovascular core #1; #2; limbal tumor composed of fibrovascular fronds covered by squamous epithelium
Positive stains: often p53, Ki-67, bcl2 (Ann N Y Acad Sci 2004;1030:419)
Molecular: HPV 6 in 80%; also HPV 11, rarely HPV 45 (Br J Ophthalmol 2007;91:1014), rarely HPV 13 (Diagn Microbiol Infect Dis 2005;53:71); note: koilocytosis is often lacking even when HPV is present (Br J Ophthalmol 2001;85:785)
DD: adults - basal cell carcinoma, squamous cell carcinoma
References: eMedicine
Steatocystoma simplex of conjunctiva
Rare
Case report: tumor of caruncle #1 (Can J Ophthalmol 2006;41:83), #2 (Br J Ophthalmol 2003;87:240)
Micro images: cyst lined by squamous epithelium with sebaceous glands in cyst wall #1; #2
Sturge-Weber syndrome and conjunctiva
Also called encephalotrigeminal angiomatosis
Port-wine stains (capillary malformations) commonly involve skin of head and neck; may affect underlying subcutaneous tissue and bone and extend to adjacent mucous membrane and conjunctiva; ipsilateral leptomeningeal and ocular choroidal involvement occurs occasionally (J Plast Reconstr Aesthet Surg 2007 Jun 30; [Epub ahead of print])
May have choroidal hemangioma and ipsilateral glaucoma
Clinical images: nevus flammeus of skin and conjunctiva with glaucoma and secondary cataract; port wine spot and conjunctival involvement #1; #2
Micro images: diffuse hemangioma of choroid
References: eMedicine
Conjunctivitis
Usually not biopsied
Associated with reduction in goblet cells, causing reduction in surface mucin, so aqueous portion of tears does not adhere to corneal epithelium, leading to dry eye and corneal ulceration
May take 30 days for recovery (Cornea 2007;26:778)
Acute hemorrhagic conjunctivitis
First described in 1969
Rapidly progressive and contagious
Outbreaks due to Coxsackie virus A24 variant (Arch Virol 2007 Aug 6; [Epub ahead of print], J Med Virol 2007;79:748, MMWR Morb Mortal Wkly Rep 2004;53:632); also enterovirus E70 (Emerging Infectious Diseases) and adenovirus
Diagnosis: RT-PCR (J Virol Methods 2007;142:89, J Clin Microbiol 2005;43:1069), culture
Treatment: symptomatic, usually self-limited after 5-7 days, with no sequelae
References: eMedicine
Part of systemic atopic reaction to a systemic allergen; usually seasonal
Increased risk for herpetic infection (Curr Eye Res 2006;31:721)
Treatment: allergy type medications; topical cyclosporine if severe (Cornea 2007;26:1035)
Clinical images: diffuse erythema
References: eMedicine
Papillary conjunctivitis without inclusions (J Ocul Pharmacol Ther 2006;22:208)
Conjunctivitis that persists for 4+ weeks is considered chronic
Unilateral: due to keratitis, nasolacrimal duct obstruction, occult foreign body, neoplasm
Bilateral: due to bacteria, virus, trachoma, other microorganisms; also allergic or chemical causes, inflammation of eyelid meibomian glands
Conjunctival scrapings are useful for diagnosis (Eur J Ophthalmol 1997;7:19)
Case reports: patient with relapsing polychondritis and obliterative microangiopathy (Cornea 2006;25:621), bilateral inflammation in boy with X-linked hypogammaglobulinaemia (J Paediatr Child Health 1996;32:463)
Clinical images: due to trachoma
Micro: numerous goblet cells and papillary folds, chronic inflammatory cells; isolated islands of epithelium may form retention cysts that calcify; late changes are epithelial atrophy, keratinization and stromal scarring; note that lymphocytes are common within normal conjunctiva
DD: lymphoma (Ophthalmology 1999;106:757, Cornea 2001;20:427)
Cicatrizing: causing a scar
Causes: burns, discoid lupus erythematosus (Ocul Immunol Inflamm 2002;10:287), lichen planus (Am J Ophthalmol 2003;136:239), ocular cicatricial pemphigoid, ocular rosacea (Cornea 2004;23:630), paraneoplastic syndrome associated with lung tumors (Cornea 2006;25:611), post-infectious, Stevens-Johnson syndrome
References: Curr Opin Ophthalmol 2001;12:250
Giant papillary conjunctivitis
Associated with soft contact lenses (Trans Am Ophthalmol Soc 1999;97:205), exposed sutures, prostheses (Clin Experiment Ophthalmol 2007;35:535, Cont Lens Anterior Eye 2007 Sep 6; [Epub ahead of print])
Treatment: change contact lenses more frequently (Eye Contact Lens 2003;29:S37); mast cell stabilizers
Clinical images: large papillae in everted upper eyelid #1; #2
Micro: upper tarsal conjunctival biopsies show mast cells, eosinophils and basophils in epithelium and substantia propria
Cytology: impression cytology - honeycomb pattern consistent with giant papillae; increased inflammation and mucous strands (Ophthal Plast Reconstr Surg 2005;21:39)
References: eMedicine
with necrosis - tuberculosis, Parinaud’s oculoglandular syndrome due to cat-scratch fever (Ugeskr Laeger 1995;157:4137) or tularemia (Am J Ophthalmol 2001;131:283), Wegener’s granulomatosis (Ophthalmology 2003;110:1770)
without necrosis - Crohn’s disease (Br J Ophthalmol 1984;68:901), foreign bodies, Hodgkin’s lymphoma (Am J Ophthalmol 2001;131:796), sarcoidosis, syphilis
other - fungi (Cornea 1994;13:539, Ophthal Plast Reconstr Surg 1992;8:143, Rev Inst Med trop S Paulo 2002; v44 n1), acid-fast bacilli
Case reports: Sporothrix schenckii granulomatous conjunctivitis - in cat owners in in Rio de Janeiro (Cornea 2005;24:491); #2 in cattle farmer without history of trauma (Cornea 2002;21:831)
Micro images: Crohn’s disease-PAS stain of conjunctiva shows round cell infiltrate with giant cells (arrows); Paracoccidiodes brasiliensis
See also Granulomatous conjunctivitis, Trachoma, Infectious keratitis
Often due to inadequate personnel hygiene
Adenovirus conjunctivitis: 60% of ER conjunctivitis patients in Florida; detected by PCR (Optometry 2007;78:236); case report and clinical images
Alcaligenes xylosoxidans conjunctivitis: rare, can cause chronic conjunctivitis (Cornea 2007;26:868)
Bacterial conjunctivitis in children: should exclude infected children from school until asymptomatic (J Pediatr Ophthalmol Strabismus 2007;44:101); local antibiotics may not be necessary (Prescrire Int 2007;16:120); often due to H. influenzae (Ophthalmology 2007 Jun 15; [Epub ahead of print]) and Streptococcus pneumoniae, S. aureus is uncommon in children (Acad Emerg Med 2007;14:1)
Bacterial conjunctivitis in adults: often due to Staphylococcus aureus, may be methicillin resistant; Streptococcus pneumoniae is associated with outbreaks (Pediatr Infect Dis J 2006;25:906); delayed use of antibiotics may be appropriate (BMJ 2006;333:321)
Gonococcal conjunctivitis: due to autoinoculation; rare in developed countries (J Fr Ophtalmol 2007;30:e18); may cause corneal perforation (Med J Malaysia 2006;61:366); clinical image
Influenza A virus conjunctivitis: outbreak from poultry (Proc Natl Acad Sci USA 2004;101:1356)
References: Community Eye Health 2005;18:73, eMedicine (viral conjunctivitis)
“Ligneous” means resembling wood
Chronic pseudomembranous conjunctivitis with woody induration of eyelid and tarsal conjunctiva and pseudomembrane on tarsal conjunctiva; also affects other mucosa
Due to mutations in plasminogen PLG gene at 6q26 / plasminogen deficiency (J Thromb Haemost 2007 Sep 27; [Epub ahead of print])
Liesegang rings: rings of precipitated iron and calcium (a phenomenon of chemical systems) seen in conjunctiva and eyelid, associated with inflammation, necrosis, fibrosis or cysts; may resemble helminth eggs, larvae or adults (AJSP 1987;11:598, Wikipedia)
Case reports: 7 month old baby
Treatment: excision, but pseudomembrane recurs (Virchows Arch 2007;451:815)
Clinical images: conjunctival injection and dense membranous fibrosis of lid; fleshy mass involving upper palperbral conjunctiva
Gross images: fleshy mass
Micro: membrane contains large hyaline masses of fibrin and immunoglobulin but resembling amyloid; also T cells and B cells
Micro images: amorphous eosinophilic deposits of conjunctiva associated with inflammatory infiltrate and microcystic expansion of residual conjunctival epithelium; Coloration bleutée de ces dépôts, confirmant leur nature fibrineuse (Hématoxyline de Mallory X400). Mallory stains fibrin blue; granulation tissue and eosinophilic deposits surround islands of epithelial cells; eosinophilic hyalinized deposit; inflamed granulation tissue; eosinophilic hyalinized tissue with inflammation
Positive stains (hyaline masses): fibrinogen
Negative stains (hyaline masses): Congo red, keratin, vimentin
DD: Streptococcus, Klebsiella, Chlamydia, adenovirus infection, toxic epidermal necrolysis, graft versus host disease (Hum Path 1996;27:307)
References: Virchows Arch 2007;451:815, Surv Ophthalmol 2003;48:369
Trachoma (inclusion conjunctivitis)
Major cause of blindness outside US
Caused by Chlamydia trachomatis; causes scarring of corneal tissue
Stage I: conjunctival inflammatory infiltrates (lymphoid follicles and diffuse infiltrates); followed by pannus formation (fibrovascular tissue in conjunctival and corneal stroma) with Chlamydia elementary bodies and larger basophilic initial bodies seen; also lymphocytes, plasma cells, neutrophils
Stage II: florid inflammation, more follicles, epithelial thickening, severe pannus; macrophages with ingested debris (Leber cells) in conjunctiva
Stage III: scarring, no follicles, cicatricial entropion (inversion of upper lid), misdirected lashes (trichiasis)
Stage IV: arrest of disease due to entropion and trichiasis but with continuing corneal damage and infection
WHO grading system:
TF: 5 or more follicles on the upper conjunctiva; follicles must be at least 0.5 mm in diameter and are round, white, paler than surrounding conjunctiva
TI: intense trachomatous inflammation; tarsal conjunctiva appears red, rough and thickened, obscuring more than half of the normal, deep, tarsal vessels; numerous follicles are partially covered by thickened conjunctiva
TS: scarring and fibrosis of tarsal conjunctiva due to severe or chronic trachoma; also called cicatricial trachoma; scars are visible as white lines, bands or sheets
TT: trichiasis defined as at least one eyelash that rubs on eyeball due to entropion of lid
CO: corneal opacity; eyelashes have abraded and damaged cornea, causing corneal opacity and visual loss
Clinical images: stage I; stage II; pannus; stage III (cicatrization); stage IV
WHO grades: clinical images; TF; TI; TS #1; TS #2; TT; TT and CO
Micro images: intracytoplasmic inclusions; Chlamydia inclusions #1; #2; Stage II-subepithelial follicles, formation of papillae and chronic inflammatory cells
References: Wikipedia, eMedicine
Carcinoma of conjunctiva
Adenoid squamous carcinoma of conjunctiva
Also called pseudoglandular squamous cell carcinoma, acantholytic squamous cell carcinoma
More aggressive than squamous cell carcinoma due to recurrence or infiltration of deep orbital tissue
Limbus or bulbar conjunctiva
Treatment: surgical excision with negative margins and frequent follow up
Clinical images: irritated superior bulbar conjunctival mass
Micro: islands of malignant squamous cells with acantholysis or pseudoglandular spaces
Micro images: pseudoglandular pattern due to acantholysis of neoplastic squamous cells; extracellular Alcian blue positive substance that was digested by pretreatment with hyaluronidase
Negative stains: mucin
EM images: surface epithelial cells with microvillous processes; short collagen fibrils and desmosomes
References: Br J Ophthalmol 1997;81:1001
Basal cell carcinoma of conjunctiva
Usually due to adjacent lesion in skin or eyelid, only rarely arises from conjunctiva
Case reports: caruncle tumors - 24 year old man; 80 year old man (J Cutan Pathol 2005;32:502); seeding of conjunctiva (Graefes Arch Clin Exp Ophthalmol 2005;243:615)
Gross: circumscribed white nodule
Micro: nodular and cystic tumor of atypical basaloid cells arising from conjunctival surface epithelium; similar to skin tumor
Micro images: various images (fig 2)
Carcinoma in situ of conjunctiva
Also called conjunctival intraepithelial neoplasia
May present as complication of pterygium or pinguecula
Due to solar radiation or other irritation
Mainly adults
Cytology and DNA cytometry may be useful for diagnosis (Anal Quant Cytol Histol 1999;21:387)
Treatment: cryotherapy or topical chemotherapy (mitomycin C eyedrops-Klin Monatsbl Augenheilkd 2001;218:429) is preferable to surgery to preserve goblet cells and lacrimal gland ductules and prevent a painful dry eye that may compromise vision
Gross: leukoplakia or fleshy mass with increased vascularity
Gross images: circumlimbal lesion with involvement outside the interpalpebral area
Micro: full thickness changes including loss of epithelial polarity, cytologic atypia, pleomorphism and mitotic figures; no extension of atypical cells beyond basal lamina of conjunctival epithelium; resembles dysplastic changes in cervix, Bowen’s disease or Paget’s disease of skin
Micro images: full thickness atypia, no invasion #1; #2; #3; #4-marked nuclear pleomorphism; #5-loss of polarity and high N/C ratio; #6; limbal lesion with extension into cornea; irregular acanthosis simulating invasion
Negative stains: PAS (due to lack of maturation)
DD: dysplasia (atypia is less than full thickness)
Lymphoepithelioma-like carcinoma of conjunctiva
Rare in conjunctiva
Usually associated with EBV related nasopharyngeal carcinoma in China and Taiwan
Aggressive, invades cornea, eyelid and orbit
Gross: yellow-white
Micro: nonkeratinizing, undifferentiated squamous cell carcinoma with lymphocytes
References: Can J Ophthalmol 2002;37:14
Rare, even in patients with high stage disease
Most commonly from breast, lung, skin (melanoma)
Usually solitary
Poor prognosis
Case reports: melanoma of uvea (Am J Ophthalmol 1997;124:549), neuroblastoma (J Pediatr Surg 2004;39:1782), renal cell carcinoma (Clinics 2005;60:75)
Clinical images: metastatic breast carcinoma; metastatic melanoma of skin
References: Br J Ophthalmol 1996;80:5, Ophthalmology 1989;96:999 (melanoma)
Mucoepidermoid carcinoma of conjunctiva
Rare
Mean age 67 years
Locally aggressive with orbital and intraocular invasion, may metastasize to regional lymph nodes, lung, bone
More aggressive than squamous cell carcinoma
Often misdiagnosed because mucin is missed
Case reports: intraocular invasion producing a neoplastic cyst (Arch Ophthalmol 1998;116:1521), lower lid (Indian J Ophthalmol 1996;44:231), clear cell variant (Arch Ophthalmol 2005;123:1265), with ocular cicatricial pemphigoid (Surv Ophthalmol 2006;51:513)
Treatment: wide local excision with negative surgical margins; 85% recur; need extended followup (Ophthalmology 2000;107:801)
Clinical images: large, fleshy, vascular, multilobulated mass on temporal bulbar conjunctiva, extending to peripheral cornea
Micro: resembles squamous cell carcinoma but with mucus secreting cells, intermediate cells, epidermoid squamous cells and intraepithelial mucin; usually no squamous pearls
Micro images: limbal tumor with deep corneal invasion; neoplastic squamous cells with intra- and extracellular vacuoles; islands of neoplastic squamous cells with scattered vacuoles; infiltrating tumor with adjacent areas of squamous and glandular differentiation; focal mucin production (PAS); intraocular neoplastic cyst
clear cell variant - acanthotic surface epithelium infiltrated by clear cells mimicking "pagetoid" spread; lobules of clear cells (*) with islands of squamous cells (arrows); clear cells show marked nuclear pleomorphism and mitotic figures; tumor cells are mucicarmine+ (arrows); intracytoplasmic granules are PAS+ (left) and diastase sensitive (right)
Positive stains: Alcian blue, Hales colloidal iron, mucicarmine, PAS
DD: squamous cell carcinoma (negative for mucin)
References: Ophthal Plast Reconstr Surg 1994;10:163, Cancer 1976;38:1699
Sebaceous carcinoma of conjunctiva
See also sebaceous gland carcinoma of eyelid
Eyelid tumors often involve conjunctiva (Ophthal Plast Reconstr Surg 2005;21:92)
May be due to regression of primary meibomian gland carcinoma
Rarely is a primary conjunctival lesion
Intraepithelial lesions may not become invasive for many years
May be associated with Muir-Torre syndrome (Ophthal Plast Reconstr Surg 2004;20:31)
Case reports: diffuse intraepithelial sebaceous carcinoma of conjunctiva presenting as blepharoconjunctivitis (Br J Ophthalmol 1997;81:168), masquerading as blepharoconjunctivitis
Clinical images: causing corneal opacification; severe blepharitis with thickening of eyelid margins, subepithelial fibrosis with fornix foreshortening and fibrovascular pannus extending over peripheral cornea
Micro: large anaplastic cells with finely vacuolated cytoplasm, open vesicular nuclei and prominent nucleoli; tumor spreads via infiltrating lobules, nests, and cords, as well as pagetoid patterns within epithelium
Micro images: sebaceous carcinoma; malignant cells infiltrate conjunctiva and exhibit mitotic activity; pagetoid spread of malignant sebaceous cells in conjunctival epithelium
Positive stains: oil red-O in frozen tissue
References: eMedicine #1; #2
Spindle cell carcinoma of conjunctiva
Rare, but more aggressive than squamous cell carcinoma
Elderly patients
Treatment: complete excision; may recur or invade sclera or intraocular contents
Gross: elevated or flat, smooth surface, red, arises from limbus or bulbar conjunctiva
Micro: spindle cells are continuous with surface epithelium; have oval vesicular nuclei with large eosinophilic or basophilic nucleoli; often transition to squamous cells with individual cell keratinization; also acanthosis, mitotic activity, desmoplasia, variable dysplasia
Micro images: large subepithelial tumor with deep scleral and corneal invasion; sarcomatous pattern #1; #2
Positive stains: keratin, vimentin, actin, EMA
EM: desmosomes, tonofibrils
DD: atypical fibroxanthoma, MFH, spindle cell melanoma, exuberant granulation tissue
References: Ophthalmology 1990;97:711, Arch Ophthalmol 1980;98:1809
Squamous cell carcinoma of conjunctiva
See also spindle cell carcinoma, mucoepidermoid carcinoma of conjunctiva
Rare, but more common than basal cell carcinoma at this site
In US, precancerous lesions are excised, so invasive carcinoma is uncommon
Rates: 0.03 per 100K in US, 3.5 per 100K in Uganda
Mainly adults; in US commonly 60+ years, 55-70% men (Can J Ophthalmol 2002;37:14)
Associated with sunlight exposure, actinic keratosis; also xeroderma pigmentosum, albinism, toxins, HPV 16/18 (55%), possibly atopic eczema (Cornea 2003;22:135)
May invade anterior chamber of globe or orbit, but only rarely metastasizes or causes death (but see AIDS/HIV patients below)
Case reports: 2 conjunctival tumors and atypical fibroxanthoma in child with xeroderma pigmentosum (Pediatr Dev Pathol 2007;10:149), bony metastases (Klin Monatsbl Augenheilkd 2002;219:813), with prosthetic eye (J Postgrad Med 2006;52:234)
Treatment: complete excision of superficial tumors, radical surgery for deeply invasive tumors; 6% recur, rarely metastasize to lymph nodes (more common if large or multiple recurrences)
Clinical images: keratinizing squamous cell carcinoma; nodular tumor with prominent vascularity at limbus; fleshy elevated lesion at limbus
Gross: papillary or exophytic gray-white mass, often at limbus; occasionally jet black resembling melanoma (in heavily pigmented individuals); surrounded by inflamed conjunctiva
Gross images: large limbal tumor has invaded anterior chamber; tumor has destroyed eye and invaded orbit
Micro: atypia throughout full thickness of epithelium (conjunctival intraepithelial neoplasia) with individual tumor cells or nests extending into underlying stroma; dense sclera usually limits deepest margins; epithelium may be keratinized; cells have eosinophilic or clear cytoplasm, intercellular bridges, dyskeratosis, coarse chromatin, prominent nucleoli; may have pigment within benign and malignant cells in heavily pigmented patients (Ophthalmic Surg Lasers Imaging 2003;34:406)
Micro images: early invasion with corneal involvement; well differentiated tumor with deep invasion; metastasis to preauricular node and parotid gland; thick layer of parakeratosis and microinvasion (arrows); lobules of invasive keratinizing carcinoma in stroma; papillomatous pattern; tumor #1; #2; #3
Positive stains: high molecular weight keratin, EMA; also EGFR (tumor and normal, Ophthal Plast Reconstr Surg 2006;22:113)
Molecular: usually aneuploid
DD: keratoacanthoma, pseudoepitheliomatous hyperplasia, melanoma, chalazion (Eur J Dermatol 2006;16:187)
References: Br J Ophthalmol 2002;86:168, eMedicine
HIV/AIDS patients
Rising incidence, with 8% prevalence in Kenya (East Afr Med J 2006;83:267)
Recommended to screen HIV/AIDS patients for conjunctival lesions
Mean age is 35 years
Usually affects women
Patients present late with advance disease
More aggressive, with high recurrence rates
Case reports: multifocal disease with intraocular penetration (Cornea 2006;25:745)
Other malignancy of conjunctiva
Kaposi’s sarcoma of conjunctiva
See also Soft Tissue chapter
Historically present in up to 20% of AIDS patients; first manifestation of disease in 4-14%
Dugel
classification (Ophthalmology
1992;99:1127):
Type I: patchy, flat, less than 3 mm thick; thin dilated vascular
channels lined by endothelial cells, no spindle cells, no mitotic activity
Type II: flat tumors less than 3 mm thick; have empty vascular channels linked by plump, fusiform endothelial cells with hyperchromatic nuclei, few spindle cells, no mitotic figures
Type III: nodular, 3 mm or more, packed spindle cells with hyperchromatic nuclei and mitotic figures, slit-like spaces with RBCs
Case reports: conjunctival mass as initial presentation of HIV (Ophthal Plast Reconstr Surg 2005;21:314); HIV negative patient with classic (indolent) Kaposi’s sarcoma (Br J Ophthalmol 1994;78:488)
Treatment: local excision with 1-2 mm margins plus cryotherapy; type III tumors often recur
Clinical images: elevated nodule arising from fornix #1; #2; multinodular conjunctival mass
.){kind=link}
Micro: swollen endothelial type cells with slit like vessels; advanced lesions have spindle cells and mitotic figures
Micro images: subepithelial proliferation of spindle cells and vessels; biphasic subepithelial tumor with solid and edematous areas; swollen endothelial cells contain numerous hyaline globules; enlarged endothelial cell contains a cluster of hyaline globules; proliferation of vascular channels; spindle cells with extravasated red blood cells in slit like spaces; scattered endothelial lined spaces surrounded by densely proliferating spindle cells; H&E and D2-40 (lymphatic endothelial marker)-site unknown
Positive stains: CD31, HHV8 (Jpn J Ophthalmol 2006;50:7)
DD: angiosarcoma, angiolymphoid hyperplasia with eosinophilia, bacillary angiomatosis, spindle cell tumors
Usually indolent MALT lymphomas, may be preceded by apparent reactive lymphoid hyperplasia
Difficult to predict malignant potential; often remains an isolated lesion
Mantle cell lymphomas have more aggressive behavior with median survival of 3-5 years
Diagnosis: H&E for high grade lesions; for low grade lesions, need fresh tissue for flow cytometry or gene rearrangement studies, immunohistochemistry (light chain restriction)
Case reports: T cell lymphoma (Arch Ophthalmol 2002;120:508, Cornea 2007;26:1147), diffuse large B cell lymphoma (Can J Ophthalmol 2007;42:630), CD5+ MALT lymphoma (AJSP 1998;22:201), post-transplant lymphoproliferative disorder (Am J Ophthalmol 2007;143:1050)
Treatment: MALT - chemoradiation therapy (Virchows Arch 2006;448:506), possibly antibiotics (Am J Ophthalmol 2005;140:729)
Clinical images: MALT lymphoma; lymphoma-type unspecified
.){kind=link}
Gross: salmon colored mass or masses
Micro: MALT - well differentiated, monoclonal small B lymphocytes; occasionally exhibits overt monocytoid cytology, prominent plasmacytic features or lymphoepithelial lesions (AJSP 2007;31:792)
Micro images: A/B: primary MALT lymphoma of conjunctiva with monotonous centrocyte-like cells with Dutcher bodies; C/D: reactive follicles of lacrimal gland (for comparison); various lymphomas (fig 1-3)
Molecular: MALT may have t(14;18)(q32;q21) involving IgH and MALT1 genes; B cell clonality in 55% of MALT and 60% of diffuse large B cell lymphomas (Mod Path 2001;14:641)
References: Can J Ophthalmol 2006;41:753
Malignant fibrous histiocytoma of conjunctiva
Case reports: 60 year old man (Arch Ophthalmol 1999;117:685), two case reports (Br J Ophthalmol 1990;74:624), black patient with xeroderma pigmentosum at early age (Archives 1991;115:910), 25 year old woman with myxoid MFH (Ophthal Plast Reconstr Surg 2007;23:338), recurrent tumor (Arch Ophthalmol 1999;117:685),
Treatment: wide excision and cryotherapy; may recur
Clinical images: recurrent mass #1; #2; #3
Micro: atypical spindle cells and histiocytelike cells
Micro images: pleomorphic giant cells have foamy cytoplasm, irregular hyperchromatic nuclei and prominent nucleoli; pleomorphic tumor with giant cells and mitotic figures; storiform pattern of spindle cells #1; #2; pleomorphic tumor cells, giant cells and inflammatory cells; large atypical cells and mitotic figures; smooth muscle actin and CD68
Positive stains: CD68, alpha1-antitrypsin, CD34, vimentin
EM images: dilated cisterae of rough endoplasmic reticulum with granular material; spindle cells show numerous subplasmalemmal fusiform densities suggesting myofibroblastic differentiation
#2 malignancy of conjunctiva after squamous cell carcinoma
2% of ocular malignancies, 5% of ocular melanomas
Due to primary acquired melanosis, nevi (20-30%) or no apparent precursor lesion (18-25%)
Usually fair-complexioned individuals age 40+ years
Be wary of diagnosis in children as it is very rare (J Pediatr Ophthalmol Strabismus 2007;44:277)
Incidence: 0.012 cases/100K in US, 0.024/100K in Sweden, 0.052/100K in Denmark; rare in blacks
Prognosis: excellent if small, localized and bulbar; intermediate if diffuse and bulbar
poor prognostic factors: fornix, caruncle, plica semilunaris or palpebral conjunctiva; tumor thickness > 4 mm; epithelioid cells or 5+ mitotic figures/10 HPF (Br J Ophthalmol 1994;78:252)
Prognosis not related to nature of initial lesion, although acquired melanosis cases are often multicentric
Metastases to parotid or submandibular lymph nodes, but uncommon if primary tumor less than 1.5 cm
May extend directly into orbit, eyelids, sinuses, anterior chamber (Graefes Arch Clin Exp Ophthalmol 2007;245:431)
Often recurs locally; overall mortality 25%-32% (J Fr Ophtalmol 1999;22:315)
Case reports: metastasis to parotid gland (Br J Ophthalmol 2003;87:1428), arising from primary acquired melanosis, amelanotic tumor (Cutis 2006;77:377)
Treatment: complete excision or radical surgery, depending on extent of disease; cryotherapy for margins and base; also topical mitomycin C; recommended to avoid incisional biopsy (Trans Am Ophthalmol Soc 2000;98:471)
Clinical images: multifocal tumor; nodular, elevated, pigmented lesion adjacent to area of primary acquired melanosis; elevated melanotic nodule arising in area of flat melanosis; large neglected melanoma protrudes between eyelids
Gross: vascular, pigmented, nodular
Gross images: large heavily pigmented nodule covers cornea
Whole mount images: large exophytic tumor covers conjunctiva and cornea
Melanoma of conjunctiva (continued)
Micro: invasion of atypical melanocytes into epithelial connective tissue; usually thin surface epithelium; bizarre polygonal epithelioid cells with eosinophilic cytoplasm, large atypical nuclei, prominent eosinophilic nuclei; also spindle cells, smaller cells, balloon cells containing lipid; often lymphocytes at base or tumor margins
Report: presence of primary acquired melanosis or nevi - examine edge of excision for pagetoid spread, atypical intraepithelial melanocytes, nevus cells; tumor thickness from surface of lesion to deepest margin using calibrated micrometer
Micro images: nodular tumor at limbus; anaplastic melanocytes within epithelial nests infiltrate the substantial propria; large, non-cohesive, pigmented epithelioid cells with prominent nucleoli (unbleached-left, bleached-right); markedly pleomorphic tumor cells; malignant spindled melanocytes invade a lymphatic vessel; malignant epithelioid melanocytes metastatic to parotid lymph node; invasive cells with large atypical nuclei; nests of atypical pigmented cells; H&E, HMB45, S100; MelanA/Mart1 positive tumor cells
Cytology images: parotid gland metastases - pleomorphic malignant epithelioid melanocytes with scattered lymphocytes
Positive stains: HMB45, S100, MelanA, vimentin, Ki-67
Negative stains: keratin (may be focally positive in epithelioid cells), EMA
DD: metastatic melanoma (clinical history of melanoma, more circumscribed, no intraepithelial tumor), extraocular extension of melanoma (perform careful ophthalmologic examination to exclude), spindle cell squamous cell carcinoma
References: Cancer Control 2004;11:310, Hum Path 1985;16:136, eMedicine
Rhabdomyosarcoma of conjunctiva
See also rhabdomyosarcoma of orbit
Botyroid subtype of embryonal rhabdomyosarcoma affects mucosal surfaces, including conjunctiva
Children present with rapidly enlarging mass
At all ocular sites combined, recurs in 18%, metastasizes in 6%, causes death in 3% (Trans Am Ophthalmol Soc 2001;99:133)
Case reports: 14 year old girl with botyroid tumor (Graefes Arch Clin Exp Ophthalmol 2006;244:517)
Treatment: surgery, chemotherapy, radiotherapy
Gross: fleshy, gelatinous mass that may resemble a cyst; no inflammation, lid edema or conjunctival redness
Micro: hypercellular myxoid tumor separated from surface epithelium by cambium layer (multiple layers of condensed tumor spindle cells); tumor cells are spindled with minimal cytoplasm and bland nuclei or are round rhabdomyoblasts with eosinophilic cytoplasm (cross striations in <10% of patients) and large hyperchromatic and pleomorphic nuclei; background is extracellular mucopolysaccharide resembling cystic spaces
Micro images: site unspecified - botyroid; embryonal; alveolar
Positive stains: desmin, muscle specific actin, vimentin; rarely myosin
References: Mod Path 2001;14:506 (rhabdomyosarcoma-general)
Miscellaneous - conjunctiva
Tumor features to report-conjunctiva
Histologic type
Degree of differentiation
Precise anatomic location-bulbar by quadrant, palpebral (superior or inferior), fornix (superior or inferior), caruncle, plica semilunaris, limbus, cornea
Tumor size
Involvement of corneal stroma, episclera, orbital fat
Involvement (noninvolvement) of other tissues present
Margins (deep and lateral, minimum clearance)
Presence of angiolymphatic, perineural, intraocular or intraorbital invasion
Presence of ulceration
For melanomas, also indicate thickness (from top of epithelium to deepest tumor cell in substantia propria using ocular micrometer) and mitotic activity
References: AJSP 2003;27:999
TNM staging for carcinoma of the conjunctiva
Applies to clinical and pathologic staging
Note: excludes melanoma and malignancies other than carcinoma
Primary tumor (T) of conjunctiva
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 5 mm or less in greatest dimension
T2: Tumor more than 5 mm in greatest dimension, without invasion of adjacent structures
T3: Tumor invades adjacent structures, excluding the orbit
T4: Tumor invades the orbit with or without further extension
T4a: Tumor invades orbital soft tissues, without bone invasion
T4b: Tumor invades bone
T4c: Tumor invades adjacent paranasal sinuses
T4d: Tumor invades brain
Regional lymph nodes (N) of conjunctiva
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Distant metastasis (M)
M0: No distant metastasis
M1: Distant metastasis
Stage grouping of conjunctiva carcinoma
No stage grouping is presently recommended by AJCC
TNM staging for melanoma of the conjunctiva
Pathologic staging
Primary tumor (T)
pTX: Primary tumor cannot be assessed
pT0: No evidence of primary tumor
pT(is): Melanoma of the conjunctive confined to the epithelium
pT1a: Melanoma of the bulbar conjunctiva not more than 0.5 mm in thickness with invasion of the substantial propria
pT1b: Melanoma of the bulbar conjunctiva more than 0.5 mm but not more than 1.5 mm in thickness with invasion of the substantial propria
pT1c: Melanoma of the bulbar conjunctiva greater than 1.5 mm in thickness with invasion of the substantial propria
pT2a: Melanoma of the palpebral, forniceal or caruncular conjunctiva not more than 0.5 mm in thickness with invasion of the substantia propria
pT2b: Melanoma of the palpebral, forniceal or caruncular conjunctiva more than 0.5 mm but not greater than 1.5 mm in thickness with invasion of the substantia propria
pT2c: Melanoma of the palpebral, forniceal or caruncular conjunctiva greater than 1.5 mm in thickness with invasion of the substantia propria
pT3: Melanoma invades the eye, eyelid, nasolacrimal system, sinuses or orbit
pT4: Melanoma invades the central nervous system
Notes:
pT(is) melanoma in situ (includes the term primary acquired melanosis) with atypia replacing greater than 75% of the normal epithelial thickness, with cytologic features of epithelioid cells, including abundant cytoplasm, vesicular nuclei or prominent nucleoli, or presence of intraepithelial nests of atypical cells.
Regional lymph nodes (N) of conjunctiva
pNX: Regional lymph nodes cannot be assessed
pN0: No regional lymph node metastasis
pN1: Regional lymph node metastasis present
Distant metastasis (M) of conjunctiva
cM0: No distant metastasis
pM1: Distant metastasis
Stage grouping of conjunctiva carcinoma
No stage grouping is presently recommended by AJCC
Clinical staging
Primary tumor (T) - Clinical staging of conjunctiva
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T(is): Melanoma confined to the conjunctival epithelium
Malignant conjunctival melanoma of the bulbar conjunctiva
T1a: Less than or equal to 1 quadrant
T1b: More than 1 but less than or equal to 2 quadrants
T1c: More than 2 but less than or equal to 3 quadrants
T1d: Greater than 3 quadrants
Malignant conjunctival melanoma of the nonbulbar conjunctiva (palpebral, forniceal caruncular)
T2a: No caruncular, less than or equal to 1 quadrant
T2b: No caruncular, greater than 1 quadrant
T2c: Any caruncular, with less than or equal to 1 quadrant
T2d: Any caruncular, with greater than 1 quadrant
Any malignant conjunctival melanoma with local invasion
T3a: Globe
T3b: Eyelid
T3c: Orbit
T3d: Sinus
T4: Tumor invades the central nervous system
Quadrants are defined by clock hour, starting at the limbus (e.g., 6, 9, 12, 3) extending from the ceontral corneal, to and beyond the eyelid margins. This will bisect the caruncle.
Regional lymph nodes (N) of conjunctiva
NX: Regional lymph nodes cannot be assessed
N0a (biopsied): No regional lymph node metastasis, biopsy performed
N0b (biopsied): No regional lymph node metastasis, biopsy not performed
N1: Regional lymph node metastasis
Distant metastasis (M) of conjunctiva
M0: No distant metastasis
M1: Distant metastasis
Stage grouping of conjunctival melanoma
No stage grouping is presently recommended by AJCC
Cornea
Normal anatomy and histology of cornea
Wider than tall (11.7 mm horizontally vs. 10.6 mm vertically); thickness varies from 0.5 mm (central) to 0.67 mm (peripheral)
Cornea and overlying tear film are major refractive surface of eye, not the lens
6 distinct layers (outside to inside):
(1) outer epithelium: stratified squamous, nonkeratinized, 5 layers thick centrally, thicker peripherally; polygonal at basal layer but flatten as they approach surface; basal cells may have mitotic figures; Langerhans cells identifiable by special stains (CD1a); layers often “rubbed off” while grossing specimen
(2) epithelial basal lamina (basement membrane): highlighted with PAS stain
(3) Bowman’s layer: most anterior stroma; acellular, made of randomly oriented delicate collagen fibers, does not regenerate; 8-14 microns thick; not a true basement membrane
(4) stroma: also called substantia propria, no blood vessels or lymphatics; 90% of cornea’s thickness; contains regularly spaced collagen fibrils, normally separated by glycoprotein and mucoprotein which makes cornea transparent
Note: normally see stromal lamellae separated by clefts, a processing artifact; absence of clefts is caused by stroma edema, due to damage of "endothelium"; with edema, get corneal clouding
(5) Descemet’s [pronounced DEZMET’s] membrane: a true basal lamina produced by underlying corneal endothelial cells, 3-4 microns at birth, 10-12 microns in adults; does not regenerate, site of copper deposition in Kayser-Fleisher ring of Wilson’s disease
(6) “endothelium”: single layer of very flat cells, does not regenerate, functions as pump to keeps cornea dehydrated and transparent; neural crest origin (S100+); does NOT line blood vessels or lymphatic spaces; directly contacts aqueous humor of anterior chamber; often “rubbed off” while grossing specimen
Vasculature: no blood vessels or lymphatics within cornea; arterial plexus is present at junction of cornea and sclera; is also nourished by aqueous humor of anterior chamber
Hasall-Henle bodies (warts): focal excrescences that form on peripheral Descemet’s membrane with normal aging; not seen in surgically excised corneal buttons because are too peripheral in location
Myopia: eye too long for its refractive power
Hyperopia: eye too short for its refractive power
Laser assist in situ keratomileusis (LASIK): sculpt cornea and change its refractive properties to eliminate need for glasses
Micro images: full thickness #1; #2; epithelium and Bowman’s layer
Drawings: cornea (some layers have different names)
Positive stains: CK3
Negative stains: CK19
References: Hum Path 1997;28:1348 (cytokeratin)
Don't pick up with forceps
Bisect at center with sharp razor to see papillary excrescences or other lesions of interest
Embed "on edge"
Routine stains are hematoxylin & eosin and PAS (highlights basal lamina)
Acanthamoeba keratitis - cornea
Rare but serious complication of contact lenses due to contamination of contact lens cleaning systems
Organisms are ubiquitous protozoa in soil and fresh water
Infections wax and wane, may infiltrate cornea along corneal nerve and cause pain
Micro: stromal neutrophils, necrotic tissue; amoebic cysts and trophozoites identifiable with H&E, highlighted with GMS, PAS
Micro images: various images #1; #2; #3
DD: fungal or herpetic keratitis
Actinic band keratopathy - cornea
Extensive solar elastosis in superficial layers of corneal collagen in band-like area of interpalpebral fissure
Due to chronic high levels of ultraviolet light
Clinical images: band keratopathy
Gross: yellow due to solar elastosis
Micro: extensive solar elastosis
Aphakic bullous keratopathy - cornea
Secondary endothelial compensation, often after cataract extraction (with or without an intraocular lens)
Resembles Fuchs dystrophy; causes severe visual loss and astigmatism
Micro: corneal edema with bullae between corneal epithelium and Bowman’s layer; late changes are replacement of bullous cavity with fibrous tissue; no/attenuated endothelium
Due to chronic anterior chamber hemorrhage or hyphema, caused by trauma or increased intraocular pressure
Hemoglobin and other red blood cell breakdown products may diffuse into and stain cornea
May eventually clear, beginning in periphery
Clinical images: corneal blood staining
Micro: small pink-brown globules or spheres in corneal lamellae
Injury to endothelium (does not regenerate), which normally pumps fluid out from corneal stroma, leads to chronic edema of stroma and epithelium, subepithelial bullae, pain, eventually diffuse scarring and reduced vision
Causes include immunologic rejection of corneal endothelium, Fuchs dystrophy, implantation of prosthetic intraocular lens
Called aphakic bullous keratopathy (see above) if after cataract extraction
Micro: intraepithelial vesicles, bullae between epithelium and Bowman’s layer, fewer endothelial cells than normal, increased corneal thickness with loss of normal artifactual clefts between collagen lamellae
Calcific band keratopathy - cornea
Due to chronic inflammation, calcium and phosphate disorders
May complicate chronic uveitis, especially in patients with juvenile rheumatoid arthritis
Gross: brown staining material in anterior cornea within palpebral fissure
Micro: calcium deposition in Bowman’s layer and superficial corneal stroma; may be associated pannus formation
Gross/micro images: calcium deposition in superficial stroma
Positive stains: calcium (von Kossa stain)
Chronic actinic keratopathy - cornea
Also called climatic droplet keratopathy or spheroidal degeneration
Initially involves periphery of cornea, increases in severity and incidence with age
Associated with long term exposure to excessive ultraviolet light
Micro: amorphous globules of protein accumulate in superficial stroma of interpalpebral portion of cornea
DD: other disorders produce similar globules
Collagen-rich crystalloids of cornea
Rarely seen in benign salivary gland tumors with myoepithelial differentiation or cutaneous neoplasms
To date, one report in cornea
Case reports: 56 year old with scarred, vascularized cornea (Archives 2005;129:1179)
Micro: large aggregates of partially birefringent material within corneal stroma; radially arranged columns with round to pointed tips
Micro images: various images
Heterogeneous group of inherited, bilateral, symmetric corneal disorders
Most common is Fuchs dystrophy; also macular, lattice and granular corneal dystrophy
Cause severe visual loss reparable by corneal transplantation
Site of damage and types of corneal dystrophy:
Epithelium: Meesman dystrophy; microcystic, map dot and fingerprint dystrophy
Bowman’s layer and superficial stroma: granular corneal dystrophy type III; Thiel-Behnke dystrophy; familial subepithelial amyloidosis
Stroma: granular corneal dystrophy types I and II, macular corneal dystrophy, central stromal crystalline dystrophy
Endothelium: Fuchs dystrophy (see below), posterior polymorphous dystrophy, congenital hereditary endothelial dystrophy
Central stromal crystalline dystrophy: also called Schnyder corneal dystrophy, disease maps to 1p34-p32, crystals of cholesterol ester in anterior stroma
Congenital hereditary endothelial dystrophy: autosomal dominant (maps to 20q12-q13.1) or autosomal recessive; edematous epithelium with lack of Bowman’s layer, thickened stroma and Descemet’s membrane, diminished number of endothelial cells
Familial subepithelial amyloidosis: also called primary gelatinous droplike dystrophy, Bowman’s layer and superficial stroma dystrophy; autosomal recessive, usually due to mutation in M1S1 gene at 1p, has subepithelial amyloid deposits that contain lactoferrin
Fleck dystrophy: also called speckled, cloudy dystrophy; subepithelial and stromal amyloid deposits, autosomal dominant, maps to 2q35, stains with colloidal iron and Alcian blue
Granular corneal dystrophy type I: stromal dystrophy, autosomal dominant, usually due to R555W mutation in TGFB1 gene at 5q31, discrete deposits of mutated protein appear red with Masson trichrome stain
Granular corneal dystrophy type II: also called Avellino corneal dystrophy; autosomal dominant, due to R124H mutation in TGFB1 gene at 5q31, corneal deposits similar to granular corneal dystrophy type I plus amyloid
Granular corneal dystrophy type III: also called Reis-Bucklers dystrophy, Bowman’s layer and superficial stroma dystrophy; autosomal dominant, due to R124L mutation in TGFB1 gene at 5q31
Lattice dystrophy: irregular linear subepithelial and stromal amyloid deposits, normal Descemet’s membrane and endothelium; birefringent amyloid with Congo Red stain
Lattice type I: autosomal dominant, usually due to R124C mutation in TGFB1 at 5q31, lesions limited to cornea; often recurrent epithelial erosions and subepithelial amyloid or collagenous plaques
Lattice type II: autosomal dominant, mutation in GSN gene at 9q34, associated with familial amyloid polyneuropathy; amyloid is derived from fragment of mutated gelsolin
Lattice type III: autosomal recessive, amyloid deposits thicker than in types I and II, identity of amyloid unknown
Lattice type IIIA: autosomal dominant, amyloid deposits resemble type III, mutation in TGFB1 gene at 5q31
Macular corneal dystrophy: autosomal recessive, due to mutation in CHST6 gene at 16q22.1, deficiency in carbohydrate sulfotransferase, causes deposits of low sulfated keratan sulfate-related glycosaminoglycan throughout stroma, Descemet’s membrane and endothelium; also corneal guttae; deposits are positive for colloidal iron and Alcian blue
Macular type I - no/low serum keratan sulfate; keratocytes don’t react to keratan sulfate antibodies
Macular type IA - no/low serum keratan sulfate; keratocytes DO react to keratan sulfate antibodies
Macular type II - normal serum keratan sulfate; keratocytes DO react to keratan sulfate antibodies
Meesmann’s dystrophy: epithelium dystrophy, autosomal dominant, mutation in keratin KRT3 (12q) or KRT12 gene (17q), intraepithelial microcysts
Microcystic, map dot and fingerprint dystrophy: epithelium dystrophy with nonspecific features, intraepithelial basement membrane and microcysts
Posterior polymorphous dystrophy: endothelial dystrophy, autosomal dominant (may be due to mutation in COL8A2 at 1p34.3-p32.3), or autosomal recessive; may also map to 20q12-q13; abnormal Descemet’s membrane; has multilayered epithelial cells in posterior cornea
Thiel-Behnke dystrophy: transmission EM shows subepithelial “curly” fibers; due to R555Q mutation in TGFB1 gene at 5q31 or 10q23-q24; focal loss of epithelial basement membrane and Bowman’s layer
Micro images: lattice dystrophy - lattice dystrophy
DD: amyloid due to trauma; keratoconus, trachoma, uveitis, retrolental fibroplasia, sympathetic ophthalmia, glaucoma
Epithelial ingrowth into cornea
Occurs after penetrating corneal injury (trauma, surgery)
Epibulbar squamous epithelium grows through wound into anterior chamber of eye, and may replace corneal epithelium and cause bullous keratopathy
May cause intractable glaucoma if epithelium invades trabecular meshwork
Micro: squamous epithelium in cornea instead of single layered corneal epithelium
Positive stains: keratin
Fuchs endothelial dystrophy of cornea
Type of primary endothelial dystrophy or endothelial decompensation
Most common endothelial dystrophy and common indication for corneal transplantation in US
Damage (decompensation) to endothelium, which normally pumps out fluid from corneal stroma, leads to chronic edema of stroma and epithelium, pain from rupture of epithelial bullae, eventually diffuse scarring and reduced vision
Women ages 50+; some cases are autosomal dominant, some cases are due to mutation in COL8A2 at 1p34.3-p32.3
Gross: bilateral, often asymmetric
Micro: corneal edema and cysts due to endothelial damage with paucity of endothelial cells and thickening of Descemet’s membrane; epithelium is separated from Bowman's layer; papillary excrescences (guttae) in middle of cornea (must bisect cornea at equator and embed at equator to see); if severe, may see edema of basal cells, bullae formation and pannus formation (fibrovascular ingrowth between Bowman’s layer and epithelium)
DD: interstitial keratitis (inconspicuous ghost vessels in most posterior corneal stroma)
Most corneal transplants are successful and provide long term improvement in visual acuity
Matching of donor and recipient tissue is not necessary for corneal transplants, since no lymphatics or blood vessels in corneal stroma
Graft failure may be due to surgical damage of endothelium, immunologic rejection (uncommon) or recurrence of dystrophy
Clinical images: failed graft with corneal edema
Micro: fibrosis, vascularization, inflammatory cell infiltrate; full thickness scars from prior surgery are present at edge of specimen; 50% have fibrous retrocorneal membrane
Herpes simplex keratitis - cornea
Most common cause of corneal ulcers; usually unilateral, may recur
Usually HSV1
Diagnosis: difficult in recurrent cases, may need EM, PCR, ISH or immunohistochemistry since cultures are usually negative and inclusions are rarely identified
Micro: diffuse epithelial edema, causing bullae between epithelium and Bowman’s layer; also patchy loss of Bowman’s layer, irregular epithelium, infiltration of anterior stroma by lymphocytes and plasma cells with stromal fibrosis and neovascularization; severe cases have granulomatous reaction surrounding Descemet’s membrane; herpetic inclusions are rare
Micro images: giant cell and inclusions
Infectious keratitis (keratoconjunctivitis) - cornea
Contact lens wearers are susceptible to Pseudomonas and Acanthamoeba (see above)
Keratitis caused by microfilaria of Onchocerca volvulus is the leading cause of blindness worldwide, outside US
Granulomatous keratitis: due to HSV1, leprosy, juvenile xanthogranuloma, sarcoidosis
Micro: similar histologic findings for all organisms - destruction of corneal epithelium, Bowman’s layer and stroma; necrosis and prominent neutrophils; discontinuities of Descemet’s membrane with corneal perforation; crystal-like stromal opacities with Streptococcus viridans; may need special stains to detect organisms
Vernal keratoconjunctivitis
Common, incidence of 1 per 2000
Congenital ectasia of central cornea, usually identified by age 9 years; usually bilateral
Associated with Down’s syndrome, Marfan’s syndrome and atopic disorders
Progresses until fibrosis decreases vision
May have sudden rupture of Descemet’s membrane, allowing aqueous humor to enter corneal stroma, causing corneal hydrops and sudden worsening of vision
Causes scarring and astigmatism which cannot be corrected by glasses; may be corrected by rigid contact lenses
Treatment: corneal transplantation
Clinical images: normal cornea and keratoconus
Gross: wrinkled corneal button after transplantation, cornea is cone shaped; often has Fleischer ring (brown, stainable intraepithelial iron arc surrounds conical portion of cornea)
Micro: thinning and fibrosis of cornea, numerous breaks in Bowman’s layer, no inflammation or vascularization
Severe form of Vitamin A deficiency with diffuse, severe keratinization of mucous membrane epithelia, including corneal and conjunctiva epithelia (xerophthalmia)
Leading cause of blindness in developing world
Associated with secondary bacterial infection, corneal ulceration/necrosis, which causes corneal perforation and panophthalmitis
Clinical images: keratomalacia
Junction of peripheral cornea and anterior sclera
Not a distinct anatomic site but a significant clinical landmark
Composed of conjunctiva (epithelium and stroma), cornea and scleral stroma, episclera, Tenon’s capsule (fibrous tissue that covers the globe)
Descemet’s membrane terminates at limbus and gives rise to Schwalbe’s ring; 15% have prominent area of thickening at this site
1.5 to 2.0 mm wide
Contains trabecular meshwork and Schlemm’s canal
Site of incisions for surgery on anterior eye
Restrictions deeper extension of superficial tumors
Trabecular meshwork: with Schlemm’s canal, are apparatus for removal of aqueous from eye; collection of finely branching and delicately pigmented connective tissue bands; lining cells are continuous with corneal endothelium; posteriorly, trabecular meshwork extends to scleral connective tissue called scleral spur
Schlemm’s canal: anterior and superficial to trabecular meshwork; endothelial lined venous canal that completely encircles limbus; separated from trabecular meshwork by thin connective tissue and separate endothelial linings
EM: Schlemm’s canal endothelial cells contain giant cytoplasmic vacuoles
Nonspecific responses in cornea
Corneal edema may lead to intraepithelial vesicles and bullae between epithelium and Bowman’s layer
Aberrant basal lamina may develop within corneal epithelium in response to some injuries
Collagenous tissue (pannus) may accumulate between corneal epithelium and Bowman’s layer
Blood vessels may be present in superficial or deep stroma after inflammatory conditions (normally cornea is avascular)
Irregular thickening of Descemet’s membrane occurs with aging
Due to chronic inflammation in eye
Micro: proliferation of fibrovascular tissue under epithelium in anterior cornea
Pseudoexfoliation syndrome in cornea
Common systemic degenerative condition with extracellular deposition of distinctive fibrillar material on surfaces of cornea and other structures lining anterior and posterior chambers
Associated with cataract and glaucoma
May be a connective tissue disorder
Clinical images: various images
References: Hum Path 1996;27:1255
Rheumatoid arthritis in cornea
May have spontaneous thinning of corneal stroma, more common at periphery of cornea, but central thinning more often causes perforation
Keratoplasty (corneal transplantation): produces button 8 mm in diameter
Indications for keratoplasty: primary and secondary endothelial decompensation (dystrophy), fibrosis, vascularization, keratoconus, failed prior grafts, interstitial keratitis
Penetrating keratoplasty: full thickness corneal graft, 8 mm in diameter
Lamellar keratoplasty: partial thickness corneal graft
Donor corneal scleral rim: want to check for endothelial damage
Due to any process that causes uneven distribution of the tear film across cornea
Bacterial ulcers often destroy epithelium and Bowman’s layer with variable stromal destruction; due to Staphylococcus aureus, Streptococcus pneumoniae, E. coli, Klebsiella, Pseudomonas
Complications include corneal perforation and scarring
Fungal ulcers occur 8-15 days after trauma, usually involving vegetative matter; due to Candida, Aspergillus, Cephalosporium, Fusarium; satellite lesions are also present
Rarely due to ocular cicatricial pemphigoid (Eur J Ophthalmol 2007;17:121)
Case reports: Exserohilum longirostratum (dematiaceous fungus )after trauma (AJCP 1994;101:452)
Micro: eosinophils and granulomas with fungal infection
Micro images: bacterial ulcer #1; #2
Tumor features to report-cornea
Precise anatomic location-limbus by clock hour
Histologic type
Tumor size
Involvement (noninvolvement) of other tissues present
Margins (minimum clearance)
Angiolymphatic invasion
Presence of ulceration
Eyelid
Specimens received are often from cosmetic blepharoplasty or other reparative surgery, with no abnormalities
Other lesions are similar to those in skin
Creates tear film via accessory lacrimal glands embedded above fibrous tarsus of eyelid; helps to protect and lubricate the globe
Tumors may prevent complete closure of eyelid, leading to exposure and ulceration of cornea
Has cutaneous and conjunctival portion
Palpebral (tarsal) conjunctiva lines interior of eyelid; is very thin; is continuous with bulbar conjunctiva that covers the sclera; becomes papillary with allergic or bacterial conjunctivitis
Contains eccrine and apocrine glands (glands of Moll) and sebaceous glands
Sebaceous glands (Meibomian glands within eyelid fibrous tarsus and glands of Zeis associated with eyelashes) create lipid layer of tear film, which retards evaporation of tears
The
orifices of Meibomian glands open just in front of the posterior edge of the
lid margin, and are separated from the more anteriorly placed eyelashes by a
gray line.
Muscular layer is composed primary of orbicularis oculi muscle
Gray line: divides the eyelid into anterior and posterior parts. It corresponds with the position of the pretarsal orbicularis muscle.
Drawings: eyelid
Micro images: normal upper eyelid: Z-Zeis glands, O-orbicularis muscle, M-meibomian glands, T-tarsal plate; normal lower eyelid (similar to upper eyelid but smaller tarsal plate); eyelid cross section; normal Meibomian gland (sebaceous lobules connect to sebaceous duct, where ductal epithelium forms valve-like structures)
Eyelid inflammatory disorders
Very common
Deep seated lipogranuloma that develops near meibomian glands or glands of Zeis
Probably due to obstruction and nonspecific inflammation (blepharitis), leading to discharge of sebaceous material into surrounding tissue and resulting intense granulomatous inflammatory reaction
May erupt through conjunctival surface of eyelid
Initial specimens are often not submitted for pathologic examination, but recurrences suggest sebaceous carcinoma and should be examined
Treatment: curettage
Micro: multiple foci of granulomatous inflammation with microabscesses and multinucleated giant cells; center of granulomas may contain small fat globules
Micro images: chalazion
DD: