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
Conjunctiva
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
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
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: sarcoidosis, tuberculosis, fungi
Mites commonly found within hair follicles (Demodex folliculorum) or sebaceous glands (Demodex brevis)
Usually incidental findings that don’t incite an inflammatory reaction
Increase with age (100% at age 70+)
Molluscum contagiosum of eyelid
Poxvirus that produces small nodules on eyelid
Treatment: excision if on eyelid margin to prevent infection of ocular surface
Gross: multiple raised skin nodules with umbilicated centers
Micro: lobules of acanthotic epithelium that surround intracytoplasmic eosinophilic inclusion bodies (molluscum bodies), which become larger at they reach the superficial epithelium
Necrobiotic xanthogranuloma with paraproteinemia of eyelid
Multiple nodules or plaques in periorbital areas and elsewhere in body
Patients always have IgG paraprotein dysproteinemia
Micro: granulomas with collagen necrobiosis, foamy macrophages, Touton giant cells
Case report of 5 year old Chinese girl in Taiwan with Prototheca wickerhamii in eyelid (Archives 1987;111:737)
Treatment: ketoconazole
Micro: symmetrically arranged endospores
Pseudorheumatoid nodules of eyelid
Also called deep granuloma annulare
May involve eyelid and eyebrow
Post-traumatic or post-surgical
Gross: red, fleshy, often pedunculated
Micro: inflammatory lesion composed of granulation tissue with mixed inflammatory infiltrate
Noncaseating, composed of epithelioid cells, multinucleated giant cells and birefringent silica crystals, surrounded by fibrosis
Also called hordeolum, chalazion (by some)
Acute suppurative inflammation of sebaceous glands or follicles of eyelid
Usually due to Staphylococcal infection
Internal - affects meibomian glands; external - affects glands of Moll or Zeis and adjacent hair follicles and cilia
Treatment: medical
Tumors
Consist of epithelial tumors originating in skin and conjunctival surfaces (squamous cell and basal cell carcinoma), glandular tumors originating from sebaceous, sweat and apocrine glands and hair follicles
Also lymphoid and melanocytic tumors
Occasionally Kaposi’s sarcoma, fibrous histiocytoma and other sarcomas
Regional lymph nodes are pre-tarsal and post-tarsal plexuses, which are anastamosed
Lateral 2/3 of upper eyelid and lateral 1/3 of lower eyelid drain into preauricular nodes; remaining lymphatics drain into submandibular nodes
Local extension includes soft tissue of orbit, lacrimal gland and globe
Frozen section (Mohs’ technique) useful to minimize size of excised tissue
Metastases to cervical, axillary and mediastinal lymph nodes, lung, liver and other viscera
Eyelid adnexal tumors
Malignant sweat gland tumor, often mucinous
Similar to adenocystic carcinoma of skin at other sites
Local recurrences are common, rarely distant metastases
Micro images: multinodular tumor within dermis contains numerous mucin filled cysts #1; #2-cysts are lined by cuboidal epithelium
Micro images: ductal type - mimics syringoma but invades deeply into eyelid; bland cells arranged in ducts and cords infiltrating the orbicularis muscle; histiocytoid type - anaplastic cuboidal epithelial cells with intracytoplasmic vacuoles are arranged in single file pattern; marked desmoplasia hides neoplastic cells, but keratin staining (inset) shows them arranged in single file pattern; mucinous type - small islands of epithelial cells float in pools of mucin
DD: metastatic breast carcinoma resembles histiocytoid pattern (image)
Sebaceous gland adenoma of eyelid
Also called sebaceous cell adenoma
Arise from cutaneous sebaceous glands, glands of Zeis (surrounding eyelashes at lid margin) or meibomian glands (in tarsus) or sebaceous glands of caruncle
Solitary adenomas: rarely biopsied, may be curetted as likely chalazion with disposal of tissue
Recurrent tumors should be examined histologically to rule out malignancy
Micro images: multilobular tumor is composed of sebaceous cells with orderly maturation
Sebaceous gland carcinoma of eyelid
Also called sebaceous cell carcinoma
Commonly misdiagnosed as chalazion or chronic blepharoconjunctivitis
1-3% of eyelid malignancies in US
75% women, mean age 61 years, range 28-82 years
10% are multicentric
May arise after radiation therapy for retinoblastoma
1/3 recur, 25% die of metastases (parotid and submandibular nodes), may spread to lacrimal drainage system and nasopharynx
Intraepithelial (pagetoid) spread to adjacent structures is common
Poor prognostic factors: orbital or vascular invasion, bilateral involvement of eyelids, poorly differentiated or multicentric tumors, large size, infiltrative pattern, pagetoid spread
Case reports: fatal tumor after radiation therapy for bilateral retinoblastoma (AJSP 1978;2:305)
Clinical images: tumor involves upper and lower eyelids with loss of lashes, and invades conjunctiva and cornea with scarring and vascularizaiton; exenteration specimen with tumor invading orbit from upper eyelid
Micro: nesting, comedonecrosis or papillary patterns; morphology varies from well differentiated to anaplastic; often pagetoid spread or carcinoma in situ
Well differentiated: contain cells with foamy, finely vacuolated cytoplasm and distinct cell borders; better differentiated cells are usually in center of nests, often near tarsus and meibomian glands
Anaplastic: often scant cytoplasm with indistinct vacuoles; central necrosis, pagetoid involvement of overlying skin
Micro images: Meibomian glands are replaced by tumor lobules in a comedocarcinoma pattern, and conjunctival epithelium is replaced by tumor cells (top); center of tumor lobules shows sebaceous differentiation; cords of poorly differentiated tumor cells invade eyelid connective tissue and resemble basal cell carcinoma-morphea type; pagetoid tumor spread involving cilia epithelium in Zeis gland and epidermis; pagetoid tumor spread into eyelid epidermis; pagetoid invasion of conjunctival epithelium by tumor cells with foamy cytoplasm; neoplastic cells have replaced conjunctival epithelium in bowenoid pattern; neoplastic cells have invaded into corneal epithelium; fig 1A: Oil Red O; 1B: pagetoid tumor spread
Positive stains: Oil Red O (on frozen sections)
DD: basal cell carcinoma (less pleomorphic, has peripheral palisading), chalazion (clinically), ocular cicatricial pemphigoid
References: AJSP 1984;8:597
Sweat gland carcinoma of eyelid
Case reports of in situ and invasive sweat gland carcinomas with endocrine differentiation (AJSP 1997;21:1501)
Micro: resemble solid papillary carcinoma of breast
Usually young women with multiple lesions
Micro: comma shaped lesions
Trichilemmal cell tumor of eyelid
Also called pilar cyst
Micro: cyst composed of dense keratin without a granular cell layer
Originates from outer hair sheath
Benign
May involve eyelid or eyebrow
Micro: glycogen rich cells
Micro images: small nodule involving a hair follicle is composed of polyhedral clear cells
Sporadic or autosomal recessive
Multiple epidermal inclusion like cysts plus rudimentary hair follicles
Micro images: numerous dermal horn cysts are surrounded by several layers of basaloid cells
Solitary large cyst with hair in center
Eyelid melanocytic tumors
Rare; may originate from nevus, acquired melanosis or de novo
Poor prognosis due to early metastasis via lymphatics or bloodstream
Sentinel lymph node biopsy has been used for melanoma of eyelid
Micro: resembles skin tumors more than globe tumors; spindled or epithelioid cells with marked atypia and invasion into dermis
Also called ocular melanocytosis
Rare congenital anomaly with variable hyperpigmentation of conjunctiva, episclera, sclera, uveal tract, possibly optic nerve
May be variant of nevus of Ota
Associated with ocular melanoma
Sclera appears blue due to deep uveal pigmentation (see Tyndall effect)
On cutaneous or conjunctival surface, commonly on lid margin
Usually junctional (nests of nevus cells at border of epidermis and dermis) or compound (nests at junction and within dermis); usually acquired
Rarely give rise to melanoma
Micro: nevus cells with bland nuclei; may be multinucleated; no/rare atypia, no/rare mitotic figures
Also called congenital oculodermal melanosis
More common in Orientals and blacks
A form of extrasacral mongolian spot involving the distribution of the first and second branches of trigeminal nerve in face
Diffuse and deeply seated melanocytic lesion
Slight risk of uveal melanoma if skin of eyelid or periorbital area is affected
Clinical images: congenital subepithelial melanosis involving skin, eyelid and sclera
Eyelid other tumors
Gross: thickened or raised red-brown lesions
Micro: acanthosis or hyperkeratosis, with atypia of squamous cell layer but normal polarity and maturation; basophilic degeneration of dermal collagen
Micro images: irregular acanthosis with atypia and parakeratosis #1; #2 with early invasive squamous cell carcinoma
May present as a mass, without systemic disease
Perivascular deposits are characteristic of systemic disease
Basal cell carcinoma of eyelid
Very common; 90% of eyelid malignancies; probably secondary to sunlight
Rarely invades orbit or nose
Arise from cutaneous surface of eyelid (usually lower lid and medial canthus), only rarely from conjunctiva
Frozen section review of margins is helpful in reducing recurrence
Excision is important to preserve vision, since tumors may prevent proper eyelid closure and cause corneal exposure and ulceration
Case reports: 34 year old woman with recurrent eyelid tumor, bony metastases, meningeal carcinomatosis and death (Hum Path 1985;16:530)
Gross: ulcerated, pigmented, superficial or sclerosing
Micro subtypes: nodular and nodular-ulcerative (anastomosing nests and cords of proliferative epidermal basal cells with minimal cytoplasm, dark nuclei and nuclear palisading at periphery), cystic (central necrosis with cystic spaces), multicentric, morphea (infiltrates into dermis as branching cords of cells within a dense stroma; margins are difficult to assess clinically)
Micro images: adenoid type has lobules with a cribriform pattern and marginal palisading of basaloid cells; metatypical type has islands of squamous cell differentiation within a basaloid tumor; morphea type in patient with heritable retinoblastoma-atrophic epidermis overlies small, irregular clusters of basaloid cells #1; #2-highly infiltrative cords of basaloid cells; nodular type with solid lobules of neoplastic basaloid cells;
DD: conjunctival papilloma
Common, represent 1/3 of eyelid lesions
Cysts below are benign; excision is curative
Dermoid cyst of eyelid: see below
Keratinous cyst of eyelid (epidermal inclusion cyst): most common eyelid cyst; either congenital, post-traumatic or post-surgical; lined by squamous epithelium and contains laminated keratin; marked foreign-body giant cell reaction if cyst ruptures; no dermal appendages
Hidrocystoma of eyelid (sudoriferous cyst): arise from eyelid sweat glands; thin-walled transparent vesicles at margin of lid, lined by atrophic cuboidal or flattened epithelial cells containing watery fluid or with an empty lumen (“sudoriferous” means carrying or producing sweat); lined by 1-2 layers of flattened cuboidal cells
Apocrine hidrocystoma of eyelid: lined by double layer of columnar cells with eosinophilic cytoplasm, papillary projections and apocrine snouts; develop from obstructed ducts of glands of Moll, are often multiple at eyelid margin
Usually upper eyelid along brow margin
May represent intraorbital mass that is pushed forward
Often attached to periosteum of bony orbital rim
Gross: soft, nontender, round/oval, 1 cm or less
Micro: lined by well differentiated epidermis and dermis, lumen filled with keratinous debris, hair, sebum; may have foreign body inflammatory reaction if cyst ruptures
DD: phakomatous choristoma (lower eyelid of infants, very rare, don’t recur even if incompletely resected, derived from lens tissue, Archives 1989;113:1175)
Small lesion of eyelid or large lesion extending into orbit
Capillary type (“strawberry marks”) usually arise congenitally or in early infancy, and are considered hamartomas
80-90% regress spontaneously by age 5 years
Clinical images: hemangioma
Micro: numerous small capillaries lined by plump endothelial cells
Develops in eyelid or conjunctiva of AIDS patients
Appears purple in eyelid due to deep location in dermis, but red in conjunctiva since superficial
Gross: thickening of conjunctiva
Micro images: Kaposi’s sarcoma
DD: hemorrhage
May involute spontaneously, or exhibit aggressive behavior with perineural invasion
Micro images: pale, acanthotic, hyperkeratotic epithelium undermining normal epidermis #1; #2
Merkel cell carcinoma of eyelid
Resembles skin tumor
Usually upper eyelid
Often presents as large, nontender, red or violet mass
Clinical images: superficial tumor of upper eyelid with thin epidermis and prominent vessels
Micro images: well circumscribed nodule of superficial dermis; tumor cells have pale round nuclei with high N/C ratio #1; #2-infiltrating lymphocytes present
Often from lung, breast or kidney
Metastatic lobular carcinoma of breast may have histiocytoid features and mimic inflammation
Rare
May be part of Carney syndrome (spotty pigmentation of skin, overactive endocrine glands, myxoma of heart)
Sporadic or part of neurofibromatosis type 1
May be present at birth, but show accelerated growth during childhood
Neurofibromatosis (facial features): often multiple tumors causing marked facial asymmetry, neurofibroma of orbit and glioma of optic nerve
Micro: increased mast cells
Phakomatous choristoma of eyelid
Micro images: islands of lens epithelial tissue with a prominent PAS+ basement membrane surrounded by desmoplastic stroma; proliferation of swollen epithelial cells similar to those in posterior subcapsular cataract; PAS+ lenticular tissue with central degeneration; PAS+ thick basement membrane surrounds an island of lenticular epithelial cells
Also known as calcifying epithelioma of Malherbe
Benign
Micro: basaloid and ghost cells
Micro images: multinodular tumor of peripheral basaloid cells and central ghost cells with central calcification
Also called nevus flammeus
Type of facial hemangioma
Sturge-Weber syndrome: ipsilateral port wine stain, choroid hemangioma, glaucoma and meningeal hemangioma
Seborrheic keratosis of eyelid
Gross: elevated irregular lesions, often crusty or greasy appearing; often pigmented
Micro: acanthosis with marked hyperkeratosis and keratin-filled cysts; also increased pigmentation in basal layer; no atypia
Micro images: plaque-like lesion with cords of basaloid cells and numerous horn cysts #1; #2; irritated seborrheic keratosis (inverted follicular keratosis) has acanthotic epithelium with massive hyperkeratosis forming a cutaneous horn #1; #2 shows numerous squamous eddies within acanthotic epithelium
Gross: resemble skin tags
Micro: acanthotic epithelium with hyperkeratosis, papillary projections with inner fibrovascular core
Squamous cell carcinoma of eyelid
10% of carcinomas in eyelid
Usually lower lid
Rarely are adenoid (pseudoglandular)
Rarely invade eye or orbit or metastasize
Gross: elevated and thickened areas of eyelid, may be ulcerated or friable
Micro: invasion of malignant squamous cells into dermis; cells are large and eosinophilic with marked atypia; often abnormal deep keratinization, may have keratin pearls
Micro images: squamous cell carcinoma-spindle cell type - atrophic epidermis overlies a highly infiltrative tumor; spindled cells resemble sarcoma
DD: pseudoepitheliomatous hyperplasia, keratoacanthoma, inverted follicular keratosis, seborrheic keratosis, actinic keratosis, papilloma
Usually not associated with systemic problems
Removed for cosmetic reasons
Yellow plaques on medial eyelids of men/women ages 40+ years
Appear in younger patients with familial hypercholesterolemia
Micro: large, pale, fat-laden histiocytes within dermis
Micro images: image
Miscellaneous eyelid
Tumor features to report-eyelid
Precise anatomic location-upper or lower eyelid, medial or lateral canthus
Histologic type and differentiation
Tumor size(s) and gland of origin (Meibomian vs. Zeis)
Presence of infiltrative growth pattern
Presence of pagetoid spread
Involvement (noninvolvement) of other tissues present
Margins (minimum clearance); includes conjunctival margins and resection margin of optic nerve if specimen includes the globe
Angiolymphatic invasion
Perineural invasion
Presence of ulceration
For melanomas, indicate thickness and mitotic activity
TNM staging for carcinoma of the eyelid
Applies to clinical and pathologic staging
Note: excludes melanoma and malignancies other than carcinoma
Primary tumor (T)
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, not invading the tarsal plate or eyelid margin
T2a: Tumor more than 5 mm, but not more than 10 mm in greatest dimension, or any tumor that invades the tarsal plate or eyelid margin
T2b: Tumor more than 10 mm, but not more than 20 mm in greatest dimension, or involving the full thickness eyelid
T3a: Tumor more than 20 mm in greatest dimension, or any tumor that invades adjacent ocular or orbital structures, or any T with perineural tumor invasion
T3b: Complete tumor resection requires enucleation, exenteration or bone resection
T4: Tumor is not resectable due to extensive invasion of ocular, orbital, craniofacial structures or brain
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
cN0: No regional lymph node metastasis, based on clinical evaluation or imaging
pN0: No regional lymph node metastasis, based on lymph node biopsy
N1: Regional lymph node metastasis
Distant metastasis (M)
M0: No distant metastasis
M1: Distant metastasis
Stage grouping of eyelid carcinoma
0: Tis N0 M0
IA: T1 N0 M0
IB: T2a N0 M0
IC: T2b N0 M0
II: T3a N0 M0
IIIA: T3b N0 M0
IIIB: Any T N1 M0
IIIC: T4 Any N M0
IV: Any T any N, M1
Glaucoma
Diverse etiologies, causes widespread degeneration of ocular tissue
Defined as optic neuropathy with distinct excavation of optic nerve head and incremental loss of visual field sensitivity
Almost always due to increased intraocular pressure (due to impaired outflow of aqueous humor), which causes optic nerve damage and degenerative changes below
Normal circulation of aqueous humor: aqueous humor is produced by pars plicata of ciliary body, discharged into posterior chamber, flows between lens and iris, through pupil, into anterior chamber, then through trabecular meshwork (in deep layers of peripheral cornea just in front of angle of anterior chamber), into Schlemm’s canal, leaves eye via plexus of intrascleral and episcleral veins along limbus
Drawings: anterior chamber #1; #2
Micro images: iris and ciliary body with open anterior chamber angle
Increased intraocular pressure due to malformation of tissues in anterior chamber angle
Causes: hereditary (incomplete separation of iris root from trabeculae, retention of embryonic membrane), congenital rubella syndrome
Unilateral congenital glaucoma is associated with neurofibromatosis type 1 (Recklinghausen’s disease) or Sturge-Weber syndrome
DD: anterior chamber cleavage syndrome (see above, more obvious architectural distortion of iris and angle of anterior chamber)
Primary means no known antecedent disease
Either open angle (chronic simple) or angle closure type
Angle refers to angle of anterior chamber formed by junction of uveal tract with corneoscleral coat, an important site of aqueous drainage
Primary open angle glaucoma: most common form of glaucoma; due to degenerative changes in trabecular meshwork and connective tissue of Schlemm’s canal; insidious process, usually does not produce pain or require enucleation; some patients have mutations in trabecular meshwork inducible glucocorticoid response gene (TIGR, GLC1A), which produces myocilin, found in trabecular meshwork, other anterior segment tissue and optic nerve
Primary angle closure glaucoma: due to anatomic or physiologic abnormalities of tissue and anterior chamber that predispose to blockage of outflow channels by iris root, often in patients with hyperopia; increased posterior chamber pressure also bows iris forward and occludes trabecular meshwork; increased pressure on lens damages its epithelium with minute anterior subcapsular opacities (glaukomflecken); multiple attacks may cause extensive anterior synechia and pain and lead to enucleation
Drawing: angle closure glaucoma
Trabeculectomy: excision of 1 mm or smaller fragment of trabecular meshwork to enhance drainage of aqueous from eye; must embed specimen in paraffin using dissecting microscope
Due to known or suspected antecedent disease, such as trauma, inflammation, tumor or malformation
May be open or closed angle
Common sites of obstruction are pupil and angle of anterior chamber
Causes:
(a) formation of pupillary membranes due to organization of hemorrhage or exudates or posterior synechiae secondary to iritis
(b) peripheral anterior synechiae (adhesions between root of iris and peripheral cornea)
(c) particulate matter clogging passages (red blood cells after hemorrhage; white blood cells after uveitis; lens proteins; iris pigment epithelial granules; melanoma or other tumor cells)
(d) epithelial downgrowth from conjunctiva or cornea after trauma, fibrous downgrowth due to corneal wound
(e) rubeosis iridis (see below)
(f) blunt trauma with retrodisplacement of iris root insertion and atrophy of ciliary body
(g) surface ocular vascular malformations that increase pressure on surface of eye, such as Sturge-Weber syndrome or arterialization in episcleral veins due to fistula
Melanomalytic glaucoma: a type of secondary open angle glaucoma in melanoma patients with pigment laded macrophages that clog the trabecular meshwork
Degenerative changes caused by glaucoma
Enlargement of globe (buphthalmos) or cornea (megalocornea) if childhood onset; atrophy of retinal ganglion cell layer and reduction of nerve fiber and inner nuclear layers, with preservation of rods and cones and outer nuclear layer
Also degeneration of nerve fibers near optic disc, causing cupping (deep excavation) of optic disc, posterior bowing of lamina cribrosa, severe atrophy of optic nerve
May have accumulation of hyaluronic acid in optic nerve (Hales colloidal iron+, Alcian blue+)
Also scleral ectasia in equatorial regions with blue color
Gross: white and atrophic optic nerve with deep cupping and extreme nasal displacement of vessels
Micro: compression of tissues of lamina cribrosa and extensive cupping with posterior bowing; also gliosis of optic nerve, retinal atrophy or loss of ganglion cell layer.
Globe
Defined as eyeball itself plus intraocular tissues, or eye proper without its appendages
Dimensions: anterior-posterior 24 mm, vertical and horizontal dimensions are both 23 to 23.5 mm
Six extraocular muscles: 4 rectus and 2 oblique muscles; arise in posterior orbit from fibrous ring called annulus of Zinn, and insert into sclera; muscles are surrounded by fascia; inferior oblique inserts on sclera, other muscles insert on tendons
Equator: midway between anterior and posterior poles
Specimen is the result of enucleation, performed because eye is nonfunctional, painful, unsightly, infectious, contains neoplasm, post-trauma (may be removed to prevent sympathetic uveitis) or has chronic glaucoma
Globe usually intact but free of extraocular muscles and orbital fat
Globe may be eviscerated, with only fragments available for microscopic study
Initial pathologic processes may be obscured by subsequent pathologic processes
Pathologic processes:
Enucleation: due to tumor (48%, usually melanoma), glaucoma (13%), phthisis bulbi (12%), recent trauma (11%)
Specimens also received after evisceration (10%) or exenteration (9%) to manage malignant orbital tumors (AJCP 2003;119:594)
During 1990 to 2000, decrease in percentages due to neoplasms, increase due to glaucoma and phthisis bulbi
Micro images: cross section
Drawings: horizontal section of eyeball
Virtual slides: whole mount of eye
Describing globe:
Measure dimensions of the eye (anterior-posterior, horizontal, vertical)
Measure length and diameter of optic nerve
Measure cornea in mm (horizontal and vertical and anterioposterior)
Look for sites of trauma (accidental or surgical)
Examine eye surface for gross evidence of extraocular extension of tumor
Describe the following:
Corneal clarity
Shape and diameter of pupil
Color of iris, lesions
Presence of lens
Anterior chamber depth, configuration of anterior chamber angle
Condition of ciliary body, lens, choroid, retina, vitreous body, optic disc
Presence of foreign bodies (in traumatic specimens)
For tumors, describe location, dimensions, shape, ulceration, color, consistency, hemorrhage, necrosis, calcification, ocular structures involved, extension into optic nerve, tumor distance to optic nerve and limbus, rupture of Bruch’s membrane
Transillumination findings
Grossing globe:
Enucleation: globe and part of optic nerve are removed from orbit
For retinoblastoma, may need fresh tissue for genetic studies:
- identify tumor location by transillumination
- submit optic nerve margin separately before cut into globe
- cut small window in sclera overlying tumor and obtain small tumor sample
- try to avoid seeding of tumor cells onto optic nerve or elsewhere
Fix in formalin (300 ml of 10% neutral-buffered formalin) for 24-48 hours before sectioning; do not open or puncture the eye (AFIP, 4th series)
Wash in running tap water for 5-15 minutes; optionally place in 60-70% ethyl alcohol for 1-2 hours (firms up eye and restores color of vessels)
Review clinical history and results of ophthalmologic examination prior to sectioning
“Temporal” is same as lateral; “nasal” is same as medial
Orient globe based on (a) cornea is wider than tall by 1 mm, (b) optic nerve distance to limbus (junction of cornea and sclera) is less medially than laterally (i.e. optic nerve is medial (nasal) to posterior pole), (c) superior oblique muscle tendon inserts in upper outer quadrant of posterior globe behind superior rectus muscle insertion and insertion points towards anterior nasal eye (d) inferior oblique muscle has muscular insertion in lower outer (temporal) quadrant of sclera and fibers run posteriorly and medially, (e) long posterior ciliary arteries are in horizontal plane, (f) four vortex veins exit posterior sclera
Transilluminate globe to find tumor and cut accordingly; can use a substage microscope lamp in a dark room; rotate globe over light, mark abnormal shadows on sclera with indelible pencil
Take Xray before opening globe if foreign body or retinoblastoma is suspected
If choroidal melanoma is suspected, sample at least one vortex vein from each of four quadrants and submit separately
Central section is called “pupil-optic nerve” section; other fragments are called calottes
Try to include optic nerve, pupil, cornea, lens and large cut surface of tumor in same section, about 8 mm thick
Use sharp razor to cut, holding globe with nondominant hand, cornea down against cutting block using blade between thumb and middle finger of dominant hand; open eye with sawing motion from back (adjacent to optic nerve) to front (1 mm inside limbus through peripheral cornea)
If no tumor, cut globe at superior and inferior edges of iris in horizontal plane from back to front (5 mm above and below the optic nerve, missing the lens); quick freeze first in liquid nitrogen to minimize artifacts
Obtain cross section of optic nerve
Drawings: landmarks of right globe; sectioning the globe
Micro images: 4A/B: exenteration for tumor includes globe
Acute inflammation of globe
Causes: usually infectious (bacteria or fungi, usually post-traumatic, also from intravenous drug use or hematogenous spread of infection); noninfectious cause is massive necrosis of uveal melanoma or metastatic carcinoma; cataract surgery may cause mild endophthalmitis due to Propionibacterium acnes
Initially endophthalmitis (affects intraocular contents including vitreous humor but not sclera or cornea) - massive purulent reaction in anterior and vitreous chambers; later panophthalmitis (involvement of retina, choroid, sclera or orbit)
Panophthalmitis exposes orbit to microorganisms but endophthalmitis does not
Late complication is phthisis bulbi (see below)
Chronic inflammation of globe (nongranulomatous)
Usually uveitis (see below)
Granulomatous inflammation of globe
Toxoplasmosis, tuberculosis, syphilis, nematodiasis, CMV, sarcoidosis, collagen vascular diseases
Often cannot determine etiology
Diagnostic lesions often found in retina, vitreous or sclera
Micro images: granulocytic leukemia - diffuse choroidal infiltration; round tumor cells with mitotic activity; lymphoblastic leukemia-choroidal vessels are filled with round neoplastic cells
Rare; usually associated with extraocular disease, often in CNS
May involve optic nerve
Involving ocular adnexa: mean age 64 years, slight female predominance, usually no other history of lymphoma; most common subtyes are marginal zone (52%), follicular (23%) (AJSP 2007;31:170)
Primary intraocular lymphomas: considered a component of primary CNS lymphoma; are usually diffuse large B cell lymphomas with IgH heavy chain gene rearrangements; some cases in HIV1 negative patients may be related to Toxoplasma gondii infection (Mod Path 2001;14:995)
Case reports: diffuse large B cell lymphoma (Archives 2005;129:1050)
Fundoscopic images: yellow-white hemorrhagic retinal infiltrates
Gross images: focally hemorrhagic white infiltrate thickens the retina; subretinal pigment epithelial infiltrate (arrow) is present at cut edge; fig 1C: mass lesion of vitreous with choiroidal thickening
Micro images: diffuse large B cell lymphoma – involvement of optic nerve head and peripapillary retina with extensive necrosis; retinal involvement and tumor cells between detached retinal pigment epithelium and Bruch’s membrane; viable and necrotic tumor cells between detached retinal pigment epithelium and Bruch’s membrane, and smaller reactive lymphocytes within choroid #1; #2; A-vitreous (arrow), B-tumor cells (asterisk) between retina (above) and choroid below (CD3 highlights reactive T cells); various images; lymphoblastic lymphoma - intravascular and perivascular retinal involvement; MALT lymphoma - various images; B cell lymphoma, unspecified - left: B cell immunostain in subretinal pigment epithelial space for tumor cells; right: T cell immunostain in choroid for reactive T cells
Cytology images: large atypical lymphocytes; marked variation in lymphocyte size; B cell staining
Metastatic carcinoma common but asymptomatic (breast, lung, GI tract)
Also metastatic melanoma or sarcoma; rarely carcinoid (Hum Path 1982;13:459)
Most common site is posterior choroid, which is diffusely thickened on both sides of optic nerve
Metastases to eye often suggests extremely short survival, and treatment is usually palliative radiation therapy
Whole mount images: metastatic adenocarcinoma - choroid; iris and ciliary body involvement, patient had prior surgical wound from iridectomy
Micro images: choroidal infiltration by poorly differentiated adenocarcinoma cells with desmoplasia; glandular pattern of tumor cells
Degenerative change of globe involving all tissues; usually takes several years to develop
Often due to accidental or post-surgical trauma; also found in eyes removed for blindness, pain, glaucoma, inflammation
Due to reduced production of aqueous humor, causing reduced intraocular pressure (hypotony) and shrinkage of globe; also due to organization of inflammatory exudate
Degenerative changes and degree of shrinkage are variable in different tissues; may be calcification and ossification with bone marrow
Note: must decalcify globe
Micro: typically disorganization of intraocular contents, opaque media, corneal scars, exudate in anterior and posterior chambers, advanced cataracts, destruction of vitreous, scleral thickening, cyclitic membrane extends from one ciliary body behind the lens to the other ciliary body, complete detachment of retina; also ossification or bone formation
Usually histology does not disclose initial condition leading to phthisis bulbi; occasionally occult melanoma or lymphoma is found
Micro images: regressed retinoblastoma - disorganized intraocular contents with ossification and calcification #1; #2; #3-fossilized tumor cells; #4-massive retinal gliosis with large dilated vessels next to calcified tumor cells
Common cause of enucleation, if no potential for visual recovery exists
Surgeon may want to know if retina is extruded through wound
Common sites of rupture are junction of cornea and sclera or posterior to insertion of rectus muscles where sclera is thinnest
Trauma may cause hyphema (blood in anterior chamber) with associated corneal blood staining, separation of ciliary body from iris (iridodialysis) or sclera (cyclodialysis), cataracts, retinal detachment or choroidal rupture
Search for metal, vegetation or cilia
Globe may contain iron (siderosis) or copper (chalcosis)
Other secondary changes are fibrosis, secondary glaucoma, sympathetic ophthalmia, phacoanaphylactic endophthalmitis, post contusion angle deformity, fibrous downgrowth, epithelial downgrowth or granulomatous inflammation in response to foreign body
Lacrimal duct / gland
Lacrimal duct / gland - general
Lacrimal gland located in superiotemporal aspect of orbit, not palpable
Contributes secretions to tear film including IgA
Accessory lacrimal glands are embedded above fibrous tarsus of eyelid and in conjunctival fornix
Serous with minor mucinous component; larger ducts have myoepithelial layer
Normally may have lymphocytes and plasma cells
Drainage apparatus is composed of puncta, canaliculi, lacrimal sac and nasolacrimal duct; tears drain toward medial canthus, then through lacrimal punctum into lacrimal canaliculi, then nasolacrimal sac, then nasolacrimal duct, then nose
Puncta: opening in medial aspect of eyelid where tear fluid drains
Canaliculi (lacrimal duct): tubular structures 0.5 mm in diameter where puncta drains; nonkeratinizing squamous epithelium surrounded by fibrous tissue
Lacrimal sac: merging of canaliculi, encased by bones of orbit; stratified columnar epithelium with goblet cells
Nasolacrimal duct: drains lacrimal sac, 1 cm long, connects to inferior meatus of nose; stratified columnar epithelium with goblet cells
Lacrimal duct disorders often cause epiphora (tears flow over lid margin onto cheek), induration, inflammation of lower eyelid
Tumors tend to displace eye downward, because adjacent orbit restricts growth
Tumors are difficult to resect completely, leading to high recurrence rate
Lacrimal gland is considered a minor salivary gland for tumor reporting
Regional lymph nodes are preauricular (parotid), submandibular and cervical
Drawings: lacrimal apparatus #1; #2; #3
Micro images: glandular lobule next to ducts lined by pseudostratified epithelium with goblet cells; lobule of acinic and mucinous cells
Adenocarcinoma of lacrimal gland / sac
Micro images: anaplastic tumor with glandular formation and mitotic activity - tumor arose de novo
Adenoid cystic carcinoma of lacrimal gland
20-30% of lacrimal gland tumors; most common malignant tumor of lacrimal gland
Aggressive, may infiltrate eyelid or brain
Xray images: CT scan shows tumor with serrated borders, indicating infiltrative growth in lacrimal fossa
Micro: basaloid growth with cribriform change; relatively bland cytology; perineural invasion, focal tumor necrosis
Micro images: classic pattern; basaloid pattern; cribriform pattern; cylindromatous or sclerosing pattern; infiltration of orbit #1; #2; perineural invasion #1; #2 (figure 4B); metastasis to lung
Dacryoadenitis - lacrimal gland / duct
Inflammation of lacrimal gland due to obstruction of lacrimal ducts by dacryoliths
Dacrocystitis / canaliculitis- lacrimal gland / duct
Canaliculitis: inflammation of lacrimal duct
Dacrocystitis: inflammation of lacrimal sac
Often obscure origin; may be due to inflammatory spread from nose or conjunctiva
Acute or chronic inflammation with suppurative, granulomatous or necrotizing features
Fistulous tracts may form to skin below eyelid near base of nose
Acute: ducts filled with purulent exudate
Chronic: lacrimal canal narrows due to inflammatory thickening, epithelial hyperplasia
Dacryolithiasis- lacrimal gland / duct
Stone (dacryolith) in lacrimal canal
Probably due to low grade inflammation, including mycoses (Arachnia propionica)
Micro: laminated concretions in lacrimal sac; may contain degenerating epithelial cells and neutrophils, often fungi
Isolated or component of other choristomas
Micro: acini and ducts resemble normal lacrimal gland tissue
Micro images: atrophic glandular tissue with chronic inflammation (from retrobulbar orbit)
Malignant mixed tumor of lacrimal gland / duct
5-10% of lacrimal gland tumors
Case reports: lacrimal gland tumor developing after 8 recurrences of pleomorphic adenoma over 32 years (AJSP 1979;3:457)
Extremely rare
Case report with surrounding melanosis (Archives 1997;121:517)
Mikulicz’s disease of lacrimal gland / duct
Mikulicz’s disease
Lymphocytic infiltration and formation of lymphoepithelial lesions
Most common cause of Mikulicz’s syndrome
Mikulicz’s syndrome
Chronic dacryoadenitis associated with enlargement of salivary glands; causes include Mikulicz’s disease, sarcoidosis, tuberculosis, syphilis, mumps, lymphoma, leukemia, Graves’ disease
Sjogren’s syndrome
Usually postmenopausal women
Mikulicz’s disease, with failure of lacrimal and conjunctival secretions and keratoconjunctivitis sicca
Complication of chronic inflammation of lacrimal sac, with distention of sac due to low grade obstructive lesion or hypersecreting mucosa
Cyst contents may be clear, milky, gelatinous, fibrinous or flocculent; may be sterile or infected
Clinical images: mucocele in infant
Micro: cyst wall is atrophic with degenerative changes; also hyperplasia and chronic inflammatory infiltrate
Oncocytoma of lacrimal duct / sac
Develops in lacrimal sac or caruncle
Usually elderly women
Treatment: excision is curative
Similar to conjunctival papilloma
Xray images: CT of well circumscribed tumor of left lacrimal sac
Micro: papillary aggregates of benign transitional epithelial cells with infiltrating neutrophils; may have pseudoepitheliomatous hyperplasia
Micro images: well circumscribed papillary tumor fills the lacrimal sac; papillary tumor with inverted growth pattern contains well differentiated squamous epithelium; papillary tumor with fronds covered by neoplastic transitional epithelium; papilloma with malignant transformation
Pleomorphic adenoma of lacrimal gland
50-60% of lacrimal gland tumors
Resemble salivary gland tumors of same type
Treatment: excisional biopsy with negative margins to prevent recurrence and implantation within the orbit
Micro: usually encapsulated, composed of benign epithelial and myxoid mesenchymal elements; often prominent component of S100+ hyaline cells (presumed myoepithelial origin) with diffuse eosinophilic staining; may have squamous metaplasia, bone, cartilage or fat
Micro images: well circumscribed, pseudoencapsulated lacrimal gland tumor; tumor composed of islands of epithelial cells, myxoid stroma and cysts; ducts are lined by a double layer of epithelial cells within a myxoid stroma; chondroid differentiation; low and high power;
with carcinoma - large round nodule of pleomorphic adenoma surrounded by smaller nodules of adenocarcinoma that have infiltrated the orbit; left-benign ducts within myxoid stroma, right-adenocarcinoma; with adenoid cystic carcinoma
Squamous cell carcinoma of lacrimal duct / sac
Uncommon; usually moderately differentiated
Similar to nasal or conjunctival squamous cell carcinoma
Often spreads along surfaces, as well as infiltrating
Lung is most common site for metastases, then bone and remote viscera
Micro: often papillary projections into lumen
Transitional cell carcinoma of lacrimal duct / sac
#2 lacrimal sac carcinoma after squamous cell carcinoma
May cause death if inadequate or delayed therapy
Poor prognostic factors: marked pleomorphism, numerous mitotic figures, stromal invasion
Case reports: 53 year old man (Archives 2005;129:1493)
Treatment: extensive surgical excision and radiation therapy; 50% recur, and recurrences may cause death
Micro: exophytic and endophytic papillary lesions; increased cellularity with spindled elongated cells and goblet cells; may have nuclear pleomorphism and mitotic figures
DD: papilloma
TNM staging for carcinoma of the lacrimal gland
Applies to both clinical and pathologic staging
Primary tumor (T) for lacrimal gland carcinoma
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor 2 cm or less in greatest dimension, with or without extraglandular extension into the orbital soft tissue
T2: Tumor more than 2 cm but not more than 4 cm in greatest dimension
T3: Tumor more than 4 cm in greatest dimension
T4: Tumor invades periosteum or orbital bone or adjacent structures
T4a: Tumor invades periosteum
T4b: Tumor invades orbital bone
T4c: Tumor invades adjacent structures (brain, sinus, pterygoid fossa or temporal fossa)
Notes:
As the maximum size of the lacrimal gland is 2 cm, T2 and greater tumors will usually extend into the orbital soft tissue
Regional lymph nodes (N) for lacrimal gland carcinoma
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Distant metastasis (M) for lacrimal gland carcinoma
M0: No distant metastasis
M1: Distant metastasis
Stage grouping for lacrimal gland carcinoma
No stage grouping is presently recommended by AJCC 7th edition
Lens and vitreous
General-lens and vitreous humor
Most surgical specimens are cataracts or prosthetic intraocular lens
Normal lens is biconvex, behind pupil / iris, in front of vitreous, in posterior chamber
10 mm in diameter by 4-5 mm in width
Usually Gross Examination Only (report as transparent - Yes or No), don’t section
Anterior lens capsule is eosinophilic acellular band overlying single layer of epithelial cells
Lens capsule is strongly PAS+, holds lens in place
Lens has thinner capsule posteriorly, without epithelial cells
Lens in held in place by zonules that connect to pars plicata of ciliary body
Lens normally opacifies with age, due to globules of degenerate lens fibers
Is a closed epithelial system, with lens capsule (epithelium) that totally envelops the lens
Vitreous humor: avascular; extends from lens to sensory retina; contains gel-like material composed of water, protein, hyaluronic acid and “hyalocytes”; gel consistency is due to randomly oriented collagen fibrils; may appear as amorphous material on H&E
Drawings: lens
Micro:
anterior but not posterior lens has
single epithelial layer
Micro images: lens
Also called hereditary nephritis
Inherited disorder of type IV collagen in basement membranes
Hematuria, progressive nephritis with proteinuria and declining renal function, deafness (55%), ocular abnormalities (15-30%)
Ocular abnormalities: anterior lenticonus (forward central protrusion of anterior surface of lens due to weakness in type IV collagen, relatively specific for Alport’s); also keratoconus, spherophakia (small, spherical lens), myopia, retinal flecks, cataracts, retinitis pigmentosa, amaurosis (blindness without an apparent ocular cause)
Defined as progressive opacity of crystalline lens that decreases visual acuity
Usually develops in older individuals, rarely in infancy or childhood
Associated with systemic diseases (galactosemia, diabetes mellitus, Wilson’s disease, atopic dermatitis), corticosteroids, radiation (ultraviolet light or radiation therapy), trauma, glaucoma, uveitis, retinitis pigmentosa, steroids
Age related cataract is due to opacification of lens nucleus, which becomes brown, and distorts perception of blue color
Changes occur in lens nucleus, cortex and subcapsular regions
Nuclear changes due to progressive crosslinking and insolubility of crystalline proteins
Cortical changes begin as small peripheral water clefts and diffuse degenerative changes that coalesce into dense bands of opaque cortical material
Anterior lens epithelial cells may undergo fibrous metaplasia, creating a thick fibrous plaque between the anterior lens capsule and the anterior epithelial cells
Congenital cataract: becomes apparent within first 6 months of life
Posterior subcapsular cataract: migration of lens epithelium posterior to lens equator
Morgagnian cataract: long standing cataract that undergoes liquefaction of lens cortex, with sinking of nucleus into fluid filled sac and clinical brown nucleus
Soemmering’s ring cataract: peripheral donut or ring shape due to loss of lens nucleus and much of anterior and posterior cortex; also proliferating lens epithelial cells in periphery and equatorial region of lens
Treatment: often high frequency sound waves are used to disintegrate the lens (phacoemulsification), then lens contents aspirated and disposed of (not submitted for examination); lens capsule is intact; then placement of prosthetic intraocular lens
Gross: senile cataracts are yellow-brown
Micro: homogenous eosinophilic lens fibers, vacuolization of superficial cortical fibers, extracellular clefts and eosinophilic globules of variable size (morgagnian globules) between lens fibers
Due to Marfan’s syndrome (weakness in zonules, leads to superiotemporal dislocation)
Due to other disruption of zonules causing anterior chamber dislocation
Persistent hyperplastic primary vitreous
Congenital, due to incomplete regression of fetal vasculature of vitreous humor, producing a retrolental mass
Usually unilateral
Associated with small eye, white reflex behind pupil (leukokoria), fibrous tissue behind lens, often cataract
Retina normal or with retinal dysplasia
CT scan images: microphthalmic eye with total retinal detachment
Gross images: mild microphthalmos with persistent hyaloid artery extending from optic nerve head to white retrolental mass
Fundoscopic images: wrinkling and rupture of posterior lens capsule caused by hemorrhagic retrolental mass
Micro: dense fibrovascular retrolental mass containing elongated ciliary processes and part of hyaloid vascular system
Whole mount images: falciform fold of detached dysplastic retina circles the persistent hyaloids artery, which extends from optic nerve head to retrolental mass
Micro images: retrolental mass with rupture of posterior lens capsule and anterior insertion of the retina; epithelium of pars plana of ciliary body is absent; retrolental fibrovascular mass has cataractous changes and elongation of ciliary processes
DD: retinoblastoma (also produces white reflex)
Phacoanaphylactic endophthalmitis - lens
Usually occurs after penetrating injuries to lens
Rarely due to spontaneous rupture of swollen lens with a cataract
Granulomatous reaction may be due to acquired hypersensitivity to lens proteins
May coexist with sympathetic uveitis
Micro: granulomatous inflammation surrounding area of lens perforation, with zonal pattern of central neutrophils around disintegrating lens fibers and peripheral macrophages, epithelioid cells and giant cells; posterior synechiae usually present; usually perivasculitis of retinal vessels; variable plasma cells in iris
Made of polymethylmethacrylate
Usually placed in space enclosed by lens capsule
Most have central optical zone (the “optic”) and peripheral extensions that secure the lens within the eye (“haptics”)
Rarely removed due to corneal injury or if they induce inflammation
Gross: flat; entire surface can be examined by light microscopy
Micro: may have adherent multinucleated giant cells, chronic inflammatory cells, fragments of lens capsule or melanin granules
Also called exfoliation syndrome
Usually affects those from Scandinavia or Northern Europe
May cause glaucoma
Gross: deposition of white fluffy material on anterior lens capsule, excludes areas corresponding to movement of iris; also deposition on zonules, iris pigment epithelium, ciliary body epithelium and trabecular meshwork
Micro: tiny pink, eosinophilic staining deposits on anterior lens capsule which are perpendicular to edge of lens capsule
Hemorrhage (from trauma or retinal neovascularization) causes opacification
Calcium soaps produce particulate matter; called asteroid hyalosis since resembles stars when viewed with ophthalmoscope
Amyloid deposits may reduce vision significantly
Age related collapse may product floaters or detachment from neurosecretory retina
Drawings: eyeball with vitreous humor in blue
Orbit and optic nerve
Orbit contains globe and its fibrous covering (Tenon’s capsule), lacrimal gland, optic nerve and its meningeal covering, extraocular muscles, cartilaginous trochlea, blood vessels and delicate fibroadipose connective tissue
Floor of orbit is roof of maxillary sinus
Medial wall of orbit (lamina papyracea) separates orbit from ethmoidal sinuses
Proptosis: forward displacement of eyeball (or other organs), due to any disease that increases orbital contents, since orbit is closed medially, laterally and posteriorly
Exophthalmos: abnormal protrusion of eyeball
Optic nerve: surrounded by meninges and part of the central nervous system; not usually biopsied; often has psammoma bodies or drusen (calcified acellular globular concretions of nerve fibers); site of convergence of one million axons from retinal nerve fiber layer; nerve head accounts for physiologic blind spot in normal visual field; receives blood supply from branches of ophthalmic artery; surrounded on both sides by short posterior ciliary arteries
Lamina cribrosa: site of myelination of optic nerve axons; highlighted with Luxol fast blue or other myelin stains
Trochlea: arc-shaped structure through which tendon of superior oblique muscle passes before insertion upon eyeball; the only cartilaginous structure in normal orbit
Exophthalmos is common symptom of orbital disease, although often due to thyroid disease and not biopsied
Other common causes of exophthalmos are mucocele from paranasal sinus, hemangioma, inflammatory pseudotumor
Tumors should be reported using formats published for their counterpart elsewhere in body
Drainage through submandibular, parotid and cervical lymph nodes through vascular anastomosis
Xray images: MR #1 (T1 weighted) shows normal eye and orbital contents; MR #2 (T2 weighted); MR #3 (T1 weighted) shows coronal section of orbital contents posterior to globe
Drawings: optic nerve; orbit; extraocular muscles in orbit
Micro images: intraocular and orbital portions of optic nerve; cross section of optic nerve parenchyma and meninges; optic nerve and fovea centralis #1; #2; #3
Alveolar soft parts sarcoma of orbit
Indolent, similar to tumor at other sites
May have late metastases
Mean age 23 years, range 1-69 years; 76% women
Micro: organoid pattern outlined by thin-walled capillaries, composed of nests of large polyhedral cells with abundant, finely granular, eosinophilic cytoplasm
Positive stains: PAS+ diastase resistant crystalline structures
DD: paraganglioma, granular cell tumor, metastatic renal cell carcinoma, vascular tumor, alveolar rhabdomyosarcoma, amelanotic melanoma
References: Hum Path 1982;13:569
Anterior ischemic optic neuropathy
Various injuries to optic nerve from ischemia to infarction
May resemble stroke
Unilateral abnormality of optic nerve head, of congenital origin
Complete coloboma may form large hole or posterior protrusion near optic nerve
Micro: large defect with mostly bare sclera, lined by fibrous or glial tissue; may involve retina and choroids along its edges
Congenital, but may not be clinically evident until age 20 years
Most common in superior temporal orbit; also eyelid
Xray images: CT shows nasally located cystic lesion
Gross: soft, nontender, round/oval cyst with thickened wall, 1 cm or less; contain yellow, cheesy material
Micro: encapsulated, lined by well differentiated epidermis and dermis, lumen filled with keratinous debris, hair, sebum; may have foreign body inflammatory reaction if cyst ruptures
Gross/micro images: inflamed cyst lined by conjunctival type epithelium; inflamed cyst lined by skin
White-yellow irregularities of optic disc, may resemble papilledema
Fundoscopy images: drusen
Micro: dark material in optic nerve head anterior to lamina cribrosa; material is acellular and basophilic, often calcified
Positive stains: acid mucopolysaccharides
EM images: drusen
Dysthyroid ophthalmopathy - orbit
Most common cause of orbital disease and exophthalmos
Associated with hyperthyroidism or thyroid-related treatment, although patient may be hyper-, hypo- or euthyroid at the time
Usually bilateral but may be unilateral
Most cases are not biopsied
Gross: marked enlargement of extraocular muscles
Gross/clinical images: upper lid retraction and exophthalmos
Micro: severe edema and chronic inflammation of orbital tissues; degeneration and hyalinization of extraocular muscles, with increase in interstitial connective tissue in muscles and other orbital tissue
Case reports: conjunctival cyst (Int Ophthalmol 2007;27:269)
Erdheim-Chester disease involving orbit
Case reports: 60 year old man with painless loss of vision in one eye (Archives 2004;128:1428)
Micro images: various images
Micro images: fibrotic tissue containing bone spicules without osteoblasts
Most common mesenchymal tumor of orbit in adults
Usually upper and nasal orbit
Mean age 43 years
Either benign, locally aggressive or malignant with recurrence rates of 31%, 57% and 64% and 10 year survival rates of 100%, 92% and 23% respectively (Hum Path 1982;13:199)
Xray images: MR shows a well circumscribed tumor in inferior orbit
Treatment: complete surgical excision
Gross images: large, retrobulbar, well circumscribed fibrous tumor
Micro: storiform pattern of fibroblast and histiocyte-like cells; variable giant cells
Micro images: fibrous tumor with storiform pattern #1; plump spindle cells; plump spindle cells with ovoid nuclei, coarse chromatin and small nucleoli; invasion of spindle cells into orbital adipose tissue
Giant cell angiofibroma of orbit
Has features of solitary fibrous tumor and giant cell fibroblastoma of soft tissue
May be a giant cell rich variant of solitary fibrous tumor
Adults, mean age 45 years; in eyelid close to lacrimal gland or orbit; also posterior mediastinum, upper back, submandibular, parascapular regions
Appears to be a slow growing tumor, with occasional local recurrence
Gross: well circumscribed, nonencapsulated, mean 3 cm
Micro: highly vascular with round/spindle cells, numerous thick-walled vessels, collagenous or myxoid background and floret type multinucleated giant cells lining pseudovascular spaces
Positive stains: CD34, CD99, vimentin, bcl2
References: AJSP 2000;24:971, AJSP 1995;19:1286
Relatively rare
Slow growing tumor within orbital segment of optic nerve
Usually ages 0-9 years with symptoms of minimal exophthalmos, optic nerve atrophy or papilledema
Associated with neurofibromatosis type 1
Radiology: thickening of nerve on CT scan; may enlarge optic canal
Xray images: MR scan shows large retrobulbar optic nerve tumor causing massive proptosis
Treatment: resection for tumors limited to optic nerve; also radiation therapy for more extensive lesions
Gross: small tumors are limited to optic nerve; larger tumors form bulbous enlargement of nerve, often infiltrate pia causing arachnoid thickening
Micro: variable cytology and cellularity, even within same tumor, but usually are low grade pilocytic astrocytomas similar to cerebellar and third ventricle tumors, with round to spindled nuclei and dendrite-like cytoplasmic processes; often Rosenthal fibers (fusiform, cigar-shaped eosinophilic structures within astrocyte cytoplasmic processes, are a nonspecific degenerative change); rarely are hypercellular with brisk mitotic activity, marked pleomorphism, necrosis and vascular proliferation; difficult to differentiate reactive vs. neoplastic resection margins; typically has intense mucinous degeneration with tumor cells in pools of mucin; infiltrating tumor may cause reactive proliferation of arachnoid cells resembling meningioma
Micro images: glioma; pilocytic astrocytoma #1-involves optic nerve parenchyma and invades meninges; #2-intraparenchymal tumor with hypercellularlity and enlargement of axonal bundles; #3-numerous Rosenthal fibers; #4-astrocytes infiltrate meninges, accompanied by fibroblasts and meningothelial cells; high grade astrocytoma with palisading cells around blood vessels and myxoid areas
Clinical images: pilocytic astrocytoma causing proptosis
Localized focus of acute myelocytic leukemia
Micro images: lysozyme positive
Xray images: CT scan shows enlargement of extraocular muscles at orbital apex; coronal CT shows enlargement of all extraocular muscles except lateral rectus
Hemangioblastoma of optic nerve
Case report in 43 year old woman, subsequently determined to have von Hippel-Lindau disease (Hum Path 1994;25:1249)
Common; more common than lymphangioma
Usually cavernous, in young adults in retrobulbar space
Benign but slowly progressive; may cause chorioretinal stria or folds
Xray images: CT scan shows intraconal, well circumscribed ovoid retrobulbar tumor
Micro: encapsulated, large cavernous vascular channels or spaces separated by scant connective tissue stroma; spaces lined by single layer of endothelial cells with variable smooth muscle in walls
Micro images:
cavernous hemangioma - well circumscribed tumor composed of dilated blood vessels; thick walled dilated blood vessels
Infants - hemangioma of orbit
Soft, blue, compressible
Diffuse throughout orbit, may extend into eyelids
Usually regress by age 4, difficult to excise
Respond to short course of systemic steroids or radiotherapy
Micro: unencapsulated; usually capillary type with thin walled vessels; may have prominent mitotic activity
Adults - hemangioma of orbit
Encapsulated, close to back of eye
Can usually shell out tumors
Micro: usually cavernous type with large, blood filled, endothelium lined channels; thrombi often present, may calcify
Resembles solitary fibrous tumor but prominent vessels
30% recur, 15% metastasize (lung, liver, bone, regional lymph nodes), usually late
Histology does not predict behavior (Hum Path 1982;13:210)
Case reports: 66 year old woman (Archives 2002;126:1555)
Micro: usually encapsulated; random pattern of polygonal and rounded cells with ill defined cytoplasm, variable nucleoli; staghorn vascular pattern and perivascular collagen, dense pericellular reticulin, occasional mitotic figures; must rule out other tumors with this pattern
Micro images: small polyhedral cells surround vascular spaces; vascular channels have a staghorn pattern; cells are polyhedral and spindled, with mild atypia; A-large left orbital mass; B-random pattern of polygonal and rounded cells with ill defined cytoplasm, some cytoplasmic clearing, variable nucleoli; C-large and small vessels with staghorn pattern and perivascular collagen; D-reticulin densely surrounds each cell; metastatic liver nodule
Positive stains: CD34 (focal or weak), dense pericellular reticulin staining, vimentin; variable XIIIa
Negative stains: EMA, GFAP, S100, keratin, desmin, muscle specific actin, smooth muscle actin
DD: meningiomas (EMA+, complex interdigitating processes and desmosomes by EM, deletions of #22), solitary fibrous tumor (CD34 strongly+), fibrous histiocytoma (predominant storiform pattern; foam cells and giant cells present)
Idiopathic sclerosing inflammation of orbit
Insidious, chronic and progressive fibrosing process
Damages orbital structures by entrapment and mass effect
May have cell mediated pathogenesis, similar to retroperitoneal fibrosis (Mod Path 1993;6:581)
Micro: desmoplasia, sparse lymphocytes (usually T cells), histiocytes, plasma cells, neutrophils, eosinophils
Inflammatory processes of orbit
Usually secondary inflammation due to lesions in adjacent structures
Granulomas are rare; caused by tuberculosis, fungi, sarcoidosis, Wegener’s granulomatosis (multiple confluent granulomas, vasculitis with thrombosis, tissue necrosis)
Inflammatory pseudotumor of orbit
May not be a specific disease process, but due to various causes (paranasal sinus tumors, Rosai-Dorfman disease, inflammatory fibrosclerosis, dysthyroid ophthalmopathy, cholesterol or keratin granulomas, traumatic fat necrosis, prior hemorrhage or abscess)
More common than infectious granulomas
Usually ages 20-49 years with good health and sudden onset of exophthalmos with variable lid or conjunctival edema
Treatment: steroids (alleviate signs and symptoms), excision
Case report: tumor filling vitreous cavity of 50 year old man (Archives 2004;128:e5)
Gross: indurated orbital mass, often surrounding optic nerve and enveloping extraocular muscles
Gross images: fibrotic mass surrounds the eye
Micro: general - edematous tissue with excessive production of ground substance, chronic inflammatory cells, vascular proliferation and hyperplastic connective tissue; may have periphlebitis with tissue eosinophilia
Inflammatory myofibroblastic tumor: combinations of fibroblasts and myofibroblasts in background of plasma cells and other inflammatory cells
Rosai Dorfman related: large histiocytes, some with lymphocytophagocytosis, lymphocytes and plasma cells, often with prominent fibrosis
Whole mount images: dense fibrotic tissue with focal lymphocytes surrounds the eye
Micro images: inflammation and fibrosis involve the orbital adipose tissue; chronic inflammatory cells infiltrate an extraocular muscle
Positive stains: inflammatory myofibroblastic tumor - smooth muscle actin, variable ALK
DD: Hodgkin’s lymphoma, temporal arteritis, systemic lupus erythematosus
Micro images: mass with lymphoid hyperplasia; hyperplastic vessels and eosinophils
Langerhans cell histiocytosis of orbit
Micro images: histiocytes, some with nuclear grooves
Usually young children
May wax and wane in size, particularly with upper respiratory infection
May rapidly increase in size due to hemorrhage
Xray images: MR shows ill defined lobulated mass with blood fluid levels
Gross: diffuse and poorly outlined
Micro: multiple, irregular lymphatic channels lined by flat endothelial cells; may have large lymphoid aggregates in wall
Micro images: large dilated lymphatic vessels contain serum and layered blood, upper right corner shows a large hemorrhage; numerous lymphatics, some containing blood; connecting tissue between lymphatics contains lymphocytes
Micro images: multinodular lymphoid tumor; mature lymphocytes and plasma cells #1; #2
Tumors composed of small lymphocytic proliferations confined to orbit are usually indolent and associated with long survival, even with minimal treatment
Xray images: CT scan shows homogeneous tumor that molds to ocular structures causing proptosis
MALT lymphoma: uniform and monotonous proliferation of small lymphocytes infiltrating into orbital fat, blood vessels and nerves; may have plasmacytoid features with Dutcher bodies (intranuclear inclusions) and serum paraproteinemia; light chain restriction
Case reports: 5 year old girl with angiocentric orbital lesion with immature NK cell immunophenotype that spontaneously resolved (Hum Path 2001;32:339), NK-T cell lymphoma, nasal type, with distant metastases (Hum Path 2003;34:290)
Clinical images: Burkitt’s lymphoma-bilateral; lymphoplasmacytic lymphoma-bilateral
Micro images:
low grade tumor - well differentiated lymphoma of orbit, conjunctiva and cornea; irregularly shaped mass; uniform population of well differentiated lymphocytes #1; #2; small cleaved cells; small population of T cells (UCHL-1 / CD45RO positive); numerous CD20+ B cells
Burkitt’s lymphoma has lymphoblasts and numerous mitotic figures; granulocytic leukemia-Leder stain positive; lymphoplasmacytic lymphoma-lymphoid cells, some with plasmacytic differentiation #1; #2
Positive stains: monotypic immunoglobulins
DD: lymphoid hyperplasia (polymorphic lymphocytes, vascular proliferation, prominent follicles with germinal centers)
Fundoscopic images: tumor is centered in inferior temporal quadrant of optic nerve head and has feathery border where it infiltrates the retina
Micro images: heavily pigmented tumor involves optic nerve head, optic nerve and peripapillary choroid; bleached preparation shows plump polyhedral melanocytes with small ovoid nuclei
Arise from meninges of optic nerve or extension of cranial meninges; less common than intracranial tumor
Associated with hearing loss, optic atrophy and exophthalmos; also papilledema if arises near inner sphenoidal ridge
Xray images: MR scan shows large tumor of orbital apex causing proptosis
Clinical images: tumor arising adjacent to sphenoid wing has invaded superior lateral orbit causing downward displacement and proptosis
Micro: meningothelial pattern of whorled spindle cells, psammoma bodies
Micro images: tumor growth within dura has markedly compressed the optic nerve; tumor of superior lateral orbit, and unrelated to meninges of optic nerve; invasion of sphenoid bone; islands of meningothelial cells infiltrate extraocular muscle; meningothelial cells arranged in small nests with a whorled pattern
DD: exuberant arachnoid hyperplasia, fibrous histiocytoma, solitary fibrous tumor/hemangiopericytoma, metastatic carcinoma, juvenile ossifying fibroma
Rarely is initial manifestation of childhood acute leukemia or adult carcinoma of breast, bronchus, kidney or prostate
Neuroblastoma and carcinoid tumor of lung or small bowel commonly metastasize to orbit (Hum Path 1982;13:459)
Primary embryonal rhabdomyosarcoma or carcinoid tumor of orbit may erroneously be interpreted as metastatic tumor
Clinical images: paranasal sinus carcinoma involving orbit
Gross images: paranasal sinus carcinoma invades nasal orbit
Micro images: histiocytoid breast carcinoma infiltrating extraocular muscle; fig 8: metastatic neuroblastoma
DD: direct spread from adjacent retinoblastoma, uveal melanoma or paranasal sinus carcinoma
Due to chronic inflammation of frontal or ethmoid sinus
Lesion erodes sinus wall, produces downward and lateral displacement of globe
Insidious onset with slow and asymptomatic enlargement
Micro: cystic mass lined by ciliated, mucus-secreting columnar epithelium with scarring and inflammation
Usually an expression of neurofibromatosis (also causes neurofibroma of eyelid and glioma of optic nerve)
May grossly deform orbit and eyelid
Xray images: MR shows large infiltrative tumor of orbit and eyelid in neurofibromatosis
Micro images: neurofibromatosis - neurofibroma with plexiform pattern; various images in case report
Micro images: cellular blue nevus shows benign, spindled melanocytes
Loss of function of optic nerve with gliosis, loss of capillaries and loss of axonal tissue
Due to damage from within the eye (optic neuritis, papilledema, glaucoma, retina-choroid lesions), to optic nerve or brain (trauma, tumor, demyelinating disorders, hydrocephalus) or congenital (Leber’s optic atrophy)
Gross: white, pale disc
Micro: loss of substance of optic nerve due to degeneration of myelin sheaths and axons; dura appears redundant due to loss of substance; gliosis within nerve
Edema of head of optic nerve, usually bilateral
Due to nerve compression from elevation of cerebrospinal fluid pressure surrounding the nerve
Fundoscopic examination shows swollen optic nerve head with elevation, edema and narrowing of optic cup; also vascular congestion, flame-shaped hemorrhage, exudates, retinal edema
Micro: edematous axons in edematous stroma with vascular congestion
Micro images: atypical plasma cells
Most common orbital sarcoma in childhood
Usually embryonal and alveolar subtypes (alveolar more aggressive)
Often rapid onset of unilateral proptosis
May occur after radiation therapy for retinoblastoma, close to previously irradiated fields
Xray images: CT shows large tumor of orbital floor invading maxillary sinus
Clinical images: botyroid tumor beneath the conjunctiva
Micro: syncytium of strap cells with abundant eosinophilic cytoplasm; also closely packed small round cells with scanty cytoplasm, coarse nuclear chromatin and increased mitotic activity; many have minimal rhabdomyoblastic differentiation except in occasional mature strap cells with cross striations; alveolar pattern has fibrovascular septa resembling lung alveoli
Tumors in retinoblastoma patients may have rosette-like structures
Whole mount images: large tumor has infiltrated orbit
Cytologic images: long cytoplasmic processes and atypical nuclei (inset-muscle specific actin positive)
Positive stains: myogenin, desmin, muscle specific actin (HHF35), vimentin, neurofilament
Negative stains: CD99; Rb in retinoblastoma patients only
References: AJSP 1998;22:1351 (post radiation therapy for bilateral retinoblastoma)
Schnabel cavernous degeneration of optic nerve
Defined as formation of cavernous spaces in retrolaminar portion of proximal optic nerve due to focal loss of myelin and axons and accumulation of hyaluronic acid
Present in < 0.1% of eyes at autopsy; 80% are women, mean age 88 years (range 54-103 years)
Associated with severe vascular anomalies (75%), glaucoma (24%)
Grading of cavernous degeneration: I-clearly present but <10% of diameter of optic nerve at point of most severe involvement; II-10-25%; III-50-75%; IV- >75%
References: Archives 2003;127:1314
Uncommon in orbit
Well encapsulated
Treatment: excision
Micro images: cellular Antoni A and myxoid Antoni B patterns; Verocay bodies due to palisading nuclei in Antoni A area
Shaken baby syndrome and optic nerve
Defined as intentional whiplash movement of infant’s head
Can be detected by beta-amyloid precursor protein immunohistochemistry to identify optic nerve damage in optic disk or distal optic nerve
Takes at least 2 hours to develop, staining intensity should exceed background
Also have severe bilateral, often multilayered retinal hemorrhages
Micro images: sheets of large pale histiocytes and lymphoid aggregates; large pale histiocytes with lymphocytic phagocytosis
Solitary fibrous tumor of orbit
Usually benign, but may be aggressive
See also giant cell angiofibroma, above
Lipomatous hemangiopericytomas may be variants of solitary fibrous tumors (Hum Path 2000;31:1108)
Radiologic images: MRI of right orbital tumor
Case reports: t(9;22)(q31;p13) in 58 year old man with orbital tumor (Archives 2000;124:756), myxoid variant (Mod Path 1999;12:463)
Micro: solid with keloid-like collagen and alternating hyper- and hypocellular areas; hemangiopericytoma-like vessels
Micro images: patternless pattern of spindle cells with bland nuclei, extensive fibrosis, ectatic thin walled vessels and scattered lymphoid infiltrates; no/rare mitotic figures; various images
Positive stains: CD34, bcl2
References: AJSP 1994;18:281
Subconjunctival herniated orbital fat
Prolapse of subconjunctival intraconal orbital fat
Rarely causes intraorbital mass lesion
May histologically resemble adipose tissue neoplasm
Mean age 65 years, 90% men
Prolapsed fat in superotemporal quadrant or lateral canthus around rectus muscle below lacrimal gland
Unilateral or bilateral
Treatment: excision, does not recur
Micro: mature fat, fibrous septa without hyperchromatic cells, Lochkern cells (adipocytes with intranuclear vacuoles), floret cells (multinucleated giant cells with wreathlike nuclei), variable inflammatory cells
Positive stains: floret cells - CD34 and vimentin; Lochkern cells - CD34, vimentin, S100
DD: pleomorphic lipoma (aggregates of bland spindled cells with wiry collagen), well differentiated liposarcoma (enlarged hyperchromatic cells within fibrous septae)
References: AJSP 2007;31:193
Sudden loss of vision in one eye, low grade fever, loss of appetite, general weakness
May be due to obstruction of posterior ciliary artery
Micro: granulomatous inflammation of arteries with discontinuous and fragmented internal elastic lamina; also arteriosclerosis
Micro images: temporal arteritis; figures 10C & D
Clinical images: child with congenital proptosis
Gross images: large tumor with solid and cystic areas
Micro images: cyst is lined by intestinal epithelium with cartilage in wall
Wegener’s granulomatosis of orbit
May present initially or secondarily in orbit
Micro: multiple confluent granulomas, vasculitis with thrombosis, tissue necrosis
TNM staging for sarcoma of the orbit
Includes rhabdomyosarcoma, osteogenic sarcoma, leiomyosarcoma, etc
Primary tumor (T) - sarcoma of orbit
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor 15 mm or less in greatest dimension
T2: Tumor more than 15 mm in greatest dimension without invasion of globe or bony wall
T3: Tumor of any size with invasion of orbital tissues or bony walls
T4: Tumor invasion of globe or periorbital structure, such as eyelids, temporal fossa, nasal cavity and paranasal sinuses, or central nervous system
Regional lymph nodes (N) - sarcoma of orbit
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Distant metastasis (M) - sarcoma of orbit
M0: No distant metastasis
M1: Distant metastasis
Stage grouping - sarcoma of orbit
No stage grouping is presently recommended by AJCC 7th edition
TNM staging for ocular adnexal lymphoma
Primary tumor (T)
TX: Lymphoma extent not specified
T0: No evidence of lymphoma
T1: Lymphoma involving the conjunctiva alone without orbital involvement
T1a: Bulbar conjunctiva alone
T1b: Palpebral conjunctiva, +/- fornix, +/- caruncle
T1c: Extensive conjunctival involvement
T2: Lymphoma with orbital involvement +/- any conjunctival involvement
T2a: Anterior orbital involvement (+/- any conjunctival involvement)
T2b: Anterior orbital involvement (+/- any conjunctival involvement but with lacrimal involvement)
T2c: Posterior orbital involvement (+/- any conjunctival involvement, +/- anterior involvement, +/- any extraocular muscle involvement)
T2d: Nasolacrimal drainage system involvement (+/- conjunctival involvement but not including nasopharynx)
T3: Lymphoma with preseptal eyelid involvement (infiltrates preseptal tissues such as dermis or orbicularis muscle of anterior eyelid skin) +/- orbital involvement, +/- any conjunctival involvement
T4: Orbital adnexal lymphoma extending beyond orbit to adjacent structures such as bone and brain
T4a: Involvement of nasopharynx
T4b: Osseous involvement (including periosteum)
T4c: Involvement of maxillofacial, ethmoidal or frontal sinuses
T4d: Intracranial spread
Regional lymph nodes (N)
NX: Involvement of lymph nodes not assessed
N0: No evidence of lymph node involvement
N1: Involvement of ipsilateral regional lymph nodes
N2: Involvement of contralateral or bilateral regional lymph nodes
N3: Involvement of peripheral lymph nodes not draining ocular adnexal region
N4: Involvement of central lymph nodes
Notes:
Regional lymph nodes include preauricular (parotid), submandibular and cervical
Distant metastasis (M)
M0: No evidence of involvement of other extranodal sites
M1a: Noncontiguous involvement of tissues or organs external to the ocular adnexa (e.g. parotid glands, submandibular gland, lung, liver, spleen, kidney, breast, etc.)
M1b: Lymphomatous involvmeent of the bone marrow
M1c: Both M1a and M1b involvement
Stage grouping
No stage grouping is presently recommended by AJCC 7th edition
Retina
Embryologic derivative of diencephalon, responds to injury via gliosis
Composed of photoreceptors, neurons and glial cells
Lines inside surface of eye posterior to ora serrata
Neurons give rise to retinoblastoma, glial cells to astrocytomas
No lymphatics
Bruch’s membrane: separates choroid from overlying retinal pigment epithelium, is 2-4 microns thick, has 5 distinct layers (basal lamina of overlying retinal pigment epithelium, collagenous layer, elastic fiber-rich layer, collagenous layer and basal lamina of endothelial cells of choriocapillaris), thickens with age, has focal excrescences known as drusen
Layers from outside in:
(1) retinal pigment epithelium; (2) rods and cones (photoreceptors); (3) external limiting membrane; (4) outer nuclear layer; (5) outer plexiform layer; (6) inner nuclear layer; (7) inner plexiform layer; (8) ganglion cell layer; (9) nerve fiber layer; (10) inner limiting membrane; (11) vitreous
(1) Retinal pigment epithelium: derived from primary optic vesicle, an outpouching of brain; helps maintain outer segments of photoreceptors (rods and cones); is a monolayer of cells containing intracytoplasmic melanosomes; has phagocytic function that assists in turnover of photoreceptor elements; undigested phagoliposomes become lipofuscin granules
(2) Rods and cones: rods are cylindrical, cones are longer and thicker; light is converted by photoreceptor cells into electric impulses
Hemorrhage in nerve fiber layer appears in ophthalmoscope as horizontal streaks or flames
Hemorrhage in external retinal layers appears as dots
Fovea centralis: center of macula, slightly depressed, 1.5 mm in diameter, responsible for most visual acuity; lacks blood vessels (relies on choroidal circulation) and rods
Macula: has highest density of photoreceptors and high ganglion cell/photoreceptor ratio; ganglion cells are several layers thick
Macula lutea: yellow specialized portion of retina in posterior pole of eye
Ora serrata: irregular, anterior margin of retina, internal to junction of choroid and ciliary body
Retinal detachment: separation of neurosensory retina (rods and cones) from retinal pigment epithelium
Cysts develop in peripheral retina in everyone age 20+ years
Drawings: layers of retina #1; #2; #3; retinal neurons
Micro images: layers of retina #1; #2; #3; #4; fovea centralis (no ganglion cell layer or nerve fiber layer); fovea centralis, choroid and sclera; fovea and retina; ora serrata #1; #2
Adenocarcinoma of retinal pigment epithelium
Rare, < 50 cases reported
More common in women
Often diagnosed as atypical choroidal melanoma clinically
Whole mount images: pigmented tumor of retinal pigment epithelium arises in peripheral of retina
Micro images: pigmented tumor with tubular and papillary patterns has invaded retina and choroid; variable pigmented tumor adjacent to optic nerve head has invade choroid; pleomorphic and papillary tumor area with variable pigment; heavily pigmented area of tubular tumor
Associated with tuberous sclerosis (57%), neurofibromatosis (14%), no syndromes (29%)
Tuberous sclerosis patients usually have multiple, peripheral retinal tumors with giant astrocytes vs. disc-based tumors in non-tuberous sclerosis patients
Usually benign and extremely rare in retina
Micro: interlacing, spindle-shaped astrocytes
References: Archives 1984;108:160
Obliterative vasculitis of retinal vessels
Central retinal artery occlusion
Causes a sudden, painless loss of vision
Retina is pale and white; may have edema and decreased vascularity; fovea has cherry red spot due to ischemic white retina surrounding normal choroidal blood flow
Micro: usually emboli within central retinal artery; early changes are ischemia of inner layers of retina; late changes are atrophy of inner layers of retina and gliosis
Central retinal vein occlusion
Painless decrease in vision, less severe than central retinal artery occlusion
May be partial/incomplete or complete
Fundoscopy: widespread retinal hemorrhage with swelling and edema
Micro: hemorrhage in all layers of retina with diffuse hemorrhage and ischemic changes
Usually acquired due to immunosuppression from tumors, chemotherapy, transplantation, AIDS
May be congenital
Fundoscopy: retinitis with sharply defined borders; may have brushfire appearance with necrosis and hemorrhage
Micro: coagulative necrosis with secondary choroid inflammation; retinal cells have large intranuclear and small intracytoplasmic inclusion bodies
Micro images: inclusion bodies
Exudative retinopathy associated with retinal detachment and telangiectatic retinal vessels
Usually unilateral, young children, male predominant
CT scan images: increased density within eye
Fundoscopic images: telangiectatic vessels on surface of detached retina
Gross images: total retinal detachment with subretinal exudate containing cholesterol crystals and a fibrous nodule in the posterior pole
Micro images: telangiectasia of vessels in peripheral detached and gliotic retina with intra- and subretinal exudate
Often after cataract extraction or other surgical procedures
Due to diabetic retinopathy, retinal venous occlusion or other retinal vascular disease, ocular inflammation, drugs, tumor
Xray: stellate pattern on fluorescein angiography
Fundoscopy: honeycomb appearance due to fluid-filled cavities
Micro: exudative fluid in outer plexiform layer is amorphous and eosinophilic or appears as blank spaces
Separation of neurosensory retina (rods and cone and more superficial layers) from retinal pigment epithelium
Rhegmatogenous (“due to a rupture or fracture”) detachment: associated with full thickness retinal defect, such as collapse of vitreous, causing traction on retinal internal limiting membrane, causing tears and seepage of vitreous between neurosensory layer and retinal pigment epithelium; treated by relieving vitreous traction
Non-rhegmatogenous detachment: no retinal break; due to significant exudates or conditions causing leakage of fluid from choroidal circulation beneath the retina, such as choroidal tumors and malignant hypertension
Chronic retinal detachment may cause loss of photoreceptor outer segments, gliosis and development of microcystic spaces in detached retina
Micro: early changes are degeneration of outer retinal layers and photoreceptors with subretinal exudates; late changes are disruption and atrophy of retinal architecture with marked gliosis and proliferative vitreoretinopathy
Common cause of blindness in Western society
Classified as background, preproliferative or proliferative retinopathy
Background retinopathy: initial lesion is capillary microangiopathy
Preproliferative retinopathy: changes of background diabetic retinopathy plus significant venous dilation / beading, cotton wool spots (due to focal infarcts in nerve fiber layer), extensive formation of intraretinal microvascular abnormalities (due to vascular shunts) and extensive ischemia
Proliferative retinopathy: growth of neovascular tissue from inner surface of retina into vitreous; causes retinal detachment, treat with laser photocoagulation; may occur without clinically visible background diabetic retinopathy
Retinopathy is associated with duration of diabetes - 60% at 15 years
May cause rubeosis iridis (neovascularization of iris) and secondary glaucoma
Also causes thickening of basement membrane of pars plicata of ciliary body
Also causes vacuolization of iris pigment epithelium, with glycogen containing vacuoles related to blood glucose level at time of enucleation
Micro:
Background retinopathy: retinal capillary microaneurysms and cotton wool spots (due to hypoxia from microvascular obstructions and nonperfusion) with PAS+ deposits on endothelium, basement membrane thickening, loss of pericytes; also venous anomalies, hemorrhage (flame shaped between fibers of nerve fiber layer), exudates (hard, yellow, waxy protein and lipid of outer plexiform layer appears eosinophilic), edema
proliferative retinopathy: new vessels that sprout from existing vessels on surface of optic nerve head or retina and penetrate the internal limiting membrane of the retina; thickened basement membrane, reduction in number of pericytes (causes microaneurysms and arteriovenous shunts)
Associated with von Hippel Lindau disease
Most commonly in cerebellum, spinal cord and retina
Micro images: not necessarily retina
Positive stains: factor VIII related antigen
Negative stains: GFAP (may be positive in reactive astrocytes)
References: Hum Path 1982;13:13
Retinal arteriolosclerosis causes thickened arteriolar wall; with ophthalmoscope, vessels appear narrow and blood changes from bright red to copper or silver
Since retinal arterioles and veins share a common adventitial sheath, marked arteriolosclerosis may cause compression of vein where both vessels cross
Elschnig’s spots: focal choroidal infarcts due to damage to choroidal vessels
Retinal exudates: due to damage to choriocapillaris (internal layer of choroidal vasculature), with accumulation between neurosensory retina and retinal pigment epithelium and possible detachment
Retinal arteriole damage from malignant hypertension usually accumulates in outer plexiform layer, and resembles macular star with ophthalmoscope; may cause inter-retinal flame-shaped or dot/blot hemorrhages
Infarcts in nerve fiber layer cause “cotton-wool spots”; infarcts are due to occlusion or AIDS related vasculopathy
Chronic hypertension causes onion-skin thickening of vessels
Lattice degeneration of retina
Bilateral condition that involves retina peripherally between ora serrata and equator
Associated with hyperpigmentation, condensed overlying vitreous forming adhesions to margins of lattice degeneration that may cause subsequent retinal detachment
Fundoscopy: circumferential area of involvement with small criss-crossing white lattice lines (thickened hyalinized blood vessels)
Micro: atrophic and thinned retina with superficial gliosis; thickened and hyalinized retinal vessels; overlying liquefaction of vitreous with vitroretinal adhesions at edge of lattice lesion
Age related (senile) macular degeneration is the most common cause of irreversible visual loss in US
Causes loss of central portion of vision
May be due to vascular disease in choriocapillaris and retinal pigment epithelium
Non-disciform (atrophic, dry type) causes slow, bilateral visual loss in elderly, with atrophy and degeneration of retinal pigment epithelium and choriocapillaris; also drusen
Disciform (wet, exudative type) is associated with more severe and acute vision loss; often after non-disciform degenerative changes and due to hemorrhagic retinal detachment secondary to neovascularization, as vessels from choriocapillaris penetrate through Bruch’s membrane beneath the retinal pigment epithelium and leak fluid / blood, which organizes into macular scars
Micro: small macular scars
Relatively uncommon
Large elevated scar near disc and posterior pole after hemorrhage or inflammation
Polyclonal - not a neoplasm
Case reports: 32 year old woman born with bilateral microphthalmia (Hum Path 2005;36:702)
Micro: vitreous body replaced by massively proliferating spindle cells containing fibrillary cytoplasm but no nuclear atypia
Positive stains: GFAP, NSE, S100 (focal)
Myxopapillary ependymoma - retina
Case report: primary retinal tumor in 33 year old with phthisis bulbi (AJSP 2005;29:1404)
May derive from Muller cells, intrinsic glial cells of retina
Peripheral cystoid degeneration of retina
Occurs in almost everyone age 20+ years
Pleomorphic xanthoastrocytoma - retina
Retinal tumor similar to tumor of brain and spinal cord
Gross: well circumscribed mass with cystic component
Micro: large pleomorphic cells with eosinophilic cytoplasm, enlarged vesicular nuclei with prominent nucleoli and calcium deposits; also cells with markedly swollen cytoplasm containing lipid, spindled cells and multinucleated cells
Positive stains: GFAP, CD68
References: AJSP 1999;23:79
Congenital anomaly associated with trisomy 13 (retinal pigment epithelium within optic nerve) or unilateral malformed eye not associated with other anomalies (such as persistent hyperplastic primary vitreous)
Micro: series of straight branching tubes composed of abortive rod and cone layers
References: Archives 1977;101:540
Various inherited retinal disorders that are not actually inflammatory
Common (incidence of 1/3600) with variable inheritance or as part of Refsum’s disease
Usually causes loss of rods and cones to apoptosis and focal proliferation of retinal pigment epithelium
Loss of rods causes early night blindness and restricted visual fields (bilateral loss of peripheral vision)
Loss of cones affects central visual acuity
Retinal atrophy causes constriction of retinal vessels, optic nerve head atrophy and accumulation of retinal pigment around blood vessels
Micro: migration of macrophages and retinal pigment epithelial cells with melanin into retina, particularly around vessels; also atrophy of photoreceptors in retina and choriocapillaris
Most common intraocular tumor of children, with incidence of 1 per 20,000 live births
May be congenital, but not recognized until ages 6 months to 2 years
60% sporadic, 40% familial (autosomal dominant)
Develops in 80-90% of those with mutant alleles in retinoblastoma (Rb) gene at 13q14
Need mutations in both alleles to inactivate Rb gene, a negative growth regulator
Patients with hereditary retinoblastoma have a germline mutation in one allele; develop tumors after somatic mutation in second allele (“second hit”); in sporadic cases, both alleles have somatic mutations
Bilateral in 30% of all cases, 90% of familial cases; some patients with bilateral tumors also have similar tumor of pineal gland, termed “trilateral” retinoblastoma, associated with poor prognosis
White reflex (leukokoria) present in affected eye; also retinal detachment
Tends to invade optic nerve (particularly large exophytic tumors with secondary glaucoma); can invade uveal tract
Distant metastases to cranial vault, skeletal system
Second primaries for familial tumors: 6-20% after 10-20 years, usually osteosarcoma (50% of tumors) and rhabdomyosarcoma, close to irradiated fields; also rhabdoid tumors
5 year survival: 90% if unilateral, slightly less if bilateral
Poor prognostic factors: invasion of optic nerve (report as prelaminar or retrolaminar involvement, with or without resection line involvement), invasion of uveal tract or sclera, seeding of vitreous, involvement of anterior segment; extensive ocular tissue and tumor necrosis is associated with other factors (Archives 2006;130:1669); differentiation does not appear to have prognostic value
Treatment: early - radiation therapy, cryopexy, xenon arc photocoagulation; large tumors - enucleation; involvement of optic nerve margin - radiation of orbit and systemic chemotherapy; bilateral tumors - radiation therapy to less affected eye with possible chemotherapy or bilateral radiation; recurrences - photocoagulation, cryotherapy or cobalt disks
Case reports: bladder leiomyosarcoma 47 years after enucleation (but no radiation) of unilateral familial retinoblastoma (Archives 2001;125:1231), sinonasal small cell neoplasm 18 years after radiation therapy (Hum Path 1992;23:896)
CT scan images: ovoid retinal tumor; round retinal tumor with focal calcification
Gross: creamy white with chalky areas of calcification and yellow necrotic areas; may grow inward (endophytic) or outward toward choroid (exophytic); rarely are diffusely infiltrative; typically seeds intraocularly
Retinoblastoma - retina (continued)
Gross images: marked advanced tumor with massive extraocular extension in 6 year old from 1917 (typical of US cases at that time); advanced tumor from African patient with destruction of anterior segment of eye and extraocular extension; small retinal tumor with large white areas of necrosis; small retinal tumor with foci of calcification; three small retinal tumors; large area of choroidal invasion next to partially necrotic retinal tumor; large exophytic tumor with focal calcification causes total exudative retinal detachment; large exophytic tumor with enlargement of optic nerve due to invasion
Clinical images: leukocoria (white reflux) due to retinal tumor; strabismus without leukocoria (early clinical sign)
Fundus images: translucent intraretinal tumor with focal opacified areas representing calcification; fluffy retinal tumor has grown into vitreous, retinal vessels are obscured by tumor; retinal tumor invades subretinal space-retinal vessels pass over tumor
Micro: sheets, trabeculae and nests of small blue cells with scant cytoplasm, hyperchromatic nuclei and scanty stroma; frequent necrosis of tumor cells away from vessels and calcification; also Flexner-Wintersteiner rosettes (cells line up around empty lumen delineated by a distinct eosinophilic circle composed of terminal bars analogous to outer limiting membrane of normal retina); also Homer-Wright rosettes (nuclei are displaced away from lumen), fluerettes (tumor cells arranged side by side which show differentiation towards photoreceptors); frequent Azzopardi phenomena (basophilic deposits around blood vessels, also seen in small cell carcinoma); frequent mitotic figures; variable apoptotic cells
Differentiated retinoblastoma: bipolar-like cells are present
Undifferentiated retinoblastoma: large, anaplastic cells without rosette formation
Retinocytoma: marked photoreceptor differentiation; cells have abundant cytoplasm, less hyperchromatic nuclei; benign, with calcification but without necrosis or mitotic activity
Whole mount images: small endophytic tumor; total retinal detachment and collapse of anterior chamber due to partially necrotic tumor with viable cells surrounding blood vessels in a sleeve pattern, no involvement of choroid, sclera or optic nerve; large tumor fills globe with massive choroid and extraocular invasion; bilateral tumor (patient died of intracranial tumor) – left: multicentric tumor without optic nerve invasion; right: regressed tumor after radiation therapy without optic nerve invasion
Micro images: nodules of tumor cells seed inner surface of retina; tumor cells involve anterior chamber, iris and angle structures; viable tumor cells surround blood vessels and form sleeves; endophytic tumor adjacent to optic nerve head with sleeve pattern; sleeve pattern and Flexner-Wintersteiner rosettes #1; #2; Flexner-Wintersteiner rosettes; Homer-Wright rosettes; poorly differentiated tumor cells with large hyperchromatic nuclei and numerous mitotic figures; DNA deposition (basophilic staining) in blood vessel walls (Azzopardi phenomenon); small blue cell tumor-low power; high power; spindle-shaped glia; necrotic tumor; benign cytology-fleurettes consisting of small clusters of eosinophilic bulbous processes extending into lumen resembling photoreceptors #1; #2; invasion of optic nerve head; invasion of optic nerve to level of lamina cribrosa; invasion of optic nerve parenchyma posterior to lamina cribrosa but not involving the margin
Cytology images: clumps and individual tumor cells; invasion of full thickness of choroid
Positive stains: neuron-specific enolase, synaptophysin, S100, Leu7, GFAP, myelin basic protein, p53; high Ki-67
Negative stains: CD99
EM: evidence of photodifferentiation
EM images: bulbous process of fleurette contains numerous mitochondria
DD: traumatic retinal detachment, retrolental fibroplasia, persistent hyperplastic primary vitreous, massive retinal gliosis, Coats’ disease, visceral larval migrans, astrocytoma of tuberous sclerosis, medulloepithelioma
Micro images: uniform cells without necrosis, confined to retina; tumor cells have small, round, hyperchromatic nuclei, no mitotic activity; also scattered fleurettes
Retrolental fibroplasias - retina
Also called retinopathy of prematurity
Previously was leading cause of blindness in US
Occurs in premature infants given oxygen therapy; related to level and duration of oxygen, degree of prematurity at birth, status as carrier for defect in Norrie disease gene
Immature vessels of premature infants are damaged by high or even physiologic oxygen; rarely occurs in term infants
Pathophysiology: oxygen therapy causes vasoconstriction and obliteration of immature retinal vessels in lateral (temporal) retina, which causes ischemia and failure of retina to vascularize; then vasoproliferative phase and angiogenesis; vessels grow into vitreous or leak serum or fluid, 25% have associated scarring, which causes retinal detachment
Either proliferative or nonproliferative; both lead to vascular occlusion
Reduced oxygen tension causes sickling, then microvascular occlusions cause hemorrhages; organization may cause traction and retinal detachment or neovascularization
Common as an entity, rare in surgical specimens
May be due to reactivation of congenital infection
Diffuse retinal necrosis is associated with AIDS
Fundoscopy: optic nerve appears as “headlight in fog”, leading to large scar
Micro: focal areas of coagulative necrosis in retina, surrounded by granulomatous inflammation of choroid and sclera; scar shows abrupt transition of normal retina to scarring with extension disruption of retina, retinal pigment epithelium and choroid with marked disruption of pigment; cysts of Toxoplasma gondii within necrotic retina
Also called Bourneville’s syndrome
A type of phakoma
Phakoma: hamartomatous malformation associated with extraocular lesions as part of a well-defined clinicopathologic syndrome
Micro: glial plaques and nodules in retinal nerve fiber layer, which may simulate retinoblastoma
Visceral larva migrans - retina
A type of nematodiasis (parasitic disease)
Somewhat common in US and Great Britain
Usually produced by Toxocara canis in children ages 3-14 years without systemic disease
Single migrating larva enters eye hematogenously and rests in vitreous or inner surface of retina, with accompanying acute and chronic inflammatory cells and intense eosinophilia
Late changes are scarring, retinal detachment and leukokoria, simulating retinoblastoma
Dead larvae may cause minute granulomas, found with serial sectioning
Gross images: white sclerotic vitreous mass causing traction related total retinal detachment
Micro images: vitreous mass contains collagen (trichrome stain) and causing total retinal detachment; larva is surrounded by acidophilic material (Splendore-Hoeppli phenomenon) and scattered eosinophils
von Hippel-Lindau disease - retina
Also called angiogliomatosis
Abnormally large tortuous arteries and veins leading to a retinal nodule composed of vascular, endothelial and glial tissue
Associated with retinal detachment and vitreous disturbance
Micro images: lesion adjacent to optic nerve head with osseous metaplasia; vascular proliferation with vacuolated stromal cells
Wyburn-Mason syndrome - retina
A phakoma with arteriovenous shunts of retinal vessels
Miscellaneous
Tumor features to report-retinoblastoma
Tumor location
Number, size and location of lesion(s)
Differentiation (poorly differentiated, Flexner-Wintersteiner rosettes, Homer-Wright rosettes, fleurettes)
Growth pattern (diffuse, unifocal, multifocal)
Extraocular extension or choroidal invasion
Presence or absence of vitreous seeding
Presence of absence of retinal detachment
Invasion into optic nerve (prelaminar, to lamina cribrosa, retrolaminar, posterior resection margin)
Involvement or noninvolvement of other structures submitted
Margins (minimum clearance)
Angiolymphatic invasion
Tumor necrosis, calcification, DNA deposition around blood vessels, anterior chamber seeding, retinal or iris neovascularization
Pathologic classification
Primary tumor (T) - retinoblastoma
pTX: Primary tumor cannot be assessed
pT0: No evidence of primary tumor
pT1: Tumor confined to eye with no optic nerve or choroidal invasion
pT2: Tumor with minimal optic nerve or choroidal invasion
pT2a: Tumor superficially invades optic nerve head but does not extend past lamina cribrosa OR tumor exhibits focal choroidal invasion, but not both
pT2b: Tumor superficially invades optic nerve head but does not extend past lamina cribrosa AND exhibits focal choroidal invasion
pT3: Tumor with significant optic nerve or choroidal invasion
pT3a: Tumor invades optic nerve past lamina cribrosa but not to surgical resection line OR tumor exhibits massive choroidal invasion, but not both
pT3b: Tumor invades optic nerve past lamina cribrosa but not to surgical resection line AND exhibits massive choroidal invasion
pT4: Tumor invades optic nerve to resection line OR exhibits extraocular extension elsewhere, but not both
pT4a: Tumor invades optic nerve to resection line but no extraocular extension identified
pT4b: Tumor invades optic nerve to resection line AND extraocular extension identified
Regional lymph nodes (N) - retinoblastoma
pNX: Regional lymph nodes cannot be assessed
pN0: No regional lymph node involvement
pN1: Regional lymph node involvement (preauricular, cervical)
N2: Distant lymph node involvement
Metastasis (M) - retinoblastoma
cM0: No metastasis
pM1: Metastasis to sites other than CNS
pM1a: Single lesion
pM1b: Multiple lesions
pM1c: CNS metastasis
pM1d: Discrete mass(es) without leptomeningeal or CSF involvement
pM1e: Leptomeningeal or CSF involvement
Stage grouping- retinoblastoma
No stage grouping is presently recommended by AJCC 7th edition
Uvea (iris, choroid and ciliary body), limbus and sclera
Uvea: the vascular middle layer of the eye constituting the iris, ciliary body, and choroid.
Middle layer of globe between outer sclera and inner retina
Highly vascular but no lymphatics
Extends from ciliary body to optic nerve
Inner aspect is adherent to retinal pigment epithelium; outer surface is loosely attached to overlying sclera
Stroma contains abundant pigmented melanocytes
Bruch’s membrane: separates choroid from overlying retinal pigment epithelium, is 2-4 microns thick, has 5 distinct layers (basal lamina of overlying retinal pigment epithelium, collagenous layer, elastic fiber-rich layer, collagenous layer and basal lamina of endothelial cells of choriocapillaris), thickens with age, has focal excrescences known as drusen
Choriocapillaris: in innermost choroidal stroma adjacent to Bruch’s membrane, connects with arterial and venous channels from vessels in outer choroidal stroma, to nourish outer retinal layers
Micro images: vascularized pigmented stroma between Bruch’s membrane (middle) and sclera (below); choroid and iris; uveal tissue extends into sclera within scleral canals around a long ciliary vessel
Middle segment of uveal tract, between iris and choroid
Composed of pars plicata and pars plana
Holds lens in place
Cyclectomy: resecting portion of ciliary body containing tumor; may also include other surrounding structures
Pars plicata: 70 sagitally oriented folds or ciliary processes that gradually merge with posterior flat pars plana, which merges posteriorly with serrated, anterior border of retina (ora serrata)
Ciliary epithelium composed of inner epithelial layer (nonpigmented, contiguous with aqueous of posterior chamber) and outer epithelial layer (pigmented, unites with retinal pigment epithelium at ora serrata)
Outer epithelial layer overlies PAS+ basal lamina that thickens in diabetes mellitus
Zonules: acellular fibers that attach crests of nonpigmented ciliary epithelium in pars plicata to capsule of crystalline lens
Ciliary body has 3 distinct bundles of smooth muscle, which assist in accommodation; as muscle contacts, ciliary body extends forward, reducing pressure on zonules, enabling lens to become less concave, thereby increasing its refractive power
Micro images: ciliary body, iris and lens; ciliary process zonule fibers
Thin diaphragm of tissue with central opening (pupil)
Forms boundary of anterior and posterior chamber
Highly textured with folds and crypts
Part of middle layer of eye (also ciliary body and choroid)
Normally rests gently upon lens and bulges slightly forward
Consists of stroma and posterior epithelial lining (two closely apposed epithelial layers, with numerous melanosomes); contains sphincter muscle within stroma that controls pupil
Anterior iris lacks a cellular lining
Color is due to number of stromal melanocytes; blue irises have few stromal melanocytes; brown irises have numerous melanocytes
Blood vessels are usually surrounded by a thick collar of collagen fibers, resembling arteriolosclerosis
Fewer melanosomes and melanocytes in patients with ocular and oculocutaneous albinism
Regulates amount of light reaching pupil; muscles of iris dilate or constrict pupil in response to parasympathetic or sympathetic nerve impulses; normal diameter of pupil is 1-8 mm
Iridectomy: excision of small segment of iris; place on filter paper to avoid folding
Ectropion uveae: fibrovascular tissue on anterior surface of iris everts the papillary margin and pulls pigmented epithelia onto anterior surface of iris
Drawings: iris-front view
Micro images: iris and lens; choroid and iris; iris and ciliary body with open anterior chamber angle; normal iris
80% of surface area of eye
Begins at periphery of cornea, extends posteriorly to optic nerve
Relatively rigid; protects eye from trauma and maintains intraocular pressure
Visible anteriorly under transparent conjunctiva; white in adults
Thickness varies; 0.3 mm at insertion of rectus muscles, 0.8 mm at limbus, 1.0 mm at insertion of optic nerve
Weakly attached to underlying choroid by thin collagen fibers
Heals poorly due to few blood vessels or fibroblasts
Aging related changes include calcification between collagen fibers, senile scleral plaques
Composed of episclera, stroma, lamina fusca
Episclera: most superficial part of sclera, located between fibrous structure that envelopes the globe (Tenon’s capsule) and scleral stroma; composed of loose collagen fibers and fibroblasts with numerous vessels, occasional melanocytes and mononuclear white blood cells
Stroma: largest component of sclera, randomly arranged bands of collagen with occasional elastic fibers and fibroblasts; minimal blood vessels except in perforating emissiary canals, accompanied by nerves and scattered melanocytes; rarely contains a prominent nerve (nerve loop of Axenfeld) in an emissiarial canal near limbus, which may mimic a neurofibroma; anterior ciliary arteries perforate sclera near insertion of rectus muscles, posterior ciliary arteries pass through sclera near optic nerve; vortex veins exit sclera posterior to equator of eye
Lamina fusca: innermost layer of sclera with loose collagen fibers, fibroblasts and scattered melanocytes
Adenocarcinoma of ciliary epithelium
Micro images: nonpigmented tumor has invaded ciliary muscle and root of iris; plemorphic mixture of spindled and epithelial cells; partially pigmented tumor with tubular and papillary patterns
Adenoma of pigmented ciliary epithelium
Case report of tumor causing unilateral cataract (Hum Path 2000;31:882)
Microscopic foam cells are actually artifacts
Congenital absence of all but the root of the iris
Associated with Wilm’s tumor
Anterior chamber cleavage syndrome
Also called iridogoniodysgenesis
Obvious architectural distortion of iris and angle of anterior chamber
Causes congenital glaucoma
Due to scleritis, thin sclera secondary to high intraocular pressure, osteogenesis imperfecta, congenital melanosis oculi (heavily pigmented congenital nevus of underlying uvea)
Defective formation of iris and ciliary body
Clinical images: coloboma of iris
Diffuse uveal melanocytic proliferation
Bilateral paraneoplastic syndrome associated with poorly differentiated tumors of uterus and ovary
May lead to blindness
Also called benign ciliary epithelioma, coronal adenoma
Benign tumor of ciliary body
Usually incidental finding in enucleated eye or at autopsy
Micro: interlacing trabeculae of uniform, nonpigmented ciliary epithelial cells, surrounded by amorphous, PAS+ hyaline material
Rare benign choristomatous malformation of ciliary body and iron
Micro: well differentiated, resembles disorganized brain
Micro images: ciliary body tumor of glial cells with scattered calcification - insert is large neuron
Micro images: cavernous hemangioma - focalized choroid tumor with cystoid degeneration of overlying retina and serous retinal detachment #1; #2-blood filled, dilated, thin walled vessels; degeneration of retinal pigment epithelium and early cystoid edema of retina overlying vascular tumor
Micro: chronic inflammatory infiltrate around posterior ciliary nerves and vessels
Hypertensive changes - choroid
Includes intimal thickening due to smooth muscle cell migration, hyaline deposits in subendothelium, degeneration (moth-eaten atrophy and necrosis) of medial smooth muscle cells, recanalization and obstruction
Also thrombotic occlusion or narrowing of choroidal artery in patients with hypertension and diabetes mellitus and either chronic azotemia or renal insufficiency
References: Hum Path 1988;19:99
Idiopathic solitary granuloma of uveal tract
Unilateral, associated with uveal effusion and total retinal detachment
Usually between pars plana ciliaris and equator
May arise from posterior iris pigment epithelium or at papillary margin
Usually benign
Attached to iris or free floating; may resemble melanoma
Micro: lined by epithelial cells
Juvenile xanthogranuloma - iris
Iris lesion of young children causing spontaneous hyphema (hemorrhage into anterior chamber) or secondary glaucoma
Associated with similar skin lesions
Clinical images: white tumor masses on surface of iris
Micro images: infiltrative histiocytic cells of iris and anterior chamber angle; tumor invades iris stroma and anterior chamber; histiocytic cells with mitotic activity; foamy histiocytic proliferation with Touton giant cells
Leiomyoma - ciliary body / iris
Ciliary body or iris
Micro images: amelanotic tumor of ciliary body #1; #2-spindle shaped neoplastic cells with cigar shaped nuclei arranged in irregular bundles; mesectodermal leiomyoma - large amelanotic tumor of ciliary body; benign cells with interlacing fibrillar cytoplasmic processes resembling glial tissue, and round nuclei with fine chromatin; benign cells form clusters separated by fibrillar cytoplasmic processes resembling neural tissue
Pigmented iris hamartomas
Associated with neurofibromatosis type 1, also familial angiolipomatosis, a benign condition with no malignant potential (Archives 1999;123:946)
Clinical images: Lisch nodules
Micro: dome shaped papules on anterior surface of iris, consisting of aggregates of ovoid to round cells
Positive stains: S100, vimentin
DD: iris melanoma, nevi, neurofibromatosis, trauma
Medulloepithelioma - ciliary body
Also called dikytoma
Rare, resembles embryonic retina
Usually arises from ciliary epithelium, rarely from optic nerve or retina
Micro images: network of cords of neuroepithelial cells; less differentiated cells with structures resembling rosettes; malignant teratoid medulloepithelioma #1-malignant neuroepithelial cells surround anaplastic cartilage; #2-rhabdomyoblastic differentiation;
Micro images: pigmented tumor of ciliary body
Most common adult intraocular neoplasm in US and Western Europe (20 per million annually)
8x more likely in whites vs. blacks; rare in Africa and Asia
Arises from pigmented or potentially pigment producing cells of uvea, usually choroid, least commonly in iris
All ages
Associated with malignancies at other sites as a paraneoplastic process; etiology is unclear; probably does not evolve from nevi (found in 10% of all whites)
Usually presents with visual disturbance due to retinal detachment or symptoms from tumor necrosis such as endophthalmitis, intraocular hemorrhage or secondary glaucoma
5 year survival: 90-100% for pure spindle A, 66-75% for spindle B, 50% for spindle B/epithelioid, 25-33% for pure epithelioid; prognosis is based on presence of even a few cells in most aggressive category
Favorable prognostic factors: cell type (see above), small size (lateral extent), iris better than choroid which is better than ciliary body, no extension into sclera, no necrosis, no lymphocytic infiltration, indistinct nucleoli, low MDR1 expression, no looping patterns of PAS+ laminin surrounding packets of tumor cells (Archives 2005;129:884)
Tends to spread through scleral emissary canals, rarely to optic nerve; distant metastases to liver, lung, pleura, brain, bone, skin (resembles blue nevi)
Regional lymph nodes are preauricular (parotid), submandibular and cervical
Treatment: traditionally enucleation; also iridectomy or iridocyclectomy if tumors are small; also thermoradiotherapy, photocoagulation
Melanoma of iris: presents as elevated mass with variable pigmentation, often with distortion of pupil and prominent vessels
Melanoma of choroid: irregular, slate-gray, solid, subretinal tumor that commonly extends through Bruch’s membrane into retina and vitreous, producing retinal detachment, macular edema, choroidal hemorrhage; occasionally spreads along scleral canals into orbit, rarely invades optic nerve
Melanoma of ciliary body: may interfere with accommodation or cause localized cataract
Melanoma of uvea (continued)
Micro: mixtures of spindle A, spindle B and epithelioid cells
Spindle A: cohesive cells, slender, bland, with indistinct cell borders, scant cytoplasm, small fusiform nuclei and no nucleoli; chromatin arranged in linear axis along central axis; may represent pigmented nevi; appear benign
Spindle B: cohesive cells are larger and more pleomorphic than spindle A with more cytoplasm, large oval nuclei and prominent nucleoli, prominent mitotic activity
Epithelioid: cells are even larger and irregular than spindle B, with abundant cytoplasm and well demarcated cell borders; may be marked enlarged or multinucleated; has large nuclei and very prominent nucleoli; usually less cohesive than spindle A or B
Fundoscopic images: small tumor with orange pigment on surface; vessels over tumor dome are out of focus due to elevation of tumor #1; #2
Clinical images: ciliary body tumor with extraocular extension mimics a primary conjunctival tumor
Gross images: small, heavily pigmented choroidal tumor; heavily pigmented, mushroom shaped choroidal tumor; large transillumination defect due to pigmented tumor of ciliary body and choroid; small pigmented tumor confined to choroid; variably pigmented, mushroom shaped choroidal tumor has ruptured Bruch’s membrane and grown into subretinal space; mushroom shaped choroidal tumor has caused a subretinal hemorrhage and total retinal detachment #1; #2-hemorrhage is partially organized; amelanotic mushroom shaped choroidal tumor has caused a total retinal detachment; diffusely pigmented choroidal tumor with massive extraocular extension; heavily pigmented ciliary body tumor excised by iridocyclectomy; lightly pigmented tumor of ciliary body; large iris and ciliary body tumor with subluxation of lens; amelanotic large choroidal tumor with extraocular extension; vortex vein invasion
Whole mount images: tumor is composed of tightly packed melanoma cells; tumor extends from ciliary body to optic nerve, and has caused an exudative retinal detachment; diffuse tumor involving entire uveal tract, with extraocular extension anteriorly in a ring configuration; large choroidal tumor with extraocular extension
Micro images: spindle cell melanoma #1; #2; nodular area of spindle cells with extraocular extension; mushroom shaped choroidal tumor with exudative retinal detachment; focal necrosis and scleral invasion; ciliary body tumor with necrosis and hemorrhage; seeding of anterior chamber angle by small epithelioid cells; partially necrotic tumor; tumor infiltrating lymphocytes; spindle A cells #1; #2; spindle B cells #1 in bundles; #2 with prominent nucleoli; spindled and epithelioid cells; small epithelioid cells; large epithelioid cells with large nucleoli and lack of cohesion; vasocentric pattern with tumor cells palisading around blood vessels; Verocay-like pattern; HMB45+
iris - large iris tumor has extended to ciliary body; recurrent diffuse tumor of iris post-iridectomy; iris involvement by small epithelioid cells; iridectomy specimen containing a spindle cell tumor #1; #2-nevus cells, spindle shaped melanoma cells and large thrombosed vessel; #3-spindle A and B cells;
Positive stains: S100, HMB45, vimentin, CAM5.2, p53, bcl2 (Archives 1996;120:497)
Molecular: monosomy 3, trisomy 8q, abnormalities of #6; spindle A are diploid, some spindle B and epithelioid melanomas are aneuploid (Hum Path 1995;26:99)
DD: metastatic carcinoma (if amelanotic), metastatic melanoma, retinal hemorrhage, focal proliferation of retinal pigment epithelium, posterior scleritis, nevi, hemangioma
Melanosis oculi of uveal tract
Gross images: congenital diffuse anterior scleral pigmentation; congenital diffuse posterial scleral pigmentation
Whole mount images: melanosis oculi with melanoma-choroidal tumor with retinal detachment
Micro images: diffuse uveal and scleral pigmentation; diffuse proliferation of benign, heavily pigmented polyhedral melanocytes (bottom is bleached)
Very rare
Case report of 21 year old woman with malignant tumor on whole iris, causing intractable glaucoma (Archives 1995;119:844)
Micro: anaplastic tumor with rhabdomyosarcomatous and liposarcomatous characteristics
Common
Detected during ophthalmic exams
Most do not progress; at risk for malignancy if thick or enlarging circumference
Iris nevi are elevated on iris surface
Micro images: choroid nevus #1-thickened choroid due to proliferation of benign melanocytes with drusen of overlying retinal pigment epithelium and mild disruption of photoreceptors; #2-spindled and small polyhedral shaped melanocytes
dysplastic nevus syndrome - spindle cell nevus of choroid #1; #2-hypocellular and hypercellular areas are present; nevus cells have benign cytologic features
Micro images: choroidal tumor composed of mature bone at posterior pole #1; #2
Often granulomatous uveitis that may lead to sympathetic uveitis
DD: lens-induced endophthalmitis (phacoanaphylaxis), foreign bodies, blood in vitreous
Neovascular membrane on surface of iris
Leads to peripheral anterior synechiae. outflow obstruction and secondary glaucoma
Associated with diabetes, occlusion of central retinal artery/vein or carotid artery, longstanding retinal detachment, chronic uveitis, intraocular tumor
Systemic granulomatous disease, usually affecting young adult blacks
Uvea involved in 1/3
May cause “mutton-fat” corneal precipitates; also granulomas in choroid, retinal perivascular inflammation with candle wax drippings near retinal vessels and retinal hemorrhages
Patients often have conjunctival granulomas (non-caseating)
Micro: noncaseating granulomas; also asteroid bodies (small, eosinophilic star-shaped inclusions in epithelioid cells) or Schaumann’s bodies (darker ovoid inclusions)
DD: tuberculosis, leprosy, syphilis, tularemia, CMV, varicella zoster virus, fungi, parasites
Necrotizing scleritis may be part of collagen vascular disease (rheumatoid arthritis)
Just anterior to insertion of lateral or horizontal rectus muscles
Apparently due to accumulated actinic damage from solar radiation
Micro: increased hematoxylinophilia of scleral collagen, decreased stromal cellularity, scleral fibers with corkscrew appearance, calcium deposition, elastosis
References: Hum Path 1991;22:557
Also called sympathetic ophthalmia
Rare; injury in one eye causes severe inflammation that may progress to blindness in uninjured as well as injured eye via presumed autoimmune response to retinal antigens
Lesion usually confined to uveal tissues and involving entire uveal tract
Retina may develop perivasculitis; injured lens develops phakogenic endophthalmitis
Treatment: immunosuppressive agents
Micro: diffuse and dense infiltration of choroid by lymphocytes and granulomas; also similar involvement of ciliary body and iris; patchy accumulations of small, irregular pale-staining epithelioid cells (Dalen-Fuchs’ nodules) containing fine melanin granules; moderate eosinophils, rare plasma cells, no neutrophils
Anterior uveitis (iridocyclitis)
Diffuse infiltration by plasma cells, occasionally nodular lymphocytic infiltrates
Associated with obliteration of anterior chamber and adherence of iris to cornea
May be seen in juvenile rheumatoid arthritis
Posterior uveitis (choroiditis, chorioretinitis)
Diffuse, focal or scattered chronic inflammatory infiltrate, often involving retina
May form cyclitic membrane that contracts, leading to detachment of retina and ciliary body
Not painful, so enucleation often not necessary
Enucleation if recurrence leads to adhesions between iris and cornea (anterior synechiae) or iris and anterior surface of lens (posterior synechiae) causing secondary glaucoma
Cause usually cannot be determined; known causes are herpes zoster, Behcet’s disease (obliterative vasculitis of retinal vessels), pneumocystis carinii
Sympathetic uveitis and post-traumatic uveitis are described above
Granulomatous uveitis: may be due to sarcoidosis; also tuberculosis, leprosy, syphilis, tularemia, CMV, varicella zoster virus, fungi, parasites
Uveomeningoencephalitic syndrome
Also called Vogt-Koyanagi-Harada syndrome
Rare multisystemic autoimmune disease affecting eyes, meninges, ears and skin
Sudden onset of blindness, pleocytosis and temporary hearing loss; no history of eye trauma or surgery (by definition)
Blindness is due to severe bilateral panuveitis with serous retinal detachments
HLA-DRB1*0405 is present in chronic phase
Case reports: 47 year old man (Archives 2006;130:1070)
Micro: chronic inflammation of choroid and iris, loss of choroidal melanocytes, dense chorioretinal adhesions
Miscellaneous
Tumor features to report-uveal tumors
Histologic type
Cell types present (for melanomas)
Precise anatomic location (iris, ciliary body, choroid), relative to clock hour
Tumor size
Extraocular extension
Growth pattern (diffuse, ring, focal)
Dimension of largest diameter in contact with sclera
Color of surface lesion and cut surface of lesion
Involvement or noninvolvement of other structures present
Margins (minimum clearance)
Mitotic figures per 40 high power fields
Presence of absence of 100 tumor infiltrating lymphocytes per 40 high power fields
Presence of matrix rich microcirculation associated loops, networks or parallel with cross linking structures
Angiolymphatic invasion
Presence of retinal detachment or hemorrhage
Involvement of intrascleral emissary channels
For melanomas, indicate thickness and mitotic activity, color of surface lesion
Other features present: drusen, neovascularization, nevi, etc.
References: Archives 2001;125:1177 (uveal melanoma)
Apply to both clinical* and pathologic staging
Primary tumor (T) - all uveal melanomas
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Iris
T1: Tumor limited to the iris
T1a: Tumor limited to the iris, not more than 3 clock hours in size
T1b: Tumor limited to the iris, more than 3 clock hours in size
T1c: Ttumor limited to the iris with secondary glaucoma
T2: Tumor confluent with or extending into the ciliary body or choroid
T2a: Tumor confluent with or extending into the ciliary body or choroid with secondary glaucoma
T3: Tumor confluent with or extending into the ciliary body or choroid with scleral extension
T3a: Tumor confluent with or extending into the ciliary body or choroid with scleral extension and secondary glaucoma
T4: Tumor with extraocular extension
T4a: Tumor with extraocular extension less than or equal to 5 mm in diameter
T4b: Tumor with extraocular extension more than 5 mm in diameter
Notes:
Iris melanomas originate from, and are predominantly located in, this region of the uvea. If less than half of the tumor volume is located within the iris, the tumor may have originated in the ciliary body, and consideration should be given to classifying it accordingly.
Melanomalytic glaucoma: a type of secondary open angle glaucoma in melanoma patients with pigment laded macrophages that clog the trabecular meshwork
Ciliary body and choroid
T1: Tumor size category 1
T1a: Tumor size category 1 without ciliary body involvement or extraocular extension
T1b: Tumor size category 1 with ciliary body involvement
T1c: Tumor size category 1 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter
T1d: Tumor size category 1 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter
T2: Tumor size category 2
T2: Tumor size category 2 without ciliary body involvement or extraocular extension
T2b Tumor size category 2 with ciliary body involvement
T2c: Tumor size category 2 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter
T2d: Tumor size category 2 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter
T3: Tumor size category 3
T3a: Tumor size category 3 without ciliary body involvement or extraocular extension
T3b: Tumor size category 3 with ciliary body involvement
T3c: Tumor size category 3 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter
T3d: Tumor size category 3 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter
T4: Tumor size category 4
T4a: Tumor size category 4 without ciliary body involvement or extraocular extension
T4b: Tumor size category 4 with ciliary body involvement
T4c: Tumor size category 4 without ciliary body involvement but with extraocular extension less than or equal to 5 mm in diameter
T4d: Tumor size category 4 with ciliary body involvement and extraocular extension less than or equal to 5 mm in diameter
T4e: Any tumor size category with extraocular extension more than 5 mm in diameter
Classification for ciliary body and choroid uveal melanomas
based on thickness and diameter
*When basal dimension and apical height do not fit this classification, the largest tumor diameter should be used for classification. In clinical practice, the tumor base may be estimated in optic disc diameters (dd) (average: 1 dd = 1.5 mm). The height may be estimated in diopters (average: 3 diopters = 1 mm). Techniques such as ultrasonography, visualization and photography are frequently used to provide more accurate measurements.
Regional lymph nodes (N)
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
M1a: Largest diameter of the largest metastasis is 3 cm or less
M1b: Largest diameter of the largest metastasis is 3.1 to 8.0 cm
M1c: Largest diameter of the largest metastasis is 8 cm or more
Stage grouping
I: T1a N0 M0
IIA: T1b-d N0 M0 or T2a N0 M0
IIB: T2b N0 M0 or T3a N0 M0
IIIA: T2c-d N0 M0 or T3b-c N0 M0 or T4a N0 M0
IIIB: T3d N0 M0 or T4b-c N0 M0
IIIC: T4d-e N0 M0
IV: Any T, N1 M0 or Any T, any N, M1a-c
Diagrams: staging form (SUNY Downstate)
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