Ординатура / Офтальмология / Английские материалы / Veterinary Ocular Pathology A Comparative Review_Dubielzig, Ketring, McLellan_2010

•The characteristic clinical feature is the hard and rigid ‘wooden’ consistency of the affected tissue

•There is a reported link to renal glomerular disease, and to respiratory disease in affected dogs.

•Morphologic characteristics:

■Ulcerative lesions

■Hyaline, cell-poor matrix with epithelial elements buried deeply within this matrix

–Fails to stain for amyloid

–Stains bright red with trichrome stain, and does not demonstrate birefringence with polarized light

■In humans there is a condition, also called ligneous conjunctivitis, which has a very similar morphologic appearance

–The human disease is thought to be linked to plasminogen deficiency

–This link has been reported in one Golden retriever but has not been definitively established in other affected dogs.

Episcleritis and canine nodular granulomatous episclerokeratitis (NGE, fibrous histiocytoma, nodular fasciitis) (Figs 7.36, 7.37)

There are 234 cases of NGE in the COPLOW collection. Although in clinical practice, Collie dogs are over-represented, this is not the case

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in the COPLOW collection. The COPLOW collection has only 14 cases in Collies out of the 234 total cases.

•This is an idiopathic, inflammatory disease of the conjunctival substantia propria and/or episcleral tissue in dogs. Lesions may occur anywhere on the episclera and conjunctiva

•Rather than a single, well-defined, clinical and histological entity, this represents a broad spectrum of episcleral inflammatory disease

■Clinical presentation ranges from relatively diffuse subconjunctival thickening (episcleritis) to well-defined, firm nodules (NGE)

■Relative numbers of different inflammatory cell types and presence and extent of fibroblast proliferation and collagen deposition are highly variable

•Collie dogs are reported to have a predisposition to the development of nodular granulomatous episcleritis NGE (but, see above)

■This may be a reflection of clinicians’ ability to recognize very characteristic disease features and response to treatment in this breed, and thus reach a clinical diagnosis without pursuing histologic confirmation

■Some clinicians refer to this condition as proliferative keratoconjunctivitis in the Collie breed

■The disease in Collies is relatively aggressive but generally responds well to anti-inflammatory treatment (Fig. 7.38)

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•The classic disease is a nodular mass lesion deep to the conjunctival epithelial surface and abutting the sclera at the limbus. However, particularly in Collies, the conjunctiva and tissues of the third eyelid and eyelid may also be involved in the disease process

•The nodular disease often responds to anti-inflammatory treatment or debulking surgery. Therefore, only atypical lesions tend to be sampled and submitted to the pathology laboratory

•Typical morphologic features include:

■The lesion forms a nodule. There should be a well-defined margin, with adjacent near normal connective tissue

■The lesion subtends the conjunctival epithelium which is characteristically intact over the mass

■There is a mixture of lympho-plasmacytic inflammatory cells and larger cells resembling histiocytes, with minimal or no suppurative component. The histiocytic component may include multi-nucleate cells

■There is often a variable population of spindle cells with or without collagen matrix deposition:

–Mass lesions which are primarily made up of spindle cells and collagen are diagnosed at COPLOW as NGEnodular fasciitis variant

■Nodular granulomatous episcleritis lacks features of classical granulomatous inflammation, with no distinct nodules of epithelioid macrophage cells surrounding a necrotic center

A B

C D

■Recently it has been reported that not all of the large cells are histiocytic, and some may be smooth muscle or myofibroblasts.

Feline herpesvirus keratoconjunctivitis, FHV-1 (Fig. 7.39)

•Feline herpesvirus-1 causes both a primary and secondary inflammatory disease of the conjunctiva and cornea, i.e. conjunctivitis or keratoconjunctivitis

•The primary disease occurs in kittens and is accompanied by signs of systemic infection such as fever, lethargy, upper respiratory disease, and inflammatory disease widespread on mucosal epithelial surfaces, as well as ocular disease

■Biopsies are seldom submitted from cats with primary disease, but FHV-1 infection likely plays an important role in feline symblepharon formation (see above) and neonatal corneal defects (see Ch. 8)

•The virus becomes dormant in the trigeminal ganglion and stress-related recrudescence leads to clinical disease involving the conjunctiva and cornea. Prior or recrudescent FHV-1 infection may contribute to chronic stromal keratitis, corneal stromal sequestration or eosinophilic keratitis that may be biopsied in adult cats (see Ch. 8)

Figure 7.36  Canine nodular granulomatous episcleritis (NGE).

(A) Pembroke Welsh Corgi, 14 years old: this firm mass originated in the superior episclera and had not invaded the cornea. (B) Golden Retriever, 9 years old: this pink elevated mass originated from nasal episclera with mild extension into the adjacent cornea (arrow). (C) Shetland Sheepdog, 10 years old: this mass extended into the superficial cornea. Lipid keratopathy (arrow) is present at the leading edge of the lesion.

(D) Greyhound, 6 years old: the pink mass originated temporally and did not significantly invade the cornea.

•There are no morphologic hallmarks that allow the pathologist to establish a cause-and-effect relationship in FHV-1 conjunctivitis, so the importance of the role of FHV-1 in non-specific feline conjunctivitis is not well understood

•Distinct morphologic patterns of conjunctivitis that might be related to FHV-1 recrudescence include eosinophilic conjunctivitis and keratoconjunctivitis.

Eosinophilic keratoconjunctivitis (see also Ch. 8) (Fig. 7.40)

•Blepharitis involving the eyelid margins, conjunctivitis and keratitis associated with eosinophilic inflammation are common clinical presentations in cats. Lesions may occur together or separately, and may be unior bilateral

•Morphologic features include:

■Eosinophilic keratoconjunctivitis is a regional lesion which often extends onto the corneal surface but does not involve the deep stroma

■There is irregular distortion of the surface contour of the cornea, with or without ulceration

■There is often a plexus of relatively large blood vessels within the underlying stroma

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■Lympho-plasmacytic inflammatory cells may out-number eosinophils

•The role played by FHV-1 infection in the development of feline eosinophilic ocular disease remains controversial, despite the findings of studies that provide molecular evidence of prior or active FHV-1 infection.

Feline conjunctival papillary mastocytosis (Fig. 7.41)

This is an uncommon disease. There are seven cases in the COPLOW collection.

•This presents as a poorly delineated, proliferative conjunctival lesion and most of the samples submitted are from the palpebral surface of the nictitans

•The underlying cause remains unknown

•Morphologic features of feline conjunctival papillary mastocytosis include:

■Papillary proliferation of an intact epithelium

■Mixed inflammatory infiltrate and edema in the substantia propria

■Large numbers of mast cells including many mast cells directly within or on the surface of the conjunctival epithelium.

conjunctiva from the lid margin to the fornix. Less frequently, the bulbar conjunctiva or the nictitans are involved

•Reports suggest that older cats with sparse peri-ocular pigmentation (e.g. orange cats) are predisposed. There are 81 cases in the COPLOW collection diagnosed as feline lipogranulomatous conjunctivitis:

■28 of the 81 cases have a concurrent neoplasm including 17 cases with conjunctival squamous cell carcinoma

■Pathologists should be aware that lipogranulomas and neoplasia may go together. Thus, a careful search should be made to rule out neoplasia

•The lesions, involving the palpebral conjunctiva, are nonulcerative, nodular, and pale in color, ranging from opaque white to light yellow

•Characteristic morphologic features include:

■A bland granulomatous inflammatory reaction surrounding large, cell-free lakes of lipid dissolved during processing

■Large empty spaces which may be surrounded by inconspicuous multi-nucleated macrophages

■In some areas, and in some lesions, the characteristic profile is that of solid sheets of large, multinucleate, foreign body macrophage cells, or of smaller epithelioid cells with foamy cytoplasm

■Lympho-plasmacytic or suppurative inflammation are seldom prominent.

•Feline lipogranulomatous conjunctivitis presents as a regional, nodular disease which usually involves the palpebral

•This is a common clinical presentation in breeds that are predisposed to chronic superficial keratitis (CSK), in

which conjunctivitis may accompany keratitis, or occur in isolation

•Thickening and hyperemia of the nictitating membrane, with depigmentation of the leading edge, is observed bilaterally

•The disease is considered to have a similar immunopathogenesis to CSK, which is discussed in further detail in Chapter 8.

Triamcinolone (depot corticosteroid preparation) injection site granulomas (Fig. 7.43)

•Several inflammatory conditions of the eye or conjunctiva are treated by sub-conjunctival injection of a long-acting corticosteroid preparation

•The injected formulation is associated with a distinctive granulomatous inflammatory reaction, with the following characteristics:

■Reaction to recently injected product is characterized by the presence of an acellular, flocculent, amphophilic material with scant macrophage cells

■The mature granuloma is characterized by a cell-free center, surrounded by epithelioid or multinucleate macrophage cells

■Macrophage cells have a, very distinctive, rounded rectangular, clear vacuole in the cytoplasm

■The granuloma may be surrounded by minimal lymphoplasmacytic infiltrate or minimal fibrosis.

Canine conjunctival onchocerciasis (Fig. 7.44)

•This parasitic condition is discussed in detail elsewhere in this text (Ch. 6)

•In North America, the disease has been recorded in the Western United States, in or near California

•The conjunctival manifestations of this disease may be recognized as a raised, irregular inflammatory lesion of the limbal conjunctiva that may be submitted as a biopsy specimen

•Morphologic features that should point toward the diagnosis of onchocerciasis include:

■Tissue fibrosis

■An eosinophilic component to the inflammatory response

■A granulomatous component to the inflammatory response.

Equine onchocerciasis

•Microfilaria of Onchocerca cervicalis have been proposed as a cause of inflammation and depigmentation of the temporal limbal conjunctiva in horse

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•However, the causal relationship between onchocerciasis and ocular lesions in horses has not been definitively established.

CONJUNCTIVAL NEOPLASMS AND OTHER

NODULAR LESIONS

Conjunctival squamous cell carcinoma

Equine squamous cell carcinoma (Figs 7.45, 7.46)

There are 80 cases of conjunctival squamous cell carcinoma in the COPLOW collection, 10% of equine submissions.

•This is a relatively common condition in horses, and demonstrates increasing incidence with age

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•Ultraviolet (UV) light exposure is thought to be involved in the pathogenesis of equine conjunctival squamous cell carcinoma for the following reasons:

■A high percentage of these neoplasms have mutant p53 protein/altered p53 expression

■Ocular squamous cell carcinoma has a higher prevalence in those geographic regions where UV light exposure is likely to be greater

■Squamous cell carcinoma is more likely to occur in horses that are lacking in conjunctival and peri-ocular melanin pigment

■Solar elastosis and actinic keratosis is often seen in association with the early stages of disease

–Deep in the connective tissue the normal collagen matrix is disrupted by areas with an amphophilic matrix deposition, often with wavy elastin fibers