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

–The Antoni B cellular pattern is a more random distribution of cells with a diffuse mixing of cell bodies and delicate collagen and myxoid stroma

■Characteristic immunohistochemistry profile:

–Vimentin positive

–S100 positive

–Collagen IV positive

–Laminin positive

■PNST of the eyelid is a locally infiltrative tumor, requiring wide margins of excision that may necessitate enucleation, but is unlikely to metastasize.

Equine sarcoid and bovine fibropapilloma (Fig. 7.23)

Both of these common, cutaneous proliferative diseases are thought to be caused by bovine papilloma virus.

•Equine sarcoid is a very common peri-ocular tumor

■Sarcoid is more common in young horses

■The clinical/gross appearance is highly variable. While sarcoid may be categorized into as many as six different subtypes based on clinical appearance, it is not easy to hold

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to these carefully defined categories. The spectrum of disease may be summarized as follows:

–Small isolated or clustered nodular or wart-like growths, which are strictly superficial

–Large sessile, or deep nodular mass lesions extending into the dermis or subcutis

•The histologic appearance of both sarcoid and bovine fibropapilloma is characterized by a close association between proliferative disease in the stroma and the epidermis

■The stromal proliferation resembles a spindle cell sarcoma and, in invasive disease, can extend deep into the subcutaneous connective tissue

■At the dermal-epidermal junction the stromal proliferation abuts the epidermis and there is exaggerated epithelial down-growth, forming characteristic angular spikes pointing into the adjacent region of stromal proliferation

■The treatment of equine sarcoid may involve surgery, cryotherapy, immunotherapy, laser, radiation or combination therapy

–Surgical excision alone is associated with very high recurrence rates

–The response to treatment is unpredictable

–Management of periocular tumors is complicated by anatomic considerations

A

B

Figure 7.20  Feline cutaneous mast cell tumor. (A) DSH, 16 years old: this mass was present for 10 years, when it became hemorrhagic. (B) Photomicrograph showing well-differentiated neoplastic mast cells filling the space between preexisting dermal collagen and follicles. Higher magnification (inset) showing the bland morphology and monomorphic features which are typical.

Comparative Comments

Tumors of the lid epithelium in humans are common and can be divided into three main groups: benign, precancerous, and malignant. These are in fact a microcosm of the epithelial tumors that occur elsewhere on the human skin.

1.Benign lesions of the eyelid in humans include:

–Cutaneous horns

–Papillomas

–Seborrheic keratoses

–Inverted follicular keratoses

–Pseudoepitheliomatous hyperplasia

–Keratoacanthoma

–Large cell acanthomas.

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2.Non-melanocytic pre-cancerous lesions of the human eyelid include:

–Actinic keratoses

–Carcinoma in situ

–Radiation dermatosis

–Xeroderma pigmentosum.

3.The major epithelial malignancies of the human lid are basal cell carcinoma and squamous cell carcinoma:

–Basal cell carcinoma is a tumor of the basal cells, located at base of the epidermis

It is the most common malignancy of the eyelids and accounts for approximately 90% of all malignant tumors of the lid and 20% of all lid tumors in humans

–Squamous cell carcinoma (SCC) constitutes less than 5% of epithelial neoplasms of the human eyelid

SCC in humans typically arises in sun-damaged skin in elderly, fair-skinned individuals

–Sebaceous gland carcinoma is the most significant of the many malignant tumors arising from the adnexal structures of the lid

This is the second most common malignancy of the eyelids in humans, and occurs most commonly in elderly women and in Asians

The preferred sites of involvement are the upper lid, brow, and caruncle

Sebaceous gland carcinoma is often clinically misdiagnosed as unilateral blepharoconjunctivitis or recurring chalazion

This is an aggressive tumor that commonly exhibits local extension, as well as lymphatic and hematogenous spread

The finding of intracytoplasmic lipid in the tumor cells is essential for diagnosis.

EYELID MARGIN MASSES

Canine meibomian gland adenoma/ epithelioma (Fig. 7.24)

Meibomian adenoma and epithelioma represent 10% of tumor submissions to COPLOW. This is probably a gross under-estimate of the frequency of this tumor, since small masses are likely to either not be submitted when excised; treated in such a way that the tissue is destroyed, or submitted to a general rather than ophthalmic pathology laboratory.

•Benign meibomian gland tumors present as focal or multifocal nodular masses which are often exophytic and papillary

•They may cause problems related to their contact with the corneal surface causing irritation, or may be considered a cosmetic problem

•Meibomian gland adenoma

■Most of the tumor is made up of fully differentiated meibomian glandular tissue:

–Holocrine secretory cells

–Keratinizing ducts

■As a general rule: adenoma is smaller, more superficial, and more likely to be exophytic than epithelioma

•Meibomian gland epithelioma

■Most of the tumor is made up of undifferentiated basal cells with rare sebaceous or squamous differentiation

■Epitheliomas are more likely to be pigmented

■Epitheliomas are slightly larger and more likely to be deeper in the lid margin dermis than adenomas

•Lipogranuloma surrounding adenoma or epithelioma (Fig. 7.25)

■Either variant of the benign meibomian gland tumors is likely to be surrounded by a variably sized lipogranuloma with:

–Epithelioid macrophage cells

–Multi-nucleated cells

–Large, empty ‘lipid lakes’

■Linear, birefringent material within the cytoplasm of the macrophage cells

–Forms complex membranous electron-dense material in the cytoplasm of the macrophage cells

–Birefringent material is not seen in lipogranuloma surrounding canine cutaneous sebaceous gland tumors.

Canine meibomian gland adenocarcinoma

There are only three examples of this tumor in the COPLOW archive.

•This is a rare, malignant variant of the meibomian gland tumor

•The tumor is characterized by anaplastic cellular features, rare meibomian gland secretory features and local invasion.

Lid margin melanocytic tumors (melanocytoma) (Fig. 7.26)

There are 52 cases in the COPLOW collection (0.9% of tumor submissions). The reader is referred to the section above on melanocytic tumors of the haired eyelid skin

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•Multifocal eyelid margin melanocytomas are seen in Vizslas, and in Doberman Pinschers, particularly those with the so-called white color-dilute coat color (Fig. 7.27).

Lipogranuloma (chalazion) (Fig. 7.28)

•As mentioned above, lipogranuloma formation is common surrounding benign tumors of meibomian gland origin. However, lipogranulomata can form a nodular mass lesion in isolation, without a co-existing meibomian gland tumor

■White nodular mass at the lid margin

■Histologically the lipogranuloma surrounds the nonneoplastic meibomian gland

■It is postulated that the granuloma reflects a reaction to release of meibomian lipid within the tissues

■As with the lipogranuloma that surrounds adenoma, there is often linear birefringent material in the cytoplasm of macrophage cells in lipogranulomas surrounding meibomian glands.

Squamous cell carcinoma of the lid margin in cats (multifocal squamous cell carcinoma) (Figs 7.29, 7.30)

There are 10 cases of multifocal squamous cell carcinoma involving the lid margin in the COPLOW collection.

•Squamous cell carcinoma in cats, when it involves the lid margins, usually also extends into the haired skin and is part of

a complex of dysplastic epithelium with multicentric squamous cell carcinoma

•There is often diffuse conjunctival disease with multifocal areas of epithelial dysplasia but not necessarily neoplasia. A similar situation exists in the horse, but in that species the neoplasm commonly involves conjunctival tissue and will, therefore, be addressed in the next section.

•Careful evaluation of the margins of the neoplasm in the haired skin of the eyelid reveals disorganized and dysplastic epithelium, often most easily identified in the follicular epithelium.

Squamous cell carcinoma of the lid margin in dogs (Fig. 7.31)

There are only three canine cases of lid margin squamous cell carcinoma in the COPLOW collection.

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Squamous cell carcinoma of the lid margin in horses and cattle

•This is a very common clinical presentation, particularly in breeds that lack periocular pigmentation

•As described above for cats, squamous cell carcinoma of the lid margin in horses and cattle generally shows extensive conjunctival involvement and is therefore considered later in this chapter, as a conjunctival neoplasm.

Mesenchymal hamartomas of the lateral canthus (Fig. 7.32)

There are seven of these tumors in the COPLOW collection, six of which involved the temporal orbital rim.

•A hamartoma is a mass lesion associated with fully differentiated, non-neoplastic tissue, appropriate to the location of the mass

•Mesenchymal hamartomas, composed of collagenous connective tissue, adipose tissue and, usually, skeletal muscle tissue, are occasionally removed from the orbital rim in dogs.

CONJUNCTIVITIS

General philosophy on the pathology of conjunctivitis

•Small conjunctival biopsies are often submitted in the hope that the morphology will reveal a cause of inflammatory disease. Unfortunately, there are seldom morphologic features that suggest a specific diagnosis

•In COPLOW submissions, the diagnosis of conjunctivitis is generally made by describing the kind of inflammatory exudates and/or infiltrates seen

•If there is an apparent increase in the relative number of mast cells, the suggestion is made that conjunctivitis might be related to hypersensitivity.

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Comparative Comments

The opportunity to study conjunctival pathology in humans usually occurs in the following instances:

•A biopsy specimen, from an inflammatory, degenerative, or neoplastic process. These may either be excisional or partial biopsies

•Conjunctival scrapings, e.g., in the diagnosis of trachoma

•Impression cytology, in which surface cells have been removed and are stained for recognition of malignant cells, inclusions, or other abnormalities for exenteration specimens submitted following the removal of advanced malignant processes.

In the organization and teaching of human conjunctival pathology, the following categories are usually considered:

•Congenital and developmental anomalies

•Inflammations and infections

•Degenerations

•Systemic diseases

•Tumors.

A B

C D

Comparative Comments (continued)

Within these categories are encompassed many of the entities described in this chapter in various other species, such as pseudopterygia, pterygia, non-specific chronic conjunctivitis, ligneous conjunctivitis, fibrous histiocytoma, herpes virus infection, lipogranulomas, granulomas associated with injection sites, and onchocerciasis.

The frequency and specific appearance of these lesions in man appear to vary in many instances from that described in other species.

Figure 7.29  Feline eyelid margin squamous cell carcinoma, clinical.

(A)DSH, 5 years old: this erosive lesion has not yet involved the free lid margin.

(B)DSH, 7 years old: the free lid margins, lower lid and medial canthus are involved in this case. (C) DSH, 17 years old: the tumor is elevated and erosive. The nictitans and palpebral conjunctiva are also involved. (D) DSH, 8 years old: the tumor has disfigured the superior lid and extended into the superior palpebral conjunctiva.

–The axial opening in the conjunctival fold is always circular, and has smooth margins

■Surgical debridement of the base of the conjunctival fold results in re-growth

■Histopathology

–Minimal inflammation or edema

–The stroma is generally the typical loose connective tissue of the conjunctival substantia propria

–Rarely, at the axial, migrating margin, contractile cells rich in actin may be observed, that are morphologically similar to smooth muscle cells.

Pseudopterygium in rabbits (Fig. 7.33)

•This is an idiopathic disease of the conjunctiva in rabbits, which has the following characteristic features:

■The disease is often unilateral, although some rabbits show bilateral ocular involvement

■Signs of pain, irritation or inflammation are minimal or absent

■The hallmark of the disease is a circumferential inward folding of the bulbar conjunctiva, thus closing over the clear cornea like a purse-string. The condition has also been termed ‘epicorneal conjunctival membrane’

–In contrast to pterygium in humans, the space between the conjunctival fold and the corneal surface is only rarely interrupted by an adhesion

Ligneous conjunctivitis in dogs (Figs 7.34, 7.35)

There are six cases of ligneous conjunctivitis, four in Doberman Pinschers and two in littermate Golden Retrievers, in the COPLOW collection (Fig. 7.35).

•This is a rare condition. Ligneous conjunctivitis has been reported as an entity only in Doberman pinschers and Golden retrievers

•Clinically, the condition presents as a bilateral ulcerative conjunctivitis, with an adherent dense pseudomembranous exudate

•In some cases, there are oral mucosal lesions of similar appearance

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