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

–Stains for elastin are positive, or stain a ‘murky’ gray rather than the distinct black staining of individual elastin fibers

•Biopsy is done at all stages of this disease process, and multiple stages may be represented within the conjunctival tissues of an individual subject, so one will see a variety of morphological presentations:

■Dysplastic epithelium, presumed to be pre-neoplastic:

–Disorganization of epithelium, or abnormal keratinization patterns

–Minimal anaplastic cellular features

–Does not invade the epithelial basal lamina

■Carcinoma in situ

–Epithelial disorganization and atypical keratinization deep within the epithelium (dyskeratosis)

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–Anaplastic cellular features

Large nucleus to cytoplasm ratio

Karyomegaly

Binucleate cells

Large nucleoli

–Affected cells do not extend beyond the epithelial basal lamina

■Non-invasive squamous cell carcinoma

–Fully neoplastic epithelial features with invasion beyond the basal lamina

–Atypical features of keratin formation such as keratin pearls

–Infiltration of lymphatic or vascular structures is not seen

A B

C D

–Desmoplastic, stromal fibrous proliferation is not seen or is not prominent

■Invasive squamous cell carcinoma

–Deep invasion of the sub-epithelial tissues is a prominent feature with vascular invasion or lymphatic invasion

–Individual neoplastic cells are often seen and they may be difficult to distinguish from stromal spindle cells

■Stromal invasive squamous cell carcinoma (Fig. 7.47)

–This distinctive variant invades the cornea specifically and will be discussed further in Chapter 8.

Bovine squamous cell carcinoma (Fig. 7.48)

Bovine ocular squamous cell carcinoma is very common but underrepresented in the COPLOW collection. This may result from a bias towards companion animals in clinical veterinary ophthalmology, the client base for a mail-in comparative ocular pathology service. There are 16 submissions of ocular squamous cell carcinoma in cattle, representing 18.8% of all bovine submissions.

•Squamous cell carcinoma is the second most frequently reported tumor of cattle with only lymphoma being more common

•Most common in the Hereford breed and its crosses, that show a characteristic lack of periocular pigment

•The condition is often bilateral

•More common when the conjunctiva is not pigmented

•An estimated 75% occur on the bulbar conjunctiva at the limbus and the rest are widely dispersed

Figure 7.46  Equine squamous cell carcinoma, pathology. (A,B) Gross photographs of a horse with exophytic, poorly invasive, limbal squamous cell carcinoma. (C) Subgross photomicrograph showing an exophytic, and also invasive, squamous cell carcinoma. (D) Subgross photomicrograph showing invasion into the corneal stroma.

•UV light is thought to be an important factor in pathogenesis

•The morphologic subtypes are similar to those of the horse, except there is no reported equivalent of the stromal invasive form.

Canine squamous cell carcinoma (Fig. 7.49)

Conjunctival squamous cell carcinoma is very uncommon in dogs. There are 24 cases in the COPLOW collection, representing 0.4% of all canine tumor submissions.

•The morphologic variations are similar to those seen in other species.

Feline squamous cell carcinoma (Fig. 7.50)

Conjunctival squamous cell carcinoma is relatively rare in cats. There are 61 cases in the COPLOW collection, representing 2.2% of feline tumor submissions.

•A higher proportion of the feline tumors are highly invasive, extending into the globe

•Care must be taken to rule out metastatic squamous cell carcinoma because tumors of the lung or middle ear can spread to the conjunctival area

•Multicentric squamous cell carcinoma is mentioned above. This tumor is associated with epithelial dysplasia or neoplastic transformation of the conjunctival epithelium or corneal epithelium and should be ruled out in all cases.

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Comparative Comments

•Considering precancerous lesions and cancerous lesions of the surface epithelium, there appears to be a close association between the entities seen in humans and in other species

•In humans, the term ‘conjunctival intraepithelial neoplasia’ (CIN) is used to describe a spectrum of patterns of cellular proliferation, extending from dysplasia to carcinoma in situ. Tumors with this designation have not penetrated the underlying basement membrane

•Frank squamous cell carcinoma of the conjunctiva is an uncommon tumor in humans, occurring most frequently in tropical countries.

Feline conjunctival mucoepidermoid carcinoma (Fig. 7.51)

Although this tumor is not reported in the literature, there are 10 cases in the COPLOW collection.

•Morphologic features of conjunctival mucoepidermoid carcinoma:

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■The primary cell is a poorly-differentiated secretory cell forming acinar or tubular features

■The tumors often form papillary fronds on the conjunctival surface but they also invade into the tissue

■Too little is known about this neoplasm to speculate as to the prognosis.

Canine conjunctival melanoma and melanocytoma (Figs 7.52, 7.53)

There are 149 cases of canine conjunctival melanocytic tumors in the COPLOW collection, representing 2.6% of canine tumor submissions.

•Of the canine conjunctival melanocytic tumors in the COPLOW collection, 81% are malignant by morphologic criteria and 19% are melanocytoma

•By histologic observation, most of the affected dogs have pigmentation of their normal conjunctival tissues

•The breeds most commonly affected by conjunctival melanocytic tumors are retrievers, Rottweilers, and Cocker spaniels

■It is noteworthy that, despite their intraocular pigmentary problems that lead to glaucoma, there are no Cairn Terriers with conjunctival melanomas

•Morphologic features of canine conjunctival melanocytoma

■Melanocytomas were always heavily pigmented

■The cells are mostly large heavily pigmented round cells, mixed with pigmented spindle cells

■Melanocytoma, like melanoma cells, tend to form tight aggregates or clusters subtending or within the conjunctival epithelium

■No satellite aggregates of neoplastic or dysplastic melanocytic cells were apparent within the conjunctival epithelium away from the tumor location

•Morphologic features of canine conjunctival melanoma

■Melanomas have variable pigmentation but many in the COPLOW collection were totally amelanotic

■The tumor cells had anaplastic features:

–Large single nucleoli are a common and useful diagnostic feature that point to the melanocytic origin of tumors

–Large nucleus to cytoplasm ratio

–Hyper-chromatic nuclear profiles

–Abundant mitotic activity

■Neoplastic cells near the conjunctival epithelium tend to form aggregated clusters, and are often seen within the epithelium

–This feature is useful in recognizing tumors as being of melanocytic origin but it is not a feature which predicts biological behavior

■Many of the melanomas had dysplastic or neoplastic melanocytic cells subtending or within the epithelium well away from the site of the primary mass

•Of 23 cases where the location of the primary mass was known, 61% were on the third eyelid, 22% were

on the bulbar conjunctiva, and 17% were on the palpebral conjunctiva

•Follow-up information was available for only 21 cases

■Half of the tumors recurred in the conjunctiva, often away from the primary site or multi-focally

■Metastasis was only documented in two of these 21 cases and both of these were neoplasms that originally involved the palpebral conjunctiva

•Recommendations based on known behavior:

■Careful observation for local recurrence followed by aggressive surgical excision (with enucleation of the globe) after the first recurrence.

Feline conjunctival melanoma (Fig. 7.54)

There are 26 conjunctival melanocytic tumors in cats, representing 0.9% of feline tumor submissions.

•All 26 cases had a malignant potential

■There was a wide variation in the degree of pigmentation

■Some of these malignant neoplasms have shown aggressive infiltration or metastatic disease, despite features that would suggest benign behavior in dogs

–This feature is similar to the reported behavior of cutaneous melanoma in cats

■The most common location for the primary tumor is the bulbar conjunctiva with extension deep into the orbit adjacent to the globe.

Comparative Comments

•Melanocytic neoplasia in humans is seen more frequently in the pathology laboratory than other precancerous lesions and cancerous lesions of the surface epithelium

•These melanocytic lesions may occur as congenital or acquired, benign or malignant lesions. Nevocellular nevi are the most common conjunctival tumors. The malignant potential of these nevi vary, with junctional and compound nevi thought to have low malignant potential, while the subepithelial nevus usually remains benign

•Primary acquired melanosis (PAM) is a condition seen in adults as stippled brown conjunctival pigmentation. The onset is usually at 40–50 years of age and includes a spectrum that extends from benign acquired melanosis (PAM without atypia) to PAM with mild, moderate, or severe atypia. PAM with atypia can evolve into melanoma

•Approximately 50% of conjunctival melanomas arise de novo, and 50% arise from acquired melanosis or conjunctival nevi

•The histopathologic features of conjunctival melanoma in humans have prognostic significance for survival. Metastases are more likely to occur in invasive melanomas that are more than 0.8 mm thick.

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