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

•In the interest of caution and completeness, this diagnosis should always be made only after first ruling out infectious causes of granulomatous disease by using special stains for bacteria and fungi.

Miscellaneous other causes of blepharitis:

•Other infectious causes of blepharitis include:

■Staphylococcus spp.

■In endemic areas, such as the Mediterranean countries and South and Central Americas, Leishmaniasis frequently involves the periocular skin

•Atopy and auto-immune diseases, including pemphigus complex disorders and uveodermatologic syndrome (for detailed discussion of the latter, see Ch. 9)

•Detailed consideration of periocular dermatoses is outwith the scope of this text. The reader is referred to a veterinary dermatopathology text for more detailed discussion of specific skin diseases.

Comparative Comments

•Diffuse inflammation of the lids, termed blepharitis, occurs commonly in humans and is caused by either seborrheic dermatitis or a chronic bacterial infection

•A hordeolum, also commonly seen in man, is an acute purulent inflammation of either the superficial eccrine or sebaceous glands (external hordeolum, or stye) or the meibomian glands (internal hordeolum) of the eyelids

•Chalazia, together with hordeolum, constitute one of the most common causes of lid swelling in people. A chalazion is a chronic, lipogranulomatous inflammation in the tarsus, resulting from an obstruction in the meibomian gland ducts, often with secondary bacterial infection

•Other bacterial infections of note in humans include Mycobacterium leprae and the synergistic infection of

Streptococcus pyogenes and Staphylococcus aureus, which may result in necrotizing fasciitis, a disease that causes massive destruction of the eyelid and adjacent orbital tissue

•The principal viral infections of the human eyelid are molluscum contagiosum, an infection caused by a poxvirus, that leads to formation of small, discrete waxy papules with umbilicated centers; verruca vulgaris, papillomatous lesions caused by the human papillomavirus; and herpes simplex, herpes varicella, and herpes zoster, all of which begin as vesicles or blisters on an erythematous base.

PROLIFERATIVE AND NEOPLASTIC LESIONS

OF THE EYELID SKIN

Canine juvenile cutaneous histiocytoma (Figs 7.7, 7.8)

This is a common, benign, typically self-limiting, mass lesion on the haired skin of dogs. There are 38 cases in the COPLOW collection. Canine juvenile cutaneous histiocytoma is predominantly seen in young dogs, decreasing in frequency in dogs older than 3 years.

•The purported cell of origin is the cutaneous antigen-presenting macrophage known as the Langerhans cell

•Grossly, the lesions are characterized by a well-circumscribed, round flattened nodule with hair loss and often central, superficial ulceration

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•Histological features

■The characteristic histiocytic cells are mixed with a variable population of lymphocytes

–Lymphocytes often make up the majority of the cellular infiltrate

–The lymphocytic infiltrate is often most prominent at the deepest extent of dermal involvement and les prominent superficially

■The histiocytic component infiltrates between pre-existing collagen bundles, often forming single-file rows of cells

■The characteristic cells are often seen invading the epidermis or follicular epithelium as individual cells, or in small aggregates.

Cutaneous and systemic histiocytosis (Fig. 7.9)

There are 18 cases in the COPLOW collection. Four are in Bernese Mountain dogs and four are in Labrador Retrievers.

•Cutaneous histiocytosis (see above) and systemic histiocytosis represent the regional proliferation of histiocytes. There is little agreement regarding the malignant potential of these conditions, however systemic histiocytosis has the potential to recur or to spread

•Cutaneous histiocytosis is less likely to spread beyond the skin whereas systemic histiocytosis is likely to lead to signs of systemic disease

•Both forms are reported to be familial in the Bernese mountain dog, but the disease is not limited to this breed (see above)

•Ocular lesions may include masses within the eyelid skin or episclera, exophthalmos, uveitis, retinal detachment and glaucoma

•Both diseases are characterized by a deep intra-dermal and subcutaneous infiltrate of large histiocytes, lacking the features of classical granulomatous inflammation

•The characteristic cells in cutaneous histiocytosis are bland and demonstrate few features of malignancy

•The characteristic cells of systemic histiocytosis have only mildly anaplastic features and may also show a dramatic vasocentric tendency and reticulin deposition.

Canine cutaneous melanocytic tumors (melanocytoma) (Fig. 7.10)

Cutaneous melanocytic tumors in dogs are almost always benign melanocytomas. There are 27 cases in the COPLOW collection.

•The superficial dermis is effaced and infiltrated with neoplastic spindle cells, polygonal cells, or large round cells which are usually, but not always, heavily pigmented

•Individual or tight clusters of neoplastic cells are seen immediately below the epidermis or within the epidermis or follicular epithelium

■ This feature does not suggest malignancy

•Malignant melanomas of the haired skin are seen rarely and should only be diagnosed upon identification of compelling anaplastic cellular features and evidence of aggressive infiltration.

Feline cutaneous melanocytic tumors

Although cutaneous tumors of melanocytic origin are rare in cats, they are often very malignant in their biological behavior, despite the fact

that their cytologic features may not be particularly alarming. There is only one case in the COPLOW collection.

Comparative Comments

•In humans, benign melanocytic disorders and tumors involving the lid include ephelides or freckles, lentigo, nevocellular nevi, blue nevi, nevus of Ota, and compound nevus of Spitz

•The malignant melanocytic tumors in humans are generally divided into four major subtypes of cutaneous malignant melanoma: lentigo maligna melanoma, acral lentiginous melanoma, superficial spreading melanoma, and nodular melanoma. Several rare variants of malignant melanoma are also seen.

Intradermal epithelial cysts (Fig. 7.11)

•Epidermal inclusion cyst: stratified squamous epithelial lined cyst with keratin accumulation

•Follicular cyst: the anatomic location of the cyst is suggestive of origins in an isolated or obstructed hair follicle

•Dermoid cyst: containing additional epithelial differentiation of hair follicle and/or glandular elements.

Comparative Comments

The principal cystic lesions affecting the eyelid in humans are:

•Epidermoid cysts (present at birth)

•Epidermal inclusion cysts (acquired but otherwise identical to epidermoid cysts)

•Dermoid cysts (which include adnexal structures)

•Sweat gland cysts.

Cutaneous sebaceous adenoma/epithelioma (Fig. 7.12)

•These are benign tumors of sebaceous glands occurring commonly in dogs, which are also recognized in cats

•Adenoma is a very common periocular tumor and is largely made up of fully differentiated sebaceous glandular tissue

■Some pathologists make a distinction between sebaceous adenoma and sebaceous hyperplasia based on the orientation of the secretory tissue around the duct. If the duct is appropriately positioned it is typical of hyperplasia

■Sebaceous adenoma is frequently exophytic, or even papillary, in appearance, often with central cavitation

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•Epithelioma is mainly composed of undifferentiated basal cells, with occasional areas of sebaceous or squamous ductular differentiation

•Surrounding lipogranulomatous inflammation may accompany both tumor types.

Canine trichoblastoma (basal cell tumor) (Fig. 7.13)

•Trichoblastoma is a common benign tumor occurring on the head and neck of dogs

•The tumor replaces tissue of the dermis with a distinct loose cellular stroma, and cords, ribbons or nests of poorlydifferentiated epithelium reminiscent of hair bulb epithelium.

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Trichoepithelioma (Fig. 7.14)

•This is an epithelial tumor of hair follicular origin

•The neoplasm is often continuous with the surface epidermis and extends deeply into the dermis showing variable features of hair follicle differentiation.

Canine infundibular keratinizing acanthoma (intracutaneous epithelioma, keratoacanthoma) (Fig. 7.15)

•This benign neoplasm remains connected to the epidermis by a stalk or pore and forms a central core of solid keratin with prominent keratin pearls.

Canine sweat gland adenoma (Fig. 7.16)

•Cyst adenoma: this tumor is usually very well-differentiated and made up of multiple widely dilated cysts filled with watery fluid

•Sweat gland adenoma: this tumor is a nodular, solid to cavitated dermal mass which typically shows clear apocrine glandular differentiation

■Look for evidence of a double cell lining of the glandular structures

■Occasionally, these tumors have a component of myoepithelial cell proliferation (complex adenoma) or cartilage/bone differentiation (mixed adenoma).

Feline apocrine gland tumor (Fig. 7.17)

•This is a common dermal mass lesion, which is frequently cavitated

•The tumor is a solid mass of poorly-differentiated epithelial cells showing glandular features, often with focal areas demonstrating prominent doubling of the glandular epithelium. There can also be a myoepithelial component to the tumors making them a complex tumor or a mixed tumor

■Because these tumors are poorly-differentiated, they are often referred to as adenocarcinoma, but they are benign in their biologic behavior.

Apocrine cystadenomas in Persian cats (hidrocystomas) (Fig. 7.18)

•These multifocal, pigmented, nodular lesions on the eyelids are most often seen in Persian cats

•Each lesion is made up of one or more dilated epithelial cysts

■Based on the position of the cystic tumors and the cuboidal nature of the epithelial cells, these cysts are thought to arise from sweat glands

•The cysts are filled with thick brown material and often a predominantly histiocytic cellular infiltrate

•There is a potential for additional lesions to occur at other sites on the eyelids following excision.

Canine mast cell tumors (Fig. 7.19)

•One of the most common cutaneous or subcutaneous tumors of the dog

•Their clinical appearance on the eyelid is no different from other sites on the integument

•Surgical management of peri-ocular mast cell tumors is complicated by the difficulty in obtaining sufficiently wide margins in this location, while preserving ocular function

•There is a morphological grading scheme consisting of three grades, from grade 1 (most benign) to grade 3 (most malignant).

Grade 1 mast cell tumor

•A well-defined, circumscribed nodule located entirely within the dermis.

•Well-differentiated neoplasm:

■Oval cell shape with little or no cellular pleomorphism

■Oval, bland, centrally-positioned nuclei

■Abundant metachromatic cytoplasmic granules

■Small nucleus to cytoplasm ratio

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Veterinary Ocular Pathology

A B

C

■No mitotic activity

■Little or no remodeling of the stroma.

Grade 2 mast cell tumor

•The morphologic features of grade 2 mast cell tumor are intermediate between those of grade 1 and grade 3 tumors.

Grade 3 mast cell tumor

•Extends deeply into the subcutaneous tissue, and may not be present in the dermis at all

•Cellular characteristics of anaplasia, and may not be readily recognizable as mast cells:

■Highly variable nuclear shape and nuclear size

■Large nucleus to cytoplasm ratio

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Figure 7.10  Canine melanocytic cutaneous tumors. (A) Doberman Pinscher, 5 years old: this well-delineated mass on the lid margin was confirmed to be a melanocytoma. (B) Golden Retriever, 10 years old: this poorly-delineated lobulated mass involved the inferior lid and medial canthus. The mass was confirmed to be a melanoma. The translucent spherical mass in the pupil is a uveal epithelial cyst. (C) Photomicrograph showing nonpigmented clusters of neoplastic melanocytes abutting the epidermis (arrows).

■Few metachromatic cytoplasmic granules

■Prominent, large and variably shaped nucleoli

■Easily detected mitotic activity

■Extensive stromal remodeling

–Abundant , glassy collagen

–Pronounced tissue edema

–Areas with scant neoplastic cells.

Feline mast cell tumors (Fig. 7.20)

•One of the most common skin tumors of cats

•Occur anywhere on the skin, with neither predilection for, nor specific characteristic appearance or behavior in, the periocular region

•Primary feline mast cell tumors are typically small and occur in the dermis. Morphologically, they resemble the grade 1 mast

*

A B

Figure 7.16  Canine sweat gland adenoma. (A) Photomicrograph of a solid tumor with numerous glandular lumina

(*). (B) Higher magnification, of the tumor depicted in (A), showing the glandular structures. (C) Cystic tumor with papillary epithelial structures (arrow). (D) In this fully differentiated tumor the sweat glands are markedly dilated (*).

Figure 7.17  Feline sweat gland tumor. Photomicrograph showing a solid tumor with small glandular lumina (*) and other areas that are more cystic (arrow).

cell tumor of dogs, but there is no grading system for feline mast cell tumors

•These tumors often recur at other sites, and visceral involvement (spleen, liver, bone marrow), although less common than cutaneous involvement, is more likely than with canine mast cell tumors

•The ‘histiocytic’ subtype occurs in younger cats and is rare

■‘Histocytic’ feline mast cell tumors are composed of neoplastic cells with abundant cytoplasm and few

cytoplasmic granules, that are difficult to recognize as mast cells.

Epitheliotropic lymphoma (mycosis fungoides) of the eyelid skin (Fig. 7.21)

There are 10 cases of epitheliotropic lymphoma involving the eyelid skin in the COPLOW collection.

•Epitheliotropic lymphoma (mycosis fungoides) of the

eyelid has been reported to resemble blepharo-conjunctivitis in dogs

•This tumor is, characteristically, a T-cell lymphoma arising in the dermis. The hallmark of this form of lymphoma is the invasion of the epidermis and/or follicular epithelium by neoplastic cells, often aggregated in clusters referred to as Pautrier’s microabscesses.

Peripheral nerve sheath tumors (PNST) in cats (Fig. 7.22)

There are 25 cases in the COPLOW archive, representing 1% of feline ocular tumors.

•The feline eyelid appears to be particularly at risk for developing this tumor

•The designation of PNST is based on recognition of a characteristic morphologic and immunohistochemical appearance:

■This is a low grade (usually grade 1) spindle cell tumor with features of Antoni A or Antoni B cellular organization

–The Antoni A cellular pattern is characterized by spindle cells arranged in such a way that the nuclei line up to make rows or palisades, leaving adjacent areas free of nuclei

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