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

END-STAGE DISEASE (ATROPHY OF THE

GLOBE AND PHTHISIS BULBI) (Fig. 5.25)

Many of the consequences of trauma to the globe result in a proliferative response which extends into the anterior and posterior chambers and the vitreous body, and this may be accompanied by tissue atrophy.

•Cell types that participate in the proliferative response include:

■Corneal endothelium and deep corneal stromal cells

■Ciliary body epithelial cells

■Vascular endothelial cells and spindle cells from the anterior iris, posterior iris, ciliary body, or choroid

■Vascular endothelial cells or spindle cells associated with the optic nerve head

•It is noteworthy that the proliferative response in the globe seldom causes pronounced distortion or fibrosis of the uvea itself.

■Tissue proliferation within ocular compartments and chambers can undergo contracture, a feature of granulation tissue throughout the body

•Contracture of the proliferating tissues of the globe, in combination with a failure to produce aqueous humor leads to

atrophy and shrinkage of the globe. Often, this shrinkage of the globe is accompanied by disorganization and distortion of ocular tissues, and is termed ‘phthisis bulbi’

•Other effects often seen are mineralization and osseous metaplasia.

Comparative Comments

Phthisis bulbi in the human consists of shrinkage, atrophy, and degeneration similar to that seen in animal eyes.

Feline post-traumatic ocular sarcoma (FPTOS) (Figs 5.26–5.37)

This malignant neoplasm is the third most common intraocular tumor in cats in the COPLOW collection, with 234 diagnosed. There are three morphological variants of FPTOS, all of which tend to line the inner aspect of the globe:

1.Spindle cell variant (lens epithelial cell-derived): 70% (Fig. 5.26)

2.Round-cell variant (B-cell lymphoma): 24% (Fig. 5.27)

3.Osteosarcoma/chondrosarcoma: 6% (Fig. 5.28).

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Spindle cell variant FPTOS (Figs 5.26 and 5.29–5.33)

Of the FPTOS cases in the COPLOW collection, 70% are spindle cell variant.

•Epizootiologic features of spindle cell variant FPTOS:

■This neoplasm typically occurs in cats with a prior history of severe ocular disease

■The tumors typically demonstrate a long latency period after the initiating injury, but can be recognized from 2 months (rare) to more than 10 years (common) after a traumatic injury. The average time between a traumatic event and enucleation for FPTOS is 7 years

■Almost all cases have histologically identified lens capsule rupture

■Only about 20% of cases submitted to COPLOW have a history that documents a known traumatic incident, but many of the cats reportedly had abnormal eyes when acquired as kittens or as adopted adults

•Morphologic features of spindle cell variant FPTOS (Fig. 5.29):

■Distribution in the globe

–There is generally extensive involvement of the tissues of the globe, with infiltration of the iris, ciliary body, peripheral cornea, and the atrophic remnants of retinal tissue

–Tumors tend to line the inner aspect of the choroid internal to the choriocapillaris

–Tumors may infiltrate the sclera, peripheral nerve tissue and the optic nerve

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–Tumors that are sampled at a relatively early stage in the neoplastic process occur adjacent to the wrinkled lens capsule

•Cellular features of spindle cell variant FPTOS (Fig. 5.30):

■These are pleomorphic, mesenchymal neoplasms, with cellular features that can range from fusiform spindle cells to polygonal cells, with marked anaplastic features

■About 10% of tumors have prominent multinucleate giant cells with large numbers of nuclei. The phenotype of these giant cells differs from that of the main population of neoplastic cells, in that:

–Their nuclear profile is not as anaplastic

–They do not demonstrate positive intranuclear p53 antigen staining even when all the surrounding cells do (Fig. 5.31)

–Many tumors have at least some localized areas where PAS-positive staining, suggestive of thick basement membranes, surrounds individual tumor cells, or segments of individual tumor cells

•Immunohistochemical features of spindle cell FPTOS (Fig. 5.32)

■Neoplastic cells may be positively immuno-labeled with the following immuno-histochemical markers:

–Vimentin, in almost 100% of affected eyes

–Smooth muscle actin, in about 20% of affected eyes

–Broad spectrum cytokeratin, in about 15% of affected eyes

–Alpha A Crystallin, in about 33% of affected eyes

–The PAS-positive extra-cellular matrix labels positively for collagen type IV, which is characteristic of basement membrane/basal lamina

•Features that support a lens epithelial origin for FPTOS:

■Lens capsule rupture is almost universally present in affected cats

■In large tumors other than FPTOS, lens capsule rupture is only occasionally observed

■Early tumors develop around the lens (Fig. 5.33)

■The presence of lens capsule-like basement membrane surrounding the neoplastic cells in at least some areas of many of these tumors.

■Positive labeling of alpha A crystallin in some tumors

•Prognosis

■Spindle cell variant FPTOS can be highly locally invasive, with extension into optic nerve, peripheral nerve and through the sclera into the orbital soft tissues

■Local orbital recurrence is common following enucleation.

■Extension along the optic nerve or peripheral nerve to the brain is common.

■Distant metastasis may occur, but its incidence is unknown

■One should carefully evaluate the specimen, attempting to gather evidence of prognostic value:

–Evidence of extension beyond the sclera indicates a poor prognosis. The prognosis appears to be better if the tumor is confined within the globe

–A careful evaluation of the optic nerve should be made, including examination of the portion of the nerve farthest away form the globe. Evidence of optic nerve involvement carries a poor prognosis.

Round-cell variant FPTOS (Figs 5.27 and 5.34)

There are 54 cases of round-cell variant FPTOS in the COLPOW collection, representing 24% of the total FPTOS cases. The round-cell variant is also associated with longstanding ocular disease, and the vast majority have lens capsule damage. However, there are a few cases in the collection where the lens is either intact or had been previously removed

•Morphologic features of round-cell variant FPTOS (Fig. 5.34):

■Distribution in the globe

–The round-cell variant also fills the globe, but the tumor is much more likely to be effacing than the spindle cell variant, and is less likely to line the inner aspect of the globe

–The round-cell variant may extend beyond the sclera, but does not infiltrate deeply into the optic nerve or peripheral nerves

•Cellular features of round-cell variant FPTOS:

■Typically there is extensive tumor necrosis, with viable neoplastic cells surviving around blood vessels

■This neoplasm lacks a rich blood supply

■The neoplastic cells are predominantly pleomorphic round-cells, with a large nucleus-to-cytoplasm ratio, hyperchromatic nuclear features, and abundant mitoses

•Immunohistochemical features of round-cell variant FPTOS:

■These tumors are not positively labeled for vimentin, smooth muscle actin, or cytokeratin

■They stain with a complex staining pattern and are not easily categorized as T-cell or B-cell lymphoma.

•Prognosis

■Insufficient follow-up information is available to allow accurate prognostication

■Local recurrence and systemic spread are both seen, but the features that are predictive of a poor prognosis have not been elucidated

■Primary ocular or systemic lymphoma

–Lymphoma in feline globes is often seen in conjunction with inflammation. It is likely that the round-cell variant of feline post-traumatic sarcoma represents an example of lymphoma developing in association with the chronic inflammation that may ensue following trauma to the globe.

Post-traumatic osteosarcoma and/or chondrosarcoma Figs 5.28 and 5.35)

There are 29 cases of osteosarcoma or chondrosarcoma FPTOS in the COLPOW collection representing 10% of the total FPTOS cases.

•Morphologic features of FPTOS-osteosarcoma type (Figs 5.35, 5.36):

■The distribution of tumor is diffuse within the globe

■All cases have lens rupture

■Features suggestive of lens epithelial cell origin are variably present

■The tumor may demonstrate areas of chondromatous differentiation or, as in four cases, contain only cartilaginous differentiation and no osteoid

•A lack of follow-up information makes it difficult to predict the biological and clinical behavior of these tumors.

Prophylactic enucleation of traumatized feline globes (Fig. 5.33)

Approximately 8% of feline globes in the COPLOW collection, where it could be determined that the globe was removed primarily for prophylactic reasons, had an early spindle cell variant FPTOS

•This percentage does not take into consideration the long latency period that often precedes the development of a clinically apparent neoplasm

•The prophylactic removal of feline globes with trauma and lens capsule rupture should be considered, particularly if vision has already been lost and long-term diligent monitoring is unlikely.