Signalment (JPC #4066796): 12-year-old intact domestic shorthair cat.

HISTORY: This cat had corneal perforation of unknown duration, suspected cataracts, and suspected anterior lens luxation of the right eye (OD), and the eye was enucleated. Grossly, the right globe was 1.9 cm in nasolateral diameter, and had a white-tan, raised mass at 3-6 o'clock. On cut section, the mass was firm to slightly gritty and obscured the ciliary body and a portion of the iris. The lens was opaque and slightly irregular. The retina was detached, and the peripheral iris was irregular segmentally.

HISTOPATHOLOGIC DESCRIPTION: Eye: Within the anterior chamber, extending from the lens epithelium from a break in the lens capsule, extending partially circumferentially around the lens, and incorporating the detached atrophic retina is a well-demarcated, infiltrative, moderately cellular, unencapsulated, multilobulated neoplasm composed of neoplastic chondrocytes evenly dispersed within a light purple, multifocally mineralized chondroid matrix. In the center of the neoplastic lobules, chondrocytes are within lacunae, have a moderate amount of clear to highly vesiculated cytoplasm, and a round, pink nucleus with 1-3 prominent nucleoli. At the periphery of neoplastic lobules, neoplastic cells are more spindle to stellate with a moderate amount of wispy, amphophilic cytoplasm and an ovoid to elongate to stellate nucleus with finely stippled chromatin and 0-1 variably distinct nucleoli. Mitotic figures are predominantly within the peripheral spindle cell population and average 3 per 2.37mm². Lens fibers multifocally undergo marked subcapsular spindle cell metaplasia, mild subcapsular cartilaginous metaplasia, and mineralization. There is a multifocal fibrovascular membrane that is up to 100 µm thick, occasionally contains cholesterol clefts, and extends around the lens (retrolenticular membrane) to the ciliary body (cyclitic membrane). The neoplasm distorts the ciliary body and is unilaterally confluent with the iris, which is elevated, partially effaced, and adhered to the corneal endothelium (anterior synechia) by a membrane of loosely arranged collagen (pre-iridal fibrovascular membrane) and moderate numbers of lymphocytes, plasma cells, and pigment-laden macrophages. There is abundant clear space separating layers of the choroid (edema). The retina displays marked atrophy of all layers, most prominently of the inner retinal layers with cystic degeneration of the outer retinal layers. There is a small amount of subretinal proteinaceous exudate and hypertrophy of the retinal pigment epithelium. Both the posterior and anterior aspects of the iris distant to the neoplasm are covered by a thin fibrovascular membrane (post- and pre-irididal fibrovascular membrane). The pre-iridial fibrovascular membrane extends across and occludes the iridocorneal angle, and onto the corneal endothelium and contains moderate numbers of lymphocytes and fewer macrophages and plasma cells that infiltrate the edematous anterior aspect of the iris (uveitis). There is a central break in Descemet’s membrane (stria) with associated corneal thickening due to stromal infiltration with numerous lymphocytes, plasma cells, fewer macrophages, and melanin-laden macrophages, and ingrowth of small caliber blood vessels (neovascularization). There is loss of clefting in the corneal stroma (edema). There is a thin fibrovascular membrane covering the corneal endothelium (retrocorneal fibrovascular membrane). There is diffuse vacuolation and hypertrophy of the corneal endothelium and mild hyperplasia of the corneal epithelium.

MORPHOLOGIC DIAGNOSIS:

Eye: Chondrosarcoma (post-traumatic ocular sarcoma).
Eye: Endophthalmitis, lymphoplasmacytic and histiocytic, multifocal, moderate with lenticular rupture, subcapsular fibrous, mineralization and chondroid metaplasia (cataract), fibrovascular membranes, synechia, and retinal detachment and atrophy.
Eye, cornea: Keratitis, lymphoplasmacytic and histiocytic, focally extensive, chronic, moderate, with corneal stria, pigmentation, fibrosis, edema and neovascularization.

ETIOLOGIC DIAGNOSIS/CONDITION: Feline post-traumatic ocular sarcoma (FPTOS); primary ocular sarcoma

GENERAL DISCUSSION:

Feline posttraumatic ocular sarcoma (FPTOS), first recognized as a condition in 1990, is the second most common primary ocular neoplasm in cats
FPTOS is nearly unique to cats, however, there 2 recent case reports in rabbits and one in a calf
FPTOS can be highly invasive with extension along the optic nerve or peripheral nerve to the brain being common; local orbital recurrence following enucleation is common, and distant metastasis may occur (up to 60% of cases)

PATHOGENESIS:

Ocular trauma (especially penetrating injury) or severe ocular disease is the presumed initiating event, followed by a period of dormancy that typically lasts multiple years (average 5-7 years)
The neoplasm is believed to arise from a malignant transformation of lens epithelial cells because:
1. Lens capsule rupture is noted in almost all cases, whereas it is rarely present in other non-FPTOS large ocular tumors
2. Neoplasms are initially centered on the lens
3. Some neoplasms are immunoreactive for lens structural protein crystalline α, less often are immunoreactive for smooth muscle actin (SMA, which lens epithelium can express in diseased states such as cataracts), and occasionally express cytokeratin (which may reflect the origin of the lens epithelium from surface ectoderm, although cytokeratin expression is usually lost during embryogenesis)
4. Neoplastic cells multifocally deposit lens capsule/basement membrane-type material

TYPICAL CLINICAL FINDINGS:

FPTOS typically occurs in cats with a prior history of severe ocular disease
Tumors typically demonstrate a long latency period (range 2 months to >10 years), with an average of 5-7 years

TYPICAL GROSS FINDINGS:

Most neoplasms are recognized late in the disease process when the globe is almost filled by the neoplasm, the lens may be collapsed, and the neoplasm may extend into the sclera and/or optic nerve

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Cellular morphology: Features vary from fibrosarcoma to osteosarcoma to giant cell tumor (even within the same eye) - most appear to be fibrosarcomas
1. Neoplastic cells are typically spindloid with severe pleomorphism, a high mitotic count, +/- multinucleate cells
2. There is a less common FPTOS variant composed of pleomorphic round cells that may closely resemble pleomorphic lymphoma – in many cases, neoplastic cells express both B- and T-cell markers
Progression:
1. Early: Streams of spindle cells bordering lens in the area of capsule rupture
2. Progresses to spindle cells lining the uveal tract (especially choroid) ->
  - The inclination to “line the globe” is a repeatable feature to distinguish primary ocular sarcoma (FPTOS) from metastatic sarcomas (rare)
3. Later: Neoplasm effaces the uvea +/- extension into the sclera and/or optic nerve
Neoplastic cells may be separated by basement membrane-type material; occasional neoplasms may have osteoid and/or chondroid deposition
Lens: The lens is often ruptured; advanced cases may only have remnant lens capsule fragments

ADDITIONAL DIAGNOSTIC TESTS:

Immunohistochemistry/histochemistry:
1. Vimentin (almost 100%)
2. +/- Lens structural protein crystalline αA (33%)
3. +/- Smooth muscle actin (SMA, ~20%)
4. +/- Broad spectrum cytokeratin (~15%)
5. Matrix material: PAS positive, type IV collagen immunoreactive

DIFFERENTIAL DIAGNOSIS:

Feline intra-ocular neoplasms:

Feline diffuse iris melanoma (S-N02) is the most common ocular neoplasm in cats and the eventual outcome is virtually always glaucoma
Tumors of ocular neuroectoderm: Iridociliary epithelial tumor (adenoma or carcinoma) (S-N03), medulloepithelioma, retinoblastoma (rare in veterinary medicine)
Intraocular chondrosarcoma, not related to trauma, has been documented very rarely in cats and rabbits; the tissue origin is unclear, possibly multipotent mesenchymal stem cells of the trabecular meshwork, cancer stem cells, or vascular pericytes; neoplastic cells are compressive rather than infiltrative, and there appears to be favorable survival rates following enucleation

COMPARATIVE PATHOLOGY:

Posttraumatic ocular sarcoma is almost exclusively a condition of cats
1. Post-traumatic ocular sarcomas are rare in animals but have been described in cats, rabbits, dogs and discus (fish)
2. FPTOS has similarities with feline vaccine associated sarcomas: Traumatic initiating event, long period of dormancy, and similar histologic characteristics; there is no known association between the two
Rabbit:
1. A recent review of rabbit oncology reported, among many other tumors, 4 cases (out of >1,200) of interocular neoplasm: 1 iridociliary adenocarcinoma, 1 iridal lymphoma, 1 round cell tumor, and 1 spindle cell tumor (suspicious for amelanotic melanoma); authors commented on historical cases of post-traumatic interocular sarcomas (Baum, Vet Pathol, 2021)
2. 1 case of interocular chondrosarcoma in an 8-year-old rabbit; there was no lens rupture, but there was serological evidence of Encephalitozoon cuniculi infection (hence possible lens-induced inflammation) (Mikiewicz, J Comp Path 2020)
Bovine: Post-traumatic intraocular leiomyosarcoma described in a calf with visceral metastasis; vimentin and alpha smooth muscle actin (+); origin may have been cells lining the pectinate ligament of the ciliary body (Kleinschmidt, J Comp Pathol. 2019)
Primary ocular neoplasms are most frequently reported in dogs and cats, and are inexplicably rare in other domestic species; most primary intra-ocular neoplasms have negligible metastatic potential
Metastatic ocular neoplasms are not uncommon; with the exception of malignant lymphoma, carcinomas are reported more frequently than sarcomas

REFERENCES:

Baum B. Not Just Uterine Adenocarcinoma-Neoplastic and Non-Neoplastic Masses in Domestic Pet Rabbits (Oryctolagus cuniculus): A Review. Vet Pathol. 2021;58(5):890-900.
Kleinschmidt S, Mammen S, Puff C. Post-traumatic intraocular leiomyosarcoma in a domestic bovine calf (Bos primigenius taurus). J Comp Pathol. 2019; 168:41-45.
Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1420-1421.
Mikiewicz M, Pazdzior-Czapula K, Gesek M, et al. Intraocular chondrosarcoma in a rabbit. J Comp Pathol. 2020; 179:41-44.
Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. St. Louis, MO: Elsevier Inc; 2016:459, 486-488.
Young KM, Teixeira LBC. Eyes and Associated Structures. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:155.