JPC SYSTEMIC PATHOLOGY
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, globe: Within the anterior chamber, extending from the lens epithelium, adherent to the fragmented lens capsule, infiltrating the choroid, 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 blue partially 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 a prominent nucleolus. At the periphery of neoplastic lobules, neoplastic cells are more spindled to stellate with a moderate amount of vesicular amphophilic cytoplasm, an ovoid to elongate 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 10 40x HPF (2.37mm2). The cartilaginous matrix contains foci of mineralization. The neoplasm adheres to a break in the lens capsule and extends partially circumferentially around the lens. Lens fibers multifocally undergo marked subcapsular spindle cell metaplasia, mild subcapsular cartilaginous metaplasia, and mineralization. There is a multifocal thin prelenticular fibrous membrane that is up to 250um thick and extends around the lens and extends to the ciliary body (cyclitic membrane). The neoplasm distorts the ciliary body and is unilaterally confluent with the iris which is elevated 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. The neoplasm extends under (external to) the ciliary body and into the choroid and along a detached segment of retina; 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 pigmented epithelium. The anterior aspect of the iris distant to the neoplasm is covered by a thin fibrovascular membrane (pre-iridal fibrovascular membrane) that extends across and occludes the iridocorneal angle, and onto the corneal endothelium. This fibrovascular membrane contains moderate numbers of lymphocytes and fewer macrophages and plasma cells that infiltrate the edematous anterior aspect of the iris. There is a central break in Descemet’s membrane 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 diffuse vacuolation and hypertrophy of the corneal endothelium and mild hyperplasia of the corneal epithelium.
- Eye, globe: Chondrosarcoma (post-traumatic ocular sarcoma).
- Eye, lens: Lenticular rupture with subcapsular fibrous and chondroid metaplasia.
- Eye, cornea: Keratitis, lymphoplasmacytic and histiocytic, focally extensive, chronic, moderate, with Descemet’s membrane rupture.
ETIOLOGIC DIAGNOSIS/CONDITION: Feline post-traumatic ocular sarcoma (FPTOS); primary ocular sarcoma
- Feline posttraumatic ocular sarcoma (FPTOS), first recognized as a condition in 1990, is the second most common primary ocular neoplasm in cats according to one primary source, and the third most common according to another
- FPTOS can be highly locally invasive, extension along the optic nerve or peripheral nerve to the brain is common, local orbital recurrence following enucleation is common, and distant metastasis may occur
- 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:
- Lens capsule rupture is noted in almost all cases, whereas it is rarely present in other non-FPTOS large ocular tumors
- Neoplasms are initially centered on the lens
- Some neoplasms are immunopositive for lens structural protein crystalline αA, less often are immunopositive for smooth muscle actin (SMA, which lens epithelium can express in diseased states such as cataracts), and occasionally express cytokeratin (this may reflect the origin of the lens epithelium from surface ectoderm, although cytokeratin expression is usually lost during embryogenesis)
- 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:
- Initially, the tumor tends to surround the lens (especially in the area of lens capsule rupture or wrinkled lens capsule), then lines the inside of the eye (especially the choroid); the inclination to “line the globe” is a repeatable feature that is useful in distinguishing primary ocular sarcoma (FPTOS) from rare metastatic sarcomas, and eventually the highly infiltrative neoplasm effaces the uvea +/- extension into the sclera and/or optic nerve
- Cellular morphology: features vary from fibrosarcoma to osteosarcoma to giant cell tumor (even within the same eye); typically, neoplastic cells are spindle with severe pleomorphism, a high mitotic index, and multinucleate cells may be present
- Matrix: Individual neoplastic cells or segments of individual neoplastic cells may be separated by basement membrane-type material, and a small percentage of neoplasms have osteoid and/or chondroid material deposition
- Lens: The lens is often ruptured, and in advanced cases there may only be remnant lens capsule fragments
- Infiltration: extension beyond the sclera is a poor prognostic indicator, optic nerve involvement is a poor prognostic indicator, intracranial extension along the optic nerve and rare metastasis have been described (present in up to 60% of cases according to one source)
- Vimentin (almost 100%)
- +/- Lens structural protein crystalline αA (33%)
- +/- Smooth muscle actin (SMA, ~20%)
- +/- Broad spectrum cytokeratin (~15%)
- Matrix material: PAS positive, type IV collagen immunoreactive
- There are three morphological variants of FPTOS, all of which tend to line the inner aspect of the globe:
- Spindle cell variant: lens epithelium derived, 70% of FPTOS
- Round cell variant: cells are pleomorphic and express both T- and B-lymphocyte markers and may represent post-traumatic/chronic inflammatory lymphoma, 24% of FPTOS; this tumor is more likely to be effacing than the spindle cell variant and is less likely to line the inner aspect of the globe; it may extend beyond the sclera but is less likely to infiltrate the optic or peripheral nerves; there is often extensive necrosis with peritheliomatous growth pattern; cells are not immunoreactive for vimentin, SMA, or cytokeratin
- Osteosarcoma/chondrosarcoma variant: 6% of FPTOS; similar features to the spindle cell variant with the addition of chondroid, cartilaginous, and/or osteoid material
- 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; 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
- Posttraumatic ocular sarcoma is almost exclusively a condition of cats, with two reports described in rabbits (both rabbits were negative for cuniculi and bacterial infection via histochemical staining and PCR)
- FPTOS has similarities with feline vaccine associated sarcomas: traumatic initiating event, long period of dormancy, and similar histologic characteristics
- 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
- Beckwith-Cohen B, Teixeira LBC, Dubielzig RR. Presumed primary intraocular chondrosarcoma in cats. J Vet Diag Invest. 2014; 26(5):664-668.
- Dubielzig RR, Everitt J, Shadduck JA, Albert DM. Clinical and morphologic features of post-traumatic ocular sarcomas in cats. Vet Pathol. 1990; 27(1):62-65.
- Dubielzig RR. Non-surgical trauma. In: Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Veterinary Ocular Pathology, a Comparative Review. Philadelphia, PA:Elsevier; 2010:81-114.
- Labelle P. The eye. In: Zachary JF, Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Inc; 2016:1303-1304, 1306.
- Morrison WB, Starr RM. Vaccine-associated feline sarcomas. J Am Vet Med Assoc. 2001; 218:697-702.
- McPherson L, Newman SJ, McLean N, McCain S, et al. Intraocular sarcomas in two rabbits. J Vet Diagn Invest. 2009(4); 21:547-551.
- Lin H, Ouyang H, Zhu J, Huang S, et al. Lens regeneration using endogenous stem cells with gain of visual function. Nature. 2016; 531:323-328.
- 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; 2016:478-488.
- Zeiss CJ, Johnson EM, Dubielzig RR. Feline intraocular tumors may arise from transformation of lens epithelium. Vet Pathol. 2003; 40(4):355-362.