JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
SIGNALMENT (AFIP # 2051261): Tissue from a 9-year-old ox
- Conjunctiva: Arising from the mucosal epithelium, effacing the subepithelial connective tissue and extending to all margins is an unencapsulated, densely cellular, infiltrative neoplasm composed of polygonal cells arranged in islands, cords, and anastomosing trabeculae a moderately dense fibrovascular stroma. Neoplastic cells mature in an disorganized manner which multifocally includes a granular cell layer and neolastic cells occasionally surround concentric lamellations of keratin (keratin pearls). Neoplastic cells have variably distinct cell borders, a moderated amount of eosinophilic cytoplasm which is often vacuolated, round to oval nuclei with coarsely clumped chromatin, up to three multifocally distinct nucleoli, and a mitotic rate of 2 per 10 HPF. Neoplastic cells exhibit widespread scattered individual cell necrosis. Many lymphocytes, plasma cells, macrophages and neutrophils admixed with hemorrhage, fibrin, and edema diffusely infiltrate the fibrovascular stroma and extend into the superficial conjunctival subepithelial connective tissue. There are large areas of necrosis often associated with the keratinized surface, and multifocally few vessels contain fibrin thrombi. Focally the epithelium is eroded or ulcerated and replaced by a serocellular crust, and subepithelial lymphatics are diffusely dilated.
- Lymph node, site unspecified: No significant lesions.
- Conjunctiva: Squamous cell carcinoma, breed unspecified, bovine.
- Lymph node, site unspecified: No significant lesions.
- Squamous cell carcinoma arises from the conjunctival epithelium of the limbus, nictitating membrane, or eyelid in cattle, horse, cat, and dog, in that order of frequency
- BOSCC is the most common and economically important neoplasm of North American cattle
- Etiology is multifactorial; predisposing factor is lack of periocular pigment (Hereford breed); incidence increases with age and exposure to ultraviolet light; Bos taurus cattle are more often affected than are Bos indicus
- Metastatic or invasive potential has not been correlated with histologic criteria, but there is a correlation between site of origin and subsequent behavior; parotid lymph node initial site of metastasis; intraocular invasion is uncommon
- Site of origin (order of precedence):
- Bulbar conjunctiva of the limbus (70% of all occurrences)
- Nictitating membrane
- Palpebral conjunctiva of the true eyelid
- Ultraviolet light (wavelength B) induces cutaneous neoplasia through genomic damage through the formation of pyrimidine dimers in DNA; an attempt to repair this damage occurs through nucleotide excision repair (NER), but when NER is overwhelmed, some DNA escapes repair, leading to transcriptional errors and neoplasia
- Ocular SCC in all species develops through a series of premalignant stages: epidermal plaque (acanthosis) > keratoses (localized focal hyperkeratosis) > papilloma (before malignant transformation over months or years) > dysplasia > carcinoma in situ > SCC
- Thus so far no viral particle or viral genome has been demonstrated in ocular SCC
- Spontaneous regression of precancerous lesions may occur an estimated 25-50% of the time; rarely, ocular SCC regresses spontaneously
- Systemic metastasis occurs late, and local invasion may be aggressive
- Associated with increased p53 immunohistochemical staining
TYPICAL CLINICAL FINDINGS:
- In general, premalignant squamous cell tumors are small, white, and elevated with hyperplastic plaques or papilloma-like structures; in contrast, malignant tumors are more irregular, nodular, pink, erosive, and are often necrotic
- The bulbar conjunctiva at the limbus is the most frequent site of origin in cattle
TYPICAL GROSS FINDINGS:
- Variably sized, poorly demarcated, firm, white, nodular, papillary, plaque-like, or crateriform masses that are often ulcerated and red
- Neoplasm may protrude through the palpebral fissure; invade anterior chamber; infiltrate entire globe; secondary changes of hemorrhage, necrosis, ulceration and inflammation are present in more than 40% of invasive carcinomas
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Tumor cells breach the basement membrane (only absolute proof of malignancy) to form islands, cords, and trabeculae within the subepithelial connective tissue and are usually contiguous with the overlying epidermis
- Tumor cells have vesicular nuclei with one or multiple very prominent nucleoli; cytoplasm is typically abundant and eosinophilic
- Tumor cell invasion is usually associated with marked desmoplasia; mitotic figures are often numerous and in proportion with the degree of anaplasia
- Range from well-differentiated carcinoma with prominent intercellular bridges and keratin pearl formation (concentric lamellae of keratin) to anaplastic carcinoma; poorly differentiated tumors may only show keratinization of individual cells
- Marked lymphoplasmacytic infiltration may be present
- Progression of histologic lesions in the development of SCC:
- Epidermal plaque: marked acanthosis with variable keratinization and dyskeratosis, and epidermal down-growth into subconjunctival connective tissue
- Papilloma: acanthosis, parakeratosis and hyperkeratosis with papillary projections supported by vascularized connective tissue core
- Carcinoma in situ: increasing dysplastic cell nests in deeper layers of plaques or papillomas
- Carcinoma: squamous cell invasion across the basement membrane; often accompanied by lymphocytic-plasmacytic infiltration
- Epidermal plaque - single or multiple; opaque or gray/white; raised; variable shape; smooth or irregular surface
- Papilloma - sessile or pedunculated mass that is an exophytic growth of papillary projections; merges with underlying plaque
- Carcinoma in situ (noninvasive carcinoma) resembles the papilloma grossly
- Epidermal plaque - epithelial hyperplasia with atypia, marked acanthosis, variable hyperkeratosis, dyskeratosis, and epidermal downgrowth into subconjuctival connective tissue; no invasion through basement membrane
- Papilloma - multiple papillary projections (fronds) that are covered by hyperplastic and hyperkeratotic epithelium and supported by a vascularized connective tissue core; there is marked para-and hyperkeratosis
- Carcinoma in situ arises by focal or multifocal transformation of dysplastic cell nests in the deep layers of plaques or papillomas; there is lack of invasion across the basement membrane
- Horses: Ocular SCC is common, especially in horses with unpigmented palpebrae; in contrast to cattle, SCCs in horses arise most commonly at the edge of the third eyelid followed by limbic bulbar conjunctiva; bilateral involvement is seen in 15-20% of the reported cases of SCC; approximately 10-15% of equine SCC has regional to distant spread; most common in paints and quarter horses
- Dogs - SCC infrequently involves the eye; SCC accounts for approximately 2% of ocular neoplasms
- Cats - Ocular SCC is rare and often affects skin of the eyelid
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