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Journal of comparative pathology2026; 225; 1-3; doi: 10.1016/j.jcpa.2026.01.012

Clear cell squamous cell carcinoma in the third eyelid of a horse.

Abstract: Squamous cell carcinoma (SCC) is the most common ocular and periocular neoplasm of horses, typically arising from the limbus, third eyelid mucosa or mucocutaneous junctions of the upper and lower eyelids. Tumours are locally invasive, prone to recurrence and may rarely metastasize. Histological evaluation is required for definitive diagnosis and atypical SCC subtypes may be diagnostically challenging. Here we describe a clear cell SCC in the third eyelid of a 16-year-old female Quarter Horse. The red and invasive mass was surgically excised for histological evaluation. The lesion consisted of a poorly demarcated, exophytic proliferation of neoplastic cells arranged in lobules supported by a scant stroma. Neoplastic cells had round, mostly clear cytoplasm with distinct cell borders and round to oval nuclei with coarse chromatin and a prominent nucleolus. Squamous differentiation was observed throughout. The mitotic count was 23 in 2.37 mm (equivalent to 10 FN22/ × 40 fields). There was one area of vascular infiltration by neoplastic cells. Dysplastic epithelial plaques were observed in the adjacent third eyelid mucosa. Most neoplastic cells had no cytoplasmic staining with periodic acid-Schiff reaction and were negative for mucus and lipid using Mayer mucicarmine and Sudan IV stains, respectively. A mild degree of submucosal elastosis was observed using Verhoeff-van Gieson stain. Neoplastic cells had widespread, robust cytoplasmic labelling for pancytokeratin (AE1/AE3). Ocular or periocular clear cell SCCs have not been previously reported in domestic animals.
Publication Date: 2026-02-04 PubMed ID: 41643487DOI: 10.1016/j.jcpa.2026.01.012Google Scholar: Lookup
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Summary

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Overview

  • This study reports on a rare case of clear cell squamous cell carcinoma (SCC) found in the third eyelid of a horse, which is a unique subtype of a common eye tumor in equines.
  • The tumor was surgically removed and analyzed histologically to understand its characteristics, and it represents the first documented case of clear cell SCC in the eye region of a domestic animal.

Background Information

  • Squamous cell carcinoma (SCC) is the most frequent tumor affecting the eyes and surrounding areas of horses.
  • Typical locations for SCC in horses include the limbus (the border area between the cornea and the sclera), the third eyelid mucosa, and the mucocutaneous junctions of the upper and lower eyelids.
  • SCC tumors are locally invasive, have a tendency to recur, and although rare, they can metastasize (spread to other parts of the body).
  • Definitive diagnosis of SCC requires a histological examination due to the possibility of atypical tumor subtypes that can be diagnostically challenging.

Case Description

  • The subject was a 16-year-old female Quarter Horse presenting with a red, invasive mass on the third eyelid.
  • The tumor was surgically excised for further pathological examination.

Histological Findings

  • The tumor appeared as a poorly defined, outward-growing proliferation of cancerous cells arranged in lobules with minimal supporting stromal tissue.
  • Neoplastic cells demonstrated clear (mostly transparent) cytoplasm with sharp cell borders, round to oval nuclei, coarse chromatin, and a prominent nucleolus, indicating a distinctive clear cell morphology.
  • Squamous differentiation was evident throughout the mass, meaning the tumor cells showed characteristics typical of squamous (skin-like) cells despite the clear cell appearance.
  • The mitotic count (number of cells undergoing division) was high, measured as 23 mitoses in an area of 2.37 mm², suggesting active tumor proliferation.
  • There was one observed area where cancer cells had infiltrated blood vessels, which is indicative of potential for metastasis.
  • Dysplastic epithelial plaques, which are abnormal precancerous lesions, were found adjacent to the tumor on the third eyelid mucosa.

Special Staining and Immunohistochemical Results

  • Most tumor cells lacked cytoplasmic staining with the periodic acid-Schiff (PAS) reaction, indicating a lack of certain carbohydrates typically found in some cell types.
  • Cytoplasmic staining tests for mucus (using Mayer mucicarmine stain) and lipids (using Sudan IV stain) were negative, ruling out the presence of mucus or fat in the cells.
  • There was a mild increase in submucosal elastosis (abnormal elastic fiber accumulation beneath the mucosa) detected using Verhoeff-van Gieson stain.
  • Immunohistochemistry showed strong cytoplasmic labeling for pancytokeratin (AE1/AE3), confirming the epithelial origin of the tumor cells.

Significance of Findings

  • This clear cell variant of SCC has not been previously reported in the ocular or periocular regions of domestic animals, marking this as a novel clinical and pathological finding.
  • The case highlights the importance of comprehensive histological and immunohistochemical analysis in identifying rare tumor subtypes, which can influence diagnosis and treatment planning.
  • The presence of vascular infiltration and high mitotic activity underscores the tumor’s aggressive potential.

Conclusion

  • The researchers documented a rare case of clear cell squamous cell carcinoma in a horse’s third eyelid.
  • This tumor subtype shows distinct histological and staining characteristics that differ from typical SCC but retains squamous features.
  • The study provides valuable insights into equine ocular tumors and may aid veterinarians in recognizing and managing unusual SCC variants.

Cite This Article

APA
Rissi DR, Mendes RE. (2026). Clear cell squamous cell carcinoma in the third eyelid of a horse. J Comp Pathol, 225, 1-3. https://doi.org/10.1016/j.jcpa.2026.01.012

Publication

ISSN: 1532-3129
NlmUniqueID: 0102444
Country: England
Language: English
Volume: 225
Pages: 1-3
PII: S0021-9975(26)00019-8

Researcher Affiliations

Rissi, Daniel R
  • Athens Veterinary Diagnostic Laboratory, Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA. Electronic address: rissi@uga.edu.
Mendes, Ricardo E
  • Athens Veterinary Diagnostic Laboratory, Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.

MeSH Terms

  • Animals
  • Horses
  • Eyelid Neoplasms / veterinary
  • Eyelid Neoplasms / pathology
  • Female
  • Horse Diseases / pathology
  • Carcinoma, Squamous Cell / veterinary

Conflict of Interest Statement

Declaration of competing interest The authors declared no conflicts of interest in relation to the research, authorship or publication of this article.

Citations

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