Suspected malignant transformation of B lymphocytes in the equine cornea from immune-mediated keratitis.
Abstract: To describe clinical, in vivo confocal microscopic, histopathologic, polymerase chain reaction assay for antigen receptor rearrangement (PARR) and immunohistochemical features of a horse with suspected malignant transformation of corneal B lymphocytes in immune-mediated keratitis (IMMK) and to also report surgical management and adjunctive treatment including topical and radiation therapies. Methods: A 15-year-old Oldenburg gelding was examined for presumptive progressive stromal IMMK of the right eye which became refractory to medical management. Corneal in vivo confocal microscopy revealed a marked infiltration of neovascularization, leukocytes, and dendritic cells. Superficial keratectomy was performed. Histopathologic and immunohistopathologic abnormalities of the cornea were restricted to the anterior and mid-stroma and included sheets of medium-size atypical lymphocytes which stained positively for CD79a and CD20 and also demonstrated clonal rearrangements of immunoglobulin heavy chain 2 (IGH2) and 3 (IGH3) confirming B-cell lymphoma. Complete physical examination, complete blood count, serum chemistry, thoracic radiographs, and thoracic ultrasound were performed. No evidence of systemic metastasis was found. Adjunctive local therapy included topical dexamethasone, mitomycin C, and radiation therapy using electronic surface brachytherapy. Follow-up at 16 months revealed a lack of corneal infiltrate and progressive clearing of corneal fibrosis and superficial pigment. Conclusions: This case represents a unique presentation of primary corneal lymphoma in the horse. Tumor development was associated with chronic IMMK and chronic topical anti-inflammatory therapy. Surgical excision with adjunctive therapy using mitomycin C and electronic surface brachytherapy was well tolerated and considered curative. Future immunohistochemistry and PARR will be important in characterizing the IMMK syndrome and its variations.
© 2015 American College of Veterinary Ophthalmologists.
Publication Date: 2015-04-28 PubMed ID: 25919039DOI: 10.1111/vop.12275Google Scholar: Lookup
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Summary
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This study discusses a rare case of B-cell lymphoma in a horse’s eye. The horse, which had been suffering from immune-mediated keratitis (an inflammation of the cornea), underwent a range of diagnostic and treatment procedures, from confocal microscopy to physical examination to histopathology. Researchers confirmed the presence of lymphoma and, after ruling out systemic metastasis, administered a combination of surgical and local therapies. Sixteen months after the interventions, the horse’s condition showed significant improvement.
Background and Case Overview
- This case study involves a 15-year-old Oldenburg gelding (a type of horse) diagnosed with immune-mediated keratitis (IMMK) – which is an inflammation of the cornea – in its right eye.
- The condition was progressive, meaning it was worsening over time, and had become resistant to medical treatment.
- Via in vivo confocal microscopy, a type of advanced imaging technique, the researchers observed that the cornea had severe encroaching of new blood vessels, and was heavily populated by leukocytes (white blood cells) and dendritic cells.
Diagnostic Procedures and Findings
- The horse underwent a surgical procedure known as superficial keratectomy – the removal of the outer layer of the cornea.
- Upon examining the tissue thus removed, the researchers found that the cornea displayed histopathologic and immunohistopathologic abnormalities, specifically in the front and middle layers of the cornea’s tissue (anterior and mid-stroma).
- The abnormalities were characterised by clusters of unusually large lymphocytes that tested positive for CD79a and CD20 – markers of B lymphocytes, a type of white blood cell.
- These lymphocytes also demonstrated clonal rearrangements of immunoglobulin heavy chain 2 (IGH2) and 3 (IGH3), which confirmed the diagnosis of B-cell lymphoma, a type of cancer.
Treatment and Outcomes
- After confirming that the cancer had not spread systemically, the treatment team administered a series of topical drugs, including dexamethasone (a steroid) and mitomycin C (a chemotherapy drug) to the eye.
- They also employed radiation therapy using electronic surface brachytherapy – a type of radiation therapy that uses an electronic source.
- 16 months following treatment, the horse’s cornea no longer showed signs of infiltration and demonstrated progressive reduction of corneal fibrosis (growth of excess tissue) and superficial pigment.
Conclusions and Future Directions
- This single case presented a unique instance of primary corneal lymphoma in a horse.
- The researchers suggest that the chronic IMMK and the long-term anti-inflammatory therapy may have triggered this unique malignancy.
- They also conclude that the combination of surgical resection and adjunctive therapy with mitomycin C and electronic surface brachytherapy proved to be successful and well-tolerated.
- The researchers expect that future applications of immunohistochemistry and tests such as PARR will help better understand IMMK syndrome and its variants.
Cite This Article
APA
Vallone LV, Neaderland MH, Ledbetter EC, Dubielzig RR.
(2015).
Suspected malignant transformation of B lymphocytes in the equine cornea from immune-mediated keratitis.
Vet Ophthalmol, 19(2), 172-179.
https://doi.org/10.1111/vop.12275 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Animal Eye Clinic, 123 West Cedar Street, Norwalk, CT, 06854, USA.
- Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, 14853, USA.
- Department of Pathological Sciences, College of Veterinary Medicine, University of Wisconsin, Madison, WI, 53706, USA.
MeSH Terms
- Animals
- B-Lymphocytes
- Cell Transformation, Neoplastic
- Chronic Disease
- Horse Diseases / immunology
- Horse Diseases / pathology
- Horses
- Keratitis / immunology
- Keratitis / pathology
- Keratitis / veterinary
- Lymphoma, B-Cell / pathology
- Lymphoma, B-Cell / veterinary
- Male
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