Pathology in Practice

Kendra M. Andrie Michigan State University Veterinary Diagnostic Laboratory, Lansing, MI 48910.

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Caroline E. Andrews Michigan State University Veterinary Diagnostic Laboratory, Lansing, MI 48910.
Frederick National Laboratory for Cancer Research, National Cancer Institute, 1050 Boyles St, Frederick, MD 21702.

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Janine Chapman VCA Portage Animal Hospital, 8037 Portage Rd, Portage, MI 49002.

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Dodd G. Sledge Michigan State University Veterinary Diagnostic Laboratory, Lansing, MI 48910.

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History

A 9-week-old male domestic shorthair cat was evaluated because of a bulging, proliferative lesion within the left orbit that had been present since the cat was adopted at the age of 8 weeks. The cat was reported to have been sneezing but was otherwise acting normally at home.

Clinical and Gross Findings

On physical examination, the cat was in adequate body condition (body condition score, 4.5/9) and was bright, alert, and responsive. No cardiac or pulmonary abnormalities were auscultated. Findings of an aural examination and abdominal palpation were unremarkable. The result of a test to detect circulating FeLV antigen and anti-FIV antibody was negative.

The left palpebral fissure was dramatically widened by a firm, tan, multilobulated mass that partially filled the orbit and displaced the globe caudally, resulting in lagophthalmos (Figure 1). The mass also extended into the bulbar conjunctiva, where it was dark red and tan, smoothly marginated, and adherent to the medial orbital rim. The globe was displaced caudally but was grossly normal, and the exposed conjunctiva was pink and moist. Excision of the mass with enucleation of the globe by a transconjunctival approach was elected. The globe and surrounding mass were placed in neutral-buffered 10% formalin and submitted to the Michigan State University Veterinary Diagnostic Laboratory for histologic examination.

Figure 1—
Figure 1—

Preoperative photograph of the head of a 9-week-old male domestic shorthair cat that was evaluated because of a bulging, proliferative lesion within the left orbit that had been present since the cat was adopted at the age of 8 weeks. In the left eye, a large, tan, firm, multilobulated mass has markedly expanded the third eyelid, displacing the globe caudally and preventing closure of the eyelids. The globe and orbital mass were subsequently removed.

Citation: Journal of the American Veterinary Medical Association 252, 10; 10.2460/javma.252.10.1223

The cat was evaluated 10 days after enucleation and mass excision, and all sutures were removed at this time. There was a firm swelling along the medial aspect of the orbit, consistent with granulation tissue at the excision site. This swelling contracted over the following 2 months, and no further complications were reported.

Gross Findings

On gross examination of the formalin-fixed specimens, the mass expanded the base of the third eyelid and adjacent inferior and nasal bulbar conjunctivae. The mass was approximately 2.0 × 2.0 × 1.5 cm, lobulated, pale tan, and semi-firm with few, poorly demarcated, darker tan to dark red areas; few cystic spaces; and occasional firm to hard foci. The mass did not extend into the eye, and no lesions were observed within the globe.

Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→

Histopathologic Findings

Histologically, the orbital mass and expanded portions of the third eyelid were composed of a multilobulated, highly cellular neoplasm with cells representing all 3 germ layers. The neoplasm included foci of haired skin embedded in sheets of white and brown adipose tissue; focally extensive areas containing abundant, large ganglion cells randomly scattered within neuropil; clusters of mucinous glands; bands of skeletal muscle; islands of cartilage; trabeculae of bone with bone marrow; bands of transitional and respiratory epithelium; and sheets and streams of poorly differentiated spindle cells (Figures 2 and 3). The neoplasm was supported by variable fibrovascular stroma and contained few scattered foci of hemorrhage and mild perivascular lymphoplasmacytic infiltrates.

Figure 2—
Figure 2—

Photomicrographs of sections of the orbital mass removed from the left eye of the cat in Figure 1. The mass did not extend into the eye, and no lesions were observed within the globe. A—In the orbital mass, islands of haired skin (arrows) and bone with bone marrow (asterisk) are scattered within sheets of white and brown adipose tissue. H&E stain; bar = 2 mm. B—In a densely cellular portion of the neoplasm, nervous tissue and poorly differentiated mesenchymal tissue surround occasional islands of cartilage (asterisks) and occasional epithelium-lined cystic structures (arrow). H&E stain; bar = 3 mm.

Citation: Journal of the American Veterinary Medical Association 252, 10; 10.2460/javma.252.10.1223

Figure 3—
Figure 3—

Photomicrographs of multiple components of the mass and expanded portions of the third eyelid removed from the left eye of the cat in Figure 1. A—In an island of haired skin, notice the distended hair follicle containing numerous intact hair shafts. H&E stain; bar = 270 μm. B—Mineralized trabeculae of bone are lined by osteoblasts and surrounding sheets of hematopoietic cells. H&E stain; bar = 240 μm. C—Respiratory epithelium is supported by bands of smooth muscle and fibrovascular stroma. H&E stain; bar = 75 μm. D—A large number of ganglion cells are haphazardly scattered within sheets of neuropil. H&E stain; bar = 125 μm.

Citation: Journal of the American Veterinary Medical Association 252, 10; 10.2460/javma.252.10.1223

Immunohistochemical analyses to reveal components of the neoplasm from various germ cell layers were performed. In sections of the orbital mass and the expanded third eyelid, segments of respiratory and stratified squamous epithelium diffusely had strong positive cytoplasmic labeling for pancytokeratin.a There was strong immunoreactivity for neurofilament proteinb within the neuropil surrounding the ganglion cells and, to a lesser extent, within the neuronal cell bodies.

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: orbital and third eyelid (extragonadal) teratoma in a young cat.

Comments

Differential diagnoses for a mass associated with the orbit and third eyelid of a cat include, but are not limited to, orbital teratoma, focal inflammatory reaction (eg, foreign body granuloma or abscess), conjunctival inclusion cyst, primitive neuroectodermal tumor, lymphoma, mast cell tumor, adenocarcinoma of the gland of the third eyelid, squamous cell carcinoma, and soft tissue sarcoma (including fibrosarcoma and myofibroblastic sarcoma). Of these differential diagnoses, only orbital teratoma, inclusion cyst, primitive neuroectodermal tumor, or inflammatory lesion would be considered likely in a young cat. The case described in the present report involved an extragonadal teratoma intimately associated with the orbit and third eyelid in a 9-week-old cat.

Germ cell tumors (eg, dysgerminomas, seminomas, and teratomas) most commonly arise in the genital region because they are composed of embryonic germ cells that normally differentiate into spermatogonia and oogonia.1,2 However, during embryonic development, germ cells can become ectopically distributed, which may result in the partial somatic differentiation of tissues in abnormal locations.1 Extragonadal teratomas are best described as an arbitrary, misplaced compilation of well-differentiated tissues containing more than 1 germ cell layer. These tumors can have extensive differentiation; however, most often they do not share the functions of the organs they resemble.1,3 Teratomas contain unique combinations of nearly completely formed or disorganized segments of organs, including, but not limited to, skin, bone, cartilage, teeth, glands, muscle, fibrous tissue, nervous tissue, and various types of epithelium.1,4 In the cat of the present report, the mass within the left third eyelid and along the orbital rim was consistent with an extragonadal orbital teratoma, given that it contained distinct, well-differentiated mesodermal, ectodermal, and endodermal tissue.

In human medicine, teratomas are classified on the basis of tissue maturity and biological behavior as either mature and benign or immature and malignant.5,6 An overwhelming proportion of these neoplasms are mature and benign and develop in infants or within the ovaries of women of reproductive age.5,6 Immature malignant teratomas resemble embryonal tissue, and are frequently rapidly growing with local invasion and metastasis. Ovarian teratomas in women are graded histologically on a scale of I to III on the basis of the amount of immature neuroepithelium present, with the risk for metastasis increasing with tumor grade.5 In addition, the development of non-germ cell malignancies within teratomas in humans has been reported.5 These malignant neoplasms are of particular concern because they are apparently chemoresistant.5 Teratomas in other animals are rarely reported,1,2 and as such, a histologic grading scale has not been established. However, when these neoplasms do develop in domestic species, they are most frequently benign.1,2

Orbital teratomas in children have been described as benign unilateral masses, most commonly affecting the left eye of females.7 Typically in these cases, a child has unilateral proptosis at birth, which may progress to compression of the globe.7 Once these masses are removed, cosmetic and functional return is favorable; however, neglect can lead to advanced lesions, which may result in vision loss.7 A more radical approach of exenteration has been performed in severely affected children in whom tumor components had deeply infiltrated the retro-orbital tissue, encasing the optic nerve.8 In the cat of the present report, enucleation with excision of the mass was sufficient because the mass was anterior to the globe and well circumscribed, with no gross evidence of local invasion. In this case, the successful recovery of the cat and lack of tumor re-growth in 3.5 years since the surgery also support the approach used as opposed to more radical excision.

To our knowledge, there are only 3 other reports4,9,10 of extragonadal teratomas in cats. All of those reported lesions affected the head, and 1 lesion, similar to the case described in the present report, involved an orbit. Wray et al4 described a retrobulbar teratoma that caused exophthalmos in a 3-year-old cat. Magnetic resonance imaging revealed that the mass was located along the ventral aspect of the right orbit and extended between the right zygoma, pterygoid process of the maxilla, and the vertical ramus of the mandible. Similar to that in the cat of the present report, this mass was discretely marginated, and there was no evidence of invasion of adjacent bone or soft tissues.4

In addition to humans and cats, extragonadal teratomas have been identified in a variety of veterinary species. Teratomas within or around the orbit of various birds, including a retrobulbar teratoma in a lesser kestrel, great blue heron, and chicken and a teratoma anterior to the left eye of a turkey, have been reported.11 Although rare, teratomas have developed in the orbits of humans and other animals and should be considered as a differential diagnosis for orbital masses in veterinary species.

Footnotes

a.

Pan Cytokeratin Plus, BioCare, Concord, Calif.

b.

Neurofilament protein, Dako, Carpinteria, Calif.

References

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