Case #3 2025

Interpretation

Carcinoma (likely squamous cell carcinoma) with concurrent mixed inflammation (heterophils, macrophages)

Explanation

The smears of the aspirate were moderately cellular and contained small to medium-sized clusters of medium to large oval to angular epithelial cells (Figures 2-3), along with low to moderate numbers of admixed heterophils (Figure 5) and macrophages (including binucleated and multinucleated variants), and a few small aggregates of uniform spindle-shaped mesenchymal cells (Figure 4) in a background with a scant blood. The epithelial cells had distinct cell borders and moderate amounts of moderate to dark blue cytoplasm. Anisocytosis and anisokaryosis were overall moderate, with rare clusters containing large cells with large nuclei. Nuclei were centrally located, round to slightly ovoid, with finely stippled chromatin, and 1-2 prominent nucleoli. A few binucleated cells, but no mitotic figures, were observed on scanning. Low numbers of cells had smooth blue cytoplasm with perinuclear vacuolation, features suggestive of squamous differentiation (Figures 2-3).

Based on the presence of epithelial cells with features suggestive of squamous differentiation and the location of the mass, a squamous cell carcinoma (SCC) was considered the primary differential diagnosis (Question 1). The aggregates of mesenchymal cells likely represented a scirrhous response (desmoplasia); however, reactive fibroplasia secondary to heterophilic inflammation could also explain their presence (Question 2).

Figure 2: Peri-orbital mass aspirate (50x objective)

Figure 3: Peri-orbital mass aspirate (50x objective)

Figure 4: Peri-orbital mass aspirate (50x objective)

Figure 5: Peri-orbital mass aspirate (50x objective)

 

Follow up

The mass was surgically excised and the right eye was enucleated. Strontium radiation therapy was applied intraoperatively around the surgical edges. The formalin-fixed mass was submitted for histopathologic examination. Histopathologic evaluation of hematoxylin-&-eosin-stained slides of the mass showed an expansile, infiltrative, poorly demarcated, highly cellular, and unencapsulated neoplasm, composed of islands and anastomosing trabeculae of squamous epithelial cells, showing disorderly maturation (Figure 6-8). The squamous epithelial cells were polygonal with distinct borders and abundant eosinophilic cytoplasm. Nuclei were round to slightly oval, with open to clumped chromatin, and contained up to 2 prominent basophilic nucleoli. Anisokaryosis and anisocytosis were moderate to marked, with occasional karyomegalic cells. There was 1 mitotic figure per 2.37mm2. The squamous epithelial cells were frequently surrounded by dense streams of fibrous tissue (scirrhous response) (Figure 8), corresponding to the aggregates of mesenchymal cells observed in the cytologic smears (Figure 4). The islands of squamous epithelial cells were concentrated multifocally around concentric whorls of lamellar keratin (keratin pearls) (Figure 6-7) and variable amounts of cellular debris, surrounded by a rim of heterophils and macrophages (Figure 6). In one section, there was a serocellular crust composed of degenerate heterophils, eosinophilic fluid (serum), and keratin. The epithelial cells either abutted or extended to all the surgical margins (Figure 6). The histologic diagnosis was a SCC.

Figure 6: Histologic section of the peri-orbital mass

Figure 7: Histologic section of the peri-orbital mass

Figure 8: Histologic section of the peri-orbital mass

Follow up

After initial good healing, an extensive tissue proliferation arising from the region of the excision site in the orbit was noted approximately 3 months post-surgery. This tissue was suspected to represent neoplastic regrowth, particularly in the light of the incompletely excised tumor margins, although the possibility of abnormal scarring was also considered. The animal was thought to be inappetent and, due to difficulties with managing the patient with syringe feeding, humane euthanasia was elected. A post-mortem examination was not performed.

Discussion

The prevalence of cancer in lizards varies widely in the literature, ranging from 6 to 23%.1,2  Based on a retrospective analysis of neoplasia in captive lizards (including bearded dragons) in the United Kingdom over a 10-year period, SCC was the most commonly diagnosed neoplasm, accounting for 18% of all tumors and 36% of skin tumors. The eyelids and peri-ocular tissues were the commonly affected sites, with the authors stating that nearly all masses in the peri-ocular tissues were SCC.2 In contrast to the latter study, a review of cancer diagnoses in bearded dragons from two different zoological pathology laboratories in the United States identified a lower incidence of SCC, accounting for 6% of all neoplasms detected over 10 years. In the latter study, 75% (9/12) of SCC were found in the eyelid or peri-ocular tissue. The authors suggested a predilection of SCC near mucocutaneous junctions, especially in the peri-ocular region, in bearded dragons.3 In addition to the mucocutaneous junction of the eyelid, the skin on the head and the body wall were other common primary sites of SCC in squamata reptiles.4

Squamous cell carcinoma typically manifests as slow-growing, nodular, firm, single or multiple, often ulcerated lesions, similar to the presentation in our case. Although they often appear to have well-defined margins, they can be invasive and, in cases involving the peri-ocular area, enucleation is required to achieve complete tumor removal. Metastasis, however, is uncommon.4 Accordingly, the neoplasm in this case was infiltrative, but did not show any signs of metastasis as evaluated in a full-body CT scan at the time of surgery, although microscopic metastatic lesions cannot be ruled out.

While it is postulated that exposure to ultraviolet (UV) light may be linked to SCC – as seen in other species such as in cats and cattle5,6 – particularly in association with the use of UV lamps, a direct correlation to UV exposure has not yet been established in reptiles.4 The bearded dragon in our case was exposed to UV lamps, which is a common part of the husbandry of pet reptiles.

Surgical excision is the most commonly reported treatment option for SCC in lizards.3,7,8 In a cohort of SCC cases in squamates, curative-intent surgery was performed on 13/14 cases, with recurrence observed in 3 cases over a follow-up period of 1 to 7 years.4 In contrast, radiation therapy for cancer in reptiles has been rarely described. There is a single report of successful radiation therapy of an eyelid SCC in a bearded dragon that recurred after surgical debulking. However, the overall effectiveness of radiation therapy for reptile neoplasms remains unknown.9

In addition to SCC, other types of carcinomas reported in the peri-ocular tissues of lizards include basal cell carcinomas and adenocarcinomas.4,10 Although these occur less frequently than SCC,4 they should still be considered as differential diagnoses when squamous differentiation is not evident from cells in cytologic smears. In such cases, the definitive determination of tumor type would require histopathologic confirmation, as seen in this case, which only showed subtle features of squamous differentiation.

Author: I. Alvarado-Hidalgo, edited by T. Stokol and J. Korchia

The author would like to thank Dr. Friel for providing the CT images and description. Drs. Coffin and Champion examined the histopathologic sections. Dr. Di Girolamo was the case clinician.

References

  1. Hernandez-Divers SM, Garner MM. Neoplasia of reptiles with an emphasis on lizards. Veterinary Clinics of North America: Exotic Animal Practice. 2003;6(1):251-273. doi:10.1016/S1094-9194(02)00028-2.
  2. Kubiak M, Denk D, Stidworthy MF. Retrospective review of neoplasms of captive lizards in the United Kingdom. Veterinary Record. 2020;186(1):28-28. doi:10.1136/vr.105308
  3. Hannon DE, Garner MM, Reavill DR. Squamous Cell Carcinomas in Inland Bearded Dragons (Pogona vitticeps). Journal of Herpetological Medicine and Surgery. 2011;21(4):101. doi:10.5818/1529-9651-21.4.101
  4. Solanes‐Vilanova F, Chiers K, Gil‐Lianes J, Hellebuyck T. Clinical features, surgical management and outcome of squamous and basal cell carcinoma in squamates and chelonians. Veterinary Dermatology. 2024;35(6):626-640. doi:10.1111/vde.13282
  5. Anderson DE, Badzioch M. Association between solar radiation and ocular squamous cell carcinoma in cattle. Am J Vet Res. 1991;52(5):784-788.
  6. Dorn C, Taylor D, Schneider R. Sunlight Exposure and Risk of Developing Cutaneous and Oral Squamous Cell Carcinomas in White Cats2. JNCI: Journal of the National Cancer Institute. Published online May 1971. doi:10.1093/jnci/46.5.1073
  7. Van Der Weyden L, O’Dell N, Avenant A, Pazzi P, Koeppel KN. Successful Treatment of Cutaneous Squamous Cell Carcinoma in a Captive Green Iguana (Iguana Iguana). Topics in Companion Animal Medicine. 2022;46:100610. doi:10.1016/j.tcam.2021.100610
  8. Abou‐Madi N, Kern TJ. Squamous cell carcinoma associated with a periorbital mass in a veiled chameleon ( Chamaeleo calyptratus ). Veterinary Ophthalmology. 2002;5(3):217-220. doi:10.1046/j.1463-5224.2002.00244.x
  9. Kent MS. Principles and Applications of Radiation Therapy in Exotic Animals. Veterinary Clinics of North America: Exotic Animal Practice. 2017;20(1):255-270. doi:10.1016/j.cvex.2016.07.008
  10. Darrow BG, Johnstone McLean NS, Russman SE, Schiller CA. Periorbital adenocarcinoma in a bearded dragon ( Pogona vitticeps ). Veterinary Ophthalmology. 2013;16(s1):177-182. doi:10.1111/vop.12053
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