Oral masses in African pygmy hedgehogs

Abstract

African pygmy hedgehogs (Atelerix albiventris) frequently develop oral neoplasms, and most of these neoplasms are malignant. We characterized oral masses detected in hedgehogs at clinical examination. During a 1-y period, we diagnosed oral cavity masses in 27 privately owned hedgehogs; 16 were female and 11 were male, with ages of 2–7 y (mean: 4.3 y). Eight masses were non-neoplastic and were diagnosed as gingival hyperplasia (GH). Nineteen masses were neoplastic, of which 17 were squamous cell carcinomas (SCCs) and 2 were mesenchymal tumors (1 spindle cell tumor of probable neural origin, and 1 hemangiosarcoma). The GHs were noninvasive, exophytic, and did not recur after surgical excision. The SCCs were highly invasive tumors that induced facial deformation and were located in the caudal portion of the oral cavity, with 12 of them arising from the right-caudal maxilla. Thus, clinical signs, growth pattern, and anatomic location can be used to suspect a diagnosis of SCC among the other possible diagnoses, such as GH, in this location. However, histopathology is necessary for confirmation. Also, hemangiosarcoma should be considered among the differential diagnoses.

African pygmy hedgehogs (Atelerix albiventris) have become popular pets in several countries.³ They have a life expectancy of 3–4 y in the wild and 5–8 y in captivity.^1–3 This species is prone to develop a wide range of oral lesions, some of which can manifest as oral masses, including neoplastic and non-neoplastic growths.^3,5,7 Non-neoplastic lesions that may manifest as masses include periodontal abscesses and gingival hyperplasia (GH).^3,5,7 Three retrospective studies have reported the frequency of oral lesions, among which, squamous cell carcinoma (SCC) was the most common.^10,13,14 These previous studies have focused on the prevalence of disease in hedgehogs by analyzing biopsy results from all anatomic locations. In a 2001 study, oral SCC accounted for 5 of 35 tumors.¹⁴ A 2015 study reported that 5 of 14 tumors diagnosed in hedgehogs were oral SCCs.¹³ A 2018 study reported that, of 105 biopsies, 5 were oral SCCs and 4 were GH; 2 SCCs were located in the mandible and 2 in the maxilla.¹⁰ No location was reported for GH. Other oral neoplasms reported in this species include single cases of peripheral odontogenic fibroma,¹⁶ osteoma,⁵ and osteochondroma,¹² 2 cases of osteosarcoma,^3,5 and 4 cases of fibrosarcoma.^10,14 To our knowledge, no previous study has focused specifically on oral masses in African pygmy hedgehogs.

Privately owned African hedgehogs were selected after diagnosis of an oral mass during examination in various exotic animal veterinary clinics from Santiago, Chile over a 1-y period (October 2015 to October 2016). For each case, the gross appearance of the mass and its associated clinical signs were recorded. The masses were classified according to the anatomic location in the oral cavity, as reported previously in dogs: rostral maxilla or rostral mandible (first incisor tooth to the second premolar tooth), caudal maxilla or caudal mandible (dentate region caudal to the second premolar tooth), tongue, and palate.⁹ The masses were also classified grossly according to their growth pattern as exophytic (outward growing mass) and endophytic (inward growing, with focal ulceration). Tissue specimens were collected from each hedgehog either through biopsy or during autopsy. All protocols involving animals were approved by the Bioethics Committee of the Faculty of Veterinary and Animal Sciences at the University of Chile (17-2016).

Data were analyzed (Excel 2013; Microsoft, Redmond, WA). All tissues were fixed in 10% neutral-buffered formalin, processed routinely, and stained with hematoxylin and eosin. The sections were examined by 2 of the authors (FR Carvallo and FF Cifuentes). Immunohistochemistry (IHC) for S100, vimentin, melan A, factor VIII, smooth muscle actin, desmin, glial fibrillary acidic protein (GFAP), and laminin was performed on tumor sections from case 3 (spindle cell tumor) following standard operating procedures (SOPs) of the Veterinary Teaching Hospital of the School of Veterinary Medicine, University of California–Davis. A similar procedure was performed for case 24 (hemangiosarcoma), using the endothelial marker CD31. All markers were tested with the corresponding control lacking a primary antibody; however, appropriate hedgehog tissue controls were not available at the time of testing.

A total of 1,034 African hedgehogs were examined for various reasons during the study period. In 73 of 1,034 (7%), the owners noticed a swollen face or a mass in the oral cavity. Tissue samples were obtained from 27 of 73 of these animals. Of these, 11 of 27 were biopsies (incisional and excisional); 16 of 27 were collected postmortem. Sixteen of 27 of the animals were female; 11 of 27 were male. All 27 animals were adult, with ages of 2–7 y (median: 4.2 y ± 1.3).

Of all of the analyzed oral masses, 8 cases were GH. The most commonly associated clinical signs and lesions reported in these animals were reduced food intake, gingivitis, oral plaques, and focal gingival thickening. Grossly, 6 of these masses were pedunculated polyps and 2 were sessile polyps (Fig. 1). All of these had a smooth, non-ulcerated surface, always attached to the gingiva. Their location in the oral cavity was variable; 4 were located in the mandibular gingiva and 4 in the maxillary gingiva (Figs. 2, 3). Histologically, the lesions consisted of moderate-to-marked epithelial hyperplasia characterized by the growth of irregular rete pegs of the epithelium into the subjacent stroma without breaching the basement membrane. Sometimes, epithelial projections formed anastomosing cords (Fig. 4). The fibrous stroma was paucicellular, with diffuse, moderate-to-marked lymphoplasmacytic infiltrate with a few eosinophils.

Figures 1–16.

Morphologic characteristics and anatomic location of oral cavity masses in African pygmy hedgehogs. Figure 1. Gingival hyperplasia (GH). Non-ulcerated exophytic pedunculated mass (arrow) in the gingiva near the canine tooth of the maxilla, which caused reduced food intake. Figures 2, 3. Schematic representation of the location of 8 cases of GH in the oral cavity. L = left; R = right. Figure 4. GH. Epithelial hyperplasia characterized by the growth of multiple irregular rete pegs that, in this case, form anastomosing cords. The fibrous stroma was paucicellular and infiltrated by lymphocytes, plasma cells, and eosinophils. Bar = 100 μm. Figure 5. Oral squamous cell carcinoma (SCC). Gingival endophytic ulcerated mass (arrow) with swelling of facial bones, located in the right caudal maxilla, associated with exophthalmia (arrowhead). Figures 6, 7. Schematic representation of the location of 17 cases of SCC in the oral cavity. SCC cases tend to concentrate in the right caudal maxilla. Caudal location = caudal to the second premolar tooth. Figure 8. Islands and nests of SCC epithelial neoplastic cells invade the gingival stroma. Bar = 100 μm. Inset: SCC cells (right; *) invade a salivary gland (left). Bar = 50 μm. Figure 9. Exophytic, ulcerated spindle cell tumor located in the hard palate. Figures 10, 11 Schematic representation of the location of the spindle cell tumor. Figure 12. Numerous spindle cells form solid masses with formation of whorls and interwoven bundles (circle) admixed with numerous neutrophils (arrowhead) in the spindle cell tumor. Bar = 100 μm. Inset: Detail from main figure. Bar = 50 μm. Figure 13. Ulcerated hemangiosarcoma located at the mucocutaneous junction of the lower lip. Figures 14, 15. Schematic representation of the location of the hemangiosarcoma. Figure 16. The epithelium covering the hemangiosarcoma is ulcerated, and neoplastic cells form solid sheets and vascular spaces. Bar = 100 μm. Inset: Detail from main figure. Bar = 50 μm.

All other masses were neoplastic and included 17 SCCs, 1 spindle cell tumor of probable neural origin, and 1 hemangiosarcoma. All animals with SCC exhibited facial swelling, 14 had lost teeth, 13 had diffuse gingival thickening, 6 had decreased appetite, and 5 had weight loss. Other oral cavity alterations detected during physical examination included oral plaques with halitosis (14) and moderate gingivitis (9). Of the 17 cases of oral SCC, 10 were endophytic and 7 were exophytic. The great majority of SCCs (12 of 17) were located in the right caudal portion of the maxilla (Figs. 5, 6), including 1 that arose from the right palate. One case was located in the left caudal portion of the maxilla, and 4 were located in the caudal mandible (2 on each side). All of these tumors were associated with nasal or mandibular deformation. On gross examination, 13 SCCs were ulcerated (Fig. 5), and 10 of them were bleeding. In 8 cases, the tumor invaded the hard palate and nasal cavity, effacing nasal turbinates and causing inspiratory dyspnea. In 5 cases, the mass caused ipsilateral exophthalmia, and in 2 cases, the mass grew cranial to the ocular globe causing endophthalmia. One case had a fracture of the mandible subsequent to the invasive growth of the tumor. In all 17 hedgehogs, euthanasia was elected because of local tumor progression that caused poor quality of life. Of these, only 2 animals were submitted for autopsy, in which neither metastases nor other lesions were noted.

Histologically, all SCCs were poorly differentiated. Most of them had neoplastic cells arranged in nests or islands, with low or absent keratinization and with scarce amounts of stroma (Fig. 8). In 8 samples, ~10% of the neoplastic cells had spindle cell morphology. Bone invasion was observed in 7 cases, wherein immature bone was identified as irregular spicules with dense bands of connective tissue between neoplastic cells. In 1 case, neoplastic cells invaded the submandibular salivary gland (Fig. 8, inset). Acantholysis was observed in 8 samples. Anisocytosis, anisokaryosis, and nuclear pleomorphism were mild-to-moderate in all SCCs. More than 5 mitotic figures per 10 high-power fields (HPFs) were counted in all sections. In 14 cases, a moderate, diffuse, lymphocytic inflammatory infiltrate with fewer macrophages and groups of neutrophils was associated with the tumor.

The mass diagnosed as a spindle cell tumor was an exophytic, ulcerated, pedunculated growth located in the hard palate (case 3; Figs. 9–11). Histologically, the tumor consisted of a monomorphic population of spindle cells that formed solid masses with the formation of whorls and interwoven bundles, all embedded in a fine fibrovascular stroma (Fig. 12). Nuclei had moderate anisokaryosis, and were elongate-to-ovoid, with finely stippled chromatin and 1–2 small nucleoli. Numerous neutrophils diffusely infiltrated the stroma (Fig. 12). Mitotic count was 6 per 10 HPFs. Neoplastic cells had immunostaining for S100 and vimentin, but no staining was detected for melan A, factor VIII, smooth muscle actin, desmin, GFAP, and laminin (data not shown). Based on cellularity, monomorphic features, anisokaryosis, and IHC results, we propose a diagnosis of neoplasia of probable neural origin. The mass diagnosed as hemangiosarcoma was a nodular, ulcerated growth in the lower rostral lip (mucocutaneous location; Fig. 13). Histologically, the surface epithelium was ulcerated, and neoplastic cells invaded the submucosa and formed vascular spaces separated by connective tissue with high vascularization and foci of hemorrhage (Fig. 16). The cells were highly pleomorphic, had prominent hyperchromatic nuclei, and had marked anisokaryosis. Mitotic count was 3 per 10 HPFs. The cells had immunostaining for CD31 (data not shown). In both tumors, IHC results indicate the probable tissue of origin, but it is important to note that the specificity of these markers for hedgehog tissue has not yet been validated.

Our approach to the diagnosis of an oral mass in a hedgehog was to characterize the gross features and associate them with the clinical signs. Biopsies were obtained in only one-third of the animals affected by an oral mass, likely because of the associated cost or reluctance of the owner to accept an invasive procedure. Although fine-needle aspiration (FNA) cytology is a simple diagnostic procedure, this resource was not used in these animals.^3,4 In the cases that were diagnosed, owners elected to perform biopsy over FNA cytology, thus choosing the most definitive diagnostic method. We detected oral masses in hedgehogs > 2 y old, which is in agreement with the age range described previously (2–5.5 y).^13,14 No sex predilection was found.

Oral SCC was the most frequent growth in the oral cavity of African hedgehogs. This is similar to previous retrospective studies, in which oral SCC was highly prevalent among other oral and non-oral neoplasms.^10,13,14 Such studies considered tumors in all anatomic locations, including oral, and therefore the number of oral tumors reported is relatively low. Given that we focused only on oral tumors, we were able to analyze a higher number of oral SCCs and GH and hence, present in more detail their anatomic location and clinical behavior.

As reported in other species, oral SCC occurs in hedgehogs as a mass invading soft tissues and bone.^8,14,15 The masses that we diagnosed as oral SCCs caused extreme facial deformation that prevented the hedgehog from eating solid food. When these masses grow deeply, infiltrating the subjacent tissues and replacing the nasal turbinates or the mandibular bone, they induce obvious clinical signs. Bone invasion by SCC is a feature common to humans, cats, and dogs, and is characterized by osteoclastic bone resorption, new bone formation, and desmoplasia.⁶

Only one previous study reports the diagnosis of GH, which accounted for 4 of 105 histologic diagnoses, including all anatomic locations.¹⁰ The previous study does not mention a specific anatomic location, clinical signs, or gross features of GH. We observed that, in comparison to SCC, clinical signs were few and mild, and given that some lesions (gingivitis and oral plaques) are common in hedgehogs, they may be unrelated to the growth of the mass.⁵ To our knowledge, no causal association has been reported between oral inflammation and propensity for tumor growth in hedgehogs.

The cases of spindle cell tumor and hemangiosarcoma were not associated with specific clinical signs, other than the detection of the oral mass itself. In other species, oral sarcomas have been reported as highly malignant masses that can result in multi-organ metastases.¹¹ However, the hedgehogs did not show any evidence of local recurrence after the excision of the masses.

The 2 oral growths found most commonly in our study were SCCs and GHs. SCCs were located mainly in the caudal portion of the oral cavity, especially in the right caudal maxilla. Although GH can occur in the same location, it has a more random distribution and it occurs as a slowly growing non-ulcerated mass. Hence, an ulcerated, rapidly growing mass located in the caudal portion of the oral cavity of a hedgehog, especially close to the maxillary molars and associated with facial deformation and overt clinical signs, is most probably a SCC. However, histology is necessary for definitive differentiation. To our knowledge, this is the largest series of oral SCCs reported in this species focusing on anatomic location and morphologic features.^3,10,13,14 Also, we know of no other reports of a hemangiosarcoma and a mesenchymal tumor of probable neural origin in this location.

Research Data

Research_data for Oral masses in African pygmy hedgehogs

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Research_data for Oral masses in African pygmy hedgehogs by Gabriela Del Aguila, Cristian G. Torres, Francisco R. Carvallo, Carlos M. Gonzalez and Federico F. Cifuentes in Journal of Veterinary Diagnostic Investigation