Oral squamous cell carcinoma in a pigtailed macaque (Macaca nemestrina)

Abstract

An adult, gravid, female pigtailed macaque (Macaca nemestrina) presented for facial swelling centered on the left mandible that was approximately 5 cm wide. Differential diagnoses included infectious, inflammatory, and neoplastic origins. Definitive antemortem diagnosis was not possible, and the macaque's condition worsened despite supportive care. Necropsy findings included a mandibular mass that was locally invasive and expansile, encompassing approximately 80% of the left mandibular bone. The mass replaced portions of the soft palate, hard palate, sinuses, ear canal, and the caudal-rostral calvarium and masseter muscle. Histologically, the mass was a neoplasm that was poorly circumscribed, unencapsulated, and infiltrative invading regional bone and soft tissue. The mass consisted of polygonal squamous epithelial cells with intercellular bridging that breached the epithelial basement membrane and formed invasive nests, cords, and trabeculae. The mitotic rate averaged 3 per 400× field of view, with occasional bizarre mitotic figures. Epithelial cells often exhibited dyskeratosis, and the nests often contained compact lamellated keratin (keratin pearls). The neoplasm was positive via immunohistochemistry for pancytokeratin, variably positive for S100, and negative for vimentin, smooth muscle actin, and desmin. The gross, histologic, and immunohistochemical findings were consistent with an aggressive oral squamous cell carcinoma. The neoplasm was negative via PCR for papilloma virus. In general, neoplasia in macaques is rare. Although squamous cell carcinomas are one of the most common oral neoplasia in many species, to our knowledge this case represents the first reported oral squamous cell carcinoma in a pigtailed macaque.

Figure 1.

Gross and radiographic findings. (A) Animal at gross necropsy imaged in right lateral recumbancy. The epidermis overlying the left cheek is ulcerated from the buccal margin and along the maxilla. The left maxilla and mandible are expanded by a firm tissue mass. (B) Section of the skull at gross necropsy imaged in right lateral recumbancy. A wedge section of the mass was removed with a scalpel and demonstrates maxillary bone loss and replacement. Neoplastic tissues (3.5 × 4 cm) extend from the epithelium, through the bone, to the mucus membranes and gingiva (arrow). Horizontal white lines on the photo stand are 2.5 cm apart. (C) Rostral image of animal at gross necropsy; the epidermis overlying the left maxilla (cheek) is ulcerated and excoriated. The left maxilla and mandible are enlarged. (D) Rostral image of skull at gross necropsy; the neoplasm expands the left maxilla, crossing the midline. (E) Cross-sectional image of the skull taken at gross necropsy, brain removed. Note the different opacities and color of the calvarial tissues on either side of the optic chiasm. The tumor has invaded the bone on the left side (white to pink tissues are circled); the right side is unaffected. (F) Antemortem radiographic image of the skull, ventrodorsal view. Note the expansile, osteolytic lesion of the left mandible, with invasion across the symphysis. (G) Antemortem radiographic image of the skull with the animal in the right lateral position. Note the expansile, osteolytic lesion on the mandible.

Figure 2.

Histology and immunohistochemistry of SCC lesion. (A) Low-power photomicrograph (white bar, 1mm) of buccal mucosa. On the upper left, the squamous epithelium is acanthotic, whereas on the upper right the epithelium demonstrates neoplastic transformation. Neoplastic cells extend through the basement membrane into the deep submucosa and form packets, nests, and whorls, with central cores of eosinophilic, laminated keratin (keratin pearls). A higher-magnification inset (white bar, 250 μm) demonstrates islands of neoplastic squamous cells within a fibrovascular stroma. Central cores of laminated keratin contain apoptotic and necrotic cells. (B) High-magnification photomicrograph (white bar, 25 µm) of squamous neoplastic cells demonstrating the loss of intercellular bridges, lack of organization, anisokaryosis, anyisocytosis, dyskeratosis, and neutrophilic inflammation. (C) Low-power photomicrograph (white bar, 1 mm) of positive 3,3′-diaminobenzidine (DAB) immunohistochemical staining for the intermediate filament cytokeratin. Neoplastic cells are positive (brown) for this protein, whereas the fibrovascular stroma is negative (blue). The inset (white bar, 250 μm) illustrates the epithelial–stromal border, with 2 islands of cytokeratin-positive neoplastic cells within stromal tissues. (D) Low-power photomicrograph (white bar, 1 mm) of negative DAB immunohistochemical staining for the intermediate filament vimentin. Neoplastic cells are negative (blue) for this protein, whereas the fibrovascular stroma is positive (brown). The inset (white bar, 250 μm) illustrates the epithelial–stromal border with scattered positive stromal cells within neoplastic (negative) epithelilal cells. (E) Low-power photomicrograph of negative DAB immunohistochemical staining for desmin intermediate filament. Neoplastic cells and stroma are negative (blue) for this protein whereas overlying myocytes are positive (brown). The inset (white bar, 250 μm) illustrates the junction of muscle (upper right) and neoplastic tissue. (F) Low-power photomicrograph (white bar, 1 mm) of intermediate DAB immunohistochemical staining for calcium binding protein S100. Neoplastic cells are variably positive (brown) for this marker. The inset (white bar, 25 μm) illustrates a positive internal control; nerve fibers show positive (brown) staining. (G) Neoplastic cells invading and replacing mandibular bone (white bar, 1 mm). To the left, neoplastic cells and stroma abut bone (right) and invade marrow spaces. (H) Myocytes of the masseter muscle are replaced by neoplastic cells within fibrovascular stroma containing abundant inflammatory cells (white bar, 100 μm). (I) Photomicrograph (white bar, 1 mm) of the left maxillary premolar illustrating neoplastic invasion of alveolar bone and cementum; the dentin and pulp cavity are preserved. For orientation, the inset image illustrates the tissue origin (after fixation) and demonstrates the mandibular neoplastic tissue surrounding a premolar in cross section (grid, 5 mm).