History and Clinical Findings
A stray 3- to 4-year-old 3.15-kg (6.93-lb) sexually intact male Siamese cat was brought to a veterinary hospital for evaluation. Initial examination revealed respiratory signs (characterized by stertor), epistaxis, and severe stomatitis. Hematologic and serum biochemical analyses revealed low PCV (25.7%; reference interval, 30% to 45%), eosinophilia (1.10 × 103 eosinophils/μL; reference interval, 0.10 × 103 eosinophils/μL to 0.79 × 103 eosinophils/μL), high platelet count (1,106 × 103 platelets/μL; reference interval, 175 × 103 platelets/μL to 600 × 103 platelets/μL), and slight hyperglobulinemia (5.7 g/dL; reference interval, 2.8 to 5.1 g/dL). Serologic analyses for retroviruses detected antibodies against FeLV. The cat was treated with antimicrobials (cefovecin and spiramycin with metronidazole) and an antiparasitic (mebendazole). Two months later, the stomatitis worsened, the epistaxis continued, and a purulent nasal discharge developed. Laser resection of the area of stomatitis and a full-mouth tooth extraction were performed. Histologic examination of the resected tissue revealed severe lymphoplasmacytic gingivostomatitis. Three months after the laser resection, the cat again developed stertor; 3 weeks after development of stertor, facial swelling on the right side was evident. Radiography revealed a mass in the right nasal cavity. A biopsy specimen of the mass was obtained. On the basis of histologic examination of the specimen, chemotherapy with toceranib was started and antimicrobial treatment was changed to amoxicillin-clavulanic acid; corticosteroids and analgesics (buprenorphine) were also administered. After 2 months, chemotherapy was discontinued because it was considered ineffective. One month later, the mass grew considerably, causing severe facial deformity (Figure 1) At the same time, multifocal alopecic areas appeared on the skin over the thorax, and dermatophytosis was suspected. A swab sample of the alopecic areas was obtained, and fungal culture yielded an Aspergillus sp; subsequent molecular studies identified the fungus as Aspergillus tubingensis. Two weeks later, the cat's condition worsened, and it was euthanized (by IV administration of pentobarbital sodium) because of its poor prognosis.
Photographs of the face (A) and sectioned lesion (B) of a 3- to 4-year-old Siamese that developed a rapidly growing mass in the right nasal cavity and was euthanized. In panel A, notice the severe facial deformity caused by the mass. Inset—Appearance of the cat's face 3.5 months earlier. The facial deformity was mild at that time. In panel B, the mass in the right side of the face is rounded, approximately 8 cm in diameter, multilobulated, soft to firm, and whitish.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
Photographs of the face (A) and sectioned lesion (B) of a 3- to 4-year-old Siamese that developed a rapidly growing mass in the right nasal cavity and was euthanized. In panel A, notice the severe facial deformity caused by the mass. Inset—Appearance of the cat's face 3.5 months earlier. The facial deformity was mild at that time. In panel B, the mass in the right side of the face is rounded, approximately 8 cm in diameter, multilobulated, soft to firm, and whitish.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
Photographs of the face (A) and sectioned lesion (B) of a 3- to 4-year-old Siamese that developed a rapidly growing mass in the right nasal cavity and was euthanized. In panel A, notice the severe facial deformity caused by the mass. Inset—Appearance of the cat's face 3.5 months earlier. The facial deformity was mild at that time. In panel B, the mass in the right side of the face is rounded, approximately 8 cm in diameter, multilobulated, soft to firm, and whitish.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
Gross Findings
Grossly, an approximately 8-cm-diameter, rounded, multilobulated, soft to firm, whitish mass occupied the right nasal cavity. The mass was nonencapsulated, locally invasive, and highly compressive; it had caused turbinate and septum destruction and severe facial deformity. The skin overlying the mass was alopecic. On cut section, the mass was white and multilobulated (Figure 1). Two small (0.5- and 1-cm-diameter), white, firm, superficial nodules were present in the left caudal lung lobe. Moderately fatty liver was the only other abnormality.
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic and Immunohistochemical Findings
Microscopically, the nasal tumor was characterized by irregular nests of mildly pleomorphic epithelial cells separated by dense irregular bands of spindle-shaped cells set in a fibrous stroma (Figure 2) The epithelial cells were mainly arranged in an acinar pattern with occasional more solid areas. The acini were composed of 1 to 6 layers of cuboidal to columnar cells. Some acini contained intraluminal nonstaining, faintly eosinophilic amphophilic material, whereas others contained brightly eosinophilic amphophilic material that was sometimes mucinous. Some acini were centrally necrotic (consistent with comedonecrosis), and some were embedded within the bands of spindle-shaped cells. Epithelial cells had a scarce to moderate amount of eosinophilic cytoplasm with indistinct borders. Cells in the solid areas had a higher nuclear-to-cytoplasmic ratio. The nuclei were generally round to oval, were basally or centrally located, and had a single eosinophilic, round nucleolus located centrally and sparse chromatin. Moderate anisocytosis and anisokaryosis were observed in some areas. The mitotic count was approximately 2 mitoses/hpf (400×), although > 3 mitoses/hpf were present in some areas. Hemorrhage and necrosis were occasionally observed.
Photomicrographs of sections of the nasal mass from the cat in Figure 1. A—Irregular nests of mildly pleomorphic epithelial cells are separated by dense irregular bands of spindle-shaped cells. The epithelial component of the mass has an acinar pattern with comedonecrosis in some acini (lower right of the image). H&E stain; bar = 100 μm. B—Following immunohistochemical staining for cytokeratins, the epithelial cells are strongly immunostained. Cytokeratin A1/A3-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining for Ki67, the nucleus of numerous epithelial cells and some of the cells of the sarcomatous component of the tumor are immunostained. Ki67-specific immunohistochemical reaction; bar = 20 μm. C—Following immunohistochemical staining for vimentin, both epithelial and sarcomatous cells are strongly labeled. Vimentin-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining specific for α-smooth muscle actin, some of the sarcomatous cells but none of the multinucleated giant cells are stained; strong labeling is evident around blood vessels. α-Smooth muscle actin-specific immunohistochemical reaction; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
Photomicrographs of sections of the nasal mass from the cat in Figure 1. A—Irregular nests of mildly pleomorphic epithelial cells are separated by dense irregular bands of spindle-shaped cells. The epithelial component of the mass has an acinar pattern with comedonecrosis in some acini (lower right of the image). H&E stain; bar = 100 μm. B—Following immunohistochemical staining for cytokeratins, the epithelial cells are strongly immunostained. Cytokeratin A1/A3-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining for Ki67, the nucleus of numerous epithelial cells and some of the cells of the sarcomatous component of the tumor are immunostained. Ki67-specific immunohistochemical reaction; bar = 20 μm. C—Following immunohistochemical staining for vimentin, both epithelial and sarcomatous cells are strongly labeled. Vimentin-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining specific for α-smooth muscle actin, some of the sarcomatous cells but none of the multinucleated giant cells are stained; strong labeling is evident around blood vessels. α-Smooth muscle actin-specific immunohistochemical reaction; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
Photomicrographs of sections of the nasal mass from the cat in Figure 1. A—Irregular nests of mildly pleomorphic epithelial cells are separated by dense irregular bands of spindle-shaped cells. The epithelial component of the mass has an acinar pattern with comedonecrosis in some acini (lower right of the image). H&E stain; bar = 100 μm. B—Following immunohistochemical staining for cytokeratins, the epithelial cells are strongly immunostained. Cytokeratin A1/A3-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining for Ki67, the nucleus of numerous epithelial cells and some of the cells of the sarcomatous component of the tumor are immunostained. Ki67-specific immunohistochemical reaction; bar = 20 μm. C—Following immunohistochemical staining for vimentin, both epithelial and sarcomatous cells are strongly labeled. Vimentin-specific immunohistochemical reaction; bar = 20 μm. Inset—Following immunohistochemical staining specific for α-smooth muscle actin, some of the sarcomatous cells but none of the multinucleated giant cells are stained; strong labeling is evident around blood vessels. α-Smooth muscle actin-specific immunohistochemical reaction; bar = 10 μm.
Citation: Journal of the American Veterinary Medical Association 255, 6; 10.2460/javma.255.6.669
The spindle-shaped cells were arranged in interwoven sheets and bundles and occasionally around blood vessels. These cells had an oval nucleus with coarse chromatin and 1 or 2 nucleoli and moderate slightly eosinophilic cytoplasm. Some cells appeared vacuolated, and multinucleated giant cells were also observed (Figure 2). Occasional mitoses were observed. Mature collagen was generally scarce, although in some areas it was prominent. Mild osseous and cartilaginous metaplasia was focally seen in the sarcomatoid component. Neoplastic emboli composed of epithelial components were sporadically present in some vessels. Nasal respiratory epithelium was mostly well conserved, although in some areas, it was distorted by variably sized polyps. The polyps had a variably sized base and protruded through the epithelial lining; they were composed of a variable number of inflammatory cells, mainly neutrophils, immersed in a stroma of fusiform cells. The epithelium overlying each polyp was hyperplasic or desquamated, and the fusiform cells were haphazardly oriented with some degree of atypia. Suppurative rhinitis, with abundant exudate in the lumen of the nasal cavity, was evident in some areas. Pulmonary lesions had the same pattern as that of the nasal tumor. Tumor growths were also observed on the pleura and were mainly sarcomatous. The skin had evidence of necrotic dermatitis with neutrophilic exudate and thrombosis, but no fungal structures were detected.
Immunohistochemical analyses revealed similar staining patterns for both the primary and metastatic lesions. Most of the epithelial cells had strong cytoplasmic immunostaining with antibodies against cytokeratin AE1/AE3 and against vimentin; the spindle-shaped cells were strongly positive for vimentin and occasionally positive for cytokeratin (Figure 2). Within the acini, staining was stronger toward the centers. In some areas in which a solid pattern rather than an acinar pattern was observed, cytokeratin labeling was absent but vimentin immunostaining was present. Most spindle-shaped cells had moderate to intense labeling for α-smooth muscle actin, whereas few cells expressed S100. Giant cells were only immunostained by vimentin antibody. No neuron-specific enolase expression was found in either epithelial or spindle-shaped cells. Most epithelial cells and some of the sarcomatous cells were Ki67 positive; factor VIII was expressed only by endothelial cells.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: carcinosarcoma of the nasal cavity with lung metastasis in a young sexually intact male Siamese cat.
Comments
Nasal tumors are the main cause of nasopharyngeal disease in cats.1 Of all tumors in cats, nasal tumors represent < 1% (or as much as 8.4% if nasal planum tumors are also included).2 In cats, lymphoma is the most frequent nasal tumor followed by adenocarcinoma.1 The main clinical signs of nasal tumors are stertor, nasal discharge, and facial deformity. Generally, cats with nasal tumors are 8 to 10 years old. Carcinosarcomas are aggressive tumors characterized by malignant epithelial and mesenchymal elements, and they are uncommon in all species including humans. Most reports of carcinosarcomas have involved dogs and, rarely, other species. With regard to cats, there are 6 reports3–8 of carcinosarcomas in various anatomic locations, such as the lungs, digital apocrine sweat gland, salivary gland, mammary gland, pancreas, and the biliary system. However, carcinosarcomas of the nasal cavity in domestic animals have not been reported, to our knowledge, and only a few cases in humans have been described.9 In the cat of the present report, histologic and immunohistochemical features of the tumor were consistent with a carcinosarcoma and were similar to those of the reported pulmonary carcinosarcoma in a domestic shorthair cat.3 The epithelial component predominated over the sarcomatous component although both components were present to a similar extent in some areas. The sarcomatous component was consistent with a low-grade myofibroblastic sarcoma on the basis of the immunoreactivity for vimentin and smooth muscle actin and the scarce immunoreactivity for Ki67. Giant cells were only positive for vimentin, suggesting a mesenchymal origin. Giant cells have been identified in humans with carcinosarcomas of the nasal cavity and in the pulmonary carcinosarcoma of the aforementioned domestic shorthair cat.3 In the cat of the present report, some areas of the epithelial component resembled olfactory neuroblastoma because of the presence of small acini with cuboidal cells, but the absence of neuron-specific enolase expression eliminated this diagnosis. Immunoreactivity for S100 is unusual in myofibroblastic sarcomas, although it could be evident in myofibroblastic sarcomas that are located in the head given the neural crest origin of some mesenchymal structures.10
Prognosis for animals of any species with carcinosarcomas is poor. Carcinosarcomas in cats are typically aggressive with rapid death or the need for euthanasia. In the case described in the present report, the cat was euthanized for reasons of animal welfare. Increased aggressiveness of carcinosarcomas in humans has been shown to be associated with predominance of sarcomatous elements; however, in this cat, the epithelial component of the tumor predominated. Additionally, higher metastatic potential has been observed in carcinomas with epithelial mesenchymal transition, which is characterized by the vimentin-specific labeling of epithelial cells.11 In the cat of the present report, this transition was marked and also was more pronounced than that observed in the unique reported case of pulmonary carcinosarcoma with this characteristic in a domestic shorthair cat.3 High-level expression of Ki67 is often considered a marker of aggressiveness in tumors because it denotes active proliferation. In the cat of the present report, a high level of expression of Ki67 was seen in the epithelial cells with a lesser level of expression in the spindle-shaped cells, which suggested more aggressiveness of the epithelial component of the tumor. Carcinosarcoma metastases can be composed of either epithelial or sarcomatous elements or both.3 In this cat, vessel invasion appeared to be mainly composed of epithelial cells; however, lung metastases were composed of variable amounts of both epithelial and sarcomatous components.
In the cat of the present report, the clinical signs were characteristic of nasal tumors; however, the cat's age was considered unusual for such cases. Nasal tumors most commonly develop in cats of 8 to 10 years of age, and carcinosarcomas in even older animals have been reported. The cat of the present report was 3 to 4 years old. Treatment of cats with nasal tumors depends on the tumor type, and early and accurate diagnosis of nasal carcinosarcomas in humans has been shown to be imperative for a successful treatment outcome.9 Toceranib is increasingly being used as tumor treatment in dogs and cats.12 It is mainly intended for treatment of mast cell tumors and is associated with apparently good results. However, the clinical efficacy of toceranib administration in dogs and cats with other solid tumors is as of yet uncertain. In the case described in the present report, toceranib was administered after the initial diagnosis of fibrosarcoma; however, no notable effect was achieved after 2 months, and treatment was discontinued.
In cats, FeLV infection has been associated with several tumors, including olfactory neuroblastomas within the nasal cavity.13 Although carcinosarcomas have been associated with papillomavirus infection in humans,14 no data exist about its possible relation to retrovirus infections, to our knowledge. For the cat of the present report, FeLV infection was considered to be associated with stomatitis15 but unrelated to the development of the tumor.
Reports of cases of carcinosarcoma in the human and veterinary medical literature are scarce. However, as knowledge of this type of tumor improves, the number of reports of carcinosarcoma in humans is increasing.8 The case described in the present report has highlighted the fact that some carcinosarcomas may be misdiagnosed; the initial diagnosis was fibrosarcoma of low-level malignancy, which suggested that the examined biopsy specimen was obtained from the sarcomatous component of the tumor.
Acknowledgments
The authors received no financial support for the research, authorship, or publication of this article.
Presented in poster form at the 28th Reunión de la Sociedad Española de Anatomía Patológica Veterinaria, Zaragoza, Spain, June 2016.
References
1. Reed N, Gunn-Moore D. Nasopharyngeal disease in cats: 2. Specific conditions and their management. J Feline Med Surg 2012;14:317–326.
2. Mukaratirwa S, van der Linde-Sipman JS, Gruys E. Feline nasal and paranasal sinus tumours: clinicopathological study, histomorphological description and diagnostic immunohis-tochemistry of 123 cases. J Feline Med Surg 2001;3:235–245.
3. Ghisleni G, Grieco V, Mazzotti M, et al. Pulmonary carcinosarcoma in a cat. J Vet Diagn Invest 2003;15:170–173.
4. Herráez P, Rodríguez F, Ramírez G, et al. Multiple primary digital apocrine sweat gland carcinosarcoma in a cat. Vet Rec 2005;157:356–358.
5. Kim H, Nakaichi M, Itamoto K, et al. Malignant mixed tumor in the salivary gland of a cat. J Vet Sci 2008;9:331–333.
6. Fusaro L, Panarese S, Brunetti B, et al. Quantitative analysis of telomerase in feline mammary tissues. J Vet Diagn Invest 2009;21:369–373.
7. Yamamoto R, Suzuki K, Uchida K, et al. Pancreatic carcinosarcoma in a cat. J Comp Pathol 2012;147:223–226.
8. Cavicchioli L, Ferro S, Callegari C, et al. Carcinosarcoma of the biliary system in a cat. J Vet Diagn Invest 2013;25:562–565.
9. Lim AL, Zahirrudin Z, Pua KC. A rare case of nasopharyngeal carcinosarcoma. Med J Malaysia 2012;67:428–429.
10. Bell CM, Schwarz T, Dubielzig RR. Diagnostic features of feline restrictive orbital myofibroblastic sarcoma. Vet Pathol 2011;48:742–750.
11. Thiery JP. Epithelial-mesenchymal transitions in tumour progression. Nat Rev Cancer 2002;2:442–454.
12. London C, Mathie T, Stingle N, et al. Preliminary evidence for biologic activity of toceranib phosphate (Palladia(®)) in solid tumours. Vet Comp Oncol 2012;10:194–205.
13. Schrenzel MD, Higgins RJ, Hinrichs SH, et al. Type C retroviral expression in spontaneous feline olfactory neuroblastomas. Acta Neuropathol 1990;80:547–553.
14. Hickman RA, Bradshaw AD, Cassai N, et al. A rare case of anal carcinosarcoma with human papilloma virus infection in both biphasic tumor elements: an immunohistochemical, molecular and ultrastructural study. Papillomavirus Res 2016;2:164–166.
15. Kornya MR, Little SE, Scherk MA, et al. Association between oral health status and retrovirus test results in cats. J Am Vet Med Assoc 2014;245:916–922.
