Pathology in Practice

Bayard S. Grillis An externship student at the Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Elizabeth W. Howerth Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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Daniel R. Rissi Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602.

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History

A 9-year-old spayed female domestic shorthair cat was evaluated at a private veterinary clinic because of a 24-hour history of not drinking water following routine vaccination against rabies virus, feline herpesvirus-1, feline calicivirus, and feline panleukopenia virus.

Clinical and Gross Findings

Physical examination revealed dehydration; the cat was administered fluid therapy and discharged from the clinic. Nine days later, the cat was returned to the same clinic because of anorexia. A diagnosis of upper respiratory tract infection was made, and the cat was treated with doxycycline and supplemental lysine, PO, for 10 days. Thoracic radiography did not reveal any notable findings. Treatment was changed from doxycycline to azithromycin PO, fluids SC, mirtazapine PO, and a nasal decongestant for 3 days at home, but the cat developed anorexia and dyspnea 2 days after treatment started. Clinicopathologic analyses revealed high blood glucose concentration, which was attributed to stress. Intravenous fluid therapy and antimicrobials were administered, but no improvement was evident and the cat became disoriented and ran into a wall. Repeated physical examination revealed horizontal nystagmus with a fast phase to the left. The pupillary light reflex was absent in the right eye but normal in the left eye. The cat was ataxic in all 4 limbs with no conscious proprioception in the right forelimbs. Euthanasia (by means of barbiturate overdose) was elected by the owner because of the deterioration of the cat's condition despite supportive care.

Grossly, the cat was in moderate body condition. The cerebellar vermis was partially herniated through the foramen magnum. The brain was difficult to remove because of multiple adhesions to the right rostral portion of the skull base from a white to pale yellow, irregular, moderately firm mass that originated from the right cribriform plate and extended along the floor of the cranial vault to near the right tympanic bulla (Figure 1). The associated frontal telencephalic lobes were compressed and soft and had an irregular surface. A longitudinal sectioning of the head revealed that the mass had also infiltrated and effaced the mid to caudal portions of the nasal cavity. Multiple tissue samples were collected and fixed in neutral-buffered 10% formalin, routinely processed, and stained with H&E stain for histologic examination.

Figure 1—
Figure 1—

Photographs of the calvarium (A) and a cross section of the nasal cavity and calvarium (B) of a 9-year-old cat with a 3-week history of anorexia, dyspnea, and progressive neurologic signs. In panel A, notice the white soft tissue mass (arrow) in the right cranioventral portion of the calvarium. In panel B, a white soft tissue mass (arrow) extends from the right caudal nasal sinuses through the right aspect of the cribriform plate and into the right cranial portion of the calvarium.

Citation: Journal of the American Veterinary Medical Association 251, 3; 10.2460/javma.251.3.303

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

Histopathologic Findings

Histologically, the mass in the nasal cavity and cranial vault was a poorly demarcated and densely cellular neoplasm that multifocally extended into the surrounding tissues (Figure 2) with disruption of the ethmoid turbinates and meninges and compression of the rostral telencephalic cortex. Neoplastic cells were arranged in multiple acini and tubules or small packets with variable accumulations of faintly eosinophilic mucinous material supported by marked desmoplasia. There were small areas of coagulative necrosis admixed with neutrophils occupying approximately 5% of the total tumor area. Neoplastic cells had a moderate amount of polygonal, eosinophilic, homogeneous cytoplasm with indistinct cell borders. Nuclei were round and had finely stippled or dense chromatin and 1 or 2 nucleoli. There was moderate anisocytosis and anisokaryosis, and the mitotic activity ranged from 1 to 2 mitoses/hpf (400X). Disruption of the ethmoid turbinates was characterized by invasion of their osseous structure in multiple areas. There were multiple foci of lymphoplasmacytic inflammation throughout the neoplasm. The disrupted meningeal areas had mild lymphoplasmacytic inflammation, and the compressed rostral telencephalon had multiple areas of neuronal damage characterized by hypereosinophilic neurons with pyknotic nuclei. No evidence of infection was observed in the nasal cavity.

Figure 2—
Figure 2—

Photomicrographs of a section from the intranasal mass in the cat in Figure 1. In the main image, notice a large mass of neoplastic cells (asterisk) that has disrupted the ethmoid turbinates (right). H&E stain; bar = 500 μm. Inset—At higher magnification, notice that neoplastic cells have formed small tubules (arrows). H&E stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 251, 3; 10.2460/javma.251.3.303

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: unilateral (right-sided) nasal adenocarcinoma, with invasion through the cribriform plate and into the right frontal telencephalic lobe, and cerebellar herniation through the foramen magnum.

Case summary: nasal adenocarcinoma with rostral cerebral invasion in a cat.

Comments

Nasal neoplasms account for approximately 1% of all types of neoplasia in felids, but they are a common cause of nasal disease in domesticated cats.1,2 The median age of cats at the time of diagnosis of a nasal tumor is approximately 10 years. Although both sexes appear to be affected, there may be a predilection for males.3 There are many types of nasal neoplasms in cats, which can be classified as epithelial (eg, adenoma, adenocarcinoma, squamous cell carcinoma, undifferentiated carcinoma, and olfactory neuroblastoma) or mesenchymal (eg, lymphoma, fibrosarcoma, plasma cell tumor, and melanoma).3,4 Similar to the cat of the present report, most feline nasal neoplasms are primary and malignant, with lymphomas and adenocarcinomas being the most commonly reported types.3 These tumors usually compress and invade adjacent tissues and typically lead to secondary bacterial infections.3,5

The gross appearance of malignant tumors is usually similar, regardless of whether they are epithelial or mesenchymal in origin.6 Therefore, histopathologic findings are critical for differentiating tumor types and subtypes, although no prognostic value has ever been proven useful from these classifications.4 A recent study7 revealed that nasal lymphomas in cats are more likely to be misdiagnosed as carcinomas on the basis of examination of H&E-stained sections. However, immunohistochemical analysis can be a valuable aid in differentiating these tumors and allowing determination of the correct diagnosis, formulation of a therapeutic plan, and provision of an accurate prognosis. The main immunomarkers used to identify carcinomas include anti-cytokeratin antibodies (clones AE1 and AE3), whereas lymphomas can be confirmed by use of anti-CD3 and anti-CD79a antibodies.7 Immunohistochemical analyses were not necessary in the case described in the present report because the neoplasm was well differentiated with clearly defined morphological characteristics (eg, acini, tubules, and mucinous secretions) that were consistent with a nasal adenocarcinoma. Nasal adenocarcinomas are likely one of the most common nasal tumors in cats because they originate from the superficial respiratory epithelium that is found throughout the entire nasal cavity.3 Different morphological types of feline nasal adenocarcinomas have been observed when these tumors develop from sub-mucosal glandular elements or minor salivary glands.3 These tumors have been further categorized as acinous adenocarcinomas, mucinous adenocarcinomas, cystic adenocarcinomas, and papillary adenocarcinomas.3 On the basis of its histologic features, the tumor in the cat of the present report was classified as an acinar adenocarcinoma.

Clinical signs are typically not definitive for differentiation of nasal tumors from other upper tract respiratory diseases.2,8 The cat of the present report had a more abrupt onset of clinical signs than is typical, which was likely a result of the disruption of the cribriform plate and compression of the forebrain. Although disruption of the cribriform plate appears to be more commonly associated with nasal neoplasia than with rhinitis, this difference has not been shown to be statistically valid.9,10 Although no particular type of neoplasia has a predilection for invasion through the cribriform plate,9 it is known that seizures may develop more often in cats with neuroblastomas, compared with cats with other tumors, because of the extension of the neoplasm into the brain.3 Appropriate diagnostic imaging in affected cats with neurologic compromise may include radiography, CT, or MRI. The dorsoventral (intraoral) view of the nasal cavity and the rostrocaudal view of the frontal sinuses are useful in most cats, but rostrocaudal radiography in breeds of cats with a short nose, such as Persians, may be more difficult.11 The lateral view is useful in identifying lesions that may be causing neurologic signs by their extension through the nasal or frontal bones or disruption of the cribriform plate.11 Radiography aids in the presumptive diagnosis of nasal neoplasms, and radiographic changes most closely associated with neoplasia include displacement of midline structures, unilateral generalized soft tissue opacity, unilateral generalized loss of turbinate detail, and evidence of bone invasion.11 The CT findings that are significantly associated with nasal neoplasia include unilateral abnormal soft tissue or fluid within the sphenoid sinus, frontal sinus, or retro-bulbar space as well as unilateral lysis of the ethmoid bones and turbinates, dorsal and lateral aspects of the maxilla, vomer bone, and ventral aspect of the maxilla and bilateral lysis of the orbital lamina.10

Histologic examination of biopsy specimens is the gold standard for diagnosis and typing of nasal neoplasms. Various techniques can be used to obtain biopsy specimens of nasal tumors in cats; however, rhinoscopy should not be relied upon for collection of nasal biopsy specimens in such cases because a sample from deep within the lesion is desirable for histologic examination.12 Cytologic methods, including examination of brush samples and imprint preparations, can be helpful, but they should not be solely relied upon for definitive diagnosis.5

The lack of studies regarding treatment of feline nasal adenocarcinoma makes it difficult to develop the most effective treatment plan, especially as most available data are from studies in which nasal lymphoma was investigated. Radiation therapy has been the treatment of choice, although chemotherapy is also widely used to treat nasal tumors and combination therapy has been advocated.13 A recent study8 evaluating 97 cats with nasal lymphoma revealed no significant difference in outcome between cats treated with only radiation therapy, only chemotherapy, or a combination of both. Photodynamic therapy has been used to effectively treat a cat with nasal adenocarcinoma.14 Even with treatment, the prognosis is usually guarded to poor for cats with nasal neoplasms. Thus, feline nasal adenocarcinoma is a challenging disease that requires early diagnosis, which is best achieved through histologic examination of tumor sections. However, more research is needed to improve the prognosis for most cats affected by this type of neoplasia.

References

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