What Is Your Diagnosis? Fine‐Needle Aspirate From a Lingual Mass in a Cat

A 15-year-old neutered male domestic shorthair cat was drooling and had difficulty eating for 1 month. The cat had a history of intermittent upper respiratory disease since being a kitten, but no signs of respiratory illness during the prior year. On physical examination, an ulcer (~1 × 1 cm) in the center of the dorsal aspect of the tongue and a mass on the ventral aspect of the tongue were noted. Amoxicillin/clavulanic acid and buprenorphine therapy were initiated. Clinical signs and lesion appearance did not improve after 1 week. Chest radiographs at this time revealed a mass (~1.3 cm2) in the right caudal lung lobe, and doxycycline therapy was initiated. Reassessment after another week also showed no improvement in clinical signs, and the cat was referred. During physical examination at the Ontario Veterinary College teaching hospital, the previously noted tongue lesion and hypersalivation were confirmed. Point-of-care laboratory and bi-cavitary ultrasound assessment did not show abnormalities. Review of the prior radiographs considered the lung mass to be most compatible with a neoplasm. The cat was anesthetized for placement of an esophageal feeding tube, and aspiration and punch biopsy of the lingual mass (Figure 1). The aspirate of the tongue mass yielded moderately cellular slides with mild blood contamination, suppurative inflammation, and necrotic debris. Neither erythrophagia nor heme pigments were noted. Multiple, variably sized clusters of cohesive epithelial cells with a polygonal shape, distinct cell borders, and small amounts of basophilic cytoplasm were present. The nuclei were round to oval with fine chromatin and a single, prominent, centrally located nucleolus. Admixed throughout the background were occasional vacuolated macrophages and non-degenerate neutrophils. Cells in some clusters had perinuclear vacuoles, and there was up to threefold anisokaryosis and anisocytosis. The cytologic interpretation was carcinoma with pyogranulomatous inflammation and necrosis. Sections from the incisional biopsy showed a poorly circumscribed mass composed of neoplastic cuboidal to columnar epithelial cells arranged in tubules and clusters located in the subepithelial stroma (Figure 2). Cells had a small amount of cytoplasm and large round to oval nuclei with a prominent central nucleolus. There was up to threefold anisokaryosis, and mitotic figures were readily identified. Collagen bundles dissected the clusters of epithelial cells and were admixed with neutrophils, fibrin, and cellular debris. The interpretation was adenocarcinoma with necrosis and glossitis. Since the upper surface of the tongue is devoid of glands, the mass was considered most likely a metastatic lesion. Immunohistochemistry (IHC) for cytokeratin-7 (CK-7) and thyroid transcription factor 1 (TTF-1) showed cytoplasmic labeling for CK-7 and absence of TTF-1, consistent with an epithelial neoplasm of non-pulmonary origin. Therapy with toceranib was initiated. Due to the likely metastatic nature of the tongue mass, achieving stable disease, though not regression, was considered possible. The cat's condition declined over the subsequent 2 weeks, and abdominal effusion and respiratory distress developed. Abdominal ultrasound showed a right renal mass effect, a left pancreatic lobe mass, and hepatic nodules. Fine needle aspirates of the renal mass yielded cohesive large cells with similar cytomorphology to those from the tongue mass and were interpreted as carcinoma (Figure 3). Aspirates from the liver were cytologically unremarkable. Due to the progressive disease and poor quality of life, the cat was euthanized. A postmortem examination was not permitted. Since the cytologic appearance of the tongue and renal mass was similar, and there are reports in humans of renal cell carcinoma metastatic to the oral cavity, the tongue biopsy was further interrogated by IHC for kidney injury molecule-1 (KIM-1) and CD117 expression. 10% to 20% of the neoplastic epithelial cells were immuno-reactive for KIM-1 (Figure 4). CD117 IHC results were negative. Lingual neoplasms are uncommon in cats. More than 90% of neoplasms in that location are of epithelial origin, and 94% are squamous cell carcinomas 1. In this case, neither the cytologic nor histologic findings were consistent with a squamous cell carcinoma. The histologic features of adenocarcinoma, and location on the dorsal aspect of the tongue, indicated that the mass was most likely a metastasis. Due to the limited size of the punch biopsy, further characterization with a few select IHC assays was pursued. Pulmonary carcinoma metastatic to the digit and tongue was previously reported, but was considered unlikely in this case since TTF-1 IHC was negative 2. The similar cytologic appearance of the lingual and renal samples suggested that the lingual mass could be of renal origin, and in humans, metastases of renal cell carcinoma to the oral cavity have been reported, and they are most often in the tongue and are ulcerated 3. Hence, IHC for KIM-1 was applied. KIM-1 is a highly specific marker of renal tubular epithelium that is upregulated with injury and de-differentiation. Positivity for KIM-1 among feline urothelial neoplasms varied from ~1% to > 50% of cells and was up to 70% in samples of human renal cell carcinoma 4. In this case, 10%–20% of cells were positive, which was considered supportive of renal origin of the tongue mass. CD117 (KIT) positivity was reported in some cases of feline renal carcinoma, but it is not specific for renal tissue 5. Other antigens that might have been useful for assessing a possible renal origin are CK20, aquaporin, and uroplakin-III; however, the limited biopsy size precluded such assays. Histopathologic evaluation of the kidney mass, or of the lesions in the lung, pancreas, and liver, could not be performed; a postmortem examination was declined. This limits confidence in the interpretation. However, the microscopic features of the tongue and renal mass were strikingly similar and comparable to those described for solid renal carcinoma in cats 5. Therefore, tentatively, a pathogenesis whereby a renal carcinoma metastasized to the tongue, resulting in clinical signs of ptyalism and difficulty eating, which then prompted veterinary attention with subsequent identification of additional metastatic masses by imaging and eventual disease progression, has been considered. The authors declare no conflicts of interest.