History

A 13-year-old spayed female domestic shorthair cat was presented to the University of Florida Veterinary Hospital because of vomiting, weight loss, and a palpable abdominal mass.

Clinical and Gross Findings

On physical examination, a mass was palpable in the mid cranial aspect of the abdomen. Initial diagnostic testing included a CBC, serum biochemistry panel, urinalysis, thoracic radiography, and abdominal ultrasonography.

A CBC revealed mild leukocytosis (16,820 WBCs/µL; reference interval [RI], 5,400 to 15,400 WBCs/µL) characterized by mild lymphocytosis (7,670 lymphocytes/µL; RI, 900 to 5,500 lymphocytes/µL) with a neutrophil count within reference limits (8,700 neutrophils/µL; RI, 2,300 to 9,800 neutrophils/µL). Mild (1⁺) toxic changes were noted in the neutrophils consisting of many (> 30%) Döhle bodies and interpreted as accelerated hematopoiesis likely secondary to cytokine stimulation in response to low-grade inflammation. Small, mature lymphocytes predominated in the lymphoid population, with fewer intermediate-sized lymphocytes with mature chromatin; this lymphocyte distribution was suspected to be secondary to physiologic or epinephrine-induced lymphocytosis, yet an emerging lymphoproliferative disorder could not be entirely excluded and monitoring of the lymphocyte population was recommended. Serum biochemical abnormalities included mildly increased creatine kinase (869 U/L; RI, 20 to 440 U/L), aspartate aminotransferase (77 U/L; RI, 13 to 45 U/L), alanine aminotransferase (263 U/L; RI, 25 to 79 U/L), and alkaline phosphatase (56 U/L; RI, 8.5 to 33.5 U/L) activities; moderate hyperglycemia (275 mg/dL; RI, 72.1 to 156.1 mg/dL); mild hypernatremia (158.1 mEq/L; RI, 148 to 155.3 mEq/L); moderate hypokalemia (2.5 mEq/L; RI, 3.5 to 5.4 mEq/L); and mild hypercalcemia (11.4 mg/dL; RI, 8.8 to 10.4 mg/dL).

Abdominal ultrasonography revealed a large (at least 5.2 X 4 cm) hypoechoic right kidney with decreased corticomedullary distinction, surrounding steatitis, and moderate right renal and ileocecocolic lymphadenomegaly. The left renal pelvis was mildly dilated and contained a focal, lobular, echogenic structure measuring 4 mm in diameter; there was mildly decreased renal corticomedullary distinction, likely compatible with chronic kidney disease. Additionally, a hypoechoic jejunal mass with loss of normal wall layering, multifocal small intestinal and cecal muscularis layer thickening, and mild hepatomegaly and splenomegaly with small, hypoechoic nodules in both organs were observed. The right pancreatic limb was mildly enlarged with hypoechoic nodules, and mild left adrenomegaly with scant peritoneal effusion was seen. Peritoneal effusion was not sufficient for collection.

Analysis of a urine sample obtained by means of cystocentesis showed a specific gravity of 1.011 with 1⁺ hematuria, 1⁺ proteinuria, and a pH of 6.5. Sulfosalicylic acid precipitation confirmed the presence of 1⁺ proteinuria. Lipid droplets, mucous clumps and threads, squamous epithelial cells, and 4 to 8 leukocytes/low-power field were noted on examination of a wet-mount preparation of the sediment (Figure 1). A dry-mount preparation was created by placing a drop of the urine sediment in a cytology funnel and centrifuging for 5 minutes. The preparation was stained with aqueous Romanowsky-type stain, and examination revealed poorly staining round cells.

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Photomicrographs of an unstained wet-mount preparation (A) and a stained dry-mount preparation (B) of urine sediment from a 13-year-old spayed female domestic shorthair cat with vomiting, weight loss, and a palpable abdominal mass. A—The unstained wet-mount preparation revealed numerous unidentified cells. Bar = 20 µm. B—The dry-mount preparation revealed poorly staining round cells. Aqueous Romanowsky-type stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.06.0307

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Cytologic Findings

Numerous mononuclear cells with partial granular staining were observed on the dry-mount preparation stained with aqueous Romanowsky-type stain. Therefore, Wright-Giemsa staining was performed for further identification (Figure 2). Mast cells and eosinophils predominated, with fewer transitional epithelial cells and small lymphocytes. The mast cells were round with a moderate amount of colorless cytoplasm containing numerous fine, pale-purple granules. The round to oval, paracentral to central nucleus was 1.5 times the diameter of an erythrocyte with coarse chromatin and no nucleolus. Anisocytosis and anisokaryosis were minimal with rare binucleation seen.

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Photomicrographs of a cytocentrifuged, dry-mount preparation of urine sediment (A), a fine-needle aspirate from the enlarged right kidney (B), and a fine-needle aspirate from an enlarged colic lymph node (C). Notice the mast cells in all 3 specimens. In the specimen from the kidney, cells are variably preserved, and ultrasound coupling gel (arrows) can be seen in the background. Wright-Giemsa stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.21.06.0307

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Results of cytologic examination of a fine-needle aspirate of the right kidney were compatible with mast cell tumor (Figure 2). Cytologic examination of an aspirate from a colic lymph node demonstrated metastasis, indicating mast cell disease within an area drained by this node, likely the intestines. Many atypical mast cells were arranged individually and in loosely associated sheets. The cells contained moderate amounts of colorless cytoplasm with pale-purple granules and punctate vacuoles. The round to oval nucleus had reticular chromatin and a small, round, distinct nucleolus. Moderate anisokaryosis with occasional binucleation and karyomegaly was noted. Examination of a splenic aspirate revealed low numbers of well-granulated mast cells with a heterogenous lymphoid population. The findings raised concerns regarding early or focal metastasis, and monitoring with potential resampling was recommended to reassess this population. Mastocytemia was not observed on a buffy-coat preparation.

An oncology consultation was offered, but palliative care was elected with initiation of corticosteroids and gastrointestinal protectants. The patient was lost to follow up.

Morphologic Diagnosis and Case Summary

Mast cell tumor with renal involvement, mast cell-uria, and eosinophiluria, with colic lymph node metastasis and probable intestinal involvement.

Comments

Mast cell-uria and eosinophiluria are uncommon findings, with the first reported veterinary case¹ of mast cell-uria recently published and involving a cat with a mast cell tumor of the bladder wall. In the case reported here, a mast cell tumor with renal involvement was suspected along with secondary mast cell-uria, although metastasis along the ureter or urinary bladder wall could not be excluded. Considering the imaging findings and metastasis to the colic lymph node, which drains the ileum, cecum, and colon, mast cell disease involving the intestines was also considered likely. Possible additional areas of metastasis in this case include the pancreas, liver, and spleen although a cytologic sample was obtained only from the spleen, and examination identified an increased population of mast cells but was inconclusive for definitive metastatic disease. Unfortunately, the extent of the metastatic mast cell disease was not entirely determined in this cat. Published cases of feline visceral mast cell disease aside from intestinal, splenic, or hepatic lesions are lacking, and reports of atypical locations are needed to improve our understanding of mast cell disease pathogenesis, especially given that the initial site of mast cell disease was not determined in this case. This case also emphasizes the importance of cytologic examination of the urine sediment when atypical or unknown cells are seen on wet-mount preparations.

The initial microscopic evaluation of urine sediment involves use of an unstained wet-mount preparation to quantify RBCs, WBCs, epithelial cells, and casts and identify any infectious agents. Cytologic examination of a dry-mount preparation of the urine sediment is used to evaluate abnormal findings identified in the wet-mount preparation and is a more sensitive indicator of bacteriuria and cellular morphology.² Recent studies^3,4 concluded that examination of air-dried, Romanowsky-stained preparations of the urine sediment resulted in improved detection of bacteriuria, compared with examination of unstained, wet-mount preparations. Although evaluation of wet-mount preparations of urine sediment stained with a urine sediment stain (Sedi-Stain; BD Biosciences) or new methylene blue can differentiate WBCs from epithelial cells,⁵ the use of stained dry-mount preparations is preferred.

Cytologic examination of dry-mount preparations of urine sediment aids in further evaluating atypical or suspected neoplastic cells, and dry-mount preparations are more stable than wet-mount preparations. Neoplastic cell populations previously identified include transitional cell carcinoma (urothelial carcinoma), round cell neoplasia (eg, lymphoma),^6–8 and most recently mast cell-uria.¹ Although the use of urine cytologic examination is beneficial, limitations include poorly exfoliative lesions, concurrent urinary tract inflammation, and altered cellular morphology secondary to urine-induced cell degeneration. Cell preservation variability may result in reduced diagnostic accuracy of urothelial cell atypia.^9,10

Romanowsky-type stains are commonly used in veterinary medicine and involve a variety of combinations of red and blue dyes, methanol, and phosphate buffers.¹¹ Rapid Romanowsky-type stains (Diff-Quik [Dade Behring Inc] and Hemacolor [Merck KGaA]) are preferred in clinic owing to low cost and short (3 to 5 minutes) turnaround time. Substantial staining variations are observed among rapid aqueous Romanowsky-type stains, compared with classic methanolic Romanowsky-type stains (eg, Wright-Giemsa stain). Aqueous Romanowsky-type stains may not stain granules of mast cells, basophils, or large granular lymphocytes,¹² although failure of methanolic Romanowsky-type stains to stain mast cells is also documented.¹³ In the present case, we observed an absence of mast cell granule staining with the use of an aqueous Romanowsky-type stain, but granules were visualized with the use of a methanolic Romanowsky-type stain (ie, Wright-Giemsa stain). This allowed identification of mast cells in the urine sediment, kidney, colic lymph node, and spleen. Because variations exist among the Romanowsky-type stains, in certain situations more than one type of stain may be needed for diagnosis.

Mast cell tumors are typically categorized as cutaneous or visceral and are further subdivided into gastrointestinal and splenic mast cell tumors.^14,15 Alternative classification schemes propose division into cutaneous, intestinal, and hematopoietic system (spleen, liver, and bone marrow) tumors.^16,17 The occurrence of feline mast cell tumors varies, but they are the second most common type of cutaneous tumor, representing 8% to 21% of cutaneous neoplasms, with visceral mast cell tumors accounting for roughly 50% of mast cell disease in cats.^18–23 Litster and Sorenmo²⁴ evaluated a subset of feline mast cell cases and found that 12% (5/41) were splenic mast cell tumors, 5% (2/41) had lymph node involvement with no evidence of cutaneous disease, 2% (1/41) were intestinal tumors, and the remainder were cutaneous disease. Splenic mast cell tumors comprise roughly 15% to 27% of all splenic tumors in cats.^25,26 Gastrointestinal mast cell tumors are reported to be rare in cats, yet are still recorded as the third most common tumor in this site, following lymphoma and adenocarcinoma.²⁷ Other sites are uncommonly reported in the literature.^15,27–32 To our knowledge, there are no reports of domestic feline renal mast cell tumor with secondary mast cell-uria in the literature. A case of a male Sumatran tiger (Panthera tigris) with metastatic mast cell disease and splenic, hepatic, lymphoid, renal, and pulmonary infiltration has been reported, but cells were not seen in the urine.³³

Evidence of mast cell disease in the urine is rare, but the presence of mast cells should not be overlooked. Cytologic examination of dry-mount preparations of urine sediment is simple and inexpensive. This test can easily be performed in clinic as a screening test or for laboratory submission.