Pathology in Practice

Joanna E. Hyland Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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Eva A. Sartin Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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Elizabeth A. Spangler Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

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History

An 8-year-old spayed female domestic longhair cat was referred to Auburn University Small Animal Teaching Hospital for evaluation of abdominal distension. Two years earlier, a diagnosis of chronic renal failure had been made, and the cat was receiving fluids SC every 2 weeks. Three weeks prior to the referral evaluation, the owners noted the development of abdominal distension and that the cat had decreased appetite, activity, and frequency of bowel movements.

Clinical and Gross Findings

On physical examination, the cat was quiet and lethargic and had signs of depression; the eyes were sunken, and pinching the skin resulted in a slight skin tent. On the basis of these findings, the cat was estimated to be 5% dehydrated. Abdominal palpation elicited signs of pain, and an abdominal fluid wave was detected. A large, firm, irregular mass was palpated in the area of the spleen, but detailed interpretation was not possible because of severe ascites. Serum biochemical analysis revealed hypoproteinemia (5.84 g/dL; reference interval, 6.2 to 7.7 g/dL), hyperbilirubinemia (0.6 mg/dL; reference interval, 0.1 to 0.2 mg/dL), azotemia (creatinine concentration, 3.1 mg/dL [reference interval, 0 to 2.0 mg/dL]; SUN concentration, 57.9 mg/dL [reference interval, 5 to 30 mg/dL]), hyperglycemia (140 mg/dL; reference interval, 58 to 116 mg/dL), and low serum iron concentration (34 μg/dL; reference interval, 48 to 175 μg/dL). Hematologic abnormalities included nonregenerative anemia (Hct, 25.9%; reference interval, 30% to 45%), neutrophilia (12.615 × 103 neutrophils/μL; reference interval, 2.5 × 103 neutrophils/μL to 12.5 × 103 neutrophils/μL), and lymphopenia (0.403 × 103 lymphocytes/μL; reference interval, 1.5 × 103 lymphocytes/μL to 7.0 × 103 lymphocytes/μL). A fluid sample was collected via abdominocentesis for microscopic examination; on the basis of those findings, the fluid was classified as a high-protein transudate (nucleated cell count < 5,000 cells/L; protein concentration, 3.1 g/dL) with 80% nondegenerate neutrophils, 18% macrophages, and 2% small lymphocytes, but no infectious organisms or neoplastic cells were seen. Abdominal ultrasonography revealed a markedly enlarged spleen (from which fine-needle aspirate samples were collected) with variable echogenicity, a small left kidney, an enlarged right kidney (twice the size of the left kidney) with mild hydronephrosis, bilateral adrenal gland enlargement of uncertain relevance, and a mildly coarse, hyperechoic liver. Thoracic radiography did not reveal abnormalities. Splenectomy and liver biopsies were performed following cytologic evaluation of the splenic aspirate samples. At surgery, the spleen was diffusely enlarged, dark red to gray, and firm. It was comma shaped, had rounded edges, was approximately 10.0 × 5.0 × 3.0 cm, and was covered by strands of fibrin (Figure 1).

Figure 1—
Figure 1—

Photograph of the markedly enlarged spleen removed during surgery from a cat that was evaluated because of abdominal distension and decreased appetite, activity, and frequency of bowel movements. The spleen has been fixed in formalin; it is comma shaped and has rounded edges. Notice the presence of fibrin strands and icteric perisplenic adipose tissue. Bar = 3 cm.

Citation: Journal of the American Veterinary Medical Association 242, 5; 10.2460/javma.242.5.627

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

Histopathologic and Cytologic Findings

Microscopically, smears of the ultrasound-guided fine-needle aspirate samples obtained from the spleen were densely cellular and consisted primarily of well-granulated mast cells. The mast cells had mild anisocytosis and anisokaryosis with rare binucleation (Figure 2). Following splenectomy, histologic examination of sections of spleen tissue revealed complete obliteration of normal parenchyma by neoplastic round cells (Figure 3). The cells had a moderate amount of granular, poorly stained cytoplasm and large, round, vesicular, hyperchromatic nuclei with marginated chromatin and prominent nucleoli. The cytoplasmic granules were metachromatic after staining with periodic acid-Schiff or toluidine blue stain. The mitotic rate was moderate, with 3 mitoses/5 (400X) fields. The splenic capsule was thickened by layers of fibrin. Histologic examination of liver biopsy specimens revealed randomly distributed, multifocal nodular masses composed of neoplastic round cells similar to those seen in the spleen (Figure 4).

Figure 2—
Figure 2—

Photomicrograph of a smear made from a fine-needle aspirate sample obtained during surgery from the spleen of the cat in Figure 1. Notice that the sample is densely cellular; most of the cells are well-granulated mast cells. Modified Wright stain; bar = 50 μm.

Citation: Journal of the American Veterinary Medical Association 242, 5; 10.2460/javma.242.5.627

Figure 3—
Figure 3—

Photomicrograph of a section of the spleen from the cat in Figure 1. There is complete obliteration of normal parenchyma by neoplastic round cells. H&E stain; bar = 200 μm.

Citation: Journal of the American Veterinary Medical Association 242, 5; 10.2460/javma.242.5.627

Figure 4—
Figure 4—

Photomicrograph of a section of a liver biopsy specimen obtained from the cat in Figure 1. Throughout the liver are multifocal nodular masses composed of neoplastic mast cells, which are similar to those seen in the spleen. The cytoplasmic granules appear metachromatic following staining with either periodic acid-Schiff or toluidine blue stain. Toluidine blue stain; bar = 100 μm.

Citation: Journal of the American Veterinary Medical Association 242, 5; 10.2460/javma.242.5.627

Morphologic Diagnosis and Case Summary

Morphologic diagnosis and case summary: splenic mast cell tumor with metastasis to the liver in a cat.

Comments

The case described in the present report was consistent with visceral mast cell tumor of cats. One study1 indicated that mast cell disease is the most common splenic disease of cats, accounting for 66 of 455 (approx 15%) cases of feline splenic disease over a 6-year period. Ages of cats reported to have mast cell disease range from 3 to 16 years, with no apparent sex predilection.2 Feline mastocytosis exists in 2 forms that can occur simultaneously but are considered to be separate diseases. The more common form is cutaneous mast cell tumors, whereas systemic mastocytosis is the visceral form of the disease. Systemic mastocytosis is characterized by primary involvement of the spleen or intestines.3 For cats, it has been reported that approximately 20% of all mast cell tumors occur primarily in the spleen, with metastasis to the liver, lymph nodes, bone marrow, and lungs.4 The most common clinical signs include decreased appetite, vomiting, and diarrhea, all of which are often caused by gastric or duodenal ulceration. Ulceration of the gastrointestinal tract is thought to be due to excessive histamine production by the neoplastic mast cells.5

Results of cytologic examination of fine-needle aspirate samples obtained from an affected organ are usually diagnostic, and additional procedures for disease staging include radiography, cytologic examination of bone marrow aspirate samples and buffy coat smears, and histologic examination of biopsy specimens of affected tissues. Mastocythemia, anemia, and bone marrow involvement may be present.6 Unlike dogs, mastocythemia in cats is limited to those cats with mast cell tumors and is most frequently associated with the splenic visceral form.2 Abdominal ultrasonography is useful for identifying splenomegaly. Ultrasonographically, the spleen of a cat with systemic mastocytosis has been described as either diffusely hypoechoic or nodular or mottled.7 Similar findings have been described in lymphoproliferative and myeloproliferative diseases.7 Therefore, these diseases cannot be differentiated solely on the basis of ultrasonographic findings. Abdominal effusion is common with splenic mastocytosis; however, abdominal effusion is a nonspecific finding that has also been reported in association with other hematologic neoplasms.7

Often, splenectomy results in marked clinical improvement, including a resolution of emesis, and survival time for cats with mastocythemia following splenectomy can be as long as 38 months.2 Administration of antihistamines for at least 48 hours before surgery is performed is highly recommended. Chemotherapy (lomustine administration) appears to be ineffective when administered as a primary treatment to cats with splenic mast cell tumor or as a treatment for secondary cutaneous mast cell tumors following splenectomy.5 Despite improvement following splenectomy, the median survival time of cats with visceral mastocytosis is short (283.5 days), and prognosis should therefore be guarded.8 Death or euthanasia is often the result of anaphylactoid reaction or gastrointestinal tract hemorrhage and perforation.4

The cat of the present report was evaluated because of signs of depression, lethargy, and ascites, rather than because of emesis. There was no evidence of mastocythemia. The low serum iron concentration was attributed to sequestration of blood in the spleen as a result of chronic inflammation. Multiple factors, including dehydration, mild chronic renal disease, chronic inflammation, and possible gastrointestinal bleeding, were believed to contribute to the azotemia, hypoproteinemia, and anemia in the cat of this report. Hyperglycemia, neutrophilia, and lymphopenia were consistent with stress. The high total bilirubin concentration was consistent with mild intrahepatic cholestasis and could have been associated with infiltration of the liver by neoplastic cells. Ultrasonographically, the spleen was described as enlarged with variable echogenicity. The definitive diagnosis of mast cell tumor was made on the basis of cytologic and histopathologic findings. The cat recovered well after surgery but continued to be anorexic with worsening anemia (PCV, 13%) the following day. It was suspected that gastric or intestinal hemorrhage may have occurred. The cat was euthanized 2 days after splenectomy because of the continued decline of its clinical condition. A necropsy was not permitted.

References

  • 1. Spangler WL, Culbertson MR. Prevalence and type of splenic diseases in cats: 455 cases (1985–1991). J Am Vet Med Assoc 1992; 201: 773776.

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  • 2. Skeldon NCA, Gerber KL, Wilson RJ, et al. Mastocytemia in cats: prevalence, detection and quantification methods, haematological association, and potential implications in 30 cats with mast cell tumours. J Feline Med Surg 2010; 12: 960966.

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  • 3. Lamm CG, Stern AW, Smith AJ, et al. Disseminated cutaneous mast cell tumors with epitheliotropism and systemic mastocytosis in a domestic cat. J Vet Invest 2009; 21: 710715.

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  • 4. Rogers KS. Mast cell tumors: dilemmas of diagnosis and treatment. Vet Clin North Am Small Anim Pract 1996; 26: 87102.

  • 5. Rassnick KM, Williams LE, Kristal O, et al. Lomustine for treatment of mast cell tumors in cats: 38 cases (1999–2005). J Am Vet Med Assoc 2008; 232: 12001205.

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    • Search Google Scholar
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  • 6. Dank G, Chien MB, London CA. Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats. Am J Vet Res 2002; 63: 11291133.

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  • 7. Hanson JA, Papageorges M, Girard E, et al. Ultrasonagraphic appearance of splenic disease in 101 cats. Vet Radiol Ultrasound 2001; 42: 441445.

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    • Search Google Scholar
    • Export Citation
  • 8. Litster AL, Sorenmo KU. Characterization of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia. J Feline Med Surg 2006; 8: 177183.

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    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Photograph of the markedly enlarged spleen removed during surgery from a cat that was evaluated because of abdominal distension and decreased appetite, activity, and frequency of bowel movements. The spleen has been fixed in formalin; it is comma shaped and has rounded edges. Notice the presence of fibrin strands and icteric perisplenic adipose tissue. Bar = 3 cm.

  • Figure 2—

    Photomicrograph of a smear made from a fine-needle aspirate sample obtained during surgery from the spleen of the cat in Figure 1. Notice that the sample is densely cellular; most of the cells are well-granulated mast cells. Modified Wright stain; bar = 50 μm.

  • Figure 3—

    Photomicrograph of a section of the spleen from the cat in Figure 1. There is complete obliteration of normal parenchyma by neoplastic round cells. H&E stain; bar = 200 μm.

  • Figure 4—

    Photomicrograph of a section of a liver biopsy specimen obtained from the cat in Figure 1. Throughout the liver are multifocal nodular masses composed of neoplastic mast cells, which are similar to those seen in the spleen. The cytoplasmic granules appear metachromatic following staining with either periodic acid-Schiff or toluidine blue stain. Toluidine blue stain; bar = 100 μm.

  • 1. Spangler WL, Culbertson MR. Prevalence and type of splenic diseases in cats: 455 cases (1985–1991). J Am Vet Med Assoc 1992; 201: 773776.

    • Search Google Scholar
    • Export Citation
  • 2. Skeldon NCA, Gerber KL, Wilson RJ, et al. Mastocytemia in cats: prevalence, detection and quantification methods, haematological association, and potential implications in 30 cats with mast cell tumours. J Feline Med Surg 2010; 12: 960966.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Lamm CG, Stern AW, Smith AJ, et al. Disseminated cutaneous mast cell tumors with epitheliotropism and systemic mastocytosis in a domestic cat. J Vet Invest 2009; 21: 710715.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Rogers KS. Mast cell tumors: dilemmas of diagnosis and treatment. Vet Clin North Am Small Anim Pract 1996; 26: 87102.

  • 5. Rassnick KM, Williams LE, Kristal O, et al. Lomustine for treatment of mast cell tumors in cats: 38 cases (1999–2005). J Am Vet Med Assoc 2008; 232: 12001205.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6. Dank G, Chien MB, London CA. Activating mutations in the catalytic or juxtamembrane domain of c-kit in splenic mast cell tumors of cats. Am J Vet Res 2002; 63: 11291133.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7. Hanson JA, Papageorges M, Girard E, et al. Ultrasonagraphic appearance of splenic disease in 101 cats. Vet Radiol Ultrasound 2001; 42: 441445.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8. Litster AL, Sorenmo KU. Characterization of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia. J Feline Med Surg 2006; 8: 177183.

    • Crossref
    • Search Google Scholar
    • Export Citation

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