An abdominal mass on unknown origin in an adult cat
Signalment, clinical history and clinical examination
A 12-year-old female domestic short hair cat was presented to a first opinion veterinarian with a 2 weeks history of anorexia and occasional episodes of vomiting in the last 3 months. The cat was initially treated with symptomatic therapy (antiemetic therapy with maropitant) without any clinical improvement and was then admitted to a veterinary referral centre for further investigations. The cat was not insured therefore a limited budget was available for diagnostic investigations.
Physical examination, haematology and biochemistry
On presentation, the patient was bright, alert and responsive. He was underweight with a body condition score of 2/9 and a slightly distended abdomen. Oral mucous membranes were pink and moist with a capillary refill time of <2 seconds. Heat rate was 150 beats per minute and thoracic auscultation was within normal limits.
Blood samples were collected for haematology and biochemistry. Haematology showed a mild normocytic normochromic poorly regenerative anaemia (PCV 24%, reference range 30-44) and biochemistry showed only a mild elevation in urea (11.4 mmol/L, reference range 5.4-10.7) and a mild decrease in chloride (105 mmol/L, reference range 110-127). Given the history and the absence of any other haematologic abnormalities, the anaemia was considered to be anaemia of chronic disease. Mild elevation in urea with normal creatinine likely reflected dehydration and was confirmed by the evaluation of the urinary specific gravity (1.050). The mild decrease in chloride was interpreted as secondary to vomiting (chloride loss).
Diagnostic imaging
Radiographs and abdominal ultrasound were performed and showed the presence of a well-defined mesenteric cavitary neoformation (4 cm in diameter) adjacent to the proximal duodenum but not connected to it. A minimal amount of abdominal effusion was also noted. No other abnormalities were detected.
Cytology
Ultrasound guided fine needle aspirates from the abdominal mass were suggested and were performed the day after under sedation. Clotting times were evaluated to exclude any coagulation disorder before starting the procedure and they were within reference range (PT 8.5secs, reference range 7.6-11.6secs. APTT 18.7secs, reference range 12.5-25.5secs); platelets were also within reference range (265 x 10^9/L, reference interval 150-600 x 10^9/L) and BMBT was not evaluated. Only a small amount of abdominal fluid was aspirated (see table 1).
| Parameter | Result | Reference range |
| Specific gravity | 1.035 | > 1.025 (exudate) |
| Total protein concentration | 4.0 g/dL | >3.0 g/dL (exudate) |
| Nucleated cell count | 6 x 10^9 /L | >3.0 x 10^9/L (exudate) |
| Red blood cell count | 0.1 x 10^12/L |
Table 1. Analysis of abdominal fluid from a cat with abdominal mass. Results obtained using a Sysmex XT-2000i haematology system (Sysmex Corporation, Kobe, Japan).
Three direct smears and one cytospin preparation were made. The following pictures show the most relevant cytological findings of these samples.
INTERPRETATION OF THE RESULTS
Cytology
The slides had good cell preservation. There was a clear background with moderate numbers of red blood cells. Frequent and mainly individual mononuclear cells were observed. These cells were large and had moderate to abundant basophilic cytoplasm, frequently with fringed cytoplasmic borders and occasionally containing small clear intracytoplasmic vacuoles. Nuclei was round, central to paracentral, with coarse granular chromatin and up to 3 prominent round nucleoli. Anisocytosis and anisokaryosis were moderate to marked. Few binucleated and multinucleated cells were also seen, together with some mitotic figures. Few other leukocytes, mainly small lymphocytes and neutrophils were noted. The main differentials included reactive mesothelial hyperplasia and mesothelioma. Mesothelioma was considered the most likely differential diagnosis. Reactive mesothelial hyperplasia was considered possible but unlikely because of the absence of concurrent inflammation on the slides and because of the history of a distinct mass. Cytology could not differentiate these two conditions; therefore, histology was recommended to confirm the diagnosis. Carcinoma was not included in the differential list, mainly because cell arrangement (individual cells) and cell morphology (round cells with fringed cytoplasmic borders) were not considered typical for it. An ultrasound guided trucut biopsy was performed under general anaesthesia.
Histology
A fine-needle trucut biopsy was characterized by a small area of fibrous tissue delimited by mesothelial cells and associated with a proliferation of atypical cells arranged in tubular or cystic structures with necrotic content. These structures were delimited by cuboidal cells with increased N/C ratio and poorly distinct borders. The nucleus was roundish with finely stippled chromatin and one or multiple round nucleoli. Anisocytosis and anisokaryosis were moderate and few mitotic figures were noted. Minimal multifocal lymphoplasmacytic infiltrate was also noted. These findings confirmed the previous suspicion of a malignant neoplasm, possibly mesothelioma although further investigations were recommended to confirm the mesothelial origin of the infiltrating cell population.
Immunohistochemistry
Immunohistochemistry was performed to further confirm the mesothelial origin of the cells. Cells showed a diffuse and intense cytoplasmic positivity to pancytokeratin. More than 50% of those cells were also positive to vimentin. The co-expression of those two markers (one epithelial and one mesenchymal) confirmed the mesothelial origin of the cells and a final diagnosis of mesothelioma was made. Other visceral neoplasms of epithelial origin can occasionally show co-expression of epithelial and mesenchymal markers (renal carcinoma, pulmonary carcinoma, Sertoli cell tumour, thyroid tumours), although these differentials were excluded considering the absence of a primary mass in these organs.
Follow up
The cat recovered from the general anaesthesia although clinical signs persisted (anorexia, vomiting). A piroxicam and intracavitary platinum-based chemotherapy was proposed to the owners it was refused. After 2 weeks of prolonged anorexia and lethargy the owners elected for euthanasia and did not agree to post-mortem examination.
Discussion
Mesothelioma is a rare tumour that arises from the mesothelial cells of the pleura, peritoneum and pericardium. It has been reported mainly in humans (frequently associated with asbestos exposure) and dogs. In cats, mesothelioma have been only rarely described. 1,2,3,4
This case showed the difficulties in the diagnosis of mesothelioma in domestic animals and how cytology sometimes has to be supported by other findings (clinical history, histology and immunohistochemistry) to achieve a correct diagnosis. Mesothelial cells have been reported to frequently show significant criteria of atypia in reactive conditions making difficult the distinction from neoplastic conditions.2 For this reason the cytological interpretation that has been initially made was open. However, the absence of concurrent inflammation, the presence of a distinct mass, and the presumptive origin from the peritoneal cavity raised the suspicion for mesothelioma.
Histology is an important tool for the diagnosis of mesothelioma although it may not be sufficient and may present limitation similar to cytology.2 Several forms of mesothelioma have been reported in animals: the epithelioid, the fibrous and the biphasic type. 1,2 The distinction of these forms from a carcinoma (in the epithelioid form) and a sarcoma (in the fibrous form) can be difficult. Immunohistochemistry can be helpful. Mesothelial cells are usually positive to both epithelial and mesenchymal markers and the co-expression of those markers is usually supportive of a mesothelial origin.1,2 Unfortunately this co-expression is not observed all the time and a few forms of carcinoma (e.g. renal carcinoma, pulmonary carcinoma) can be positive to both vimentin and cytokeratin.2,4 The previous findings and the absence of any primary lesions in other organs were considered to be sufficient to permit in this case a diagnosis of mesothelioma.
The diagnosis of mesothelioma is considered challenging also in human medicine. The International Mesothelioma Interest Group published in 2009 the guidelines for pathologic diagnosis of malignant mesothelioma which included a large panel of antibodies which had the primary purpose of excluding any form of carcinoma from the differentials.5 Unfortunately most of these markers (e.g. HBME-1, calretinin, anti-CEA, desmin, E-cadherin, thrombomodulin, CD15) have been tested only rarely in mesothelioma in domestic animals therefore their use has not been properly evaluated and proved.2 The identification of microvilli on the surface of those cells by electron microscopy has been considered another useful test that can support the mesothelial origin of these cells.2
References
1 Meuten DJ. Tumors of the alimentary tract. In: Tumors in domestic animals. Iowa, Wiley-Blackwell, 2002. 476-478.
2 Bacci B, Morandi F, De Meo M, et al. Ten cases of feline mesothelioma: an immunohistochemical and ultrastructural study. J Comp Pathol. 2006; 134: 347-354.
3 Marconato L, Del Piero F, In: Oncologia medica dei piccoli animali. Milano, Poletto Editore, 2005, 346-349.
4 Morini M, Bettini G, Morandi F, et al: Deciduoid peritoneal mesothelioma in a dog. Vet Pathol. 2006; 43: 198-201.
5 Usain AL, Colby TV, Ordonez EG et al. Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group. Arch Pathol Lab Med. 2009;133:1317-31.
