History
An 11-year-old 5.3-kg (11.7-lb) spayed female domestic shorthair cat was evaluated because of decreased activity and labored breathing of 1 day's duration. The cat's vaccination status was current, and it had no other notable medical history.
Clinical and Gross Findings
On physical examination, the cat had open-mouth breathing on inspiration that was labored with abdominal push, muffled heart sounds, pale mucous membranes, dilated pupils, and partially closed eyes. On compression, thoracic compliance was markedly reduced. Heart and lung sounds could only be heard on the right caudal region of the thorax.
Because of the poor clinical condition of the cat and suspicion of a large space-occupying lesion in the thoracic cavity, the cat was euthanized with an IV injection of pentobarbital sodium and phenytoin sodium. At necropsy, the thoracic cavity contained a large (18 × 8 × 6-cm), firm, cream-colored, lobulated mediastinal mass that weighed 306 g (0.67 lb; Figure 1). The mass extended from the thoracic inlet to the diaphragm, and the heart and lungs were not visible. Removal of the mass revealed displacement of the heart and lungs to the caudodorsal right thoracic quadrant. The lungs were dark red and partially collapsed. The mass had indentations on the ventral surface where it had molded against the rib cage. The cut surface of the mass revealed a cream and light red, edematous, cystic interior containing a moderate amount of serosanguineous fluid.
Photographs of a large mass in the thoracic cavity of an 11-year-old domestic shorthair cat that was initially evaluated because of sudden-onset dyspnea. A—The mass obscures the heart and lungs. B—Elevation of the mass from the thoracic cavity reveals the heart (white arrow) and lungs (black arrow) displaced to the right caudodorsal quadrant of the thoracic cavity. Ca = Caudal. Cr = Cranial. C—On complete removal of the mass with adjacent heart (white arrow) and lungs (black arrow), the size and shape of the mass are evident. D—The cut surface of the mass reveals the cystic structure of the tissue.
Citation: Journal of the American Veterinary Medical Association 253, 2; 10.2460/javma.253.2.173
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
A portion of the mass was placed in neutral-buffered 10% formalin and sectioned (thickness, 5 μm). The sections were stained with H&E stain and submitted for histologic evaluation.
Histologically, the sections (Figure 2) were composed of narrow to broad bands of round to spindle-shaped epithelial cells. These bands of epithelial cells divided variably sized aggregates of small lymphocytes. The round to spindle-shaped epithelial cells were also scattered individually throughout the aggregates of lymphocytes. There were multiple cysts, primarily within the bands of epithelial cells, which contained acellular accumulations of lightly eosinophilic material. Individual epithelial cells in the trabeculae had distinct cell borders with a single round pale-staining nucleus and a single nucleolus. There was a fine fibrovascular stroma throughout; the mass was well vascularized overall. Keratinized cells (Hassall corpuscles) were scant but present in the aggregates of lymphocytes. Mitotic figures were not noted in any section examined.
Photomicrographs of a section of the thoracic mass in the cat in Figure 1. A—Notice the wide bands of neoplastic thymic epithelium (E) and large aggregates of thymic lymphocytes (L), with acellular eosinophilic material. H&E stain; bar = 100 μm. B—Broad bands of neoplastic thymic epithelium (E) are mixed with modest numbers of entrapped thymic lymphocytes. H&E stain; bar = 100 μm. C—There is a lack of mitotic figures in the neoplastic thymic epithelium. Thymic lymphocytes (L) are present. H&E stain; bar = 100 μm.
Citation: Journal of the American Veterinary Medical Association 253, 2; 10.2460/javma.253.2.173
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: noninvasive thymoma, predominantly epithelial, in a cat.
Comments
Thymomas are rare in domestic animals. However, they have been described for several species including dogs, cats, horses, rabbits, pigs, goats, sheep, and cattle.1 In an atypical situation, thymoma developed in a closed colony of 92 Saanen dairy goats with an incidence rate of 25%.1 In dogs, cats, and sheep, thymomas are usually found in the cranial portion of the mediastinum; in cattle, the tumors are typically found at the thoracic inlet.2 Thymomas are generally categorized as invasive or noninvasive. Noninvasive thymoma is a space-occupying lesion in the mediastinum that displaces the thoracic organs as it grows, whereas an invasive thymoma invades the thoracic organs, thereby increasing the development of neoplasia-induced morbidity. Thymomas tend to have a benign biological behavior, and metastases are uncommon.1,3 When metastatic disease has been detected, it often involves lungs and mediastinal lymph nodes, although it has been reported in sites as distant as the kidneys.4,5 Most thymomas in cats are noninvasive and considered to be rare.3,6 Cats with thymomas are older animals (median age, 11 years; range, 5 to 15 years) that are usually negative for FeLV infection; a male predisposition (affected male-to-female ratio, 2.5:1) has been reported.6
Common clinical signs associated with thymoma include dyspnea, coughing, exercise intolerance, anorexia, weight loss, lethargy, vomiting, and regurgitation. Cats and dogs with invasive thymoma may have additional clinical signs such as pleural effusion (particularly chylothorax), pneumothorax, hemothorax, and cranial vena cava syndrome, wherein edema of the submandibular area, neck, thoracic inlet, and thoracic limbs is observed.3,6–10
Thymomas are frequently associated with a number of paraneoplastic syndromes, the 2 most common of which are hypercalcemia and myasthenia gravis. Generalized muscle weakness that is frequently observed in animals with thymoma is caused by paraneoplastic myasthenia gravis rather than by a direct effect of the tumor on muscle function. Several other immune-mediated diseases have been associated with the presence of thymoma including hypogammaglobulinemia, aplastic anemia, cardiac myositis with concurrent arrhythmias, exfoliative dermatitis, immune-mediated anemia, and polymyositis.3,6,8,11 Thymoma-associated exfoliative dermatitis is an interesting, yet poorly understood, paraneoplastic syndrome in cats. Clinical features of this syndrome include generalized desquamation, alopecia on the body, and multifocal crusts especially on the head. Initially, the head, neck, and pinnae are affected; subsequently, the syndrome becomes more generalized. Large, visually striking sheets of exfoliated stratum corneum develop and become entrapped in the hair. Pruritus is usually absent, unless a secondary yeast or bacterial infection develops.12 In a few cases, axillary and ventral erythema have been observed. Thymoma-associated exfoliative dermatitis is unresponsive to routine dermatologic treatments. Removal of the thymoma has resulted in regression, and in some cases, complete resolution of the paraneoplastic syndrome. These results strongly indicate that, in some manner, the tumor is linked with the development of the skin lesions.12,13
Differential diagnoses for a mediastinal mass include thymoma, lymphoma, thymic carcinoma, chemodectoma, thymic branchial cyst, ectopic thyroid or parathyroid tumor, metastatic neoplasia, granuloma, abscess, lipoma, teratoma, and schwannoma.3,11 In addition to signalment, clinical signs, and physical examination findings (such as those described for the cat of the present report), the results of some diagnostic tests aid in the identification of a mediastinal mass as a thymoma. With the exception of paraneoplastic-related changes, findings of hematologic and clinical biochemical analyses are usually unremarkable, with few cats having lymphocytosis.6,9 Thoracic radiography may reveal a soft tissue opacity (often lobulated) in the ventral aspect of the cranial mediastinum, the presence of which causes caudal displacement of the cardiac silhouette, dorsal displacement of the trachea, and variable degrees of pleural effusion. Megaesophagus with and without aspiration pneumonia has also been observed radiographically in cats with the thymoma-associated paraneoplastic syndrome of myasthenia gravis.3,6
Other imaging techniques advocated to aid in the diagnosis of mediastinal masses include ultrasonography, echocardiography, MRI, and CT (with and without contrast medium administration).3,6,9,11 Thymomas generally appear as a heterogeneous mass with multiple small or large cysts on thoracic ultrasonographic images.3,9 Advanced diagnostic imaging, such as CT and MRI, is the most reliable technique for assessment of the invasiveness of a thymoma and may also aid in the identification of rare metastatic lesions.
To support a presumptive diagnosis of thymoma, fine-needle aspirate and needle-core biopsy specimens are often obtained for examination. Differentiation of a mediastinal mass as a thymoma through cytologic and histologic evaluation of such samples is a matter of debate. Some experts believe that evaluation of these samples can actually confound the diagnosis because of a predominance of lymphocytes rather than epithelial cells.6 Others have indicated that cytologic examination of aspirate specimens can aid in making a presumptive diagnosis of thymoma on the basis of established criteria of cell types identified.14 Specifically, aspirates indicative of thymoma contain many small lymphocytes, a mixed population of thymic epithelial cells, and few eosinophils and mast cells.3 Thymomas are histologically classified on the basis of the predominant cell population within the mass, and may be lymphocyte predominant or epithelial cell predominant or of an intermediate lympho-epithelial subtype.1,15 Results of immunohistochemical analyses, such as pancytokeratin reactivity, may be required to confirm the diagnosis of thymoma.6,15 In humans, cytokeratin profiles of thymomas have been used to support histologic classifications that are clinically useful for correlation with invasiveness.6,9,13,15,16 Electron microscopy can be a valuable aid in the identification of mediastinal tumors in difficult cases.17 The ultra-structural features of thymomas resemble those of the normal thymus, and the complex thymic anatomic interrelationships among epithelial cells, lymphocytes, and blood vessels tend to be preserved.18
In cats, the 2 most common mediastinal masses are thymoma and mediastinal lymphoma. It is imperative to differentiate between the 2 types of neoplasm because the treatments for each are quite different, as is the prognosis for affected animals. Compared with cats with thymoma, cats with mediastinal lymphoma are generally younger and FeLV positive, and cytologic samples of those masses often contain lymphoblasts. The treatment of choice for mediastinal lymphoma is chemotherapy. In contrast, the treatment of choice for thymoma is excision. In most thymoma cases, the resectability of the tumor cannot be definitively determined until a thoracotomy is performed. If the tumor can be completely excised, which is common in cats with noninvasive thymoma, surgery is often curative.3 When the tumor cannot be completely resected, which is often the situation in cats with invasive thymoma, surgery may only be palliative and the use of adjunct treatments should be considered. Overall, thymomas are resistant to chemotherapy and radiotherapy without prior surgical excision.3,6,7 In cats and dogs, radiation therapy alone is associated with an overall response rate of 75%, but complete responses are rare.19 The response rate to current chemotherapeutic protocols (used as the sole treatment) is less than ideal. Thymomas appear to have the greatest response to corticosteroid treatment. Corticosteroids effectively reduce the size of the mass by having a cytotoxic effect on the T lymphocytes that often make up a large, nonneoplastic component of the tumor.3,6 Even though these treatments have poor efficacy when administered prior to surgical excision in most cases, they may delay or possibly halt the reoccurrence of a thymoma resulting from incomplete resection or metastatic disease. Moreover, the combination of radiotherapy and chemotherapy may further improve the treatment response rate.3,7
In 1 study,3 cats (n = 8) with noninvasive and invasive thymoma that underwent tumor excision alone had a 1-year survival rate of 89% and a 3-year survival rate of 74%. Although uncommon, the possibility of undetected metastatic disease should be considered when a prognosis is offered.4,5 The survival rate for cats with mediastinal lymphoma is often less favorable. Cats with mediastinal lymphoma that are positive for FeLV infection have very poor survival rates of 2 to 4 months, whereas those that are negative for FeLV infection have a somewhat better survival rate of 1 to 2 years, with some animals achieving remission.10
Thymoma should be considered a possible cause of a thoracic mass in cats, especially in older cats. The recommended treatment is surgical excision. Generally, if an affected cat survives the surgical and postoperative periods, the long-term survival rate is good.
References
1 Jacobs RM, Messick JB, Valli VE. Tumors of the hemolymphatic system. In: Meuten DJ, ed. Tumors in domestic animals. 4th ed. Ames, Iowa: Iowa State Press, 2002;165–166.
2 Parker GA, Casey HW. Thymomas in domestic animals. Vet Pathol 1976;13:353–364.
3 Zitz JC, Birchard SJ, Couto GC, et al. Results of excision of thymoma in cats and dogs: 20 cases (1984–2005). J Am Vet Med Assoc 2008;232:1186–1192.
4 Middleton DJ, Ratcliffe RC, Xu FN. Thymoma with distant metastases in a cat. Vet Pathol 1985;22:512–514.
5 Hauser B, Mettler F. Malignant thymoma in a cat. J Comp Pathol 1984;94:311–313.
6 Veterinary Society of Surgical Oncology website. Cranial mediastinal thymoma. Available at: www.vsso.org/Cranial_Mediastinal_Thymoma_-_Feline.html. Accessed Apr 30, 2016.
7 Hahn KA. An overview of thymoma in dogs and cats. Available at: www.zzcat.com/TumorTidbits/Overview-Thyoma-in-Dogs-and-Cats.txt. Accessed Mar 18, 2011.
8 Carpenter JL, Holzworth J. Thymoma in 11 cats. J Am Vet Med Assoc 1982;181:248–251.
9 Schmidt BR. Thymoma. In: Norsworthy GD, Grace SF, Crystal MA, et al, eds. The feline patient. 4th ed. Ames, Iowa: Wiley-Blackwell, 2011;509–511.
10 Vetstream Web. Mediastinal lymphoma. Available at www.vetstream.com/felis/Content/Disease/dis60628. Accessed Apr 30, 2016.
11 Robat CS, Cesario L, Gaeta R, et al. Clinical features, treatment options, and outcome in dogs with thymoma: 116 cases (1999–2010). J Am Vet Med Assoc 2013;243:1448–1454.
12 Ihrke PJ. Newly described feline skin diseases, in Proceedings. 31st World Small Anim Vet Cong 2006;241–244.
13 Rottenberg S, von Tscharner C, Roosje PJ. Thymoma-associated exfoliative dermatitis in cats. Vet Pathol 2004;41:429–433.
14 Rae CA, Jacobs RM, Couto CG. A comparison between the cytological and histological characteristics in thirteen canine and feline thymomas. Can Vet J 1989;30:497–500.
15 Allan K, Masters N, Rivers S, et al. T-lymphocyte-rich thymoma and myasthenia gravis in a Siberian tiger (Panthera tigris altaica). J Comp Pathol 2014;150:345–549.
16 Kuo T. Cytokeratin profiles of the thymus and thymomas: histogenetic correlations and proposal for a histological classification of thymomas. Histopathology 2000;36:403–414.
17 Patnaik AK, Lieberman PH, Erlandson RA, et al. Feline cystic thymoma: a clinicopathologic, immunohistologic, and electron microscopic study of 14 cases. J Feline Med Surg 2003;5:27–35.
18 Verley JM, Hollmann KH. Tumours and tumour-like conditions of the thymus. In: Gresham GA, ed. Current histopathology: tumours of the mediastinum. Vol 19. Dordrecht. The Netherlands: Kluwer Academic Publishers, 1992;11–42.
19 Smith AN, Wright JC, Brawner WR. et al. Radiation therapy in the treatment of canine and feline thymomas: a retrospective study (1985–1999) J Am Anim Hosp Assoc 2001;37:489–496.
