JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-N06

 

Signalment (JPC #2826762): Ox

 

HISTORY: Unknown

 

HISTOPATHOLOGIC DESCRIPTION: Fibrovascular tissue (pleura per contributor): Extending from and infiltrating the pleura is an unencapsulated, poorly demarcated, moderately cellular neoplasm composed of polygonal epithelioid cells arranged in papillary and micropapillary projections and fewer nests on a moderate fibrovascular stroma. Neoplastic cells have variably distinct cell borders, an abundant amount of vacuolated, eosinophilic cytoplasm, and a pleomorphic, centrally placed nucleus with finely stippled chromatin and 1 to 5 distinct nucleoli. There is marked anisocytosis and anisokaryosis, and there is an average of 1 mitotic figure per 2.37mm². There are occasional multinucleated neoplastic cells with up to 5 nuclei which occasionally compress and deform adjacent nuclei (nuclear molding); these multinucleated neoplastic cells contain phagocytized debris. There is occasional single cell necrosis.  Focally, neoplastic stroma is expanded by moderate hemorrhage, fibrin, edema, and few neutrophils. Blood vessels are often lined by plump (reactive) endothelium.

 

MORPHOLOGIC DIAGNOSIS: Pleura: Mesothelioma, epithelioid, breed unspecified, bovine.

 

GENERAL DISCUSSION: 

• Rare neoplasm arising from the pleura, pericardium, peritoneum, or tunica vaginalis mesothelium
• Three histological patterns: Epithelioid, sarcomatous, biphasic
• Most commonly reported in calves (can be congenital) and dogs
• Mesothelial cells are a dynamic cell population derived from embryonic mesoderm 
• In humans, mesothelioma is strongly associated with inhalation of asbestos fibers; there is no proven association among domestic animals and many fiber types other than asbestos are capable of causing mesotheliomas; mostly related to fiber size and solubility.
• Mesothelioma must be differentiated from activated or hyperplastic mesothelium; can be extremely challenging and no single factor or IHC can be used to distinguish. 
  1. Diagnosis of mesothelioma often relies on the presence of disseminated nodules and evidence of tissue invasion.

 

PATHOGENESIS: 

• Etiology is unknown in domestic animals
• Inducible tumor in laboratory animals, particularly rats, which serve as models for human pleural mesothelioma
• Spread via “seeding” (pleura), lymphatic invasion(distant), or direct invasion (thoracic)

 

TYPICAL CLINICAL FINDINGS:

 

TYPICAL GROSS FINDINGS: 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

Epithelial	Sarcomatous	Biphasic
Cuboidal cells Nest, ribbons, acini, papillary protrusions overlying a fibrovascular stalk Binucleate and multinucleate neoplastic cells **Most common in Fischer rat	Spindloid cells Streams, bundles, storiform pattern Binucleate and multinucleate neoplastic cells Least common in domestic animals	Features of epithelial and sarcomatous types   **Most common in ox

 

ULTRASTRUCTURAL FINDINGS:

• Microvilli (not present in sarcomatous subtypes), junctional complexes between cells, pinocytotic vesicles, distinct basal lamina
• Microfilaments often abundant, may be difficult to differentiate from endothelial cells

 

ADDITIONAL DIAGNOSTIC TESTS:

• Cytology: Generally round to slightly polygonal cells with a pink peripheral glycocalyx (fringe), homogenous medium-blue cytoplasm, and centrally located, hyperchromatic nuclei; spindle variants and multinucleated cells can be seen; often cluster and may exhibit nuclear molding
• Special Stains: Cytoplasmic mucopolysaccharides stain weakly positive with PAS; strongly positive with alcian blue
• Immunohistochemistry: Usually positive for both vimentin and cytokeratin

• Calretinin and Wilms Tumor 1 used in human medicine; unreliable indicators of mesothelioma in other species, except horses, which can have calretinin-positive mesothelioma
• Recent report of WT1, vimentin and cytokeratin positive peritoneal mesothelioma in a cat (Schleuter, JVDI 2021) 

 

DIFFERENTIAL DIAGNOSIS: 

Cytology: 

• Reactive (hyperplastic) mesothelium: Large sheets of pleomorphic and multinucleated cells; very difficult or impossible to differentiate from neoplasia or reactive hyperplasia
• Carcinomas/adenocarcinomas: Pleomorphic cells may appear similar; may form acinar structures; lack glycocalyx fringe

Gross:

• Thymoma
• Lymphosarcoma
• Carcinomatosis
• Mycobacterium bovis in white tailed deer

Histology:      

 

COMPARATIVE PATHOLOGY:

• Occasional reports of mesothelioma in sheep horses, goats, and cats
• Recent report of cat with systemic Listeria monocytogenes infection and concurrent pleural mesothelioma (Elbert, JVDI 2021)

• Wild felids (clouded leopard, Bengal tiger, cheetah): Recent study showed all were pancytokeratin, vimentin, E-cadherin, and WT1 positive; +- MUC-1 positive and calretinin positive (Coe, JVDI 2021)
• Rats: Often arise from the tunica vaginalis of the testis in male Fischer 344 rats
  1. Recent retrospective found spontaneous primary pleural mesothelioma is rare; all of which are either biphasic or epithelioid subtypes, no sarcomatoid types (Tokarz, Tox Path 2022)
• Wildlife: Approximately 1.5% of koalas autopsied at one koala hospital in Australia had lesions grossly and histologically consistent with mesothelioma
• Birds:
  1. Mesotheliomas may arise anywhere in the coelomic cavity
  2. Reported in chickens, psittacine, and other birds
  3. Gross: Often coelomic fluid, and affected serous membranes are gray-white, opaque, and thickened
  4. Histology: Papillary structures covered by cuboidal mesothelial cells
  5. Differential diagnoses: Other neoplasia, chronic peritonitis

 

References: 

1. Barthold SW, et al. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Iowa State Press; 2016:169-170.
2. Boes, KM. Body cavity fluids. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology:  A Color Atlas and Interpretation Guide. 4^th ed. St. Louis, MO: Elsevier; 2023:247, 274-278.
3. Caswell JL, et al. The respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016: 523.
4. Coe SE, Garner MM, and Kiupel M. Immunohistochemical characterization of mesothelioma in 6 large felids. J Vet Diagn Invest. 2021;33(4): 767-771.
5. Elbert JA and Rissi DR. Systemic Listeria monocytogenes infection and concurrent pleural mesothelioma in a cat. J Vet Diagn Invest. 2021;33(1): 120-123.
6. Foster RA. Male genital system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 3, 6th ed. St. Louis, MO: Elsevier; 2016: 474.
7. Higgins D, Rose K, Spratt D. Monotremes and Marsupials. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London: Elsevier/Academic Press; 2018:464.
8. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:597-598.
9. Schlueter AH, Dehghanpir, SD, Boudreaux B, Robinson C, Lima JCMP, and Langohr IM. Feline mesothelioma: case report and review of cytologic, immunocytochemical, histopathologic, and immunohistochemical findings. J Vet Diagn Invest. 2021:33(4):753-757.
10. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:287-288.
11. Tokarz DA, Gruebbel MM, Wilson GA, Hardisty JF, Pearse G, and Cesta MF. 
12. Uzal FA, Plattner BL, Hostetter JM. Alimentary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals, Vol 2, 6th ed. St. Louis, MO: Elsevier; 2016: 256-7.
13. Valenciano AC, Rizzi TE. Abdominal, Thoracic, and Pericardial Effusions. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2014:243-244. 

 

Click the slide to view.

---