JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-N03

 

Signalment (JPC #1946538): Thirteen‑year‑old, female, thoroughbred horse

 

HISTORY: Unknown

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Affecting approximately 50% of the section, centered on and effacing a large bronchus, and compressing adjacent pulmonary tissue is an encapsulated, well-circumscribed, densely cellular neoplasm composed of round to polygonal cells arranged in loose nests, rows, and sheets on a fine, fibrovascular stroma. Neoplastic cells have distinct cell borders, abundant cytoplasm filled with eosinophilic granules, and an eccentric, round nucleus with finely stippled chromatin and often one nucleolus. Neoplastic cells exhibit mild anisocytosis and anisokaryosis, and there are 0-1 mitotic figures per 2.37mm². Multifocal areas of hemorrhage are present within the parenchyma adjacent the neoplasm; these areas are admixed with moderate numbers of hemosiderin-laden macrophages (siderophages). Epithelial cells within entrapped and adjacent bronchi and bronchioles are hyperplastic, piling up to 4 layers thick, while bronchial and bronchiolar lumina are often expanded by variable amounts of mucus which also fills adjacent alveoli.

   

MORPHOLOGIC DIAGNOSIS: Lung: Granular cell tumor, thoroughbred, equine 

 

GENERAL DISCUSSION:  

• Granular cell tumors (GCTs) are the most common primary lung neoplasm in horses, but their occurrence is rare and typically an incidental finding at necropsy
• In horses, GCTs are found exclusively in the lungs; in dogs they occur most commonly in the oral cavity; and in rats they occur commonly in the brain, meninges (N-N10), and female reproductive tract   
• Thought to originate from Schwann cells in peribronchial tissue
• The eosinophilic cytoplasmic granules are interpreted ultrastructurally as autophagocytic vacuoles

 

PATHOGENESIS: 

 

TYPICAL CLINICAL FINDINGS:

• Usually asymptomatic, but will occasionally see coughing and rarely dyspnea
• Metastasis has not been described

 

TYPICAL GROSS FINDINGS:

• Tumors are firm, white to beige, and are usually multinodular and unilateral
• Typically located adjacent to large bronchi and often bulge into the bronchial lumen causing variable degrees of airway obstruction

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Well-circumscribed, densely cellular neoplasm forming sheets, nests, and rows supported by sparse stroma
• Neoplastic cells are large, round to polygonal, and contain abundant eosinophilic, granular cytoplasm; mitotic figures are rare, minimal anisocytosis    

 

ULTRASTRUCTURAL FINDINGS:

 

ADDITIONAL DIAGNOSTIC TESTS:

• Histochemical stains: Cytoplasmic granules are PAS positive and variably diastase resistant, and often stain positively with Luxol Fast Blue (suggestive of myelin)
• Immunohistochemistry:  

• Positive: S-100 and vimentin
• Inconsistent: NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein) 
• Negative: Cytokeratin, smooth muscle-specific actin, lysozyme

 

DIFFERENTIAL DIAGNOSIS:  

• Tumors with granular cytoplasm: 

• Oncocytoma: Granularity is due to mitochondria
• Rhabdomyoma: Granularity is due to mitochondria

 

COMPARATIVE PATHOLOGY:  

• Dog: Primarily tongue, but also observed in skin, heart, brain, eyelid (medial canthus), spinal cord, lung mediastinum, diaphragm, thyroid, trachea and vocal cords
• Rats: Most common CNS tumor in Sprague-Dawley and Wistar rats; may or may not be of meningeal cell lineage (N-N10)
• Cat: Tongue, vulva, digits, tonsil, and brain
• Rabbit: Testis (Reineking, J Comp Pathol. 2019)
• Other species: Mice (uterine), ferret (CNS), birds (periocular and subcutaneous tissues, tongue of psittacines [esp. Amazon parrots]), python (intracalvarial; Finnegan, J Comp Pathol. 2020), kingsnake (intra-coelomic; Reifinger, J Comp Pathol. 2020)

 

References:  

1. Boes KM. Respiratory System. In: Raskin RE, Meyer DJ, eds. Canine and Feline Cytology: A Color Atlas and Interpretation Guide. 4th ed. St. Louis, MO: Elsevier; 2023:203.
2. Caswell JL, Williams KJ.  Respiratory system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2, 6th ed. St. Louis, MO: Elsevier Limited; 2016:498.
3. Finnegan DK, Cartoceti AN, Hauck AM, LaDouceur EEB. Meningeal Granular Cell Tumour in a Green Tree Python (Morelia viridis). J Comp Pathol. 2020;174:54-57
4. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier. 2022; 1410.
5. Lopez A, Martinson SA. Respiratory System, Thoracic Cavities, Mediastinum, and Pleurae. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7^th ed. St. Louis, MO: Elsevier; 2022: 594.
6. Fox, JG, Muthupalani S, Kiupel M, Williams B.  In:   Fox JG, Marini RP, eds.  Biology and Diseases of the Ferret, 3^rd ed.  Ames, IA: Wiley; 2014: 617.  
7. Reifinger M, Dinhopl N, Gumpenberger M, Konecny M, Cigler P. Granular Cell Tumour in a California Kingsnake (Lampropeltis californiae). J Comp Pathol. 2020;175:24-28.
8. Reineking W, Seehusen F, Lehmbecker A, Wohlsein P. Predominance of Granular Cell Tumours among Testicular Tumours of Rabbits (Oryctolagus cuniculi f. dom.). J Comp Pathol. 2019;173:24-29.
9. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015:60, 260.

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