JPC SYSTEMIC PATHOLOGY
Signalment (AFIP # 1946538): Thirteen‑year‑old, female, thoroughbred horse
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, highly cellular neoplasm composed of round to polygonal cells arranged in loose nests, rows and sheets on a fine, fibrovascular stroma. Neoplastic cells exhibit mild anisocytosis and anisokaryosis, have abundant cytoplasmic eosinophilic granules, an eccentric, round, nucleus with finely stippled chromatin and often one nucleolus. 0-1 mitotic figures per 10 40x HPFs are observed. 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 lumina are often expanded by variable amounts of mucin, which also fills adjacent alveoli.
MORPHOLOGIC DIAGNOSIS: Lung: Granular cell tumor, thoroughbred, equine
- 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, GCT’s 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 and female reproductive tract
- Thought to originate from Schwann cells.
- The eosinophilic cytoplasmic granules are interpreted ultrastructurally as autophagocytic vacuoles
TYPICAL CLINICAL FINDINGS:
- Usually asymptomatic, but will occasionally see coughing and rarely dyspnea
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
- Cytoplasmic granules: Multivesicular, single membrane bound autophagosomes that contain heterogeneous, electron dense granules
ADDITIONAL DIAGNOSTIC TESTS:
- Stains: Cytoplasmic granules are PAS positive and variably diastase resistant, and often stain positively with Luxol Fast Blue (suggestive of myelin).
- Positive: Consistent expression of S-100 and vimentin; inconsistent expression of NSE (neuron specific enolase), GFAP (glial fibrillary acidic protein) and myelin basic protein
- Negative: Cytokeratin, smooth muscle-specific actin, lysozyme
- Tumors with granular cytoplasm:
- Oncocytoma: Granularity is due to presence of mitochondria
- Rhabdomyoma: Granularity is due to mitochondria
- Dog: Primarily tongue, but also observed in skin, heart, brain, 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
- Cat: Tongue, vulva, digits, tonsil and brain
- Rabbit: Testis (WSC 2016-2017; conference 11)
- Other species: Mice (uterine), ferret (CNS), birds (periocular and subcutaneous tissues)
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- Lopez A, Martinson SA. Respiratory system, mediastinum and pleurae. In: Zachary JF ed. Pathologic Basis of Veterinary Disease, 6th St. Louis, MO: Elsevier; 2017:554.
- Weber K, Garman RH, Germann PG, Hardisty JF, Krinke G, Millar P, Pardo ID. Classification of neural tumors in laboratory rodents, emphasizing the rat. Toxicol Pathol. 2011 Jan; 39(1):129-51.
- Fox, JG, Muthupalani S, Kiupel M, Williams B. In: Fox JG, Marini RP, eds. Biology and Diseases of the Ferret, 3rd 2014: 617.