JPC SYSTEMIC PATHOLOGY
RESPIRATORY SYSTEM
September 2023
P-N01 (NP)
Signalment (JPC #2507413): 7.5 year old male neutered Cocker Spaniel
HISTORY: This dog presented for congested respiration and trouble barking. There was transient intermittent response to steroids, bronchodilators, and antibiotics. Several months later, clinical signs progressed to dyspnea, inspiratory stridor, vomiting, and activity-induced cyanosis. Thoracic radiographs revealed normal appearing lungs and a soft tissue density in the laryngeal area. Laryngeal examination showed a 2-3 cm mass displacing the left side of the larynx. The animal was euthanized and the laryngeal block submitted for histopathological examination.
HISTOPATHOLOGIC DESCRIPTION: Submucosa, perilaryngeal area (per contributor): Markedly expanding the submucosa and elevating the overlying mucosa is a 1.8 x 1.9 cm, unencapsulated, densely cellular, lobular neoplasm composed of large, brightly eosinophilic polygonal cells arranged in solidly cellular areas and indistinct streams separated by thin bands of fibrous stroma. Neoplastic cells have variably distinct cell borders; moderate to abundant brightly eosinophilic, granular, occasionally vacuolated cytoplasm, and round to oval nuclei with finely stippled chromatin and 1-2 variably distinct nucleoli. Anisocytosis and anisokaryosis are moderate and there is 1 mitotic figure per 10 HPF (2.37mm2). Multifocally, there are elongate binucleate strap-like cells, multinucleate polygonal cells, and frequent single cell necrosis. There is multifocal hemorrhage and scattered hemosiderin-laden macrophages. The remaining submucosa contains low numbers of lymphocytes, plasma cells, and neutrophils that surround small caliber blood vessels or submucosal glands, scant hemorrhage and fibrin, and increased clear space and ectatic lymphatics (edema).
MORPHOLOGIC DIAGNOSIS: Submucosa, perilaryngeal area (per contributor): Rhabdomyoma, Cocker Spaniel, canine.
SYNONYM: Laryngeal oncocytoma
GENERAL DISCUSSION:
- In general, rhabdomyomas are tumors of skeletal muscle that most often occur in the myocardium, larynx, and region of the head, though they are reported to occur in sites lacking striated muscle
- Laryngeal rhabdomyomas are rare, benign neoplasms of dogs; there is a suggested female sex predilection and no breed predisposition
TYPICAL CLINICAL FINDINGS:
- Laryngeal rhabdomyomas are slow-growing tumors; metastasis is rare and recurrence is rare with complete surgical excision
- Large tumors may be partially obstructive, resulting in dysphonia, cough, dyspnea, stridor, exercise intolerance, syncope, cyanosis, and collapse
TYPICAL GROSS FINDINGS:
- Solitary, circumscribed, round or lobulated, pink to red-brown, smooth nodule protruding into the larynx, in or near lateral ventricle
- +/- secondary hemorrhage, necrosis, and hemosiderosis
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Cytology: large cells with granular or foamy to vacuolated cytoplasm, round/oval nuclei with finely stippled chromatin and a single prominent nucleolus; abundant peripheral blood is common
- Pleomorphic, polygonal to round cells forming lobules separated by thin bands of fibrous stroma
- Neoplastic cells have abundant eosinophilic granular or foamy cytoplasm and vesiculate nuclei with one or more prominent nucleoli
- Mitotic figures rare
- Multinucleated neoplastic cells with cross striations (indicative of sarcomeric differentiation), either elongate (strap cells) or ovoid (racquet cells); may be difficult to find
- Invasion uncommon
ULTRASTRUCTURE:
- Numerous mitochondria, rough endoplasmic reticulum, and glycogen granules
- Primitive myofilaments and Z band-type material
ADDITIONAL DIAGNOSTIC TESTS:
- Immunohistochemistry:
- Positive: Myosin, muscle specific actin, myoglobin, desmin positive
- Vimentin and cytokeratin negative
- Histochemical stains:
- Phosphotungstic acid hematoxylin (PTAH) to better visualize cross striations
- PAS positive due to intracytoplasmic glycogen
- Cytology: Exfoliate poorly; large cells with moderate pleomorphism, abundant granular or foamy cytoplasm, large eccentric nucleus with finely clumped chromatin, indistinct nucleolus; occasional multinucleated cells, with nuclei arranged in a row (consistent with a “strap cell”), more often seen in rhabomyosarcoma
DIFFERENTIAL DIAGNOSIS:
Laryngeal tumors in dogs:
- Rhabdomyosarcoma: Young animals; most commonly occur in oral cavity, on neck, or tongue; invasive and frequently metastasize, with high mitotic activity, +/- multinucleate strap and ovoid racquet cells; embryonal is most common variant
- Squamous cell carcinoma: Most common laryngeal neoplasm in dogs
- Granular cell tumor: Uncommon neoplasm; sites include tongue (dogs), lung (horses, P-N03), meninges/brain (laboratory rodents, N-N10); likely of Schwann cell origin; cytoplasm contains fine PAS positive, diastase-resistant granules that appear ultrastructurally as secondary lysosomes, and most are positive for S100 and vimentin
- Oncocytoma: Cords and nests of large epithelioid cytokeratin positive cells; eosinophilic cytoplasm with numerous mitochondria that yield a granular appearance and stain positive with PTAH
COMPARATIVE PATHOLOGY:
- Cardiac rhabdomyoma (C-M02): Often an incidental finding in the left ventricular wall of young animals; occur most commonly in pigs, less often in dogs, cattle, sheep, and guinea pigs; single or multifocal circumscribed, nonencapsulated nodules within the myocardium; generally considered hamartomatous or dysplastic lesions
- Pigs: Benign tumors of striated muscle most often develop in the pig heart; red wattle pig predisposed; recent evidence suggests porcine cardiac rhabdomyomas are of Purkinje cell origin, based upon positive staining for protein gene product 9.5 (a marker for Purkinje cell fibers). Rare reports of spontaneous cases in Gottingen minipigs.
- Cats: Rare reports of aural rhabdomyoma; nonulcerated, discoid, well-circumscribed mass on the convex surface, composed of spindle shaped cells with cross-striations and rare mitotic figures; strong positive staining for most muscle markers
- Rhabdomyosarcoma (RMS) (M-N08)
- Aggressive local invasion and frequent metastasis to other sites, including cardiac muscle, other skeletal muscle, and spinal cord
- Histologic variants include embryonal rhabdomyosarcoma, alveolar rhabdomyosacoma, and pleomorphic rhabdomyosarcoma. IHC (desmin, myogenin and MyoD1 positive) can be used to improve diagnosis of RMS regardless of the histological variability.
- Urinary rhabdomyosarcoma (U-N03): Botryoid (grape cluster-like shape) rhabdomyosarcoma occurs in urinary bladder and urethra, typically in animals less than 2 years of age; increased incidence in large breed dogs (e.g. Saint Bernard)
- Meningeal rhabdomyosarcoma: Recent case report in a young Labrador retriever with an infiltrative intradural mass within the T9-T11 spinal cord, nodules of melanin-containing cells in the adjacent grey matter of the spinal cord (termed “micronodular melanocytosis”), and multifocal dermal neurofibromas over the left thorax (Hoon-Hanks, J Comp Pathol 2018)
- Esophageal rhabdomyosarcoma: Recent case report in a Great Dane with clinical signs of hypertrophic osteopathy; locally invasive esophageal mass (Devriendt, J Comp Pathol 2017)
- Recent case reports: Invasive form associated with osteolysis in the dog (Shi et al., 2023), first report of RMS in the common musk turtle (Shwarz et al., 2021),
REFERENCES:
- Barger AM. Musculoskeletal system. In: Raskin RE and Meyer DJ. Canine and feline cytology. A color atlas and interpretation guide. 4th ed. St. Louis, MO: Elsevier; 2023: 498-499.
- 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; 2016:482.
- Cianciolo RE, Mohr FC. Urinary system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:464.
- Cooper BJ, Valentine BA. Tumors of muscle. In: Meuten DJ, ed. Tumors in Domestic Animals. 5th ed. Ames, IA: Wiley Blackwell; 2017:444-466.
- Cooper BJ, Valentine BA. Muscle and tendon. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 1. 6th ed. Philadelphia, PA: Elsevier; 2015:241-243.
- Devriendt N, Van Brantegem L, Willems A, Raes E, de Rooster H. Embryonal rhabdomyosarcoma of the oesophagus in a young dog. J Comp Pathol 2017;156:21-24.
- Feller LE, Sargeant A, Ehrhart EJ, Balmer B, Nelson K, Lamoureux J. Cardiac Rhabdomyoma in Four Göttingen Minipigs. Toxicol Pathol. 2023 Jan;51(1-2):61-66.
- Fielder SE. The Musculoskeletal System. In: Valenciano AC, Cowell RL, eds. Diagnostic Cytology and Hematology of the Dog and Cat. 5th ed. St. Louis, MO: Elsevier Mosby; 2020:208-209.
- Gal A, Castillo-Alcala F. Cardiovascular system, pericardial cavity and lymphatic vessels. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:667.
- Hoon-Hanks LL, Frank CB, Edmondson EF. Primary meningeal rhabdomyosarcoma of the spinal cord of a young dogs with neuromelanocytosis and multiple cutaneous neurofibromas. J Comp Pathol. 2018; 165: 57-61.
- Robinson WF, Robinson NA. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th ed. Philadelphia, PA: Elsevier; 2016:52.
- Schwarz S, Mathes K, Wohlsein P. Rhabdomyosarcoma on the Forelimb of a Common Musk Turtle (Sternotherus odoratus). J Comp Pathol. 2021;186:73-76.
- Shi J, Gao R, Zhang J, Xu R, Jia Q, Ma Y, Lu H, Zhao K, Gao F, He W. Invasive spindle-cell rhabdomyosarcoma with osteolysis in a dog: case report and literature review. J Vet Diagn Invest. 2023;35(2):168-172.
- Tuohy JL, Byer BJ, Royer S, Keller C, Nagai-Singer MA, Regan DP, Seguin B. Evaluation of Myogenin and MyoD1 as Immunohistochemical Markers of Canine Rhabdomyosarcoma. Vet Pathol. 2021;58(3):516-526.
- Valentine BA. Skeletal muscle. In: Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1015.
- Wilcock BP, Njaa BL. Special senses. In: Maxie MG ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol. 1. 6th ed. St. Louis, MO: Elsevier; 2016:505.