JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-N07 (NP)

 

Signalment (#08-12024): 10-year-old, intact male, Labrador retriever, canine.

 

HISTORY: A 10-year-old intact male Labrador retriever was diagnosed with a thoracic mass. The dog had a history of mild chronic cough, hematuria, acute right eye pain, and lethargy. Physical examination revealed blepharospasm and hyphema with clear discharge from the right eye, a firm mass in an enlarged right testicle, and an enlarged, irregular prostate. An ultrasonographic examination revealed nodules in the prostate, liver, spleen, and left kidney. The dog was euthanized a week later due to rapid deterioration with anorexia, acute blindness, and ataxia.

 

HISTOPATHOLOGIC DESCRIPTION:           

Lung: Effacing approximately 80% of the section of lung and compressing and infiltrating into adjacent pulmonary parenchyma is an unencapsulated, poorly circumscribed, multinodular, densely cellular neoplasm composed of anaplastic epitheloid to slightly spindle-shaped cells arranged in indistinct nests, streams, and solidly cellular sheets and forming variably sized blood-filled vascular channels that are separated and supported by a moderate fibrovascular stroma. Neoplastic cells have distinct cell borders, an abundant amount of eosinophilic to vacuolated cytoplasm that rarely contains a single erythrocyte, and a round to pleomorphic, nucleus with vesiculate clumped chromatin and 1-3 prominent nucleoli. Nuclei often bulge into the vascular lumens. Anisocytosis and anisokaryosis are marked. Mitotic count is five per 0.237mm² with frequent bizarre mitoses. Multifocally, there are solid large nests of neoplastic cells that penetrate and obscure pulmonary vessel lumens. Within vascular channels there are occasional fibrin thrombi. Primarily within the central areas of the neoplasm there is moderate hemorrhage, scattered single cell necrosis, viable and necrotic neutrophils admixed with necrotic cellular debirs, hemosiderin-laden macrophages, and scattered aggregates of lymphoplasmacytic inflammation.

 

Prostate gland, liver, kidney: Previously described neoplastic cells with similar morphology and architecture, hemorrhage, inflammation, and necrosis variably infiltrate and efface the small sections of prostate gland, liver, and kidney. 

 

Prostate gland: Diffusely there is hyperplasia of the glandular epithelium with multifocal variably sized dilations of the glandular epithelium (cystic change) that contain a pale homogenous eosinophilic secretory product and sloughed epithelial cells. Cysts are lined by simple cuboidal to columnar epithelium. Multifocally within the stroma there is a mild infiltration by lymphocytes and plasma cells. 

 

MORPHOLOGIC DIAGNOSES: 1. Lung, prostate gland, liver, kidney: Epithelioid hemangiosarcoma, metastatic, Labrador retriever, canine. 

2. Prostate gland: Hyperplasia, glandular epithelial with numerous cysts, diffuse, mild.

 

GENERAL DISCUSSION: 

• Epithelioid hemangiosarcoma is a rarely reported histologic variant of hemangiosarcoma, a malignant neoplasm of vascular endothelial origin
• It is a diagnostic challenge due to the epithelial-like morphology of neoplastic cells
• Most cases occur in the integument; there are uncommon reports of disseminated visceral disease without evidence of cutaneous involvement 
• +/- solar induced in dogs and horses; more likely in glabrous skin or sparsely haired areas

 

CLINICAL PATHOLOGY

 

TYPICAL GROSS FINDINGS:  

• Single or multiple well-defined mass(es); red/brown to black; soft to firm; exudes blood when incised
• Tumors can be present in multiple organs in disseminated disease
• In the skin, there is often alopecia, thickening, hemorrhage, or ulceration 

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Pleomorphic, epithelioid to spindle cells forming a papillary projections or vague blood filled vascular spaces
• There may be little to no histologic evidence of vascular origin
• Neoplastic cells have abundant, eosinophilic, granular or vesicular cytoplasm that occasionally contains a single erythrocyte
• Nuclei are vesicular, with one or more prominent nucleoli; mitotic count is highly variable

 

ULTRASTRUCTURE:

• Large pleomorphic endothelial cells with a prominent basal lamina
• Neoplastic cells rarely contain Weibel-Palade bodies (specific cytoplasmic marker for endothelial cells)

 

ADDITIONAL DIAGNOSTIC TESTS:  

• Immunohistochemistry:  Neoplastic cells are immunopositive for vimentin and at least one of the commonly used vascular markers (Factor VIII-related antigen (vWF), CD31(PECAM), and CD34).
• Neoplastic cells will be negative for cytokeratin (AE1/AE3)

 

DIFFERENTIAL DIAGNOSIS:  

• Epithelioid vascular neoplasms are characterized by peculiar epithelioid or histiocytic appearance of the endothelial cells; need to rule out anaplastic carcinoma and histiocytic sarcoma
• Immunohistochemistry for vascular endothelium is required for definitive diagnosis

 

COMPARATIVE PATHOLOGY:  

• Horses: Reported in the periocular tissue and vulva; may be associated with solar elastosis secondary to UV radiation
• Bovine: Reported in the skin, urinary bladder, regional lymph nodes, lung, kidney, and liver
• Canine: Reported case of cutaneous epithelioid hemangiosarcoma with granular cell differentiation
• Epithelioid hemangioendothelioma reported in the CNS with plump epithelial endothelia lining abundant small proliferating blood vessels or interspersed solid clusters and cords on a myxoid to hyalinized stroma (Marr, Vet Pathol 2021)

 

REFERENCES: 

1. Arenas-Gamboa AM, Mansell J. Epithelioid hemangiosarcoma in the ocular tissue of horses. J Comp Pathol. 2011;144:328-333. 
2. Aschenbroich S, Woolcock A, Rissi DR. Paraperesis in a golden retriever. Vet Pathol. 2014;51(5):996-999.
3. Bolfa P, DellaGrotte L, Weronko E, et al. Cutaneous epithelioid hemangiosarcoma with granular cell differentiation in a dog: a case report and review of the literature. J Vet Diagn Invest. 2018;30(6):951-954.
4. Gumber S, Baia P, et al. Vulvar epithelioid hemangiosarcoma with solar elastosis in a mare. J Vet Diagn Invest. 2011;23(5):1033-1036.
5. Marr J, Miranda IC, Miller AD, Summers BA. A review of proliferative vascular disorders of the central nervous system of animals. Vet Pathol. 2021;58(5):864-880.
6. Mauldin GA, Kennedy JP. Integumentary system. In: Maxie MG ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed., Philadelphia, PA: Elsevier Saunders; 2016:575-577, 726-727, 736.
7. Pires I, Silva F, et al. Epithelioid hemangiosarcomas of the bovine urinary bladder: A histologic, immunohistichemical, and ultrastructural examination of four tumors. J Vet Diagn Invest. 2010;22:116-119.
8. Shor S, Helfand SC, et al. Diagnostic exercise: Epithelioid hemangiosarcoma mimicking metastatic prostatic neoplasia in a dog. Vet Pathol. 2009; 46(3):548-552.
9. Stockham SL, Scott MA. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Hoboken, NJ: Wiley; 2013:308, 864.
10. Warren AL, Summers BA. Epithelioid variant of hemangioma and hemangiosarcoma in the dog, horse, and cow. Vet Pathol. 2007;44:15-24.

 

Click the slide to view.

---