JPC SYSTEMIC PATHOLOGY
CARDIOVASCULAR SYSTEM
April 2022
C-N02 (NP

 

Signalment (JPC #2233855):  Age, strain, and gender unspecified rat   

 

HISTORY:  None

 

HISTOPATHOLOGIC DESCRIPTION: Heart: Diffusely infiltrating and expanding the subendocardium of the left ventricle and extending into adjacent myocardium, atrium, and aortic valve, is an unencapsulated, poorly circumscribed, variably cellular neoplasm composed of spindle cells arranged in short, loose, interlacing streams, bundles, and whorls, with indistinct nuclear regimentation. The neoplastic cells are surrounded and separated by variable amounts of eosinophilic finely fibrillar matrix. Neoplastic cells have indistinct borders, a small amount of eosinophilic fibrillar to vacuolated cytoplasm, and a variably sized, oval to elongate, occasionally vesiculate nucleus with coarse chromatin and one variably distinct basophilic nucleolus. Mitoses average 5-6 per 0.237 sq mm (HPF) with occasional bizarre mitoses. Multifocally, there are moderate numbers of larger polygonal, multinucleate neoplastic cells admixed with karyomegalic cells. Along the endocardial surface, neoplastic cells are more polygonal with round nuclei, finely stippled chromatin, and a single, often prominent nucleolus. Multifocally cardiomyoctes adjacent to or entrapped within the neoplasm are pale, swollen, and vacuolated (degeneration), and there are multifocal aborted attempts at myocyte regeneration (Anitschkow cells) characterized by large, ovoid nuclei with a centrally placed, wavy ribbon of undulant chromatin.

 

MORPHOLOGIC DIAGNOSIS:  Heart:  Schwannoma, endocardial, strain unspecified, rat, rodent.

SYNONYMS:  Endocardial sarcoma, endomyocardial neurofibromatosis, neurinoma, neurilemmoma, endocardial mesenchymal tumor, Anitschkow cell sarcoma, neurosarcoma, endocardial fibromatosis

 

GENERAL DISCUSSION:

• Endocardial schwannoma has been identified by some authors as the most common primary cardiac tumor of the rat; however, there is some debate as to whether this is truly a schwannoma or even truly a neoplasm; some authors describe it as an endocardial spindle cell proliferation
• May represent a spectrum ranging from non-neoplastic endocardial fibroproliferative lesions to neoplastic spindle cell tumors or schwannomas
• Metastasis is rare, to lung, liver, spleen, mediastinum, and bone marrow

 

PATHOGENESIS:

• Cell of origin unknown; Schwann cell origin suspected because of histologic features and positive immunohistochemistry for S-100 protein
• Can progress from small proliferative or hyperplastic lesions into frank sarcoma

 

TYPICAL CLINICAL FINDINGS: 

• Sudden death with few to no premonitory signs

 

TYPICAL GROSS FINDINGS:

• Large proliferative tumors may fill the cavity of one or both ventricles; may extend across valves and along vessels
• Left ventricle is most often involved
• Interventricular septum thickened and grey
• Occasional thrombosis or aneurysm formation

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Subendocardial mass; endocardium usually intact
• Biphasic population of neoplastic cells
  • Superficial cells: Rounded, ovoid, or polygonal with large dense oval nuclei, prominent nucleoli, and finely vacuolated cytoplasm
  • Deep cells: Spindled and separated by collagen, forming whorls (Antoni type A) and herring bone patterns around chordae tendineae or around remnants of degenerate papillary myofibers
• Infiltration of myocardium with myocyte degeneration and atrophy
• Mitotic figures common
• Histologic appearance varies with size of the neoplasm: Larger and more extensive neoplasms tend to be more pleomorphic and consist either of dense, interlacing and whorled bundles of spindle cells arranged in a pattern consistent with Antoni type A pattern, or less-organized, loose-textured fibers consistent with an Antoni type B pattern; palisading, elongated nuclei (Verocay bodies) may be present

 

ULTRASTRUCTURAL FINDINGS:

• Two cell types often observed:
  • Neoplastic Schwann cells are thin, elongate to spindle with irregular nuclei, variable cytoplasm, mitochondria, rough endoplasmic reticulum, and occasional filaments; prominent interdigitation of cell processes, circumferential basal laminas, either single or multilayered and occasional junctional complex between cells
  • The second population, most likely mesenchymal in origin, is undifferentiated with vesicular nuclei and short, densely packed cell processes

 

ADDITIONAL DIAGNOSTIC TESTS:

• Immunohistochemistry: Positive for S-100 protein

 

DIFFERENTIAL DIAGNOSIS:

Proliferative lesions of the heart and vasculature in rats

• Endocardial hyperplasia: Non-invasive, subendocardial proliferation of fibroblast-like cells usually less than 20 cell layers thick; ventricular endocardium preferentially affected
• Cardiac neoplasms
  • Intramural schwannoma: Well-circumscribed, discrete nodules, left ventricle or IV septum
  • Mesothelioma:
    • Atriocaval mesothelioma: Rare; NZR/Gd strain most commonly affected followed by F344; males (tunica vaginalis) more commonly affected than females; characterized by numerous glandular/tubular structures lined with a single layer of low, non-ciliated columnar to cuboidal epithelial cells; hemorrhage and necrosis are common with invasion of surrounding myocardium and pericardial fat
    • Pericardial mesothelioma: Multiple, plaque-like tubular and papillary proliferations in the pericardial sac
  • Paraganglioma (aortic body tumor): Nests and packets of round cells with granular, faintly basophilic cytoplasm surrounded by delicate reticulum fibers; mitotic figures rare; WAG/Rij rats
  • Fibroma/fibrosarcoma, myxoma, rhabdomyoma/rhabdomyosarcoma, lymphosarcoma
• Vascular neoplasms:
  • Hemangioma/hemangiosarcoma: Blood filled spaces lined by pleomorphic spindle shaped to polygonal cells 
  • Hemangiopericytoma: Fusiform fibroblast-like cells arranged in whorls surrounding small blood vessels; basement membrane is present around pericytes; also found in spleen and subcutis

 

COMPARATIVE PATHOLOGY:

• Extracardiac benign/malignant schwannomas (benign/malignant peripheral nerve sheath tumors) occur in many species
• Cattle:
  • Neurofibromas (schwannomas) often multiple nodular masses either on the epicardial surface or within the myocardium; frequently involve the peripheral nerves, brachial plexus, autonomic ganglia, intercostal nerves, and cardiac nerves
• Donkey: A peripheral nerve sheath tumor with features of benign schwannoma, located within endocardium of right ventricle found in a gelding donkey; neoplastic cells variably strongly positive for S100 and glial fibrillary acidic protein (GFAP); findings similar to Wistar rat; first cardiac tumor reported in a donkey (Paraschou al., J Comp Pathol. 2017)
• Tumors with morphology resembling endocardial sarcomas reported in hamsters, dogs, and man

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH, eds. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:156.
2. Boorman GA, Everitt JI. Neoplastic disease. In: Suckow MA, Weisbroth SH, Franklin CL, eds. The Laboratory Rat. Burlington, MA: Elsevier; 2006:601-603.
3. Paraschou G, Suarez-Bonnet A, Priestnall SL. Endocardial peripheral nerve sheath tumor with features of a benign schwannoma in a donkey. J Comp Pathol. 2017;157(4):280-283.
4. Robinson W, Robinson N. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6^th Philadelphia, PA: Elsevier Saunders; 2016: 53.

 

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