JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2233855): Age, strain and gender unspecified rat
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 vague 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, variably sized, oval to elongate, occasionally vesiculate nuclei with coarse chromatin and one variably distinct basophilic nucleolus. Mitoses average 5-6 per HPF with occasionally 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 undulating 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
- 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
- Spontaneous incidence from 0.07 to 0.9 percent in common rat strains
- Many carcinogens increase the incidence
- Metastasis rare, to lung, liver, spleen, mediastinum, and bone marrow
- Cell of origin unknown; Schwann cell origin suspected because of histologic features and positive immunohistochemistry for S-100 protein and neuron specific enolase
- 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
- 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 and neuron specific enolase (NSE)
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
- Atriocaval mesothelioma: Rare; NZR/Gd strain most commonly affected followed by F344; males 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
- 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
- Extracardiac benign/malignant schwannomas (benign/malignant peripheral nerve sheath tumors) occur in many species
- Neurofibromas (schwannomas) often multiple nodular masses either on the epicardial surface or within the myocardium; frequently involve the peripheral nerves, brachial plexus, autonomic ganglia, intercostals nerves and cardiac nerves
- Adenomatoid tumors (myocardial epithelial inclusions) arise in genital tract and rarely in heart; characterized by epithelioid cells that form tubular structures and anastomosing channels within a fibrous stroma; common in left ventricle; immunohistochemically positive for pan-cytokeratins, vimentin, calretinin, Wilms’ tumor 1 suppressor gene, and CD 30 antigen; immunohistochemical and ultrastructural features suggest mesothelial origin; considered most likely to be a developmental anomaly and not a true neoplasm
- 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 G, Suarez-Bonnet A, Priestnall SL; 2017)
- Tumors with morphology resembling endocardial sarcomas reported in hamsters, dogs and man
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- McInnes EF. Wistar and Sprague-Dawley rats. In: McInnes EF ed. Background Lesions in Laboratory Animals. London, UK: Saunders Elsevier; 2012:17.
- 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.
- Percy DH, Barthold SW. Rat. In: Barthold SW, Griffey SM, Percy DH, eds. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Blackwell Publishing; 2016:156.
- Robinson W, Robinson N. Cardiovascular system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 3. 6th Philadelphia, PA: Elsevier Saunders; 2016: 53.
- Tursi M, Martinetti M, Gili S, Muscio M, Gay L, Crudelini M, Cenacchi G, Pucci A. Myocardial adenomatoid tumor in eight cattle: Evidence for mesothelial origin of bovine myocardial epithelial inclusions. Vet Pathol. 2009;46:897-903.