JPC SYSTEMIC PATHOLOGY
SIGNALMENT (NIEHS#15-0076): 11.5-month-old male B6.129-Trp53tm1Brd mouse
HISTORY: This mouse was exposed to a chemical via inhalation for 5 days a week for up to 8 weeks. At the end of the exposure period the mouse was held without further exposure until death. The mouse died prior to the time of scheduled sacrifice.
GROSS PATHOLOGY: Subcutaneous mass located above and around right front shoulder.
HISTOPATHOLOGIC DESCRIPTION: Striated muscle and fibrovascular tissue, right shoulder (per contributor): Infiltrating and effacing the normal adjacent skeletal muscle and subcutaneous adipose tissue is an unencapsulated, well circumscribed, 2x2cm, densely cellular neoplasm composed of tightly packed moderately to highly pleomorphic spindle cells arranged in disorganized interlacing streams bundles and solidly cellular sheets on a scant collagenous matrix surrounded by multifocal varisized areas of coagulative and lytic necrosis and hemorrhage. Neoplastic cells have indistinct borders, moderate to abundant eosinophilic fibrillar to vacuolated cytoplasm and large eccentrically located pleomorphic nuclei with finely stippled chromatin and 1-4 nucleoli. Mitoses average 1-4 per 400x hpf and are occasionally bizarre. Anisokaryosis and anisocytosis are marked. Multinucleated and karyomegalic cells are numerous and occasionally these cells contain nuclei that line up within elongated cytoplasm (strap cells), or rarely, are globoid with one end tapering into an elongate or wispy tail (racquet cell). These cells contain large, round eosinophilic glycogen inclusions and rarely very faint cytoplasmic cross striations. Multifocally scattered throughout are small numbers of neutrophils. Adjacent pre-existing muscle fibers are surrounded and separated, shrunken with loss of cross striations (atrophy).
MORPHOLOGIC DIAGNOSIS: Striated muscle and fibrovascular tissue, right shoulder (per contributor): Rhabdomyosarcoma, B6.129-Trp53tm1Brd mouse, murine.
- Rare, malignant neoplasm, a type of soft tissue sarcoma, arising from pluripotent progenitor cells that differentiate towards skeletal muscle
- May arise in locations that lack striated muscle
- Typically aggressive, rapid growth with local invasion and metastasis often to unusual location such as other muscles, as well as lung, liver spleen
- Embryonal rhabdomyosarcoma and the botryoid variants are the most common form in people and animals
- Other types -clinical significance unknown in canine
- Alveolar -rare
- Pleomorphic – exceedingly rare
- Embryonal rhabdomyosarcoma
- Round (most common) or myoblast-like or elongated myotube-like (strap cells)
- Mononuclear to multinucleated
- Most common in young animals in locations of head or neck or oral cavity
- Myoblasts have prominent cytoplasmic vacuoles, resulting in “spider-web” cells
- Botryoid variant
- Most often in trigone areas of urinary bladder in large breed dogs
- Spindle and stellate cells within myxoid stroma
- Alveolar rhabdomyosarcoma
- Sheets of undifferentiated small round cells, forming alveolar-like structure
- Pleomorphic rhabdomyosarcoma
- Rare and lack any feature of embryonal or alveolar rhabodomyosarcomas; reported in dogs, cats, cows and horses
- Cardiac rhabdomyosarcoma
- Rare, only reported in dogs, and poorly differentiated; aggressive with frequent metastasis
- Prevalence may be underestimated- misdiagnosed as undifferentiated soft tissue sarcoma or sarcoma with multinucleated cells
- May be overdiagnosed when multinucleated cells seen in sarcoma
- Young dogs are most commonly affected with botryoid or embryonal type in urinary tract
- Animal models indicate that suppression of p53 is required for tumor development
- Cytogenetic abnormalities play a role in human RMS, unknown in animal
- Possible genetic component as related litters of pigs developed RMS
TYPICAL CLINICAL FINDINGS:
- Urinary obstruction: Dysuria, stranguria, hematuria common in botryoid rhabdomyosarcoma of the urinary bladder
TYPICAL GROSS FINDINGS:
- Head, neck, tongue, larynx, heart often affected
- Trigone of bladder, grapelike masses protruding from bladder mucosa-botryoid type in young female large breed dog
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Highly variable presentation- exclusive or mix of:
- Poorly differentiated embryonal myoblast-small round cells with abundant eosinophilic cytoplasm, lymphoid in appearance, rare cross striations
- More differentiated spindle cells with myotube formation, multinucleation, frequent cross striations, and strap/racquet cells
- Often considerable pleomorphism, multinucleated cells
- Cross striations possible but often not seen
- Elongated ‘strap’ cells or ‘racquet’ cells possible
- Mucinous stroma
ADDITIONAL DIAGNOSTIC TESTS:
- Electron microscopy
- PTAH staining of cross striations- variably rewarding depending on differentiation
- Positive (often) for following IHCs: desmin; muscle specific actin; sarcomeric actin; myoglobin
- Usually negative for following IHC: vimentin; cytokeratin; smooth muscle actin
- MyoD and myogenin are specific nuclear labels and even work in poorly differentiated tumors and embryonal forms
- Myogenin positive early- associated with high proliferation
- MyoD1 positive early- associated with cell cycle exit, myotube muscle fiber formation
- Leiomyosarcoma- smooth muscle actin positive
- Tumors metastatic to muscle
- Soft tissue sarcoma
- This tumor has been most commonly described in the dog and cat, but case reports found for pigs, horses, rhesus macaques, rodents and sea dragons.
- Mice: BALBc overrepresented as well as GEMs and SCID
- Dog: Laryngeal (non-invasive, low mitoses, no mets); esophagus; cardiac (rhabdomyosarcoma); urinary bladder (botryoid rhabdomyosarcoma- young, large breed females; associated with hypertrophic osteopathy)
- Case reported of primary meningeal rhabdomyosarcoma of spinal cord
- Pig: Cardiac rhabdomyoma (some consider it a hamartoma); possible Purkinje cell orgin (PGP 9.5 expression)
- Horse: Botryoid rhabdomyosarcoma has been reported in the uterus of a yearling filly and in the urinary bladder of a 2-year-old filly; in a case series report and review of reported occurrences of rhabdomyosarcoma in horses the most common location was the tongue and limb muscles; most were classified as embryonal
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