Definition
• Malignant tumor with skeletal muscle differentiation
Pathogenesis
• Embryonal rhabdomyosarcoma: most commonly, loss of chromosome area 11p15 occurs, most likely resulting in loss of a tumor suppressor gene. Often have complex karyotypes including extra copies of chromosomes 2, 8, and 13
• Alveolar rhabdomyosarcoma: recurrent translocations t(2;13) or t(1;13) resulting in transcriptional activation by fusion proteins PAX3/FKHR or PAX7/FKHR, respectively
• Pleomorphic rhabdomyosarcoma: pathogenesis is unknown
Clinical features
Epidemiology
• Bimodal age distribution depending on subtype:
• Alveolar and embryonal rhabdomyosarcomas occur in adolescents and children
• Pleomorphic rhabdomyosarcoma occurs in adults older than 60 years
• More common in males
Presentation
• Can occur in the lung, bronchi, chest wall, mediastinum, or heart
• In adults it usually is seen as a chest wall or diaphragmatic mass
• In children it is the most common sarcoma of the heart
• Depending on location, symptoms can be coughing, dyspnea, chest pain, cardiac arrhythmias, pleural effusion
Prognosis and treatment
• Alveolar subtype has a worse prognosis than pleomorphic or embryonal
• Location in the thorax imparts a poor prognosis
• Treatment is usually chemotherapy
Pathology
Gross
• Are often very large lesions
• May have necrosis or cystic areas
• Involvement of rib is uncommon
• Embryonal: poorly circumscribed, pale, fleshy
• Alveolar: fleshy, gray-tan with some fibrous tissue
• Pleomorphic: well-circumscribed with pseudocapsule; firm, white; hemorrhage and necrosis may be present
Histology
• Histological subtypes include embryonal, alveolar, and pleomorphic
• Rhabdomyoblasts: round to spindle cells with eosinophilic fibrillary cytoplasm with or without cross striations
• “Tadpole” or “strap” cells: more elongated with eosinophilic cytoplasm
• “Spider” cells: cells in which intracellular glycogen is washed out in processing, giving a vacuolated appearance; can look similar to lipoblasts
• Terminally differentiated myocytes: multinucleated with cytoplasmic cross-striations
• Embryonal: composed of hypercellular areas with round to spindle cells and less cellular myxoid areas. May contain strap cells that are sharply angulated (“broken straw” appearance)
• Alveolar has three subtypes: typical, solid, and mixed embryonal and alveolar
• Typical: nests of tumor cells separated by fibrovascular septae; tumor cells line the septae giving a “picket fence” appearance; viable and degenerating tumor cells also “float” within the alveolar spaces; giant cells with multiple peripheral nuclei are common
• Solid: sheets of small blue cells; lacks fibrous septa
• Mixed: contains areas that look like typical alveolar and other areas with an embryonal appearance
• Pleomorphic: round, polygonal or spindle cells with abundant eosinophilic cytoplasm, large bizarre tumor cells; no areas of embryonal or alveolar patterns
Immunohistopathology/specials stains
• Primitive cells are vimentin positive
• More differentiated cells are positive for desmin, actin, myoglobin, and myosin
• MyoD1 and myogenin are very sensitive and specific markers for rhabdomyosarcoma, staining the tumor nuclei
Main differential diagnosis
• Germ cell tumor, teratoma, or carcinosarcoma with rhabdomyosarcoma component
Fig 1 Rhabdomyosarcoma. Embryonal rhabdomyosarcoma with hypercellular area adjacent to a less cellular, myxoid area.
Fig 2 Rhabdomyosarcoma. Embryonal rhabdomyosarcoma. High-power view of cellular area composed of spindle cells.
Fig 3 Rhabdomyosarcoma. Alveolar rhabdomyosarcoma with nests of discohesive round cells.
Fig 4 Rhabdomyosarcoma. Strap cells may also be present in alveolar rhabdomyosarcoma.
Fig 5 Rhabdomyosarcoma. Multinucleated “wreath-like” cells in an alveolar rhabdomyosarcoma.
Fig 6 Rhabdomyosarcoma. Pleomorphic rhabdomyosarcoma. High-power view showing rhabdomyoblasts with eccentric nuclei and abundant eosinophilic cytoplasm.
Fig 7 Rhabdomyosarcoma. Pleomorphic rhabdomyosarcoma with highly atypical multinucleated tumor giant cells.