Rhabdomyosarcoma

The first published example of rhabdomyosarcoma, the malignancy of striated muscle, was probably a tongue lesion reported in 1854.  The head and neck region is a likely site for this neoplasm to originate and tumors from this site generally occur at a younger age than do rhabdomyosarcomas of other sites. Although an uncommon lesion, this tumor is among the most common head and neck cancers in young persons.  Congenital cases have been reported.

Oral and pharyngeal rhabdomyosarcoma is typically a rapidly enlarging, painless submucosal mass in children and young adults (mean age at diagnosis: 20 years).  It is rare after 45 years of age. There is a slight male predilection (1.5:1.0 male:female ratio). The tumor surface may be smooth or lobulated, sometimes botryoid or grape-cluster in appearance, and the tumor becomes fixed to surrounding tissues at an early stage. Very few patients have waited beyond six months for a diagnosis, most present for evaluation within 1-2 months of tumor onset.

Rhabdomyosarcoma is subdivided into three general types, often with combined features, and there is little variation in biologic behavior between the types. The majority of head and neck lesions are embryonal rhabdomyosarcoma, with small round or oval tumor cells resembling embryonal or developing voluntary muscle cells.  These cells have a finely granular eosinophilic cytoplasm with infrequent cells demonstrating fasciculation or cross striations. There often is a fibrillar material imparting a clear zone around the nucleus and the nucleus itself is typically enlarged. The more well-differentiated tumors demonstrate elongated, strap-shaped or tadpole-shaped rhabdomyoblasts. Occasional giant cells with enlarged or multiple nuclei can be seen, as can muscle-like cells with rather bizarre nuclear and cellular shapes. Mitotic figures are often seen and may be abnormal, but are not necessary to the diagnosis. The background stroma consists of moderately loose to dense fibrous tissue and may be quite scant, and a background of poorly differentiated ovoid mesenchymal cells is frequently noted. Myxoid zones are commonly seen in the stroma.

Alveolar rhabdomyosarcoma is comprised of relatively small, poorly differentiated round and oval cells aggregated into irregular clusters or nests separated by fibrous septa. Degenerated cells in the center of the clusters show a decided lack of cohesiveness, while the peripheral cells adhere in a single layer to the septal walls. Multinucleated giant cells may be seen and mitotic figures are common and sometimes bizarre. It is differentiated from the alveolar soft part sarcoma by its less regular tissue pattern and more pleomorphic cells. An occasional variant, referred to as the botryoid type, demonstrates a diffuse myxoid or mucoid matrix with sparsely scattered primitive mesenchymal cells. The characteristic feature of this type is a peripheral zone of increased cellularity, sometimes known as the "cambium layer."

Pleomorphic rhabdomyosarcoma shows randomly arranged eosinophilic cells with considerable variation in cell size and shape, as well as variation in nuclear size and shape. The pleomorphic cells are often admixed with small, primitive mesenchymal cells. This tumor is often so undifferentiated that the identification of the cell of origin is difficult or impossible. Positive immunostains for desmin and myoglobin are very helpful in such cases.

Regardless of the histologic subtype, special stains are often quite useful for differentiating rhabdomyosarcoma from other neoplasms. The trichrome stain is especially useful because it colors rhabdomyoblasts bright red while myofilaments and cross-striations have fuchsinophilic properties, also highlighted by PTAH (deep purple color). Myxoid stroma may be positive for hyaluronidase with acid mucopolysaccharide staining, although many other tumors also have positive stroma with these stains.

The most useful immunoreactions are toward myoglobin and anti-skeletal muscle actin.  Antibodies to desmin and myosin will also be reactive, but cannot differentiate rhabdomyosarcoma from leiomyosarcoma (Table 1). Desmin is more reactive than myoglobin in poorly differentiated rhabdomyosarcoma.

The most problematic tumors to differentiate from alveolar rhabdomyosarcoma are neuroblastoma, lymphoma, soft tissue Ewing's sarcoma, and undifferentiated small cell carcinoma. The neuroblastoma has a much more uniform and diffuse distribution of lesional cells and often contains rosettes with neurofilament cores. It also is nonreactive for desmin, myoglobin and skeletal muscle actin, as are the lymphomas, Ewing's sarcoma and the carcinoma. The latter is an especially important distinction because oat cell carcinoma can present with a rather distinctive pseudoalveolar pattern.

Pleomorphic rhabdomyosarcoma must be differentiated from other pleomorphic sarcomas such as the pleomorphic liposarcoma and pleomorphic MFH, and the pathologist must also be careful not to confuse degenerated or metaplastic rhabdomyoblasts in other sarcomas, especially the Triton tumor (MPNST), the malignant mesenchymoma and carcinosarcoma. The latter malignancies must demonstrate an obvious component, somewhere in the specimen, of their classic histopathologic appearance.

Rhabdomyosarcoma is treated by radical surgical excision followed by multi-agent chemotherapy, usually a combination of vincristine, dactinomycin and cyclophosphamide.  Postoperative radiotherapy is used for those cases which cannot be completely resected. Five year survival rates have improved dramatically from less than 10% prior to the 1960s to 65% today.  Stage I lesions have an even better prognosis (80%). Metastasis, when it occurs, is via either blood or lymphatic vessels, usually to cervical lymph nodes, lungs, bones or brain.

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