Answer: Rhabdomyosarcoma

Histology: The submucosa is filled by solid cellular nests and lobules of primitive round blue cell. By light microscopy, there is no evidence of any more specific differentiation such as keratinization, rosette/pseudo-rosette formations, neuropil or melanin production. Immunohistochemical studies were performed. The tumor cells were found to be immunoreactive for myogenin and desmin; and they were not immunoreactive for LCA, S100, synaptophysin, cytokeratin or CD99.

Discussion: Alveolar rhabdomyosarcoma (RMS) is a primitive round cell tumor that exhibits varying degrees of skeletal muscle differentiation. For RMSs as a collective group, the head and neck region represents the most common site of origin. When orbital and non-orbital (e.g. paranasal sinuses and nasopharynx) sites are combined, as many as 35% of RMSs occur in the head and neck region such that they should always be included in the differential diagnosis of primitive round cell tumors, particularly when dealing with children and young adults.

The major challenge for the pathologist is to distinguish RMSs from other neoplasms comprised of small round blue cells, including lymphoma, olfactory neuroblastoma, Ewings sarcoma, peripheral neuroectodermal tumor and malignant melanoma. This distinction hinges on the demonstration of myogenic differentiation. At the light microscopic level, myogenic differentiation is manifest by the presence of occasional cells with abundant pink cytoplasm resembling rhabdomyoblasts. Even the cross-striations of more fully developed skeletal muscle cells may rarely be present. Because histologic evidence of rhabdomyoblastic differentiation is difficult to appreciate in the alveolar variant, the pathologist must often resort to immunohistochemistry to document myogenic differentiation. At the immunohistochemical level, the tumor cells of RMS are immunoreactive for markers of muscle differentiation (e.g. desmin, myogenin); and they are not immunoreactive for lymphoid markers (e.g. common leukocyte antigen), melanocytic markers (e.g. S-100 protein and HMB-45), neuroendocrine markers (e.g. synaptophysin) or markers characterizing Ewings sarcomas and peripheral neuroectodermal tumors (e.g. CD99). Clearly, the use of a carefully selected panel of immunohistochemical stains can be very useful in distinguishing RMS from the large group of tumors they may morphologically resemble.

Once the histopathologic diagnosis of RMS has been established, the second challenge for the pathologist is to further characterize the tumor according to its histologic subtype. The 2 major subtypes of pediatric rhabdomyosarcomas include embryonal RMS and alveolar RMS. The embryonal subtype is characterized by sheets of round and spindled cells within a myxoid matrix. The alveolar subtype is composed of aggregates of round tumor cells separated by fibrous septa. Loss of cellular cohesion within these aggregates can result in the formation of “alveolar” spaces, but this feature and the presence of well formed fibrovascular septa are not well developed in the solid form of alveolar RMS. Histologic subtyping of RMSs is important. The embryonal variant appears to be associated with a better patient outcome compared to the alveolar variant of RMS. Other factors associated with a better prognosis include the absence of distant metastasis, small tumor size, absence of regional lymph node metastases, young patient age (2 to 10 years), and complete tumor resectability.