Answer: Olfactory neuroblastoma

Histology: The tumor is a nested proliferation of small round cells growing in the sinonasal submucosa. It is positive for synaptophysin, chromogranin (not shown), and S100 in a sustentacular distribution. In addition, desmin (not shown) and myogenin highlight scattered tumor cells.

Discussion: Rhabdomyosarcoma (RMS) is a malignant mesenchymal neoplasm that exhibits skeletal muscle differentiation. About 40% of RMS affect the head and neck, in order of frequency: orbit, sinonasal tract, ear, and oral cavity, with other subsites rarely affected. Most forms of RMS are defined by the presence of rhabdomyoblasts – densely eosinophilic polygonal or spindled cells with hyperchromatic nuclei and occasional cytoplasmic cross-striations. Skeletal muscle differentiation is confirmed by nuclear immunohistochemical staining for myogenin and/or MyoD1. It must be remembered, however, that rhabdomyoblastic differentiation may be encountered in neoplasms other than RMS. This distinction is important because RMS is treated by specific chemotherapy protocols that may be different than those of other neoplasms in the differential diagnosis.

Olfactory neuroblastoma (ONB) is a malignant neoplasm that arises from the olfactory neuroepithelium of the superior nasal cavity and ethmoid sinus. By immunohistochemistry, ONB is positive for the neuroendocrine markers synaptophysin, chromogranin, and CD56 while S100 protein highlights the sustentacular supporting cells at the periphery of the tumor nests. Occasionally, ONB may exhibit unusual forms of differentiation that may obscure the diagnosis. Most common is epithelial differentiation, but rarely, ONB may exhibit melanocytic or rhabdomyoblastic differentiation.

It is important to distinguish ONB with rhabdomyoblastic differentiation from RMS, a problem compounded by both tumors being encountered in the sinonasal tract of young patients. Additionally, the alveolar subtype of RMS may express neuroendocrine markers, with nearly universal CD56 expression. An important key to this dilemma is recognizing the nature of the myogenin expression. Alveolar RMS, a nested, small round cell tumor, generally demonstrates diffuse myogenin expression, in contrast to the patchy distribution seen in ONB. Moreover, even in the face of patchy rhabdomyoblastic differentiation, classic areas of ONB should be recognizable in the background. Finally, in a very difficult case, molecular studies for the t(2;13) or t(1;13) translocations of alveolar RMS may be useful.

Reference:
– Bishop, et al. Rhabdomyoblastic differentiation in head and neck malignancies other than rhabdomyosarcoma. Head Neck Pathol. In press.