[Problems of the immunohistochemical differential diagnosis of neuroendocrine carcinoma and neuroblastomas]

Neurons arising from neural tube or neural crest do not express epithelial markers from the beginning of their differentiation and neuroblastomas arising from these anlages also do not express epithelial markers. On the other hand, neuroendocrine carcinomas, such as small cell carcinomas of the respiratory tract, express epithelial markers in addition to neuronal or neuroendocrine markers and demonstration of epithelial marker has been regarded as subtle evidence to rule out neuroblastomas. However, this general rule can not be applied to olfactory neuroblastomas. Unlike neurons derives from neural tube or neural crest, developing neurons arising from the anlage of olfactory nerve, i.e., olfactory placode, have keratin during the embryonic stage. Accordingly, it is unnatural for neoplastic neuroblasts of olfactory placodal origin to have keratin as the embryonic phenotype. In addition, neurons arising from this anlage have an epithelial antigen (EA) detected by Ber-EP4 from the beginning of their differentiation, and this antigen is preserved in the olfactory sensory nerve even in the postnatal stage, though it is lost from the neurons migrating from olfactory placode to brain, i.e., luteinizing hormone-releasing hormone producing neurons (LHRH neurons) during post embryonic stage. Therefore, demonstration of this epithelial antigen in the tumor with neurite formation can be regarded as a satisfactory diagnostic evidence of true olfactory neuroblastoma. LHRH also seems to be a useful marker to determine true olfactory placodal origin of the neuroblastoma. Finally, it is concluded that demonstration of epithelial markers could not be regarded as evidence to rule out neuroblastoma developed in the olfactory nerve region.