Genetic and pathological analysis of schwannomatosis and schwannoma to clear the hybrid schwannoma/neurofibroma tumor

In schwannomatosis, LZTR1 and SMARCB1 are known as causative genes. In previous reports of some schwannomatosis tumors, hybrid schwannoma/ neurofibroma tumor (hybrid tumor) that have both schwannoma and neurofibroma features in a tumor have been recognized. In general, neurofibroma consists of a mixture of schwann cells, fibroblasts, perineural cells, and mast cells. Neurofibroma cells are known to be CD34 positive. On the other hand, schwannoma consists of schwann cells mostly. In schwannoma, Antoni B consists of loosely cellular area and the area is sometimes CD34 positive. In some previous reports of hybrid tumor, CD34 positive cells were found in some parts of the tumor and the part was considered to be a neurofibroma, leading to the diagnosis of a hybrid tumor. However the definition of hybrid tumor has not been fully understood. The aim of this study was to define the CD34 positive loosely cellular area originated from schwannoma or neurofibroma in genetic analysis. First, we analyzed a skin tumor of schwannomatosis patient who has a novel frameshift mutation c.1844delA in the LZTR1 gene. The tumor has a highly ordered cellular component and loosely cellular area some of which are CD34 positive. However CD34 positive loosely cellular area consists of schwann cell mostly, and the tumor was diagnosed as schwannoma. In some previous reports, CD34 positive cells have been found in some single schwannomas, diagnosing them as hybrid tumor. Therefore, we analyzed 64 cases diagnosed schwannoma whether hybrid tumor was observed or not. Although CD34 positive loosely cellular area was shown in several schwannomas, the area was considered as Antoni B, and hybrid tumor were not observed.