• claudin-1
• CNPase
• dog
• GFAP
• H3K37me3
• histopathology
• immunohistochemistry
• Ki-67
• methylation
• nerve sheath tumor
• Sox10

Nerve sheath tumors (NSTs) are a group of tumors that originate from Schwann cells, perineurial cells, and/or endoneurial or epineurial fibroblasts. In veterinary pathology, the terminology of NSTs remains inconsistent and sometimes confusing, and many pathologists are guided in practice by the human classification of such tumors. In particular, malignant NSTs often lack specific histopathological and immunohistochemical (IHC) features, making them difficult to distinguish from other neoplastic lesions. This study aimed to histopathologically reevaluate archival samples of canine NSTs and assess their reactivity for the IHC markers Sox10, claudin-1, GFAP, CNPase, Ki-67, and H3K27me3. Based on the results, we classified the tumors according to the latest human WHO classification and evaluated the potential diagnostic utility of the IHC markers tested. Of 79 NSTs, 12 cases were diagnosed as benign NSTs, including six neurofibromas, three nerve sheath myxomas, two hybrid NSTs (perineurioma/neurofibroma and perineurioma/schwannoma), and one schwannoma. Sixty-seven tumors were malignant NSTs, including 56 conventional, four perineural, one epithelioid NST, and six malignant NSTs with divergent differentiation. We identified Sox10, claudin-1, GFAP, and Ki-67 as useful IHC markers whereas CNPase was found to have no role in the diagnosis of canine NSTs. We found complete loss of H3K27me3 expression in 25% of NSTs (17/68), most of which were malignant, except for one benign NST – a neurofibroma. We believe that H3K27me3, in combination with other IHC markers, may also be useful for the diagnosis of NSTs. Considering our results and incorporating data from the literature, we believe that an updated classification of NSTs in dogs using the proposed IHC panel could largely follow the recent WHO classification of such tumors in humans although prospective studies monitoring the clinical course of the disease are needed to assess its prognostic value.