Histopathological and Immunohistochemical Evaluation of Canine Nerve Sheath Tumors and Proposal for an Updated Classification

Abstract

Nerve sheath tumors are a group of tumors originating from Schwann cells, fibroblasts, and perineurial cells. In veterinary pathology, the terminology for nerve sheath tumors remains inconsistent, and many pathologists follow the human classification of such tumors in practice. Immunohistochemistry plays an important role in the diagnosis of nerve sheath tumors, but specific immunohistochemical and molecular biomarkers are lacking. In our study, we histopathologically reevaluated 79 canine nerve sheath tumors and assessed their reactivity for the immunohistochemical markers Sox10, claudin-1, GFAP, CNPase, and Ki-67. Based on the results, we classified the tumors according to the most recent human classification. Twelve cases were diagnosed as benign nerve sheath tumors, including six neurofibromas, three nerve sheath myxomas, two hybrid nerve sheath tumors (perineurioma/neurofibroma and perineurioma/schwannoma), and one schwannoma. Sixty-seven tumors were malignant nerve sheath tumors, including fifty-six conventional, four perineural, one epithelioid malignant nerve sheath tumor, and six malignant nerve sheath tumors with divergent differentiation. We believe that with the application of the proposed panel, an updated classification of canine nerve sheath tumors could largely follow the recent human WHO classification of tumors of the cranial and paraspinal nerves, but prospective studies would be needed to assess its prognostic value.

Loss of H3K27me3 expression in canine nerve sheath tumors

“…Unfortunately, we lacked data on the proliferation marker Ki-67 for 17 of the included tumors, 16 of which were malignant and one benign. According to our previous study, staining of these samples was assessed as unreliable, probably due to poor antigen preservation in old archive blocks (19,25). Previous studies from human pathology have found loss of H3K27me3 expression in a higher percentage of MNSTs, but results vary depending on the study.…”

“…In this study, we immunohistochemically investigated the expression of H3K27me3 in 68 canine NSTs that had been diagnosed, classified, and, if malignant, graded based on their histopathologic and IHC features in our previous study (19). We compared the individual histopathological features and IHC staining results for Sox10, claudin-1, GFAP, and proliferation index Ki-67 with H3K27me3 expression to assess the potential diagnostic value of the latter.…”

“…Such results raise questions about the diagnosis of neurofibroma with loss of H3K27me3 expression in our study. The diagnosis was previously made based on the histopathological and IHC features of the tumor, all of which were suggestive of its benign nature (19), but given the lack of data on the further clinical course of the disease and survival of the dog, we cannot completely rule out the possibility of low-grade MNST. However, until a larger prospective study of canine NSTs is conducted, we also cannot be certain that the interpretation of the results of NSTs in dogs can fully follow those in human medicine.…”

“…The details of the dogs included in the study, including available clinical data and final diagnoses, are provided in Supplementary Table 2. The histopathological and IHC features that led to the final diagnoses are described in detail in our previous study (19).…”

“…Tissue characteristics included evaluation of tumor shape, demarcation, encapsulation, growth type, cellularity, growth pattern, amount and type of stroma, extent of necrosis, extent of hemorrhage, blood and lymphatic vessel invasion, herniation into vessels, inflammatory infiltrates, hyalinization, and osseous and cartilaginous components. Cellular characteristics included assessment of cell morphology, anisocytosis, anisokaryosis, cell margins, nuclear/cytoplasmic ratio, nuclear pleomorphism, nucleoli, number of mitoses per 10 high-power fields (HPF, 400× magnification −0.196 mm 2 ), and presence of multinucleated cells (19). Details on the evaluation of the tissue and cellular criteria of tumors and evaluation of expression of IHC markers can be found in the Supplementary Tables 1, 2.…”