Characterization of Neurothekeoma, Plexiform Fibrohistiocytic Tumor and Other Neural and Fibrohistiocytic Neoplasms Using Neural Stem Cell Markers Nestin and Sox2
Wei-Shen Chen, Pei-Ling Chen, Jianping Li, Louis P Dehner, Dongsi Lu. Washington University School of Medicine, St Louis
Background: Neurothekeoma (NTK) is a rare dermal neoplasm that was first described in 1980 as a benign cutaneous tumor of neural origin due to its resemblance to nerve sheath myxomas. Subsequent attempts at histologic and immunohistochemical characaterization showed that only a subset of NTKs express S-100 and GFAP, and some NTKs can be morphologically indistinct from plexiform fibrohistiocytic tumors (PFT). Recent microarray-based characterization of NTK showed a gene expression profile more similar to cellular fibrous histiocytomas than neural tumors. To date, NTK remains a cutaneous tumor of uncertain histogenesis. In the present study, we sought to test the utility of neural stem cell markers Nestin and Sox2 in distinguishing NTK from its morphologic mimicker PFT, and in classifying other benign and malignant neural and fibrohistiocytic tumors, including schwannoma (SW), malignant peripheral nerve sheath tumor (MPNST), plexiform neurofibroma (pNF), dermatofibrosarcoma protuberans (DFSP), dermatofibroma (DF) and atypical fibroxanthoma (AFX).
Design: A total of 57 archival surgical pathology specimens were retrieved: 8 NTK, 6 PFT, 7 schwannoma, 5 MPNST, 6 pNF, 8 DFSP, 8 DF and 9 AFX. Immunostains were performed on FFPE tissue sections using anti-Nestin and anti-Sox2 antibodies.
Results: Cytoplasmic Nestin was diffusely/weakly positive in NTK and PFT (1-2+), diffusely/strongly positive in subset of pNF (2+), majority of SW (3+) and MPNST (3+), expressed in a patchy distribution in DFSP (2-3+) and negative in DF and AFX. Interestingly, rare giant cells, tumor cell clusters and atypical mitotic figures in AFX were positive for Nestin, and one case of multifocal PFT showed strong (3+) Nestin expression. Sox2 staining was weakly/focally positive in NTK and PFT, strongly/diffusely positive in SW, strongly/focally positive in MPNST, but negative in pNF, AFX, DFSP and DF.
Conclusions: In summary, our findings show that although some tumors of true neural differentiation (such as SW and MPNST) show strong Nestin and Sox2 staining, NTK, PFT and true fibrohistiocytic tumors such as DF and AFX lack such staining profile. In this regard, NTK can not be distinguished from its morphologic mimicker PFT based on Nestin/Sox2 immunostains alone. Interestingly, strong expression of Nestin in recurrent PFT suggests that the upregulation of stem cell markers in fibrohistiocytic tumors can confer more aggressive clinical behavior. Consistent with this, even though AFX is negative for Nestin in the majority of tumor, rare giant cells and bizarre mitotic figures in AFX show Nestin expression.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 98, Tuesday Morning