Utility of Sox-10 To Distinguish MPNST from Synovial Sarcoma with a Focus on Intraneural Synovial Sarcoma
Yuna Kang, Melike Pekmezci, Bernd Scheithauer, Ayca Ersen, Andrew Folpe, Andrew Horvai. UCSF, San Francisco, CA; Mayo Clinic, Rochester, MN
Background: Synovial sarcoma (SS) is a spindle cell tumor of unknown histotype, characterized by a reproducible t(X;18) rearrangement. Monophasic SS and malignant peripheral nerve sheath tumor (MPNST) are particularly difficult to distinguish given similar histomorphology. That SS can present intraneurally, or express S-100 protein, further blurs the distinction between these tumors. Although genetic confirmation of t(X;18) is a useful adjunct to diagnosis of such difficult cases, immunohistochemistry is more rapid and cost effective at many institutions. The Sox-10 transcription factor, a putative marker of neural crest differentiation may have diagnostic utility in this differential but immunohistochemical data are limited.
Design: Ninety-seven cases of MPNST and 97 cases of SS were retrospectively identified from the archives of UCSF Medical Center and Mayo Clinic. All SS were genetically confirmed for the presence of t(X;18) by fluorescence in-situ hybridization and/or SYT rearrangements by RT-PCR. Four SS were intraneural and 69 were monophasic. Immunohistochemical staining using standard methods for Sox-10 was performed and evaluated for nuclear positivity independently by two pathologists who were blinded to diagnosis. The intensity was scored semi-quantitatively (score 0 to 3+) accounting for both the fraction of cells staining and staining intensity.
Results: Six of 97 (6%) SS were positive for Sox-10 whereas 53/97 (54%) MPNST were positive. Most of the Sox-10 positive MPNST (n=39, 74%) showed 2+ or 3+ staining. Importantly, however, two of the intraneural SS showed 2+ Sox-10 staining, in clusters of spindle cells. The sensitivity and specificity of Sox-10 for the diagnosis of MPNST over SS were 55% and 93%, respectively with a positive predictive value of 90% and negative predictive value of 67%.
Conclusions: Nuclear Sox-10 staining is present in the majority of MPNST, consistent with the neural crest origin of these tumors. In contrast, nuclear Sox-10 staining is rarely seen in SS. Sox-10 can be a useful and specific, albeit not very sensitive, immunohistochemical test for supporting a diagnosis of MPNST over SS. However, the stain needs to be interpreted with caution in intraneural tumors, since intraneural SS are commonly positive. It remains to be determined whether Sox-10 positive cells in intraneural SS represent entrapped Schwann cells, Sox-10 staining of synovial sarcoma cells, or both.
Category: Bone & Soft Tissue
Monday, March 4, 2013 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 8, Monday Morning