Malignant Peripheral Nerve Sheath Tumor of the Femur: A Rare Diagnosis Supported by Complete Immunohistochemical Loss of H3K27me3

Abstract

The histological diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging because of the wide morphological spectrum and suboptimal performance of conventional immunohistochemical markers. MPNST arising primarily in the bone is exceptional, and its definitive diagnosis, particularly out of the neurofibromatosis type 1 (NF1) context, is even more problematic. Recurrent inactivation of EED or SUZ12 in a majority of MPNSTs results in a complete loss of trimethylated histone H3 at lysine 27 (H3K27me3) immunoreactivity, making it a highly specific biomarker of MPNSTs. In this article, we report a case of sporadic MPNST of the proximal femur that showed complete loss of H3K27me3. The patient was treated with limb-sparing surgery and postoperative radiotherapy. He developed multiple lung and bone metastases 4 months after surgery. Our case confirms the utility of H3K27me3 immunohistochemistry to yield a definitive diagnosis of sporadic MPNST in a rare primary site.

Differences in MMP-2 Expression in High- and Low-Grade MPNST and its Correlation with Prognostic Factors

“…6,12,17 The presence of a historical case of plexiform neurofibroma and NF-1 type is considered a precursor lesion of MPNST. 18 In this study, we found five cases with NF-1, in which one case was found in low grade and the other four cases in high grade, sized more than 5 cm for all. Based on the literature, patients with a history of NF-1 have multiple neurofibromatoses, so that the transformation towards malignancy is difficult to identify clinically, and most are high-grade tumors and larger than 5 cm.…”

Comparison study of clinicopathological features of cellular schwannoma between retroperitoneum and other sites

“…H3K27me3 refers to the trimethylation of lysine at position 27 of histone H3, which participates in the regulation of gene expression, gene imprinting, and X-chromosome inactivation, regulates embryonic development as well as cell proliferation and differentiation, and is closely related to cell aging and tumorigenesis. In malignant peripheral nerve sheath tumors, the expression of H3K27me3 is often reduced or absent ( 21 ). A study had found that this reduced or absent expression is often indicative of a poor prognosis or malignant transformation tendency ( 22 ).…”

Rare Primary Malignant Bone Sarcomas

“…Malignant peripheral nerve sheath tumor (MPNST) originating as a primary bone neoplasm is exceedingly rare and most often associated with the NF-1 syndrome. Classically, MPNST is most often composed of highly atypical, mitotically active, spindle cell proliferation exhibiting varied cellularity and often a distinctive perivascular aggregation of neoplastic cells [17][18][19]. Inactivation of polycomb repressive complex 2 subunit EED or SUZ12 in a majority of MPNSTs leads to loss of tri-methylation at the 27th lysine residue of the histone H3 protein, which can be detected by loss of immunoreactivity for the H3K27me3 antibody, a highly specific biomarker of MPNSTs [18].…”