Biology and Management of High-Grade Myxofibrosarcoma: State of the Art and Future Perspectives

Abstract

Myxofibrosarcoma (MFS) is one of the most common adult soft tissue sarcomas, typically arising in the extremities. Histologically, MFS is classified into three grades: low, intermediate, and high. Histological grades correlate with distant metastases and tumor-associated mortality. The diagnosis of MFS is challenging due to a lack of well-characterized immunohistochemical markers. High-grade MFS displays highly complex karyotypes with multiple copy number alterations. Recent integrated genomic studies have shown the predominance of somatic copy number aberrations. However, the molecular pathogenesis of high-grade MFS remains poorly understood. The standard treatment for localized MFS is surgical resection. The systemic treatment options for advanced disease are limited. This review provides an updated overview of the clinical and imaging features, pathogenesis, histopathology, and treatment of high-grade MFS.

Multiple cutaneous myxofibrosarcoma on the right arm: Clinicopathological features and differential diagnosis

“…Highgrade tumors display densely packed, pleomorphic cells with numerous mitotic figures, as well as regions of hemorrhage and necrosis, resembling the morphology of pleomorphic malignant fibrous histiocytoma (MFH). 8 Immunohistochemistry revealed diffuse positivity for vimentin and, in a few cases, positivity for muscle-specific actin and smooth-muscle actin, indicating myofibroblast differentiation. CD68, S100 protein, HMB45, and epithelial membrane antigen (EMA) staining, however, yielded negative results.…”

“…Pseudo‐lipoblasts can be a significant diagnostic feature of MFS, although they can also be found in myxoinflammatory fibroblastic sarcoma, pseudo‐lipoblastic melanoma, and pseudo‐lipoblastic perineurioma. High‐grade tumors display densely packed, pleomorphic cells with numerous mitotic figures, as well as regions of hemorrhage and necrosis, resembling the morphology of pleomorphic malignant fibrous histiocytoma (MFH) 8 . Immunohistochemistry revealed diffuse positivity for vimentin and, in a few cases, positivity for muscle‐specific actin and smooth‐muscle actin, indicating myofibroblast differentiation.…”

Giant Myxofibrosarcoma in the Lower Limb: An Overview of Diagnostic and Clinical Management

“…Considering the histopathological heterogeneity of this disease, Haglund et al emphasized that, for intermediate- and high-grade infiltrative cases, despite aggressive negative-margin surgery followed by radiation, the risk of LR is increased, which is associated with high morbidity [ 62 ]. High-grade MFSs usually have an infiltrative growth pattern and specific histopathological characteristics, such as tumor necrosis, high cellularity, and severe nuclear atypia [ 6 , 36 ]. Lin et al also showed that positive surgical margins, tumor necrosis, and the presence of mitoses are associated with poor outcomes [ 77 ].…”

“…The incidence is about 0.1 per 100.000 per year (versus 2–5 per 100.00/year for all soft tissue sarcomas) [ 4 , 5 ]. Considering the histopathological heterogeneity in relation to the cellularity, nuclear pleomorphism, and proliferative pattern, it can be classified as low-, intermediate-, and high-grade myxofibrosarcoma [ 6 ]. The prognosis of MFS is good, with a 5-year survival rate of about 77%.…”