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Muscle tumor is abnormal tissue growth located in or originating from muscle tissue, which generally is divided into benign tumors and malignant. Malignant muscle tumors are sarcomas of which tissues are derived from muscle. According to the type of muscle, they are commonly subtyped in rhabdomyosarcoma and leiomyosarcoma. Rhabdomyosarcoma (RMS) is a malignant tumor originating from rhabdomyoblasts or mesenchymal cells differentiated into rhabdomyoblasts, which occurs mostly in children. Rhabdomyosarcoma is prone to regional lymph node metastasis and hematogenous metastasis. Leiomyosarcoma (LMS) is most frequently found in the abdomen or uterus. hematogenous is the primary way of leiomyosarcoma metastasis in addition to local infiltration of adjacent organs and tissues.
The etiology of muscle tumors is usually genetic. In addition, chemical drug stimulation (eg, tamoxifen), radiation exposure, or viral infections, such as human herpesvirus 8 (HHV8), are also risk factors for muscle and soft tissue tumors.
Symptoms include an observable or internal muscle tissue lump or swelling. Sometimes there are no signs until the tumor grows and compresses a nearby nerve or other parts of the body.
The genesis and progression of muscle tumors are regulated by multiple signaling pathways. LMS is characterized by persistent dysregulation of the PI3K/mTOR pathway, together with significant upregulation of key HH signaling pathway members such as SMO and GLI1. The PAX3-FOXO1 fusion oncoprotein-driven pathway, which blocks the normal maturation of muscle cells by inappropriately turning genes on and off, is related to rhabdomyosarcoma invasion and metastasis. Such as, ACTA1 is inhibited by PAX3-FOXO1 through RhoA-MKL1-SRF signaling pathway and may partially contribute to the tumorigenesis and development of Alveolar Rhabdomyosarcoma. In addition, Notch, Wnt, and Hedgehog signaling pathways have been shown that are involved in the regulation of stemness maintenance of tumor stem cells, self-renewal, and tumorigenesis. In muscle tumors, the Notch pathway is extensively and persistently activated to inhibit myogenesis. Ptch1 mutations in Hedgehog signaling are associated with the ability of tumor cells to resist apoptosis. Activation of the Wnt pathway increases the expression of MyoD and MyHC, thus, promoting myoblast fusion along with myogenic differentiation. In addition, protein metabolism and programmed cell death pathways such as PP2A-mediated dephosphorylation of key metabolic factors are also in connection with muscle tumors.
Fig. 1 Model of the signaling pathways implicated in fusion-positive ARMS progression
Pathological tests, and imaging methods including MRI, CT, and positron emission tomography (PET), are generally used in the diagnosis of muscle tumors. Rhabdomyosarcoma (RMS) has two histopathological subtypes: fusion-positive (FP) RMS, characterized by the positivity of the PAX3-FOXO1 fusion protein, with predominantly alveolar histological features; fusion-negative (FN) RMS generally exhibits histological features of embryonal tumors. In addition, positive immunohistochemical (IHC) staining for desmin, smooth muscle actin, and h-caldesmon is used to confirm the origin of smooth muscle. Besides, GFPT2 is associated with poor prognosis in uterine leiomyosarcoma. Enhanced ALDH1 activity is a stem cell marker of leiomyosarcoma and an independent prognostic marker. Additionally, the Epstein Barr virus is also found to be related to increased frequency of visceral leiomyosarcomas.
The medical strategy for muscle tumors largely depends on the location and size of the tumor, and whether it has spread to other parts of the body. Generally, surgery, chemotherapy, radiation therapy, and targeted therapy are used alone or in combination for the treatment of muscle tumors.
Targeted therapy usually causes less damage to normal cells than chemotherapy or radiation therapy. Different types of targeted therapy are being used or studied including,
Fig. 2 PD-1 or PD-L1 inhibitor therapy
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