Rhabdomyosarcoma (RMS) is a highly aggressive form of cancer that develops from mesenchymal cells that have failed to fully differentiate into myocytes of skeletal muscle.

[2] Embryonal and alveolar are the main groups, and these types are the most common soft tissue sarcomas of childhood and adolescence.

[5][6][7] RMS can occur in any soft-tissue site in the body, but is primarily found in the head, neck, orbit, genitourinary tract, genitals, and extremities.

[11] Outcomes vary considerably, with five-year survival rates between 35 and 95%, depending on the type of RMS involved, so clear diagnosis is critical for effective treatment and management.

[citation needed] Embryonal rhabdomyosarcoma (ERMS) is the most common histological variant, comprising about 60–70% of childhood cases.

For this reason, it is the most common form of RMS observed in young adults and teenagers, who are less prone to the embryonal variant.

[2] This subtype is very similar to that of leiomyosarcoma (cancer of the smooth muscle tissue), and it has a fascicular, spindled, and leiomyomatous growth pattern with notable rhabdomyoblastic differentiation .

It occurs most commonly in the paratesticular region, and the prognosis for this particular form of RMS is excellent with a reported five-year survival rate of 95%.

[14] RMS often presents as a mass, but signs and symptoms can vary widely depending on the site of the primary tumor.

Parameningeal tumors may present with cranial nerve dysfunction, symptoms of sinusitis, ear discharge, headaches, and facial pain.

The cancer's prevalence in the head, face, and neck will often allow for earlier signs of the disease simply due to the obvious nature of tumors in these locations.

[14] Despite the varying presentation and typically aggressive nature of the disease, RMS has the potential to be diagnosed and treated early.

However, alveolar and embryonal types of RMS can be distinguished cytogenetically, and identification of specific genetic lesions can allow for accurate classification of the ARMS subtype when the histopathological findings are equivocal or unclear.

[27] The fusion protein presents a potential therapeutic target, and in recent years more research has been conducted to clarify the role of PAX3-FOXO1 in FP-RMS.

PAX3-FOXO1 is now known to drive key oncogenes such as MYC and MYCN by creating long-distance genetic interactions by super enhancers.

The short arm of chromosome 11 is also the site of the insulin-like growth factor 2 gene (IGF-2), which is often over-expressed in RMS.

Other oncogenes often associated with rhabdomyosarcoma, albeit with less frequency, include NMYC, NRAS, KRAS, P16, and c-Met.

[32] More recently, a mechanistic and epigenetic link between mutant RAS isoforms and a block of myogenic differentiation has been demonstrated.

Other cancers that share this classification include neuroblastoma, Ewing sarcoma, and lymphoma, and a diagnosis of RMS requires confident elimination of these morphologically similar diseases.

[14] The defining diagnostic trait for RMS is confirmation of malignant skeletal muscle differentiation with myogenesis (presenting as a plump, pink cytoplasm) under light microscopy.

[25][34][35] Myogenin, in particular, has been shown to be highly specific to RMS,[36] although the diagnostic significance of each protein marker may vary depending on the type and location of the malignant cells.

[5][34] Classification into types and subtypes is accomplished through further analysis of cellular morphology (alveolar spacings, presence of cambium layer, aneuploidy, etc.)

[citation needed] Following diagnosis and histopathological analysis, various imaging techniques may be used, including MRI, ultrasound, and a bone scan in order to determine the extent of local invasion and any metastasis.

Outcomes are strongly tied to the extent of the disease, and its early mapping is important for treatment planning.

Before the use of adjuvant and neoadjuvant therapy involving chemotherapeutic agents, treatment solely by surgical means had a survival rate of <20%.

[16][34] In children and young adults with stage IV metastatic rhabdomyosarcoma, a Cochrane review has found no evidence to support the use of high-dose chemotherapy as a standard therapy.

Radiation therapy is used when resecting the entirety of the tumor would involve disfigurement or loss of important organs (eye, bladder, etc.).

[55] Rhabdomyosarcoma was first described by Weber, a German physician, in 1845,[56] but it was not until the paper by Arthur Stout in 1946 that RMS was formally classified.

[citation needed] Cancer stem cells of rhabdomyosarcoma have been identified and fibroblast growth factor receptor 3 has been suggested as their marker.

[citation needed] A recent study by Bharathy et al. found that deacetylase inhibitor, entinostat works in aggressive subtype, alveolar rhabdomyosarcoma (aRMS) by specifically blocking the activity of HDAC3, thereby preventing epigenetic suppression of a microRNA that inhibits PAX3:FOXO1 translation.