Rhabdomyoma is definitionally a benign neoplasm that shows skeletal muscle differentiation. There are three major subtypes, each with distinct clinical and genetic features: "fetal", "adult", and "genital".

Fetal rhabdomyoma and adult rhabdomyoma occur most commonly in the head and neck,^1,2 and both show a male predominance. Genital rhabdomyoma in females most commonly occurs in the vagina.³ Genital rhabdomyoma in men occurs in paratesticular soft tissue and includes fetal and adult subtypes, as well as a "sclerosing" subtype unique to this location.⁴

Rhabdomyoma generally presents as a slow-growing, painless mass. In the head and neck, symptoms can result from impingement on cranial nerves,⁵ and laryngeal tumors can cause hoarseness and dysphagia.⁶ Adult rhabdomyoma is multifocal in about 5% of patients. Genital rhabdomyoma in females usually presents as a polypoid mass.³

Fetal rhabdomyoma is characterized by nests and bundles of neoplastic skeletal muscle cells. In so-called "classic" examples, the neoplastic cells show immature morphology and loose, myxoid stroma, while in so-called "intermediate" examples the cells show more mature skeletal muscle differentiation, with increased cellularity and less myxoid stroma.¹

Adult rhabdomyoma shows large rhabdomyoblasts with voluminous eosinophilic cytoplasm, often with scattered "strap" cells showing the striations of sarcomeres. Some round neoplastic cells show cytoplasmic clearing ("spider cells").

Genital rhabdomyoma in females shows irregularly distributed rhabdomyoblasts in a loose stroma, and it lacks the cambium layer of embryonal rhabdomyosarcoma. Genital rhabdomyoma in males can be of fetal or adult subtypes, as well as a sclerosing subtype that is unique the paratesticular body site.⁴

In general, rhabdomyoma lacks the nuclear atypia and necrosis seen in rhabdomyosarcoma.

Neoplastic cells express desmin, as well as transcription factors of skeletal muscle differentiation such as myogenin and MYOD1.

Fetal rhabdomyoma and genital rhabdomyoma are generally cured by local excision, while Adult rhabdomyoma shows local recurrence in around 20-30% of cases.^2,6 Some reported recurrences of adult rhabdomyoma might reflect regional multicentric disease.

• Fetal rhabdomyoma and adult rhabdomyoma show recurrent alterations in the sonic hedgehog signaling pathway, involving PTCH1 and SUFU.^7,8 Fetal rhabdomyoma has been described in patients with Gorlin syndrome.⁹

• Cellular fetal rhabdomyoma shows complex copy number alterations.¹⁰

• Adult rhabdomyoma has been described in patients with Birt-Hogg-Dubé syndrome.^11,12

• Female genital rhabdomyoma lacks PTCH1 inactivation or copy number alterations.³

• Paratesticular "sclerosing rhabdomyoma" harbors recurrent H3C2 p.K37I mutations.¹⁰