Rhabdomyosarcoma, alveolar

Rhabdomyosarcoma, Alveolar

Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin, specifically arising from skeletal muscle progenitors. Among the subtypes of rhabdomyosarcoma, alveolar rhabdomyosarcoma (ARMS) is one of the most aggressive forms. It is characterized by its histological appearance, genetic profile, and clinical behavior.

Histology

Alveolar rhabdomyosarcoma is named for its histological resemblance to pulmonary alveoli. Under the microscope, ARMS displays a distinctive pattern where tumor cells are arranged in nests or clusters, separated by fibrous septa. These clusters often have central areas of necrosis, giving the appearance of empty spaces, similar to alveoli in the lung.

Genetics

ARMS is frequently associated with specific chromosomal translocations. The most common translocation is t(2;13)(q35;q14), which results in the fusion of the PAX3 gene on chromosome 2 with the FOXO1 gene on chromosome 13. Another less common translocation is t(1;13)(p36;q14), involving the PAX7 gene. These translocations lead to the production of fusion proteins that act as aberrant transcription factors, driving oncogenesis.

Epidemiology

Alveolar rhabdomyosarcoma is more common in adolescents and young adults, with a peak incidence between the ages of 10 and 25. It accounts for approximately 20-30% of all rhabdomyosarcoma cases. There is a slight male predominance in the incidence of ARMS.

Clinical Presentation

Patients with ARMS typically present with a rapidly growing mass, often in the extremities, trunk, or perineal region. Due to its aggressive nature, ARMS can metastasize early, commonly to the lungs, bone marrow, and lymph nodes.

Diagnosis

The diagnosis of alveolar rhabdomyosarcoma is based on a combination of histological examination, immunohistochemistry, and molecular genetic testing. Immunohistochemical markers such as myogenin and desmin are typically positive in ARMS. Molecular testing for PAX3-FOXO1 or PAX7-FOXO1 fusion genes can confirm the diagnosis.

Treatment

The treatment of ARMS involves a multimodal approach, including surgery, chemotherapy, and radiation therapy. The specific regimen depends on the stage and location of the tumor, as well as the presence of metastases. Common chemotherapeutic agents used include vincristine, dactinomycin, and cyclophosphamide.

Prognosis

The prognosis for patients with alveolar rhabdomyosarcoma is generally poorer than for those with embryonal rhabdomyosarcoma, due to its aggressive nature and tendency for early metastasis. The presence of PAX3-FOXO1 fusion is associated with a worse prognosis compared to PAX7-FOXO1.

Also see

• Rhabdomyosarcoma
• Embryonal rhabdomyosarcoma
• PAX3
• FOXO1
• Soft tissue sarcoma