Rhabdomyosarcoma, alveolar

Alveolar rhabdomyosarcoma
Classification and external resources
ICD-O	M8920/3
MeSH	D018232
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Alveolar rhabdomyosarcoma (ARMS) is a sub-type of the rhabdomyosarcoma soft tissue cancer family whose lineage is from mesenchymal cells and are related to skeletal muscle cells. ARMS tumors resemble the alveoli tissue that can be found in the lungs. Tumor location varies from patient to patient, but is commonly found in the head and neck region, male and female urogenital tracts, the torso, and extremities. Two fusion proteins can be associated with ARMS, but are not necessary, PAX3-FKHR (now known as FOXO1). and PAX7-FKHR. In children and adolescents ARMS accounts for about 1 percent of all malignancies, has an incidence rate of 1 per million, and most cases occur sporadically with no genetic predisposition.

There is no genetic predisposition for developing ARMS, but there are a few genetic recombination events that occurs to cause the fusion protein to be synthesized. In order to have the PAX3-FOXO1 fusion there needs to be a recombination event that translocates part of chromosome 13 to chromosome 2, and for PAX7-FOXO1 fusion there must be a translocation of part of chromosome 13 to chromosome 1. The 2;13 translocation reciprocal is often balanced and not amplified, while the 1;13 translocation reciprocal is sometimes viewed as balanced and sometimes not, so it is often amplified. The PAX7-FOXO1 fusion is often amplified in tumors (about 70 percent of all PAX7-FOXO1 fusion positive tumors) and the PAX3-FOXO1 fusion is rarely amplified (only in 5 percent of all PAX3-FOXO1 fusion positive tumors). About 60 percent of all ARMS cases are positive for PAX3-FOXO1 fusion gene, 20 percent are positive for PAX7-FOXO1 fusion gene, and the remaining 20 percent are fusion negative ARMS cases. Both fusion genes are composed of either the PAX3 or PAX7 DNA binding domains and the FOXO1 transactivation domain. This fusion causes a dysregulation of transcription and acts as an oncogene promoting cancer formation.

ARMS cells are often small with little cytoplasm. The nuclei of the cells are round with normal, dull, chromatin structures. The ARMS cells often clump together and have fibrovascular septae that interrupts the aggregates. The fibrovascular septae that disrupts the aggregates often give the tumor the physiology of the alveoli found in the lungs. In a few cases, there may not be any fibrovascular septae and this gives the tumor a more solid phenotype and no alveoli physiology.Immunostaining for myogenin and for MyoD can be used to determine ARMS from other rhabdomyosarcoma tumors and immunostaining for AP2β and p-cadherin can distinguish fusion positive ARMS from fusion negative.

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