Cellular Classification
Embryonal Rhabdomyosarcoma
Botryoid and spindle cell subtypes
Alveolar Rhabdomyosarcoma
Pleomorphic (Anaplastic) Rhabdomyosarcoma
Chromosomal and Molecular Characteristics
Rhabdomyosarcoma can be divided into several histologic subsets: embryonal rhabdomyosarcoma, which has embryonal,
botryoid, and spindle cell subtypes; alveolar rhabdomyosarcoma; and
pleomorphic rhabdomyosarcoma.[1,2]
Embryonal Rhabdomyosarcoma
The embryonal subtype is the most frequently observed
subtype in children, accounting for approximately 60% to 70% of
rhabdomyosarcomas of childhood.[1] Tumors with embryonal histology typically
arise in the head and neck region or in the genitourinary tract, although they
may occur at any primary site.
Botryoid and spindle cell subtypes
Botryoid tumors represent about 10% of all
rhabdomyosarcoma cases and are embryonal tumors that arise under the mucosal
surface of body orifices such as the vagina, bladder, nasopharynx, and biliary tract.
The spindle cell variant of embryonal rhabdomyosarcoma is most frequently
observed at the paratesticular site.[3] Both the botryoid and the spindle cell
subtypes are associated with very favorable outcomes.[2]
Alveolar Rhabdomyosarcoma
Approximately 20% of
children with rhabdomyosarcoma have the alveolar subtype. An increased
frequency of this subtype is noted in adolescents and in patients with primary
sites involving the extremities, trunk, and perineum/perianal region.[1]
Pleomorphic (Anaplastic) Rhabdomyosarcoma
Pleomorphic
rhabdomyosarcoma occurs predominantly in patients aged 30 to 50 years and is
rarely seen in children.
In children, the term "pleomorphic" has been replaced by the term "anaplastic."[4]
Chromosomal and Molecular Characteristics
The embryonal and alveolar histologies have distinctive molecular
characteristics that have been used for diagnostic confirmation and which may
be useful in the future for monitoring minimal residual disease during treatment.[5-8] Unique translocations between
the FKHR gene on chromosome 13 and either the PAX3 gene on chromosome 2 or the
PAX7 gene on chromosome 1 are characteristic of alveolar rhabdomyosarcoma.[5,9]
Translocations involving the PAX3 gene occur in approximately 59% of alveolar
rhabdomyosarcoma cases, while the PAX7 gene appears to be involved in about 19% of cases.[5] Twenty-two percent of patients are negative for either PAX3 or PAX7 gene rearrangements. Patients with solid variant alveolar histology have a lower incidence of PAX-FKHR gene fusions compared to patients showing classical alveolar histology.[10] Among patients with alveolar histology and metastatic disease, those with PAX7 gene involvement and younger age may fare better.[11,12] In alveolar cases associated with the PAX3 gene, patients are older and have a higher incidence of invasive tumor (T2). Alveolar cases associated with the PAX7 gene appear to occur in patients at a younger age, and they may have longer event-free survival rates than those associated with PAX3 gene rearrangements.[11,13,14] Embryonal tumors, on the other hand, often
show loss of specific genomic material from the short arm of chromosome
11.[9,15,16] The consistent loss of genomic material from the chromosome 11p15
region in embryonal tumors suggests the presence of a tumor suppressor gene,
though no such gene has yet been identified. Breakpoints involving
the 1p11-1q11 region are relatively common (36%) in embryonal
rhabdomyosarcoma.[17] Gene expression arrays identify a cluster of genes that correlate with rhabdomyosarcomas which contain the PAX-FKHR translocation. Tumors with alveolar histology which lack the translocation have a gene expression profile more similar to embryonal rhabdomyosarcomas than alveolar rhabdomyosarcomas.[18] It is controversial whether translocation-negative rhabdomyosarcomas with some histologic features of alveolar rhabdomyosarcoma should be classified as embryonal based on gene expression profile rather than as alveolar by light microscopy findings.
References
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Leuschner I: Spindle cell rhabdomyosarcoma: histologic variant of embryonal rhabdomyosarcoma with association to favorable prognosis. Curr Top Pathol 89: 261-72, 1995.
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Kodet R, Newton WA Jr, Hamoudi AB, et al.: Childhood rhabdomyosarcoma with anaplastic (pleomorphic) features. A report of the Intergroup Rhabdomyosarcoma Study. Am J Surg Pathol 17 (5): 443-53, 1993.
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