Final Diagnosis -- High Grade Sarcoma

FINAL DIAGNOSIS:

High grade sarcoma involving skeletal muscle with associated myofiber atrophy and reactive changes.

DISCUSSION:

Rhabdomyosarcomas (RMSs) represent the most common soft tissue sarcomas of childhood. Histologically, they are classified as embryonal (including botryoid and spindle cell subtypes), alveolar, and pleomorphic. Diagnostic differentiation of these variants is important. The botryoid and spindle cell variants have a relatively good prognosis. Both alveolar and pleomorphic rhabdomyosarcomas are highly malignant tumors, and classical embryonal rhabdomyosarcoma (NOS) is considered to have an intermediate prognosis(1,2).

A specific translocation t(2;13)(q37;q14) or its variant t(1;13)(p36;q14) has been consistently identified in the alveolar subtype. The molecular lesions underlying these translocations have been fully elucidated with the discovery of fusion of the PAX3/FKHR genes in the t(2;13) and of the PAX7/FKHR genes in the t(1;13). In some alveolar RMSs,the fusion genes are amplified.(3,4).

To date, no characteristic chromosomal aberrations have been associated with the embryonal subtype of rhabdomyosarcoma. Hyperdiploid karyotypes with or without structural chromosome abnormalities have been observed frequently. However, structural abnormalities, when present, appear to be random. Extra copies of chromosomes 2, 8, 9, 11,12,13 and 20 have often been observed.(5). Comparative genomic hybridization as well as interphase fluorescence in situ hybridization studies are consistent with the cytogenetic findings(6). Karyotypic characterization of a human embryonal rhabdomyosarcoma cell line provided evidence stongly implicating alterations in chromosome 1 in the progression of rhabdomyosarcoma(7). Soft tissue tumors represent a heterogeneous group of mesenchymal lesions, and their classification is the subject of continuous debate(8). Chromosome analysis, molecular cytogenetics, and molecular assays may become increasingly useful in diagnosis, characterization and classification of soft tissue tumors. In the current case cytogenetic analysis provided evidence complementary to utrastructural findings supporting the myogenic identity of a high grade sarcoma not definitively characterized by light microscopic features or an extensive panel of immunohistochemical studies.

REFERENCES:

1. Coffin CM.The new international rhabdomyosarcoma classification, its progenitors and considerations beyond morphology.Adv Anat Pathol, 1996, 4:1-16.
2. Polito P. et al. Embryonal rhabdomyosarcoma with only numerical chromosome changes.Case report and review of the literature.Cancer Genet Cytogenet 1999, 109:161-5.
3. Barr F.G et al. In vivo amplification of the PaX3-FKHR and PkAX7-FKHR fusion genes in alveolar rhabdomyosarcoma. Hum Mol Genet 5:15-21.
4. Gunawan B.et al. Clinical Aspects of alveolar rhabdomyosarcoma with translocation t(1;13)(p36;q14) and hypotetraploidy. Pathol Oncol Res 1999,20:211-213.
5. Weber-Hall S. et al. Gains, losses and amplification of genomic material in rhabdomyosarcoma analysed by comparative genomic hybridization.Cancer Res,1996, 56:3220-3224.
6. Lee W. et al. Detection of aneploidy and possible deletion in paraffin-embedded rhabdomyosarcoma. Proc Am Assos Cancer Res.1993, 35:574.
7. Magnani I.et al.Karyotypic characterization of a new human embryonal rhabdomyosarcoma cell line.Cancer Genet Cytogenet ,1991, 54:83-9.
8. Dei Tos AP, Dal Cin P.The role of cytogenetics in the classification of soft tissue tumors.Virchows Arch 1997, 431:83-94.

Contributed by Anna Mnuskin, MD, Urvashi Surti, Ph.D, Jean Dunn, M.D.