Rhabdomyosarcoma pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Overview

The origin of rhabdomyosarcoma is straited muscle cells.The presentation sites of rhabdomyosarcoma are head and neck, extremities, Genitourinary tract, trunk, orbit, retroperitoneum, bladder, vagina, nasopharynx, and middle ear.The exact pathogenesis of rhabdomyosarcoma is unclear. However, there is causal association between MET proto-oncogene and macrophage migration inhibitory factor (MIF) and it is thought that P53 is related to oncogenic transformation and tumor progression. Multiple gene mutations are related to rhabdomyosarcoma such as loss of heterozygosity of 11p15, TP53, NRAS, KRAS, HRAS, PIK3CA, CTNNB1, FGFR4, and translocation in PAX3 or PAX7 genes with FOXO1. Immunohistochemistry can identify some specific proteins related to rhabdomyosarcoma such as desmin, actin, myogenin, and myoglobin. The other histologic procedure is transmission electron microscopy (TEM) which can be used for poorly differentiated or undifferentiated tumors and myofilaments, actin, desmin, myotubular intermediate filaments, and rudimentary Z-band material. Fusion protein is identified by reverse transcriptase polymerase chain reaction and fluorescent in situ hybridization.

Pathophysiology

Histology

Pathogenesis

Genetics

Associated conditions

Immunohistochemistry

Transmission electron microscopy

Reverse transcriptase polymerase chain reaction (RT-PCR)

Fluorescent in situ hybridization (FISH)

Gross Pathology

Gross findings Gross pathology
  • Clusters of edematous and grape-like masses
  • Protrusion into lumen of hollow organs
  • Poorly circumscribed mass
  • white and infiltrative
  • soft or firm mass
Gross feature of orbital embryonal rhabdomyosarcoma Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines
Gross pathology of alveolar rhabdomyosarcoma Source:Courtesy of Mark R. Wick, M.D., from Pathologyoutlines

Microscopic Pathology

Pathologic findings Microscopic pathology

The microscopic features of ARMS are:[18]

Alveolar Rhabdomyosarcoma- intermediate magnification Source: Nephron,from Wikimedia Commons

The microscopic features of ERMS are:[14][19]

Microscopic pathology of embryonal rhabdomyosarcoma Source: Contributed by Mark R. Wick, M.D., from Pathologyoutlines
Microscopic feature of botryoid rhabdomyosarcoma from Pathologyoutlines

The microscopic features of anaplastic rhabdomyosarcoma are:[21]

  • Presence of large hyperchromatic nuclei
  • Atypical bizarre mitotic features
  • Threefold larger nuclear size
Microscopic feature of anaplastic rhabdomyosarcoma from Pathologyoutlines

References

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  2. 2.0 2.1 Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S; et al. (2000). "Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass". Am J Pathol. 156 (2): 399–408. doi:10.1016/S0002-9440(10)64743-8. PMC 1850049. PMID 10666368.
  3. 3.0 3.1 Taulli R, Scuoppo C, Bersani F, Accornero P, Forni PE, Miretti S; et al. (2006). "Validation of met as a therapeutic target in alveolar and embryonal rhabdomyosarcoma". Cancer Res. 66 (9): 4742–9. doi:10.1158/0008-5472.CAN-05-4292. PMID 16651427.
  4. Tarnowski M, Grymula K, Liu R, Tarnowska J, Drukala J, Ratajczak J; et al. (2010). "Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts". Mol Cancer Res. 8 (10): 1328–43. doi:10.1158/1541-7786.MCR-10-0288. PMC 2974061. PMID 20861157.
  5. Xu J, Timares L, Heilpern C, Weng Z, Li C, Xu H; et al. (2010). "Targeting wild-type and mutant p53 with small molecule CP-31398 blocks the growth of rhabdomyosarcoma by inducing reactive oxygen species-dependent apoptosis". Cancer Res. 70 (16): 6566–76. doi:10.1158/0008-5472.CAN-10-0942. PMC 2922473. PMID 20682800.
  6. Scrable H, Cavenee W, Ghavimi F, Lovell M, Morgan K, Sapienza C (1989). "A model for embryonal rhabdomyosarcoma tumorigenesis that involves genome imprinting". Proc Natl Acad Sci U S A. 86 (19): 7480–4. PMC 298088. PMID 2798419.
  7. Taylor AC, Shu L, Danks MK, Poquette CA, Shetty S, Thayer MJ; et al. (2000). "P53 mutation and MDM2 amplification frequency in pediatric rhabdomyosarcoma tumors and cell lines". Med Pediatr Oncol. 35 (2): 96–103. PMID 10918230.
  8. Stratton MR, Fisher C, Gusterson BA, Cooper CS (1989). "Detection of point mutations in N-ras and K-ras genes of human embryonal rhabdomyosarcomas using oligonucleotide probes and the polymerase chain reaction". Cancer Res. 49 (22): 6324–7. PMID 2680062.
  9. Shukla N, Ameur N, Yilmaz I, Nafa K, Lau CY, Marchetti A; et al. (2012). "Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways". Clin Cancer Res. 18 (3): 748–57. doi:10.1158/1078-0432.CCR-11-2056. PMC 3271129. PMID 22142829.
  10. Taylor JG, Cheuk AT, Tsang PS, Chung JY, Song YK, Desai K; et al. (2009). "Identification of FGFR4-activating mutations in human rhabdomyosarcomas that promote metastasis in xenotransplanted models". J Clin Invest. 119 (11): 3395–407. doi:10.1172/JCI39703. PMC 2769177. PMID 19809159.
  11. Barr FG, Galili N, Holick J, Biegel JA, Rovera G, Emanuel BS (1993). "Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma". Nat Genet. 3 (2): 113–7. doi:10.1038/ng0293-113. PMID 8098985.
  12. Missiaglia E, Williamson D, Chisholm J, Wirapati P, Pierron G, Petel F; et al. (2012). "PAX3/FOXO1 fusion gene status is the key prognostic molecular marker in rhabdomyosarcoma and significantly improves current risk stratification". J Clin Oncol. 30 (14): 1670–7. doi:10.1200/JCO.2011.38.5591. PMID 22454413.
  13. Cao L, Yu Y, Bilke S, Walker RL, Mayeenuddin LH, Azorsa DO; et al. (2010). "Genome-wide identification of PAX3-FKHR binding sites in rhabdomyosarcoma reveals candidate target genes important for development and cancer". Cancer Res. 70 (16): 6497–508. doi:10.1158/0008-5472.CAN-10-0582. PMC 2922412. PMID 20663909.
  14. 14.0 14.1
  15. Hicks J, Flaitz C (2002). "Rhabdomyosarcoma of the head and neck in children". Oral Oncol. 38 (5): 450–9. PMID 12110339.
  16. Parham DM (2001). "Pathologic classification of rhabdomyosarcomas and correlations with molecular studies". Mod Pathol. 14 (5): 506–14. doi:10.1038/modpathol.3880339. PMID 11353062.
  17. Helman LJ, Meltzer P (2003). "Mechanisms of sarcoma development". Nat Rev Cancer. 3 (9): 685–94. doi:10.1038/nrc1168. PMID 12951587.
  18. Hostein I, Andraud-Fregeville M, Guillou L, Terrier-Lacombe MJ, Deminière C, Ranchère D; et al. (2004). "Rhabdomyosarcoma: value of myogenin expression analysis and molecular testing in diagnosing the alveolar subtype: an analysis of 109 paraffin-embedded specimens". Cancer. 101 (12): 2817–24. doi:10.1002/cncr.20711. PMID 15536621.
  19. Qualman SJ, Coffin CM, Newton WA, Hojo H, Triche TJ, Parham DM; et al. (1998). "Intergroup Rhabdomyosarcoma Study: update for pathologists". Pediatr Dev Pathol. 1 (6): 550–61. PMID 9724344.
  20. Neha B, Manjunath AP, Girija S, Pratap K (2015). "Botryoid Rhabdomyosarcoma of the Cervix: Case report with review of the literature". Sultan Qaboos Univ Med J. 15 (3): e433–7. doi:10.18295/squmj.2015.15.03.022. PMC 4554283. PMID 26357564.
  21. Hettmer S, Archer NM, Somers GR, Novokmet A, Wagers AJ, Diller L; et al. (2014). "Anaplastic rhabdomyosarcoma in TP53 germline mutation carriers". Cancer. 120 (7): 1068–75. doi:10.1002/cncr.28507. PMC 4173134. PMID 24382691.

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