Rhabdomyosarcoma pathophysiology: Difference between revisions
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** Mutations in FGFR4 | ** Mutations in FGFR4 | ||
** Translocations in PAX3 or PAX7 genes with FOXO1 | ** Translocations in PAX3 or PAX7 genes with FOXO1 | ||
==Associated conditions== | |||
===Immunohistochemistry=== | |||
* Through immunohistochemistry, muscle specific proteins can be identified in RMS.<ref name="pmid10666368">{{cite journal| author=Dias P, Chen B, Dilday B, Palmer H, Hosoi H, Singh S et al.| title=Strong immunostaining for myogenin in rhabdomyosarcoma is significantly associated with tumors of the alveolar subclass. | journal=Am J Pathol | year= 2000 | volume= 156 | issue= 2 | pages= 399-408 | pmid=10666368 | doi=10.1016/S0002-9440(10)64743-8 | pmc=1850049 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10666368 }} </ref> | |||
* RMS stains positive for following proteins: | |||
** Plyclonal desmin (99%) | |||
** Muscle-specific actin (95%) | |||
** Myogenin (95%) | |||
*** Expressed more in ARMS rather than ERMS | |||
*** Associated with poorer prognosis | |||
** Myoglobin (78%) | |||
===Transmission electron microscopy=== | |||
* Transmission electron microscopy (TEM) can be used for poorly differentiated or undifferentiated tumors.<ref name="pmid12110339">{{cite journal| author=Hicks J, Flaitz C| title=Rhabdomyosarcoma of the head and neck in children. | journal=Oral Oncol | year= 2002 | volume= 38 | issue= 5 | pages= 450-9 | pmid=12110339 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12110339 }} </ref><ref name="pmid11353062">{{cite journal| author=Parham DM| title=Pathologic classification of rhabdomyosarcomas and correlations with molecular studies. | journal=Mod Pathol | year= 2001 | volume= 14 | issue= 5 | pages= 506-14 | pmid=11353062 | doi=10.1038/modpathol.3880339 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11353062 }} </ref> | |||
* Prescence of following proteins are associated with TEM features of RMS: | |||
** Myofilaments | |||
** Desmin and actin) filaments | |||
** Myotubular intermediate filaments | |||
** Rudimentary Z-band material | |||
=== | |||
==Microscopic Pathology== | ==Microscopic Pathology== |
Revision as of 16:31, 30 January 2019
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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
Rhabdomyosarcoma arises from the skeletal muscle cells. Development of alveolar rhabdomyosarcoma is result of specific genetic mutations. The pathogenesis of rhabdomyosarcoma include t(2;13) and t(1;13) chromosomal translocations. The microscopic pathology of rhabdomyosarcoma depends on the histological subtype.
Pathophysiology
Histology
- The origin of rhabdomyosarcoma is straited muscle cells.[1]
- The presentation sites of rhabdomyosarcoma are:
- Head and neck (28%)
- Extremities (24%)
- Genitourinary tract (18%)
- Trunk (11%)
- Orbit (7%)
- Retroperitoneum (6%)
- Other sites such as bladder, vagina, nasopharynx, and middle ear (3%)
- Round or spindle-shaped muscle cells are present in embryonal rhabdomyosarcoma (ERMS).[2]
- Alveolar architecture with small round undifferentiated cells which are seprated by dense hyalinized fibrous septa are present in alveolar rhabdomyosarcoma (ARMS).
- Despite all muscle differentiation markers expression in ARMS, mature muscle characteristics is not seen in ARMS histology.
Pathogenesis
- The exact pathogenesis of rhabdomyosarcoma is unclear.[3]
- Distruption of skeletal muscle progenitor cell growth and related differentiation may cause rhabdomyosarcoma.[3]
- There is causal association between MET proto-oncogene and macrophage migration inhibitory factor (MIF).[4]
- It is thought that P53 is related to oncogenic transformation and tumor progression.[5]
Genetics
- According to microarray and targeted sequencing, following genomic characteristics are attributed to Rhabdomyosarcoma (RMS):[6][7][8][9][10][11]
- Loss of heterozygosity of 11p15.
- Mutations in TP53
- Mutations in NRAS
- Mutations in KRAS
- Mutations in HRAS
- Mutations in PIK3CA
- Mutations in CTNNB1
- Mutations in FGFR4
- Translocations in PAX3 or PAX7 genes with FOXO1
Associated conditions
Immunohistochemistry
- Through immunohistochemistry, muscle specific proteins can be identified in RMS.[2]
- RMS stains positive for following proteins:
- Plyclonal desmin (99%)
- Muscle-specific actin (95%)
- Myogenin (95%)
- Expressed more in ARMS rather than ERMS
- Associated with poorer prognosis
- Myoglobin (78%)
Transmission electron microscopy
- Transmission electron microscopy (TEM) can be used for poorly differentiated or undifferentiated tumors.[12][13]
- Prescence of following proteins are associated with TEM features of RMS:
- Myofilaments
- Desmin and actin) filaments
- Myotubular intermediate filaments
- Rudimentary Z-band material
=
Microscopic Pathology
Characteristic features on microscopic analysis are variable depending on the rhabdomyosarcoma subtype:[14]
Alveolar Rhabdomyosarcoma
- Characterized by Alveolus-like pattern.
- Fibrous septae lined by tumor cells.
- Cells may "fall-off" the septa, i.e. be detached/scattered in the alveolus-like space.
- Space between fibrous septae may be filled with tumor, called solid variant of alveolar rhabdomyosarcoma.
- Rhabdomyoblasts: Essentially diagnostic cells with eccentric nucleus and moderate amount of intensely eosinophilic cytoplasm.
- Nuclear pleomorphism
- Mitoses
Embryonal Rhabdomyosarcoma
- Randomly arranged small cells
- Myxoid matrix
- Strap cells: Tadpole like morphology
- Rhabdomyoblasts: Essentially diagnostic cells with eccentric nucleus and moderate amount of intensely eosinophilic cytoplasm
Botryoid Rhabdomyosarcoma
- Malignant cells in an abundant myxoid stroma.
- Non-proliferating layer deep to the surface called "Cambium layer".
- Cambium layer is defined as cellular region deep to epithelial component.
Spindlecell Rhabdomyosarcoma
- Vesicular growth pattern
- Spindle cells
References
- ↑ Barr FG (1997). "Molecular genetics and pathogenesis of rhabdomyosarcoma". J Pediatr Hematol Oncol. 19 (6): 483–91. PMID 9407933.
- ↑ 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.
- ↑ 3.0 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Hicks J, Flaitz C (2002). "Rhabdomyosarcoma of the head and neck in children". Oral Oncol. 38 (5): 450–9. PMID 12110339.
- ↑ 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.
- ↑ "librepathology".