Ewing sarcoma: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous editNext edit →
Content deleted Content added
VisualWikitext
No edit summary
No edit summary
Line 34: Line 34:
==Clinical findings==
==Clinical findings==
[[image:636039cfb96dc46674512d89a8229c big gallery.jpg|thumb|Distribution of Ewing's sarcoma. Most frequent locations are the large long bones and the [[pelvis]].]]
[[image:636039cfb96dc46674512d89a8229c big gallery.jpg|thumb|Distribution of Ewing's sarcoma. Most frequent locations are the large long bones and the [[pelvis]].]]
Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body, but most commonly in the [[pelvis]] and proximal long tubular bones, especially around the growth plates. The [[diaphyses]] of the [[femur]] are the most common sites, followed by the [[tibia]] and the [[humerus]]. Thirty percent are overtly [[metastasis|metastatic]] at presentation. Patients usually experience extreme bone pain.
Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body, but most commonly in the [[pelvis]] and proximal long tubular bones, especially around the growth plates. The [[diaphyses]] of the [[femur]] are the most common sites, followed by the [[tibia]] and the [[humerus]]. Thirty percent are overtly [[metastasis|metastatic]] at presentation. Patients usually experience extreme bone PAIN.


Signs /symptoms include: intermittent [[fever]]s, [[anemia]], [[leukocytosis]], increased [[Erythrocyte sedimentation rate|sedimentation rate]], and other symptoms of inflammatory systemic illness.<ref name="Cecil" /> Also, depending on the type, progression, and location of the tumor - great pain may occur.
Signs /symptoms include: intermittent [[fever]]s, [[anemia]], [[leukocytosis]], increased [[Erythrocyte sedimentation rate|sedimentation rate]], and other symptoms of inflammatory systemic illness.<ref name="Cecil" /> Also, depending on the type, progression, and location of the tumor - great pain may occur.

Revision as of 18:17, 12 November 2013

Ewing sarcoma
SpecialtyOncology Edit this on Wikidata

Ewing's sarcoma is a malignant small, round, blue cell tumour. It is a rare disease in which cancer cells are found in the bone or in soft tissue. The most common areas in which it occurs are the pelvis, the femur, the humerus, the ribs and clavicle (collar bone).

Because a common genetic locus is responsible for a large percentage of Ewing's sarcoma and primitive neuroectodermal tumors, these are sometimes grouped together in a category known as the Ewing family of tumors.[1] The diseases are, however, considered to be different: peripheral primitive neuroectodermal tumours are generally not associated with bones, while Ewing sarcomas are most commonly related to bone.

Ewing's sarcoma occurs most frequently in teenagers and young adults, with a male/female ratio of 1.6:1.[2]

Although usually classified as a bone tumour, Ewing's sarcoma can have characteristics of both mesodermal and ectodermal origin, making it difficult to classify.[3]

James Ewing (1866–1943) first described the tumour, establishing that the disease was separate from lymphoma and other types of cancer known at that time.[4][5]

Causes

Genetic exchange between chromosomes can cause cells to become cancerous. Most cases of Ewing's sarcoma (85%) are the result of a translocation between chromosomes 11 and 22, which fuses the EWS gene of chromosome 22 to the FLI1 gene of chromosome 11.[6]

EWS/FLI functions as the master regulator.[7]

Other translocations are at t(21;22)[8] and t(7;22).[9]

Ewing's sarcoma cells are positive for CD99 and MIC2,[6] and negative for CD45.[10]

Clinical findings

Distribution of Ewing's sarcoma. Most frequent locations are the large long bones and the pelvis.

Ewing's sarcoma is more common in males (1.6 male:1 female) and usually presents in childhood or early adulthood, with a peak between 10 and 20 years of age. It can occur anywhere in the body, but most commonly in the pelvis and proximal long tubular bones, especially around the growth plates. The diaphyses of the femur are the most common sites, followed by the tibia and the humerus. Thirty percent are overtly metastatic at presentation. Patients usually experience extreme bone PAIN.

Signs /symptoms include: intermittent fevers, anemia, leukocytosis, increased sedimentation rate, and other symptoms of inflammatory systemic illness.[6] Also, depending on the type, progression, and location of the tumor - great pain may occur.

According to The Bone Cancer Research Trust (BCRT), the most common symptoms are: localized pain, swelling, and sporadic bone pain with variable intensity. The swelling is most likely to be visible if the sarcoma is located on a bone near the surface of the body, but when it occurs in other places deeper in the body, like on the pelvis, it may not be visible.[11]

Imaging findings

X-Ray of a child with Ewing sarcoma of the tibia.
Magnetic resonance imaging slice showing Ewing's sarcoma of the left hip (white area shown right).

On conventional radiographs, the most common osseous presentation is a permeative lytic lesion with periosteal reaction. The classic description of lamellated or "onion skin" type periosteal reaction is often associated with this lesion. Plain films add valuable information in the initial evaluation or screening. The wide zone of transition (e.g. permeative) is the most useful plain film characteristic in differentiation of benign versus aggressive or malignant lytic lesions.

MRI should be routinely used in the work-up of malignant tumors. MRI will show the full bony and soft tissue extent and relate the tumor to other nearby anatomic structures (e.g. vessels). Gadolinium contrast is not necessary as it does not give additional information over noncontrast studies, though some current researchers argue that dynamic, contrast enhanced MRI may help determine the amount of necrosis within the tumor, thus help in determining response to treatment prior to surgery.

CT can also be used to define the extraosseous extent of the tumor, especially in the skull, spine, ribs and pelvis. Both CT and MRI can be used to follow response to radiation and/or chemotherapy.

Bone scintigraphy can also be used to follow tumor response to therapy.

In the group of malignant small round cell tumors which include Ewing's sarcoma, bone lymphoma and small cell osteosarcoma, the cortex may appear almost normal radiographically, while there is permeative growth throughout the Haversian channels. These tumours may be accompanied by a large soft tissue mass while there is almost no visible bone destruction. The radiographs frequently do not shown any signs of cortical destruction.

Radiographically Ewing's Sarcoma presents as "Moth-eaten" destructive radiolucencies of the medulla and erosion of the cortex with expansion.

A grouping of three unrelated teenagers in Wake Forest NC have diagnosed with Ewing's sarcoma. All three children were diagnosed in 2011 and all attended the same temporary classroom together while the school underwent renovation. A fourth teenager living nearby was diagnosed in 2009. The odds of this grouping are considered significant.[12]

Clinical differential diagnosis

Other entities that may have a similar clinical presentation include osteomyelitis, osteosarcoma (especially telangiectatic osteosarcoma) and eosinophilic granuloma. Soft tissue neoplasms such as pleomorphic undifferentiated sarcoma (malignant fibrous histiocytoma) that erode into adjacent bone may also have a similar appearance.

Diagnosis

Micrograph of a metastatic Ewing's sarcoma with the characteristic cytoplasmic clearing on H&E staining, which was showing to be PAS positive.

The definitive diagnosis is based on histomorphologic findings, immunohistochemistry and molecular pathology.

Ewing's sarcoma is a small round cell tumor, that typically has a clear cytoplasm on H&E staining, due to glycogen. The presence of the glycogen can be demonstrated with positive PAS staining and negative PAS diastase staining. The characteristic immunostain is CD99 which diffusely marks the cell membrane. Morphologic and immunohistochemical findings are corroborated with an associated chromosomal translocation, of which there are several. The most common translocation, present in approximately 90% of Ewing sarcoma cases, is t(11;22)(q24;q12).[13][14]

The pathologic differential diagnosis is the grouping of Small, round, blue cell tumours, which includes lymphoma, alveolar rhabdomyosarcoma and desmoplastic small round cell tumor, among others.

Epidemiology

Ewing's sarcomas represent 16% of primary bone sarcomas.[6]

Ewing's sarcoma in the United States is most common in the second decade of life,[6] with a rate of 0.3 cases per million in children under 3 years of age, and as high as 4.6 cases per million in adolescents aged 15–19 years. Internationally, the annual incidence rate averages less than 2 cases per million children.[15] In the United Kingdom, an average of six children per year are diagnosed, mainly males in early stages of puberty. Due to the prevalence of diagnosis during teenage years, there may possibly be a link between the onset of puberty and the early stages of this disease, although no research is currently being conducted to confirm this hypothesis.

The oldest known patient diagnosed was at age 76, He was from the Mercer County, New Jersey Area.

Treatment

Almost all patients require multidrug chemotherapy (often including ifosfamide and etoposide)[16] as well as local disease control with surgery and/or radiation.[17] An aggressive approach is necessary because almost all patients with apparently localized disease at the time of diagnosis actually have asymptomatic metastatic disease.

Treatment often consists of neo-adjuvant chemotherapy, which may include vincristine, doxorubicin, and cyclophosphamide with ifosfamide and etoposide.[6] After about three months of chemotherapy, the remaining tumor is surgically resected, irradiated, or both.[6] The surgical resection may involve limb salvage or amputation. Complete excision at the time of biopsy may be performed if malignancy is confirmed at the time it is examined.

Treatment lengths vary depending on location and stage of the disease at diagnosis. Radical chemotherapy may be as short as 6 treatments at 3 week cycles, however most patients will undergo chemotherapy for 6–12 months and radiation therapy for 5–8 weeks.[citation needed] Radiotherapy has been used for localised disease. The tumor has a unique property of being highly sensitive to radiation, sometimes acknowledged by the phrase "melting like snow". But the main drawback is that it recurs dramatically after some time.[citation needed] Antisense oligodeoxynucleotides have been proposed as possible treatment by down-regulating the expression of the oncogenic fusion protein associated with the development of Ewing's sarcoma resulting from the EWS-ETS gene translocation.[18][19] In addition, the synthetic retinoid derivative fenretinide (4-hydroxy(phenyl)retinamide) has been reported to induce high levels of cell death in Ewing sarcoma cell lines in vitro and to delay growth of Ewing sarcoma xenografts in vivo mouse models.[20][21]

Fertility preservation

In women, chemotherapy may damage the ovaries and cause infertility. To avail future pregnancies, the woman may preserve oocytes or ovarian tissue by oocyte cryopreservation or ovarian tissue cryopreservation prior to starting chemotherapy. However, the latter may reseed the cancer upon reinsertion of the ovarian tissue.[22] If it is performed, the ovarian tissue should be examined for traces of malignancy at both the pathological and molecular levels prior to the grafting of the cryopreserved tissue.[22]

Prognosis

Staging attempts to distinguish patients with localized from those with metastatic disease.[23] Most commonly, metastases occur in the chest, bone and/or bone marrow. Less common sites include the central nervous system and lymph nodes.

Five-year survival for localized disease is 70% to 80% when treated with chemotherapy.[24] Long term survival for metastatic disease may be less than 10%. However, some sources state it is 25-30%.[25]

Research, information and support

In the UK and Ireland The Bone Cancer Research Trust (BCRT) funds research and provides information on Ewing sarcoma and other bone cancers. This includes information for teenagers who have this condition.

See also

References

  1. ^ Iwamoto Y (2007). "Diagnosis and treatment of Ewing's sarcoma". Jpn. J. Clin. Oncol. 37 (2): 79–89. doi:10.1093/jjco/hyl142. PMID 17272319. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ Burt M; Karpeh M; Ukoha O; et al. (1993). "Medical tumours of the chest wall. Solitary plasmacytoma and Ewing's sarcoma". J. Thorac. Cardiovasc. Surg. 105 (1): 89–96. PMID 8419714. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  3. ^ Longtin R (2003). "Ewing sarcoma: a miracle drug waiting to happen?". J. Natl. Cancer Inst. 95 (21): 1574–6. PMID 14600088. {{cite journal}}: Unknown parameter |month= ignored (help)
  4. ^ synd/2367 at Who Named It?
  5. ^ Ewing, J. (1921). "Diffuse endothelioma of bone". Proceedings of the New York Pathological Society. 21: 17–24.
  6. ^ a b c d e f g medicine, s cecil. Goldman (24th ed. ed.). Philadelphia: Elsevier Saunders. p. 1326. ISBN 978-1-4377-2788-3. {{cite book}}: |edition= has extra text (help)
  7. ^ Owen LA, Kowalewski AA, Lessnick SL (2008). Wu, Xiaolin (ed.). "EWS/FLI mediates transcriptional repression via NKX2.2 during oncogenic transformation in Ewing's sarcoma". PLoS ONE. 3 (4): e1965. doi:10.1371/journal.pone.0001965. PMC 2291578. PMID 18414662.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  8. ^ Sorensen PH, Lessnick SL, Lopez-Terrada D, Liu XF, Triche TJ, Denny CT (1994). "A second Ewing's sarcoma translocation, t(21;22), fuses the EWS gene to another ETS-family transcription factor, ERG". Nat. Genet. 6 (2): 146–51. doi:10.1038/ng0294-146. PMID 8162068. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Jeon IS; Davis JN; Braun BS; et al. (1995). "A variant Ewing's sarcoma translocation (7;22) fuses the EWS gene to the ETS gene ETV1". Oncogene. 10 (6): 1229–34. PMID 7700648. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  10. ^ Bernstein M; Kovar H; Paulussen M; et al. (2006). "Ewing sarcoma family of tumours: current management". Oncologist. 11 (5): 503–19. doi:10.1634/theoncologist.11-5-503. PMID 16720851. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  11. ^ "Symptoms of Ewing's Sarcoma - Bone Cancer Research Trust". Bcrt.org.uk. Retrieved 2012-11-05.
  12. ^ http://www.wral.com/three-wake-students-battle-rare-cancer-cluster-or-coincidence-/12389860/
  13. ^ "Soft tissue tumors: Ewing's tumors/Primitive neurectodermal tumors (PNET)". Atlas of Genetics and Cytogenetics in Oncology and Haematology. Retrieved 5 November 2012.
  14. ^ Turc-Carel C; Aurias A; Mugneret F; et al. (1988). "Chromosomes in Ewing's sarcoma. I. An evaluation of 85 cases of remarkable consistency of t(11;22)(q24;q12)". Cancer Genet. Cytogenet. 32 (2): 229–38. doi:10.1016/0165-4608(88)90285-3. PMID 3163261. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  15. ^ Ewing Sarcoma Imaging at eMedicine
  16. ^ Lahl M, Fisher VL, Laschinger K (2008). "Ewing sarcoma family of tumours: an overview from diagnosis to survivorship". Clin J Oncol Nurs. 12 (1): 89–97. doi:10.1188/08.CJON.89-97. PMID 18258578. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Randall, RL (2005). "Ewing's Sarcoma Family of Tumours (ESFT)". ESUN. Retrieved 2009-04-15.
  18. ^ Asami S; Chin M; Shichino H; et al. (2008). "Treatment of Ewing sarcoma using an antisense oligodeoxynucleotide to regulate the cell cycle" (– Scholar search). Biol. Pharm. Bull. 31 (3): 391–4. doi:10.1248/bpb.31.391. PMID 18310898. {{cite journal}}: External link in |format= (help); Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help) [dead link]
  19. ^ Mateo-Lozano S, Gokhale PC, Soldatenkov VA, Dritschilo A, Tirado OM, Notario V (2006). "Combined transcriptional and translational targeting of EWS/FLI-1 in Ewing sarcoma". Clin. Cancer Res. 12 (22): 6781–90. doi:10.1158/1078-0432.CCR-06-0609. PMID 17121899. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Myatt SS, Redfern CP, Burchill SA (2005). "p38MAPK-Dependent sensitivity of Ewing's sarcoma family of tumors to fenretinide-induced cell death". Clin. Cancer Res. 11 (8): 3136–48. doi:10.1158/1078-0432.CCR-04-2050. PMID 15837770. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  21. ^ Myatt SS, Burchill SA (2008). "The sensitivity of the Ewing's sarcoma family of tumours to fenretinide-induced cell death is increased by EWS-Fli1-dependent modulation of p38(MAPK) activity". Oncogene. 27 (7): 985–96. doi:10.1038/sj.onc.1210705. PMID 17700534. {{cite journal}}: Unknown parameter |month= ignored (help)
  22. ^ a b Abir R; Feinmesser M; Yaniv I; et al. (2010). "Occasional involvement of the ovary in Ewing sarcoma". Hum Reprod. 25 (7): 1708–12. doi:10.1093/humrep/deq121. PMID 20472912. {{cite journal}}: Unknown parameter |author-separator= ignored (help); Unknown parameter |month= ignored (help)
  23. ^ McTiernan AM, Cassoni AM, Driver D, Michelagnoli MP, Kilby AM, Whelan JS (2006). "Improving Outcomes After Relapse in Ewing Sarcoma: Analysis of 114 Patients From a Single Institution". Sarcoma. 2006: 83548. doi:10.1155/SRCM/2006/83548. PMC 1698143. PMID 17496997.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  24. ^ "ACS :: How Is the Ewing Family of Tumors Staged?".
  25. ^ Thacker, MM; Temple, HT; Scully, SP (2005). "Current treatment for Ewing's sarcoma". Expert review of anticancer therapy. 5 (2): 319–31. doi:10.1586/14737140.5.2.319. PMID 15877528.
  • Bone Tumors - Differential diagnosis. Henk Jan van der Woude and Robin Smithuis.Radiology department of the Onze Lieve Vrouwe Gasthuis, Amsterdam and the Rijnland hospital,Leiderdorp,the Netherlands.

External links

Template:Smallblueroundcelltumors

Template:Arthritis in children

Retrieved from "https://en.wikipedia.org/w/index.php?title=Ewing_sarcoma&oldid=581364504"