出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2013/10/25 17:34:06」(JST)
Ewing sarcomas | |
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Classification and external resources | |
Micrograph of metastatic Ewing sarcoma (right of image) in normal lung (left of image). PAS stain.
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ICD-10 | C41.9 |
ICD-9 | 170.9 |
ICD-O: | M9260/3 |
OMIM | 133450 |
DiseasesDB | 4604 |
MedlinePlus | 001302 |
eMedicine | ped/2589 |
MeSH | D012512 |
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]
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]
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]
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]
This section requires expansion. (February 2013) |
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.
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.
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.
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]
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]
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]
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.
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リンク元 | 「ユーイング肉腫」 |
拡張検索 | 「primary Ewing sarcoma」 |
骨肉腫 | ユーイング肉腫 | |
概念 | 類骨を形成する悪性骨腫瘍 骨組織に原発し、腫瘍細胞が直接類骨あるいは骨組織を形成する。 |
分化の高悪性度小円形細胞肉腫。発生母細胞は神経外胚葉 |
疫学 | 15歳ピーク 10歳代:60% 20歳代:15% 男性にやや多い |
10-30歳で見られるが、10代から10代未満に好発し、80%が20歳以下である。骨肉腫より若年者に好発する。 男女比 = 2:1 |
原発性悪性骨腫様のなかで最多 | 骨肉腫、骨髄腫、軟骨肉腫に次いで多い。 | |
好発部位 |
大腿骨遠位 脛骨近位 合わせて75% 次いで上腕骨近位 |
長幹骨の骨幹部 骨盤、大腿骨、上腕骨、脛骨の順に好発する |
症状 | 腫脹、疼痛、腫瘍の増大で発赤、局所熱感、静脈怒張 | 疼痛、腫脹、全身症状(白血球増多、発熱) |
血液検査 | 血清アルカリフォスファターゼ、乳酸脱水素酵素 | 白血球増多、CRP上昇、赤沈亢進 |
単純X線写真 | 骨硬化を伴わない骨破壊、種々の程度の腫瘍性骨新生(境界不明瞭の淡い綿花様、綿球様の骨硬化) 外骨膜反応(コットマン三角、スピクラ形成) |
骨皮質を破壊しつくす前にフォルクマン管を介して軟部組織に浸潤し骨外に浸潤する。このために骨膜を持ち上げ骨膜反応(たまねぎの皮様(onion skin appearance))を呈する。 斑点状、蚕喰状の骨吸収破壊像 |
転移 | 血行性、肺転移 | |
予後 | 5年生存率50-70% | 予後不良 日本での5年累積生存率は45% |
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