伯基特淋巴瘤

伯基特淋巴瘤
Burkitt lymphoma, touch prep, Wright stain
分类和外部资源
醫學專科血液學
ICD-112A85.6
ICD-10C83.783.7、​C91.8
ICD-9-CM200.2
OMIM113970
DiseasesDB1784
MedlinePlus001308
Orphanet543
[编辑此条目的维基数据]
维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。

伯基特氏淋巴瘤、伯基特淋巴瘤（Burkitt lymphoma）是淋巴系統生長中心的B淋巴球癌症，是一种非常迅速的非霍奇金淋巴瘤。以愛爾蘭外科醫生丹尼斯·帕森斯·伯基特（英语：Denis Parsons Burkitt）命名，他於1958年赤道非洲首次描述了這疾病。[1][2]發達國家伯基特淋巴瘤的總體治愈率約為90%。不常見於成人，但見於成人情況預後更糟。[3]

分類

尼日利亞7歲男童，幾月下頜腫脹，已用抗生素治療：腫瘤已潰爛並引流。
伯基特淋巴瘤患者口腔圖片顯示牙齒破裂和氣道部分阻塞

可分為三種主要的臨床變異：地方性、散發性、免疫缺陷相關變異。[3]在形態學微觀外觀、免疫表型、遺傳學，伯基特淋巴瘤的變種是相似的。[3]

  • “地方性變種”（也稱為“非洲變種”）最常見於生活在世界瘧疾流行地區（例如，赤道非洲、巴西、巴布亞新幾內亞）[4]人類疱疹病毒第四型（EBV）感染幾乎在所有患者中發現。[3]慢性瘧疾被認為會降低對EBV的抵抗力。該疾病的特點是涉及下頜或其他面部骨骼、迴腸、盲腸、卵巢、腎臟、乳房。[4]
  • “散發性變種”（也稱為“非非洲變種”）是在瘧疾不流行的地方（例如北美、歐洲）發現的最常見的變種。[3]腫瘤細胞具有與經典地方性伯基特淋巴瘤的癌細胞相似的外觀。散發性淋巴瘤很少與EBV相關。[5]頜骨較少參與這種變體。[3]腹部區域是常見的受累部位。[3]
  • 免疫缺陷相關，通常與HIV感染有關，但也可能發生在移植後患者的環境中。[6][3]

伯基特淋巴瘤通常與人類疱疹病毒第四型（EBV）感染B淋巴球有關，在這些情況下被認為是人類疱疹病毒第四型病毒相關的淋巴組織增生性疾病（英语：Epstein–Barr virus–associated lymphoproliferative diseases）。[7]

伯基特淋巴瘤的地方性變異幾乎在所有病例中都與EBV感染有關。[8]一些伯基特淋巴瘤病例不涉及EBV的事實允許許多疾病病例不是由 EBV 引起和/或促進的，即在這些病例中病毒可能是無辜的乘客病毒（英语：Passenger virus）。然而，該病毒在伯基特淋巴瘤的地方性變體中幾乎無處不在，這表明它有助於該變體的發展和或進展。[9]最近發現伯基特淋巴瘤的突變在有沒有EBV感染腫瘤間存在差異，這進一步加強了病毒在疾病起源中的作用。[10]

病理生理學

遺傳學

已隱藏部分未翻譯内容，歡迎參與翻譯。

All types of Burkitt lymphoma are characterized by dysregulation of the c-myc gene by one of three chromosomal translocations.[11] This gene is found at 8q24.

  • The most common variant is t(8;14)(q24;q32), which accounts for about 85%[11] of cases. This involves c-myc and IGH@. A variant of this, a three-way translocation, t(8;14;18), has also been identified.[12]
  • A rare variant is at t(2;8)(p12;q24).[13] This involves IGK@ and c-myc.
  • Another rare variant is t(8;22)(q24;q11).[13] This involves IGL@ and c-myc.

Combined, the two less-common translocations, t(2;8)(p12;q24) and t(8;22)(q24;q11), account for the remaining 15% of cases not due to the t(8;14)(q24;q32) translocation.[11]

The c-myc gene found on chromosome 8 is part of the Myc family of genes that serve as regulators of cellular transcription and is associated with Burkitt lymphoma.[14][15] Expression of the c-myc gene results in the synthesis of transcriptional factors that increase the expression of other genes involved in aerobic glycolysis.[14] Ultimately, an increase in aerobic glycolysis plays a role in providing the necessary energy for cellular growth to occur.[14] The translocation of the c-myc gene to the IGH, IGK, or IGL region moves the gene to a location in the genome near immunoglobulin enhancers which increases the expression of the c-myc gene.[14] Overall, this translocation leads to increased cellular proliferation that is found in Burkitt lymphoma.[14] Point mutations can also be present in the translocated c-myc gene resulting in the expressed c-myc protein being overactive.[14] Other mutations found include the TCF transcription factor mutation, which increases cellular proliferation via the increased expression of other genes.[14] Along with mutations that support cell proliferation, Burkitt lymphoma has been found to also harbor mutations in the TP53 gene that is a tumor suppressor and would normally function to limit cellular growth.[15]

病毒學

The complete role of EBV in the pathogenesis of endemic Burkitt lymphoma is not completely elucidated, but it has been shown to cause DNA damage, dysfunction of telomeres, and genome instability.[16][15] B cell infection with EBV is latent, and the virus does not undergo replication.[16] These latently infected B cells can then go on to produce proteins that function to promote cellular growth through modification of normal signaling pathways.[16] EBV promotes the development of malignant B cells via proteins that limit apoptosis in cells that had the c-myc translocation.[15] Apoptosis is limited by EBV through various means such as the EBNA-1 protein, BHF1 protein, EBER transcripts, vIL-10 gene, BZLF1, and LMP1.[15] Malaria has been found to cause genomic instability in endemic Burkitt lymphoma.[17] Malaria can lead to the reactivation of latent EBV and also MYC translocations via activation of the toll-like receptor 9.[15] Malaria also promotes B-cell proliferation by altering the regular immune response.[16] The immune system targets antigens (e.g., EBNA2 and LMP-1) and eliminates most B cells infected with EBV.[15] Downregulation of antigens targeted by the immune system leads to the development of persistent B cells.[15] These B cells can then undergo further mutations (e.g., c-myc translocation) that promote cancer development.[15]

免疫學

伯基特淋巴瘤細胞正常表達HLA I類分子，以及一些HLA II類複合物；然而，CD4+ T 細胞沒有被正確激活。伯基特淋巴瘤細胞僅表達EBNA1，一種抗原性較差的EBV相關抗原，能夠逃避HLA I類呈遞，從而逃避免疫反應。EBNA 1可通過HLA II類分子呈遞，但HLA II類途徑無法激活CD4+T細胞。[18]

診斷

Burkitt lymphoma in a kidney biopsy

惡性B淋巴球特徵

H&E染色劑伯基特淋巴瘤高倍視圖

顯微鏡特徵

腎活檢的伯基特淋巴瘤


腫瘤由單調（即大小和形態相似）的中等大小的淋巴細胞群組成，具有高增殖和凋亡活性。[19]


免疫組織化學特徵

腫瘤細胞通常強烈表達B淋巴球分化標誌物（CD20、CD22、CD19）以及CD10和BCL6。腫瘤細胞通常對BCL2和TdT呈陰性。近100%染色陽性細胞Ki67證實了伯基特淋巴瘤有高有絲分裂活性。[20]

治療

一般來說，伯基特淋巴瘤的一線治療是化療。其中一些方案是：GMALL-B-ALL/NHL2002方案、改良Magrath方案 (R-CODOX-M/IVAC)。[21] COPADM,[22] hyper-CVAD,[23]以及癌症和白血病B組 (CALGB) 8811 方案；[23]這些可能與利妥昔單抗有關。[23][24]在老年患者中，可以使用利妥昔單抗調整劑量EPOCH（英语：EPOCH (chemotherapy)）。[25]


化療

其他治療方法包括免疫療法、骨髓移植、幹細胞移植、手術去除腫瘤、放射療法。

預後

伯基特淋巴瘤預後在兒童中較好，年齡增加則反之。[27][15] 發達國家散發性伯基特淋巴瘤的總體治愈率約為90%。[3]在成人中，伯基特淋巴瘤並不常見且預後不佳。[3]

用環磷酰胺、長春新鹼、潑尼松龍治療伯基特淋巴瘤初始反應不令人滿意表明預後不良。[15]

已隱藏部分未翻譯内容，歡迎參與翻譯。
Furthermore, failed initial treatment and return of Burkitt lymphoma after a six-month stint of time serve as a poor prognostic indicator.[15] The adequate utilization of therapeutic drugs during initial treatment limits additional treatment options following the return of the disease.[15] Notably, in areas of the world where the initial treatment of Burkitt lymphoma is inadequate further treatment options may remain for cases when the disease returns.[15] Laboratory studies such as lactate dehydrogenase (LDH), CD4 count, and other cytogenetic studies are also prognostic indicators.[15] Unsatisfactory outcomes have been associated with an LDH that is found to be two times above the upper limit of normal.[15] Specifically, there is a poor prognosis associated with a CD4 count that is decreased in the immunodeficiency-associated variant of Burkitt lymphoma.[15] Genetic mutations extending beyond the previously described MYC translocation may also serve as negative prognostic indicators.[15] Some notable genetic findings that may be associated with poor outcomes include: 13q deletion, 7q gain, ID3 and CCND3 double-hit mutations, and 18q21 CN-LOH mutations.[15] The prognosis for Burkitt lymphoma can be better determined following staging utilizing imaging modalities such as positron emission tomography and computed tomography scans where tumor burden and invasion of the central nervous system have been found to indicate a poor prognosis.[27][15]

流行病學

已隱藏部分未翻譯内容，歡迎參與翻譯。

As a non-Hodgkin lymphoma (NHL), Burkitt lymphoma makes up 1-5% of cases, and it is more common in males than females with a 3–4 to 1 ratio.[15] The endemic variant mainly impacts areas with an increased prevalence of malaria and EBV in Africa and Papua New Guinea.[15][28] For children less than 18 years of age from equatorial Africa, the annual incidence of Burkitt lymphoma is 4–5/100,000.[28] Additionally, in equatorial Africa, 50% of tumors that are diagnosed during childhood as well as 90% of lymphoma cases can be attributed to Burkitt lymphoma.[28] The peak incidence for endemic Burkitt lymphoma is from ages 4 to 7 with an average age of 6 years.[15][28] The sporadic variant with an annual incidence 2-3/million is more commonly found in North America and Europe comprising 1-2% of adult lymphomas and 30–40% of NHL cases.[15][28] This variant is 3.5 times more commonly found in males compared to females and it is more frequent in younger individuals.[28] The sporadic variant has a peak incidence at 11 years of age in children, and diagnosis typically occurs from 3–12 years of age on average.[15][28] For adults, 45 years was the median age that the sporadic Burkitt lymphoma was diagnosed.[15] The immunodeficiency-associated variant predominantly impacts the HIV-infected population.[28] For those in the United States and with AIDS, the incidence of this variant was found to be 22/100,000 person-years.[15][28] There is also an increased risk of developing this variant of Burkitt lymphoma for individuals that have received an organ transplant after 4–5 years.[28]

人類疱疹病毒第四型感染與伯基特淋巴瘤有關。[29]幾乎所有地方性伯基特淋巴瘤病例中都發現了人類疱疹病毒第四型（EBV）。[28]而伯基特淋巴瘤的散發性變異僅在10-20%病例中與EBV相關。 [30]

研究

基因目標

獨特的基因改變促進了伯基特淋巴瘤的細胞存活，這與其他類型的淋巴瘤不同。[31]TCF3（英语：TCF3） and ID3 (基因)基因突變對應於可能被發現適靶向治療的細胞存活途徑。[32]

參考

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外部鏈接

维基共享资源上的相关多媒体资源：伯基特淋巴瘤

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