40例骨髓转移癌的临床研究
摘要
目的：探讨骨髓转移癌患者的临床表现和实验室检查特点,为临床上更好地诊断和治疗骨髓转移癌提供理论依据。方法：回顾性分析40例骨髓转移癌患者的临床表现、骨髓细胞学、骨髓病理学及免疫组化和器械检查的特点。结果：骨痛、发热、消瘦等为最常见的症状;常见的血象异常包括贫血、血小板减少,外周血可出现幼红细胞、幼粒细胞;骨髓细胞学：增生度大部分患者呈增生减低,34例患者可检出转移癌细胞;骨髓活检病理形态学有11例患者检出癌细胞,免疫组化中Ki-67、Bcl-2、P21部分病例呈阳性表达;有36例患者骨ECT扫描发现骨放射性异常,有21例患者骨核磁共振成像发现异常信号影。结论：临床出现骨痛、发热、消瘦伴血象异常,尤其是出现幼红、幼粒细胞血症时应该考虑是否有骨髓转移癌。骨髓穿刺足简单而有效的确诊手段,有时需重复多次/多部位骨穿,结合骨髓活检可提高骨髓转移癌的检出率。骨髓活检病理免疫组化指标Ki-67、Bcl-2、P21等对恶性肿瘤,尤其是伴有骨髓转移癌患者的预后判断有一定的价值。
Objective:to explore the clinical and laboratory characteristics of bone marrow metastatic carcinoma patients,better for clinical diagnosis and treatment of bone marrow metastatic carcinoma to provide the theory basis.Methods:40cases bone marrow were retrospectively analyzed the clinical manifestations of patients with metastatic carcinoma, bone marrow cell biology, bone marrow pathology and immunohistochemical and equipment checkfeatures.Results:bone pain, fever, emaciation are the most common symptom; common blood picture abnormalities include anemia, thrombocytopenia, peripheral blood can appear red blood cells called young young; bone marrow cytology hyperplasia degrees, most patients reduce hyperplasia,34patients can be detected transfer cancer cells;bone marrow morphology by pathology in11patients detected the cancer cells, in immunohistochemical Ki-67, Bcl-2, P21part cases positive expression;36cases of patients ECT bone scan found bone radioactive anomalies21patients bone nuclear magnetic resonance (MRI) imaging of abnonnal signals.Conclusion:clinical pain, fever, appear bone with abnonnal blood picture appear especially thin young red young granulocyte should be considered when whether bone marrow metastatic carcinoma, bone marrow targeted was simple and effective means of diagnosis,sometimes should be repeated many times more bone wear parts, combined with bone marrow biopsy can improve the transfer of bone marrow cancer detection rate, bone marrow by pathology immunohistochemical index Ki-67, Bc1-2, P21of malignant tumor,especially associated with bone marrow transfer carcinoma of the prognostic have a certain value.
Objective:to explore the clinical and laboratory characteristics of bone marrow metastatic carcinoma patients,better for clinical diagnosis and treatment of bone marrow metastatic carcinoma to provide the theory basis.Methods:40cases bone marrow were retrospectively analyzed the clinical manifestations of patients with metastatic carcinoma, bone marrow cell biology, bone marrow pathology and immunohistochemical and equipment checkfeatures.Results:bone pain, fever, emaciation are the most common symptom; common blood picture abnormalities include anemia, thrombocytopenia, peripheral blood can appear red blood cells called young young; bone marrow cytology hyperplasia degrees, most patients reduce hyperplasia,34patients can be detected transfer cancer cells;bone marrow morphology by pathology in11patients detected the cancer cells, in immunohistochemical Ki-67, Bcl-2, P21part cases positive expression;36cases of patients ECT bone scan found bone radioactive anomalies21patients bone nuclear magnetic resonance (MRI) imaging of abnonnal signals.Conclusion:clinical pain, fever, appear bone with abnonnal blood picture appear especially thin young red young granulocyte should be considered when whether bone marrow metastatic carcinoma, bone marrow targeted was simple and effective means of diagnosis,sometimes should be repeated many times more bone wear parts, combined with bone marrow biopsy can improve the transfer of bone marrow cancer detection rate, bone marrow by pathology immunohistochemical index Ki-67, Bc1-2, P21of malignant tumor,especially associated with bone marrow transfer carcinoma of the prognostic have a certain value.
引文
[1]陈方平,主编血液学检验[M]北京：人民卫生出版社,1997：192.
[2]卢振霞,林玉梅,何淑珍.骨髓转移癌43例临床分析[J]临床血液学杂志,1999,12(1)；31-32.
[3]Lambrechts AC,van't Veer LJ,RodenhuisS. The detection of minimal numbers of con-taminating epithelial tumor cells in blood orbone marrow:use,limitations and future of RNA-based methods[J]. Ann Oncol,1998,9(12):1269-1276.
[4]金顺钱.参与肿瘤转移的表而粘连交体[J].国外医学肿瘤学分册,1994,3：131-132.
[5]卢兴国,主编造血和淋巴组织肿瘤现代诊断学[M]北京：科学出版社,2005：166.
[6]黄梅,路武,徐慧珍,等.47例骨髓转移癌的临床及血液学特点[J].临床内科杂志,2002,19(6)：424-425.
[7]古颖春,宋业琳.张春玲.等.p53、bcl-2、nm23蛋白在肺癌中的表达及与预后的关系[J].山东医药,2011,51,(13)：54-55.
[8]Reed JC..bcl-2 and the regulation of programmed cell death.J Cell Biol,1994,12(4):1-6.
[9]Quinn CM.Ostowsik.JL,Harkins L,et al.Loss of bcl-2 expression in ducal carcinoma in situ of the breast relates to poor histological differentiation and to expression of P53 and c-erB-2 protteins. Histopathology,1998,33::531-536
[10] Homma A,Furuta Y,Oridate N,etal.Correlation of cilinicopatho- logical
parameters and biological markers related to apoptosis and proliferative activity with a clinical outcome in squamous cellcarcinoma of the lary treated with concurrrent chemoradiothrerapy.Auris Nasus Larynx,2001,28:87-94
[11] Kymionis GD,Dimitrakakis CE,Konstadoulakis MM,et al.Can expression of apoptosis genes,bcl-2 and bax,predict survival and responsiveness to chemothcrapy in node-negative breast cancer patients?J Surg Res,2001,99(2):161-168
[12]Scholzen T,Gerdes J.The Ki-67 protien:from the known and the unknown[J].Cell Physiol,2000,182(3):311.
[13] Sakata K,Tamra G,Maesawa C,et al. Loss of heterozygosity on tharm of chromosome 9 without p16 gene mutation in gastric carcinomas[J].Jpn J Cancer Res,1995,333.
[14]Papaioannou G,McHugh k Neuroblastoma in childhood:review and radiological findings.Cancer Imaging,2005,5:116—127.
[15] Moyer P.Race,weight,and smoking status may influence p53 positive breast cancer[J].Am Assoc Cancer Res.2005.
[16]林子洪,廖威明,傅明,等p21WAFI的功能研究新进展[J].广东医学,2007.28(3)：482—484.
[17]黄伟,刘惠敏.胃癌P53,P-糖蛋白的表达意义与肿瘤预后关系[J].实用诊断与治疗杂志,2005;19(4)：240.1.
[18] Srivengopai KS, Aii OF. Deietion and rearrangements inactivate the p161ND4gene in human giioma ceiis [J].Oncogene,1996,12:2029.
[19] LoKW,Cheung SF. Hypermethyiation of the p16 gene in nasopharyngeai carcinoma [J].Cancer Res,1996,56:2721.
[20] Shigemasa K,Hu C,West CM,et al.p16 overexpression:a potentiai eariy indicator of transformation in ovarian carcinoma[J].J Soc gynecol Investig,1997,4(2):95
[21]Mcshea A, Harris PLR,Webster KR,et al.Abnormai expression of the ceii cycie reguiators p16 and CDK4 in Aizheimers disease [J].Pathol,1997,150 (6) 1933.
[22]吕春雷,廖建春,萧壁君,等喉癌中HPV感染和P16表达的检测及临床相关性研究[J]临床与实验病理学杂志.1999,15(5)：382-384.
[23]Tanabe M。Ohnuma N,1wai J,et al.Bone man'ow metastasis of neuroblastoma analysed by MRI and its influence on prognosis.Med Pediatr Oncol,1995,24:292-299.
[24]Moulopoulos LA·Dimopoulos M. Magnetic resonanceimaging of the bone marrow in hematologic.Blood,1997;90(6):2127—2138.
[25]奠东华,莫汉有,王晓桃.100例骨髓转移璃骨髓组织病理学的观察[J].临床肿瘤学杂志,2007；10(12)：773.4.
[26]胡响祥,朱思国,陈风.骨髓转移癌患者的外周血象特征分析[J].临床和实验医学杂志.2008；9(7)：152-3.
[27] Xiao L, Luxi S, Ying T, et al.Diagnosis of unknown non hematological tumors by bone marrow biopsy:A retrospective analysis of 10,112 samples[J].J Cancer Res Clin Oncol,2009,135 (5)687
[28]Fehm T,Becker S,Bachmann C,et al.Detection of disseminated tumor cells in patients with gynecological callcer[J]. Gynecoloneol,2006;103(3):942-7.
[29]初钊辉,周鑫莉,梁晓华,等.骨髓转移癌41例临床分析[J].肿瘤,2008,28(6)：520
[1]夏云金,刘瑜,万楚成,章正华,张霞,姜铧,杨华强.骨髓活检组织印片在骨髓转移癌诊断中的价值[J].中华实用诊断与治疗杂志.2008,23(3)：269—270.
[2]rhj GV,Moreno JG,Gomella LG.Utilization of polymerase chain reae-tion technology in the detection of solid tumors [J].Cancer,1998,82 (8):1419-1442。
[3]郑光辉,赵英智,郝凯峰.骨髓转移癌26例分析[J].中国医药导报,2007,4(29)：167-168.
[4]Foucar K.Bone marrow pathology.Chicago:ASCP Integrative Hemat-pathology,1995,442-443
[5]高菊兴,张纪云.64例骨髓转移癌骨髓象诊断分析[J].检验医学,2010,25(2)：103—106.
[6]卢兴国,黄连生,许晓华,等.骨髓组织印片评有有核细胞量的价值[J].浙江大学学报(医学版),2006,35(3)：331-335
[7]朱云芝,汪开明,罗卫华,等.89锶治疗骨转移癌骨痛疗效分析[J].实用诊断与治疗杂志,2008,22(4)：315-316.
[8]Frisch B,Lewis S M,Burkhardt R,etal.Biopsy pathology of bone and bone marrow.London:Chapman and Hall Medical,1985.243-275
[9]黄波田,李书杰.血细胞学检验[M].郑州：河南医科大学出版社,1998：374
[10]吴谨绪,邓承祺.血液病诊疗手册[M].北京：人民卫生出版社,2000：149
[11]杨文博.骨髓转移癌289例文献综合分析[J].中国实用内科杂
志,2002,(7)22：439
[12]Xiao L, Luxi S, Ying T, et al. Diagnosis of unknown nonhema-tological tumors by bone marrow biopsy;A retrospective analysis of 10,112 samples[J].J Cancer Res Clin Oncol,2009,135 (5):687
[13]Shamdas GJ,Ahmann FR, Matzner MB,etal.Leukoerythroblastic anemia in metastatic prostate cancer;Clinical and prognostic signi-ficance in patients with hormone-refractory disease[1].Cancer, 1993,71(11),3594
[14]Delsol G,Guiu-Godfrin B,GuiuM,et al.Leukoery-throblastosis and cancer frequency,prognosis,and physiopathologic significance [1.Cancer,1979,(3):1009
[15]Gebauer G, Fehm T, Merkle E, et al. Epithelial cells in bone marrow of breast cancer patients at time of primary surgery; Clinical outcome during long term follow-up[J].
[16]Braun S,Vogl FD,Naume B, et al. International pooled analysis of prognostic significance of bone marrow microme-tastasis in patients with stage or breast cancer [J].New England J Med,2005,353-793
[17]Wiedswang G,Borgen E, Karesen R,etal. Detection of isolated tumor cells in bone marrow is an independent prog- nostic factor in breast cancer[J].J Clin Oncol,2003,21:3469
[18]初钊辉,,周鑫莉,梁晓华,等.骨髓转移癌41例临床分析[J].肿瘤,2008,28(6)：520
[19]徐赛英.实用儿科放射诊断学.北京：北京出版社,1998：793-800.
[20]Papaioannou G,McHugh k Neuroblastoma in childhood:review and radiological findings.Cancer Imagingo2005,5:116—127.
[21]Tanabe M.Ohnuma N,1wai J,et al.Bone man'ow metastasis of neuroblastoma analysed by MRI and its influence on prognosis.Med Pediatr Oncol,1995,24:292-299.
[22]Moulopoulos LA.Dimopoulos M.Magnetic resonanceimaging of the bone marrow in hematologic.Blood,1997;90(6):2127—2138.
[23]王雯邈 徐兵河 王佳玉,乳腺癌骨髓转移伴重度骨髓抑制治疗后长期生存一例并文献回顾[J]中国肿瘤临床与康复,2012年2月第19卷第1期,76-77.
[24]Gatenby RA.A change of strategy in the war on cancer[J]. Nature,2009,459: 508-509.
[25]邱立华 王华庆 刘贤明,衰竭期骨髓转移癌临床表现及治疗对策[J].第十一届中国扰癌协会全国琳巴瘤学术大会2009,279.
[26]邱立华 王华庆 刘贤明,衰竭期骨髓转移癌临床表现及治疗对策[J]第十一届中国扰癌协会全国琳巴瘤学术大会,2009,279-280.
[2]卢振霞,林玉梅,何淑珍.骨髓转移癌43例临床分析[J]临床血液学杂志,1999,12(1)；31-32.
[3]Lambrechts AC,van't Veer LJ,RodenhuisS. The detection of minimal numbers of con-taminating epithelial tumor cells in blood orbone marrow:use,limitations and future of RNA-based methods[J]. Ann Oncol,1998,9(12):1269-1276.
[4]金顺钱.参与肿瘤转移的表而粘连交体[J].国外医学肿瘤学分册,1994,3：131-132.
[5]卢兴国,主编造血和淋巴组织肿瘤现代诊断学[M]北京：科学出版社,2005：166.
[6]黄梅,路武,徐慧珍,等.47例骨髓转移癌的临床及血液学特点[J].临床内科杂志,2002,19(6)：424-425.
[7]古颖春,宋业琳.张春玲.等.p53、bcl-2、nm23蛋白在肺癌中的表达及与预后的关系[J].山东医药,2011,51,(13)：54-55.
[8]Reed JC..bcl-2 and the regulation of programmed cell death.J Cell Biol,1994,12(4):1-6.
[9]Quinn CM.Ostowsik.JL,Harkins L,et al.Loss of bcl-2 expression in ducal carcinoma in situ of the breast relates to poor histological differentiation and to expression of P53 and c-erB-2 protteins. Histopathology,1998,33::531-536
[10] Homma A,Furuta Y,Oridate N,etal.Correlation of cilinicopatho- logical
parameters and biological markers related to apoptosis and proliferative activity with a clinical outcome in squamous cellcarcinoma of the lary treated with concurrrent chemoradiothrerapy.Auris Nasus Larynx,2001,28:87-94
[11] Kymionis GD,Dimitrakakis CE,Konstadoulakis MM,et al.Can expression of apoptosis genes,bcl-2 and bax,predict survival and responsiveness to chemothcrapy in node-negative breast cancer patients?J Surg Res,2001,99(2):161-168
[12]Scholzen T,Gerdes J.The Ki-67 protien:from the known and the unknown[J].Cell Physiol,2000,182(3):311.
[13] Sakata K,Tamra G,Maesawa C,et al. Loss of heterozygosity on tharm of chromosome 9 without p16 gene mutation in gastric carcinomas[J].Jpn J Cancer Res,1995,333.
[14]Papaioannou G,McHugh k Neuroblastoma in childhood:review and radiological findings.Cancer Imaging,2005,5:116—127.
[15] Moyer P.Race,weight,and smoking status may influence p53 positive breast cancer[J].Am Assoc Cancer Res.2005.
[16]林子洪,廖威明,傅明,等p21WAFI的功能研究新进展[J].广东医学,2007.28(3)：482—484.
[17]黄伟,刘惠敏.胃癌P53,P-糖蛋白的表达意义与肿瘤预后关系[J].实用诊断与治疗杂志,2005;19(4)：240.1.
[18] Srivengopai KS, Aii OF. Deietion and rearrangements inactivate the p161ND4gene in human giioma ceiis [J].Oncogene,1996,12:2029.
[19] LoKW,Cheung SF. Hypermethyiation of the p16 gene in nasopharyngeai carcinoma [J].Cancer Res,1996,56:2721.
[20] Shigemasa K,Hu C,West CM,et al.p16 overexpression:a potentiai eariy indicator of transformation in ovarian carcinoma[J].J Soc gynecol Investig,1997,4(2):95
[21]Mcshea A, Harris PLR,Webster KR,et al.Abnormai expression of the ceii cycie reguiators p16 and CDK4 in Aizheimers disease [J].Pathol,1997,150 (6) 1933.
[22]吕春雷,廖建春,萧壁君,等喉癌中HPV感染和P16表达的检测及临床相关性研究[J]临床与实验病理学杂志.1999,15(5)：382-384.
[23]Tanabe M。Ohnuma N,1wai J,et al.Bone man'ow metastasis of neuroblastoma analysed by MRI and its influence on prognosis.Med Pediatr Oncol,1995,24:292-299.
[24]Moulopoulos LA·Dimopoulos M. Magnetic resonanceimaging of the bone marrow in hematologic.Blood,1997;90(6):2127—2138.
[25]奠东华,莫汉有,王晓桃.100例骨髓转移璃骨髓组织病理学的观察[J].临床肿瘤学杂志,2007；10(12)：773.4.
[26]胡响祥,朱思国,陈风.骨髓转移癌患者的外周血象特征分析[J].临床和实验医学杂志.2008；9(7)：152-3.
[27] Xiao L, Luxi S, Ying T, et al.Diagnosis of unknown non hematological tumors by bone marrow biopsy:A retrospective analysis of 10,112 samples[J].J Cancer Res Clin Oncol,2009,135 (5)687
[28]Fehm T,Becker S,Bachmann C,et al.Detection of disseminated tumor cells in patients with gynecological callcer[J]. Gynecoloneol,2006;103(3):942-7.
[29]初钊辉,周鑫莉,梁晓华,等.骨髓转移癌41例临床分析[J].肿瘤,2008,28(6)：520
[1]夏云金,刘瑜,万楚成,章正华,张霞,姜铧,杨华强.骨髓活检组织印片在骨髓转移癌诊断中的价值[J].中华实用诊断与治疗杂志.2008,23(3)：269—270.
[2]rhj GV,Moreno JG,Gomella LG.Utilization of polymerase chain reae-tion technology in the detection of solid tumors [J].Cancer,1998,82 (8):1419-1442。
[3]郑光辉,赵英智,郝凯峰.骨髓转移癌26例分析[J].中国医药导报,2007,4(29)：167-168.
[4]Foucar K.Bone marrow pathology.Chicago:ASCP Integrative Hemat-pathology,1995,442-443
[5]高菊兴,张纪云.64例骨髓转移癌骨髓象诊断分析[J].检验医学,2010,25(2)：103—106.
[6]卢兴国,黄连生,许晓华,等.骨髓组织印片评有有核细胞量的价值[J].浙江大学学报(医学版),2006,35(3)：331-335
[7]朱云芝,汪开明,罗卫华,等.89锶治疗骨转移癌骨痛疗效分析[J].实用诊断与治疗杂志,2008,22(4)：315-316.
[8]Frisch B,Lewis S M,Burkhardt R,etal.Biopsy pathology of bone and bone marrow.London:Chapman and Hall Medical,1985.243-275
[9]黄波田,李书杰.血细胞学检验[M].郑州：河南医科大学出版社,1998：374
[10]吴谨绪,邓承祺.血液病诊疗手册[M].北京：人民卫生出版社,2000：149
[11]杨文博.骨髓转移癌289例文献综合分析[J].中国实用内科杂
志,2002,(7)22：439
[12]Xiao L, Luxi S, Ying T, et al. Diagnosis of unknown nonhema-tological tumors by bone marrow biopsy;A retrospective analysis of 10,112 samples[J].J Cancer Res Clin Oncol,2009,135 (5):687
[13]Shamdas GJ,Ahmann FR, Matzner MB,etal.Leukoerythroblastic anemia in metastatic prostate cancer;Clinical and prognostic signi-ficance in patients with hormone-refractory disease[1].Cancer, 1993,71(11),3594
[14]Delsol G,Guiu-Godfrin B,GuiuM,et al.Leukoery-throblastosis and cancer frequency,prognosis,and physiopathologic significance [1.Cancer,1979,(3):1009
[15]Gebauer G, Fehm T, Merkle E, et al. Epithelial cells in bone marrow of breast cancer patients at time of primary surgery; Clinical outcome during long term follow-up[J].
[16]Braun S,Vogl FD,Naume B, et al. International pooled analysis of prognostic significance of bone marrow microme-tastasis in patients with stage or breast cancer [J].New England J Med,2005,353-793
[17]Wiedswang G,Borgen E, Karesen R,etal. Detection of isolated tumor cells in bone marrow is an independent prog- nostic factor in breast cancer[J].J Clin Oncol,2003,21:3469
[18]初钊辉,,周鑫莉,梁晓华,等.骨髓转移癌41例临床分析[J].肿瘤,2008,28(6)：520
[19]徐赛英.实用儿科放射诊断学.北京：北京出版社,1998：793-800.
[20]Papaioannou G,McHugh k Neuroblastoma in childhood:review and radiological findings.Cancer Imagingo2005,5:116—127.
[21]Tanabe M.Ohnuma N,1wai J,et al.Bone man'ow metastasis of neuroblastoma analysed by MRI and its influence on prognosis.Med Pediatr Oncol,1995,24:292-299.
[22]Moulopoulos LA.Dimopoulos M.Magnetic resonanceimaging of the bone marrow in hematologic.Blood,1997;90(6):2127—2138.
[23]王雯邈 徐兵河 王佳玉,乳腺癌骨髓转移伴重度骨髓抑制治疗后长期生存一例并文献回顾[J]中国肿瘤临床与康复,2012年2月第19卷第1期,76-77.
[24]Gatenby RA.A change of strategy in the war on cancer[J]. Nature,2009,459: 508-509.
[25]邱立华 王华庆 刘贤明,衰竭期骨髓转移癌临床表现及治疗对策[J].第十一届中国扰癌协会全国琳巴瘤学术大会2009,279.
[26]邱立华 王华庆 刘贤明,衰竭期骨髓转移癌临床表现及治疗对策[J]第十一届中国扰癌协会全国琳巴瘤学术大会,2009,279-280.