间变性大细胞淋巴瘤临床病理特征分析

doi:10.16150/j.1671-2870.2017.03.016

摘要/Abstract

摘要： 目的: 探讨间变性大细胞淋巴瘤(anaplastic large cell lymphoma,ALCL)的临床和病理特点。方法: 回顾12例系统性ALCL 患者的临床资料,分析其病理组织的镜下形态、免疫表型特征,采用荧光原位杂交检测相关融合基因,并复习相关文献。结果: 12例ALCL患者中男女各6例,年龄为22~81岁。9例伴有反复发热、体重减轻、盗汗、贫血等B症状;5例的ALCL发生于淋巴结结外,3例同时累及淋巴结。镜下,ALCL病灶以多形性细胞为主,均可见特征性肾形细胞核,部分肿瘤呈黏附性生长,1例为小细胞变异型,2例可见肉瘤样分化。免疫组织化学检测显示,4例患者ALK阳性,8例阴性;12例均有CD30表达,7例CD2阳性,5例CD3阳性,3例CD5阳性,2例CD7阳性,2例CD4/CD8标志均阳性,5例不同程度表达细胞毒标志。4例免疫组化ALK阳性者经荧光原位杂交均检测观察到分离信号。结论: ALCL 患者B症状多见,易累及结外组织,肿瘤组织在光镜下形态多样,常失表达部分T细胞相关抗原,联合应用T细胞标志对其诊断及鉴别诊断具有重要意义。

关键词: 间变性大细胞淋巴瘤, 免疫组织化学, 诊断, 鉴别诊断

Abstract: Objective: To investigate the clinicopathological feature of anaplastic large cell lymphoma (ALCL). Methods: A total of 12 cases of ALCL were enrolled and the clinicohistopathological characteristics, results of immunophenotyping, fluorescence in situ hybridization (FISH) were analyzed. The relevant literatures were reviewed. Results: Patients were 6 males, 6 females, aged from 22 to 81 years, with an average of 47 years. B symptoms occurred in 9 cases. Extranodal lesions or also with lymph node lesions simultaneously were involved in 5 cases. Microscopically, ALCL was composed of pleomorphic large tumor cells predominantly, horseshoe-shaped nuclei cells were found in all cases, and adhesive growth pattern was seen in some cases. Small cell variant was seen in 1 case, and sarcomatoid features in 2 cases; 4 cases were positive for ALK, while 8 were negative for ALK. Positive staining for CD30 was seen in all the 12 cases, while positive for CD2 in 7 cases, CD3 in 5 cases, CD5 in 3 cases, CD7 in 2 cases, both positive for CD4/CD8 in 2 cases. In addition, cytotoxicity was found in various degree in 5 cases. Separating signal was found by FISH in all the 4 cases which were positive for ALK by immunohistochemical staining. Conclusions: ALCL patients usually present with B symptoms and tend to be involved in extranodal sites. Microscopic pathology reveals pleomorphic feature and often lacking some T lymphocyte-associated antigens. Combined detection of T cell markers is important for diagnosis and differential diagnosis.

Key words: Anaplastic large cell lymphoma, Immunohistochemistry, Diagnosis, Differential diagnosis

中图分类号:

R733.1

衣琳, 肖立, 陈燕, 殷于磊. 间变性大细胞淋巴瘤临床病理特征分析[J]. 诊断学理论与实践, 2017, 16(03): 313-319.

YI Lin, XIAO Li, CHEN Yan, YIN Yulei. Anaplastic large cell lymphoma: a clinicopathological study and review of literature[J]. Journal of Diagnostics Concepts & Practice, 2017, 16(03): 313-319.

参考文献

[1] 雅培ALK基因重组检测试剂盒(荧光原位杂交法)说明书[P].雅培ALK基因重组检测试剂盒(荧光原位杂交法)说明书[P]. Vysis ALK Break Apart FISH Probe Kit,2013.
[2] Savage KJ, Chhanabhai M, Gascoyne RD, et al.Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification[J]. Ann Oncol,2004,15(10):1467-1475.
[3] Vose J, Armitage J, Weisenburger D, et al.International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes[J]. J Clin Oncol,2008,26(25):4124-4130.
[4] Falini B, Pileri S, Zinzani PL, et al.ALK+ lymphoma: clinico-pathological findings and outcome[J]. Blood,1999, 93(8):2697-2706.
[5] Rizvi MA, Evens AM, Tallman MS, et al.T-cell non-Hodgkin lymphoma[J]. Blood,2006,107(4):1255-1264.
[6] Elaine SJ, Nancy LH, Harald S, et al.Pathology&Gene-tics: turnouts of haematopoietic and lymphoid tissues[M]. Oxford: Oxford University Press,2001:230-235.
[7] Bayle C, Charpentier A, Duchayne E, et al.Leukaemic presentation of small cell variant anaplastic large cell lymphoma: report of four cases[J]. Br J Haematol,1999, 104(4):680-688.
[8] Fraga M, Brousset P, Schlaifer D, et al.Bone marrow involvement in anaplastic large cell lymphoma. Immunohistochemical detection of minimal disease and its prognostic significance[J]. Am J Clin Pathol,1995,103(1):82-89.
[9] Ng A, Hobson R, Williams D et al. Anaplastic large cell lymphoma of bone--is it a bad tumor?[J]. Pediatr Blood Cancer,2007,48(4):473-476.
[10] Savage KJ, Harris NL, Vose JM, et al.ALK- anaplastic large-cell lymphoma is clinically and immunophenotypically different from both ALK+ ALCL and peripheral T-cell lymphoma, not otherwise specified: report from the International Peripheral T-Cell Lymphoma Project[J]. Blood,2008,111(12):5496-5504.
[11] Delsol G, Falini B, Muller-Hermelink HK, et al.Anaplastic large cell lymphoma, ALK-positive[J]. Arch Hell Med,2011,28(6):856-857.
[12] WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues[M]. Lyon: International Agency for Research on Cancer,2008:312-316.
[13] Nakamura S, Shiota M, Nakagawa A, et al.Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression[J]. Am J Surg Pathol,1997,21(12):1420-1432.
[14] Rimokh R, Magaud JP, Berger F, et al.A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma')[J]. Br J Haematol,1989,71(1):31-36.
[15] de Leval L, Bisig B, Thielen C, et al. Molecular classification of T-cell lymphomas[J]. Crit Rev Oncol Hematol,2009,72(2):125-143.
[16] Lamant L, Dastugue N, Pulford K, et al.A new fusion gene TPM3-ALK in anaplastic large cell lymphoma crea-ted by a (1;2)(q25;p23) translocation[J]. Blood,1999,93(9):3088-3095.
[17] Touriol C, Greenland C, Lamant L, et al.Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma: 2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like)[J]. Blood,2000,95(10):3204-3207.
[18] Tort F, Pinyol M, Pulford K, et al.Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma[J]. Lab Invest,2001,81(3):419-426.
[19] Damm-Welk C, Klapper W, Oschlies I, et al.Distribution of NPM1-ALK and X-ALK fusion transcripts in paedia-tric anaplastic large cell lymphoma: a molecular-histolo-gical correlation[J]. Br J Haematol,2009,146(3):306-309.
[20] Feldman AL, Vasmatzis G, Asmann YW, et al.Novel TRAF1-ALK fusion identified by deep RNA sequencing of anaplastic large cell lymphoma[J]. Genes Chromosomes Cancer,2013,52(11):1097-1102.
[21] Yatabe Y.ALK FISH and IHC: you cannot have one without the other[J]. J Thorac Oncol,2015,10(4):548-550.
[22] Cataldo KA, Jalal SM, Law ME, et al.Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue[J]. Am J Surg Pathol,1999,23(11):1386-1392.
[23] Venkataraman G, Song JY, Tzankov A, et al.Aberrant T-cell antigen expression in classical Hodgkin lymphoma is associated with decreased event-free survival and overall survival[J]. Blood,2013,121(10):1795-1804.
[24] Xing X, Feldman AL.Anaplastic large cell lymphomas: ALK positive, ALK negative, and primary cutaneous[J]. Adv Anat Pathol,2015,22(1):29-49.
[25] Delsol G, Lamant L, Mariamé B, et al.A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2; 5 translocation[J]. Blood,1997,89(5):1483-1490.
[26] Savage KJ, Chhanabhai M, Gascoyne RD, et al.Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification[J]. Ann Oncol,2004,15(10):1467-1475.