侵袭性变异型套细胞淋巴瘤临床病理特征及预后分析
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摘要
目的探讨套细胞淋巴瘤侵袭性变异型(aggressive variants of mantle cell lymphoma,AV-MCL)的临床病理学特征及预后。方法回顾性分析72例AV-MCL和同期60例经典型套细胞淋巴瘤(mantle cell lymphoma,MCL)患者的临床资料,观察AV-MCL的组织学形态及免疫表型,应用FISH法检测Ig H/CCND1融合基因,并比较两组患者的临床病理特征及生存率差异。结果 72例AV-MCL占同期(466例) MCL的15. 4%,其中母细胞变异型占12. 0%,多形性变异型占3. 4%。男女比为2. 8∶1,中位年龄62. 0岁(范围34～86岁)。有B症状者占26. 3%(10/38)。Ann Arbor分期显示Ⅲ+Ⅳ期占64. 9%(24/37)。肿瘤组织由增生的异型淋巴细胞构成,56例(77. 8%)为母细胞变异型,16例(22. 2%)为多形性变异型。肿瘤细胞均表达CD20和Cyclin D1,CD5、SOX11、CD43、MUM1的表达比例分别为95. 2%(60/63)、62. 5%(10/16)、66. 7%(6/9)和51. 4%(19/37),CD10和BCL-6异常表达的比例分别为15. 6%(10/64)和16. 1%(9/56)。AV-MCL的Ki-67增殖指数显著高于经典型MCL(60. 1%±11. 7%vs 22. 7%±11. 0%,P <0. 001)。3例CD5阴性病例FISH检测结果阳性。25例(34. 7%)获得随访,中位随访时间20个月(4～60个月)。与经典型MCL相比,AV-MCL的总生存率及对应Ⅰ+Ⅱ期和Ⅲ+Ⅳ期总生存率差异均有统计学意义(P <0. 05)。单因素分析结果显示,在AV-MCL中伴结外侵犯的患者总生存率更低(P=0. 032)。结论 AV-MCL临床较罕见,大多为母细胞变异型,预后较经典型MCL差,伴结外侵犯是其不良预后因素。
Purpose To investigate the clinicopathological features and prognosis of aggressive variants( blastoid and pleomorphic) of mantle cell lymphoma( AV-MCL). Methods Theclinical data of 72 cases of AV-MCL and 60 cases of common form of MCL( C-MCL) in the same period diagnosed were ana-lyzed retrospectively. The histological morphology and immunophenotype of AV-MCL were observed. The clinicopathological characteristics and overall survival rates( OSRs) of two groups were compared. Results Seventy-two cases of AV-MCL accounted for 15. 4% of MCL in the same period( 466 cases),12. 0%of blastoid and 3. 4% of pleomorphic. The median age was 62 years( range: 34 ～ 86 years,M ∶ F = 2. 8 ∶ 1. 0). Those patients with B symptoms accounted for 26. 3%( 10/38). The Ann Arbor stage Ⅲ + Ⅳ accounted for 64. 9%( 24/37). The tumor tissue was made up of proliferating lymphoid cells. Fifty-six cases( 77. 8%) were blastoid,16 cases( 22. 2%) were pleomorphic.All tumors were positive for CD20 and Cyclin D1. The positive expression rates of CD5,SOX11,CD43 and MUM1 in the tumors were 95. 2%( 60/63),62. 5%( 10/16),66. 7%( 6/9) and51. 4%( 19/37) respectively. The proportion of aberrant expres-sion of CD10 and BCL-6 in tumor was 15. 6%( 10/64) and16. 1%( 9/56),respectively. The AV-MCL Ki-67 marker index was significantly higher than that of C-MCL( 60. 1% ± 11. 7% vs22. 7% ± 11. 0%,P < 0. 001). FISH test was positive in 3 cases of CD5 negative. Twenty-five( 34. 7%) patients had a median follow-up time of 20. 0 months( range: 4-60 months). Compared with the C-MCL,the OSRs of the patients with AV-MCL,and the corresponding differences in the OSRs of stages Ⅰ + Ⅱand Ⅲ + Ⅳ were statistically significant( P < 0. 05). Univariate analysis showed that the OSRs was lower in AV-MCL patients with extranodal invasion( P = 0. 032). Conclusions AV-MCL is rare,most of which are blastoid variant,and the prognosis is worse than that of C-MCL. Extranodal invasion is a bad prognostic factor.
Purpose To investigate the clinicopathological features and prognosis of aggressive variants( blastoid and pleomorphic) of mantle cell lymphoma( AV-MCL). Methods Theclinical data of 72 cases of AV-MCL and 60 cases of common form of MCL( C-MCL) in the same period diagnosed were ana-lyzed retrospectively. The histological morphology and immunophenotype of AV-MCL were observed. The clinicopathological characteristics and overall survival rates( OSRs) of two groups were compared. Results Seventy-two cases of AV-MCL accounted for 15. 4% of MCL in the same period( 466 cases),12. 0%of blastoid and 3. 4% of pleomorphic. The median age was 62 years( range: 34 ～ 86 years,M ∶ F = 2. 8 ∶ 1. 0). Those patients with B symptoms accounted for 26. 3%( 10/38). The Ann Arbor stage Ⅲ + Ⅳ accounted for 64. 9%( 24/37). The tumor tissue was made up of proliferating lymphoid cells. Fifty-six cases( 77. 8%) were blastoid,16 cases( 22. 2%) were pleomorphic.All tumors were positive for CD20 and Cyclin D1. The positive expression rates of CD5,SOX11,CD43 and MUM1 in the tumors were 95. 2%( 60/63),62. 5%( 10/16),66. 7%( 6/9) and51. 4%( 19/37) respectively. The proportion of aberrant expres-sion of CD10 and BCL-6 in tumor was 15. 6%( 10/64) and16. 1%( 9/56),respectively. The AV-MCL Ki-67 marker index was significantly higher than that of C-MCL( 60. 1% ± 11. 7% vs22. 7% ± 11. 0%,P < 0. 001). FISH test was positive in 3 cases of CD5 negative. Twenty-five( 34. 7%) patients had a median follow-up time of 20. 0 months( range: 4-60 months). Compared with the C-MCL,the OSRs of the patients with AV-MCL,and the corresponding differences in the OSRs of stages Ⅰ + Ⅱand Ⅲ + Ⅳ were statistically significant( P < 0. 05). Univariate analysis showed that the OSRs was lower in AV-MCL patients with extranodal invasion( P = 0. 032). Conclusions AV-MCL is rare,most of which are blastoid variant,and the prognosis is worse than that of C-MCL. Extranodal invasion is a bad prognostic factor.
引文
[1] Swerdlow S H,Campo E,Seto M,Muller-Hermelink H K. Mantle cell lymphoma[M]//Swerdlow S H,Campo E,Harris N L,et al. WHO classification of tumors of tumors of hematopoietic and lymphoid tissues. Lyon:IARC Press,2008:229-232.
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[3] Argatoff L H,Connors J M,Klasa R J,et al. Mantle cell lymphoma:a clinicopathologic study of 80 cases[J]. Blood,1997,89(6):2067-2078.
[4]侯卫华,韦萍,谢建兰,等.套细胞淋巴瘤349例临床病理学特点及预后[J].中华病理学杂志,2018,47(6):417-422.
[5] Sen R,Gupta S,Gill M,et al. Blastoid variant of mantle cell lymphoma———a rare case report[J]. J Clin Diagn Res,2017,2(8):161-163.
[6] Swerdlow S H,Campo E,Seto M,Muller-Hermelink H K. Mantle cell lymphoma[M]//Swerdlow S H,Campo E,Harris N L,et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon:IARC Press,2017:285-290.
[7] Shrestha R,Bhatt V R,Guru Murthy G S,Armitage J O. Clinicopathologic features and management of blastoid variant of mantle cell lymphoma[J]. Leuk Lymphoma,2015,56(10):2759-2767.
[8] Bernard M,Gressin R,Lefrere F,et al. Blastic variant of mantle cell lymphoma:a rare but highly aggressive subtype[J]. Leukemia,2001,15(11):1785-1791.
[9] Raty R,Franssila K,Jansson S E,et al. Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma[J]. Eur J Cancer,2003,39(3):321-329.
[10] Seok Y,Kim J,Choi J R,et al. CD5-negative blastoid variant mantle cell lymphoma with complex CCND1/IGH and MYC aberrations[J]. Ann Lab Med,2012,32(1):95-98.
[11] Gao J,Peterson L,Nelson B,et al. Immunophenotypic variations in mantle cell lymphoma[J]. Am J Clin Pathol,2009,132(5):699-706.
[12] Pizzi M,Agostinelli C,Righi S,et al. Aberrant expression of CD10 and BCL6 in mantle cell lymphoma[J]. Histopathology,2017,71(5):769-777.
[13]陈海月,张燕林,金仁顺,等.套细胞淋巴瘤CD10异常表达1例[J].临床与实验病理学杂志,2018,34(8):934-935.
[14] Xu J,Medeiros L J,Saksena A,et al. CD10-positive mantle cell lymphoma:clinicopathologic and prognostic study of 30 cases[J].Oncotarget,2018,9(14):11441-11450.
[15]侯卫华,韦萍,谢建兰,等.探讨Ki-67增殖指数在套细胞淋巴瘤组织分型与预后中的临界值[J].临床与实验病理学杂志,2018,34(10):1085-1090.
[16] Chuang W Y,Chang H,Chang G J,et al. Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma:common Cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall[J]. Histopathology,2017,70(6):986-999.
[17] Jares P,Colomer D,Campo E. Molecular pathogenesis of mantle cell lymphoma[J]. J Clin Invest,2012,122(10):3416-3423.
[18] Bhatt V R,Loberiza F R Jr,Smith L M,et al. Clinicopathologic features,management and outcomes of blastoid variant of mantle cell lymphoma:a nebraska lymphoma study group experience[J].Leuk Lymphoma,2016,57(6):1327-1334.
[19]曾郁,易祥华,梁军,等.多形性母细胞型套细胞淋巴瘤1例并文献复习[J].临床与实验病理学杂志,2013,29(12):1373-1375.
[20] Hoster E,Rosenwald A,Berger F,et al. Prognostic value of Ki-67 index,cytology,and growth pattern in mantle-cell lymphoma:results from randomized trials of the European mantle cell lymphoma network[J]. J Clin Oncol,2016,34(12):1386-1394.
[21] Aukema S M,Hoster E,Rosenwald A,et al. Expression of TP53is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network[J]. Blood,2018,131(4):417-420.
[22] Hou W,Wei P,Xie J,et al. The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis[J]. Pathol Res Pract,2018,214(4):513-520.
[2] Tiemann M,Schrader C,Klapper W,et al. Histopathology,cell proliferation indices and clinical outcome in 304 patients with mantle cell lymphoma(MCL):a clinicopathological study from the European MCL Network[J]. Br J Haematol,2005,131(1):29-38.
[3] Argatoff L H,Connors J M,Klasa R J,et al. Mantle cell lymphoma:a clinicopathologic study of 80 cases[J]. Blood,1997,89(6):2067-2078.
[4]侯卫华,韦萍,谢建兰,等.套细胞淋巴瘤349例临床病理学特点及预后[J].中华病理学杂志,2018,47(6):417-422.
[5] Sen R,Gupta S,Gill M,et al. Blastoid variant of mantle cell lymphoma———a rare case report[J]. J Clin Diagn Res,2017,2(8):161-163.
[6] Swerdlow S H,Campo E,Seto M,Muller-Hermelink H K. Mantle cell lymphoma[M]//Swerdlow S H,Campo E,Harris N L,et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon:IARC Press,2017:285-290.
[7] Shrestha R,Bhatt V R,Guru Murthy G S,Armitage J O. Clinicopathologic features and management of blastoid variant of mantle cell lymphoma[J]. Leuk Lymphoma,2015,56(10):2759-2767.
[8] Bernard M,Gressin R,Lefrere F,et al. Blastic variant of mantle cell lymphoma:a rare but highly aggressive subtype[J]. Leukemia,2001,15(11):1785-1791.
[9] Raty R,Franssila K,Jansson S E,et al. Predictive factors for blastoid transformation in the common variant of mantle cell lymphoma[J]. Eur J Cancer,2003,39(3):321-329.
[10] Seok Y,Kim J,Choi J R,et al. CD5-negative blastoid variant mantle cell lymphoma with complex CCND1/IGH and MYC aberrations[J]. Ann Lab Med,2012,32(1):95-98.
[11] Gao J,Peterson L,Nelson B,et al. Immunophenotypic variations in mantle cell lymphoma[J]. Am J Clin Pathol,2009,132(5):699-706.
[12] Pizzi M,Agostinelli C,Righi S,et al. Aberrant expression of CD10 and BCL6 in mantle cell lymphoma[J]. Histopathology,2017,71(5):769-777.
[13]陈海月,张燕林,金仁顺,等.套细胞淋巴瘤CD10异常表达1例[J].临床与实验病理学杂志,2018,34(8):934-935.
[14] Xu J,Medeiros L J,Saksena A,et al. CD10-positive mantle cell lymphoma:clinicopathologic and prognostic study of 30 cases[J].Oncotarget,2018,9(14):11441-11450.
[15]侯卫华,韦萍,谢建兰,等.探讨Ki-67增殖指数在套细胞淋巴瘤组织分型与预后中的临界值[J].临床与实验病理学杂志,2018,34(10):1085-1090.
[16] Chuang W Y,Chang H,Chang G J,et al. Pleomorphic mantle cell lymphoma morphologically mimicking diffuse large B cell lymphoma:common Cyclin D1 negativity and a simple immunohistochemical algorithm to avoid the diagnostic pitfall[J]. Histopathology,2017,70(6):986-999.
[17] Jares P,Colomer D,Campo E. Molecular pathogenesis of mantle cell lymphoma[J]. J Clin Invest,2012,122(10):3416-3423.
[18] Bhatt V R,Loberiza F R Jr,Smith L M,et al. Clinicopathologic features,management and outcomes of blastoid variant of mantle cell lymphoma:a nebraska lymphoma study group experience[J].Leuk Lymphoma,2016,57(6):1327-1334.
[19]曾郁,易祥华,梁军,等.多形性母细胞型套细胞淋巴瘤1例并文献复习[J].临床与实验病理学杂志,2013,29(12):1373-1375.
[20] Hoster E,Rosenwald A,Berger F,et al. Prognostic value of Ki-67 index,cytology,and growth pattern in mantle-cell lymphoma:results from randomized trials of the European mantle cell lymphoma network[J]. J Clin Oncol,2016,34(12):1386-1394.
[21] Aukema S M,Hoster E,Rosenwald A,et al. Expression of TP53is associated with the outcome of MCL independent of MIPI and Ki-67 in trials of the European MCL Network[J]. Blood,2018,131(4):417-420.
[22] Hou W,Wei P,Xie J,et al. The degree of overlap between the follicular dendritic cell meshwork and tumor cells in mantle cell lymphoma is associated with prognosis[J]. Pathol Res Pract,2018,214(4):513-520.