ALK阳性大B细胞淋巴瘤3例临床病理及分子遗传学分析

目的探讨间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)阳性的弥漫性大B细胞淋巴瘤(diffuse large B-cell lym-phoma,DLBCL)的临床病理及分子遗传学特点。方法对3例ALK(+)DLBCL进行光镜观察、免疫组化及荧光原位杂交检测,并复习相关文献。结果镜下观察淋巴结结构破坏,可见淋巴窦侵犯,肿瘤细胞大,呈免疫母细胞样,免疫组化示肿瘤细胞ALK、Bob-1、CD4、CD10、CD45、CD56、CD138、EMA、MUM1、Oct-2均(+),CD20、CD79a、PAX-5、CD3和CD30均(-),3例荧光原位杂交均检测到ALK基因易位。结论 ALK(+)DLBCL是一种DLBCL的少见独立亚型,具有特征性免疫表型、形态学及分子遗传学特点。     

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting in nasal cavity: a case report and review of literature

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin’s lymphoma (NHL) with distinct morphologic and immunohistochemical features. We reported a 57-year-old female with ALK-positive DLBCL in her left nasal cavity. Histologically, the tumor cells were characterized by plasmablastic morphology and tested positive for ALK in a cytoplasmic granular staining pattern. The neoplastic cells were positive for CD38, CD4, MUM1, CD138 and Vimentin. However, they failed to express CD56, CD30, as well as mature B cells markers, such as CD79a, CD20 and T cells markers such as CD2, CD3, CD5, CD7 and CD8. The patient achieved complete response after four cycles of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide) treatment. Then she received radiotherapy of the originally involved area. This case represented a rare ALK-positive DLBCL in the nasal region.     

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting as an isolated nasopharyngeal mass: a case report and review of literature

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma is a rare and distinct variant of diffuse large B-cell lymphoma with characteristic morphologic, immunophenotypic, and cytogenetic features. We report a case of ALK-positive diffuse large B-cell lymphoma in a 44-year-old male with progressively worsening unilateral nasal congestion and obstruction secondary to a nasopharyngeal mass. Radiologically, the mass was showed to extend to orophanrynx from nasopharynx. Histologically, the tumor cells exhibited plasmablastic morphology with expression of Bob-1, CD4, CD10, CD45, CD56, CD138, EMA, MUM1, Oct-2, and kappa immunoglobulin light chain, but negative for CD20, CD30, CD79a, PAX-5, and lambda. More importantly, the neoplastic cells showed positive immunoreactivity for ALK with exclusive cytoplasmic granular staining pattern. This case represented the second reported ALK-positive diffuse large B-cell lymphoma in the nasopharyngeal region.     

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma with a complex karyotype and cryptic 3' ALK gene insertion to chromosome 4 q22-24

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare tumor that is frequently associated with t(2;17)(p23;q23), a translocation fusing the ALK gene at 2p23 to the clathrin heavy chain gene (CLTC) at 17q23. Here, we report a unique case of ALK-positive DLBCL with plasmablastic morphology and focal cytoplasmic granular ALK stain in an HIV-negative 33-year-old man. By conventional karyotyping, the lymphoma cells were near-tetraploid and included 4 structurally normal copies each of chromosomes 2 and 17. Fluorescence in situ hybridization revealed an apparently normal, intact ALK gene on each of the 4 chromosome 2 homologs plus a cytogenetically cryptic ALK gene insertion into 2 of the 4 chromosome 4 homologs at band 4q22-24. The lymphoma cells expressed CD138, lambda light chain, focal and weak CD30, and exhibited aberrant T-cell antigens, including perforin. This case indicates that ALK-positive DLBCL is more heterogeneous at the cytogenetic/molecular level than previously recognized.     

表达间变性淋巴瘤激酶蛋白的弥漫性大B细胞淋巴瘤的临床病理和免疫表型观察

目的探讨表达间变性淋巴瘤激酶（ALK）蛋白的弥漫性大B细胞淋巴瘤（DLBCL）的临床病理特点。方法根据2001年版WHO淋巴造血组织肿瘤分类收集945例DLBCL,以LSAB法作ALK-11染色。对阳性病例再用EnVision法作ALK-11染色,仅EnVision法阳性病例为最终纳入病例。对纳入病例标本用LSAB法加做CD20、CD3、CD30、上皮细胞膜抗原（EMA）、粒酶B、T细胞胞质内抗原（TIA）-1和浆细胞（PC）抗体等免疫表型检测,进行IgH基因重排检测并收集随访资料。结果945例弥漫性大B细胞淋巴瘤中仅5例表达ALK蛋白。4例男性,1例女性,年龄34—72岁,全部原发于淋巴结。临床分期Ⅰ期1例、Ⅱ期2例、Ⅲ期2例。5例随访最长32个月,最短4个月。随访截止时死亡4例,死亡病例最长存活时间32个月。表达ALK蛋白的DLBCL包括中心母细胞性2例、免疫母细胞性1例、间变性1例、浆母细胞性1例;2例中心母细胞性、1例免疫母细胞性和1例间变性均表达CD20。浆母细胞性表达K轻链而不表达CD20。5例均检测到IgH基因重排。ALK蛋白表达：在CD20阳性4例中,1例免疫母细胞性为胞膜和胞质阳性,2例中心母细胞性和1例间变性为胞质颗粒状阳性;1例浆母细胞性为胞核和胞质弥漫阳性。结论ALK蛋白阳性表达DLBLC是一种罕见的,临床过程具侵袭性且预后较差的淋巴瘤,可见于浆母细胞性、中心母细胞性、免疫母细胞性和间变性的大B细胞淋巴瘤。发现1例ALK蛋白表达于胞膜和胞质。     

The nucleophosmin-anaplastic lymphoma kinase fusion protein induces c-Myc expression in pediatric anaplastic large cell lymphomas

The majority of pediatric anaplastic large cell lymphomas (ALCLs) carry the t(2;5)(p23;q35) chromosomal translocation that juxtaposes the dimerization domain of nucleophosmin with anaplastic lymphoma kinase (ALK). The nucleophosmin-ALK fusion induces constitutive, ligand-independent activation of the ALK tyrosine kinase leading to aberrant activation of cellular signaling pathways. To study the early consequences of ectopic ALK activation, a GyrB-ALK fusion was constructed that allowed regulated dimerization with the addition of coumermycin. Expression of the fusion protein caused a coumermycin-dependent increase in cellular tyrosine phosphorylation and c-Myc immunoreactivity, which was paralleled by a rise in c-myc RNA. To assess the clinical relevance of this observation, c-Myc expression was determined in pediatric ALK-positive and -negative lymphomas. Co-expression of c-Myc and ALK was seen in tumor cells in 15 of 15 (100%) ALK-positive ALCL samples, whereas no expression of either ALK or c-Myc was seen in six of six cases of ALK-negative T-cell lymphoma. C-Myc may be a downstream target of ALK signaling and its expression a defining characteristic of ALK-positive ALCLs.     

IL-6和AG490对移植裸鼠的弥漫大B细胞淋巴瘤和伯基特淋巴瘤生长的影响

目的:观察STAT3通路对移植裸鼠弥漫大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)和伯基特淋巴瘤(Burkitt lymphoma,BL)的作用。方法:建立OCI-LY8细胞(DLBCL)和Raji细胞(BL)裸鼠移植瘤模型,并分别将其分为对照组、IL-6组和AG490组,测量裸鼠体重和肿瘤体积;应用Western blot和免疫组织化学检测移植瘤组织中p-STAT3、survivin及血管内皮生长因子(VEGF)蛋白的水平;real-time PCR检测瘤组织中survivin和VEGF的mRNA表达。结果:2种细胞株总成瘤率为83.3%(25/30),其中OCI-LY8细胞成瘤率为66.7%(10/15),低于Raji细胞成瘤率100%(15/15)(P0.05)。DLBCL和BL荷瘤鼠IL-6组在第9和10天裸鼠体重和总瘤体积较对照组均增加,2种移植瘤的IL-6组中第1天与第10天瘤体积总差值均明显大于对照组(P0.05)。pSTAT3阳性信号定位于细胞核;survivin和VEGF以细胞浆表达为阳性。与对照组相比,DLBCL移植瘤IL-6组survivin和VEGF明显升高(P0.05),p-STAT3无显著变化;AG490组p-STAT3及VEGF明显降低(P0.05),survivin无显著变化;在BL移植瘤IL-6组,p-STAT3和VEGF蛋白与相应对照相比均显著升高(P0.05),在AG490处理组中3种蛋白均明显降低(P0.05)。IL-6组和AG490组中survivin和VEGF的mRNA表达与对照组相比差异无统计学显著性。结论:IL-6和AG490可能通过STAT3通路影响DLBCL和BL的生长,STAT3通路活化可能通过调控VEGF和survivin表达而影响肿瘤的发生发展。     

Immunoreactivity of CD99 in non-Hodgkin's lymphoma: unexpected frequent expression in ALK-positive anaplastic large cell lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.     

B细胞特异性激活蛋白Pax-5在淋巴瘤组织中的表达

目的探讨B细胞特异性激活蛋白(BSAP)／Pax-5在淋巴瘤的表达情况及应用价值。方法按2001年WHO关于淋巴造血组织肿瘤分类标准收集102例弥漫性大B细胞淋巴瘤(DLBCL)、3例滤泡型淋巴瘤(FL)、3例黏膜相关淋巴组织结外边缘区B细胞淋巴瘤(MALT淋巴瘤)、1例结节性淋巴细胞为主型的霍奇金淋巴瘤(NLPHL)、10例间变性大细胞淋巴瘤(ALCL)和10例浆细胞瘤,用免疫组织化学LSAB法同步检测比较BSAP与CD20的表达情况。结果102例DLBCL全部表达CD20,100例表达BSAP,3例FL、3例MALT淋巴瘤和1例NLPHL BSAP和CD20全部阳性表达,10例ALCL、10例浆细胞瘤BSAP和CD20全部阴性表达。BSAP与CD20的表达差异无统计学意义。结论。BSAP/Pax-5是一种新的B细胞标记,阳性信号定位于细胞核,抗BSAP抗体在常规外科病理诊断工作中的应用价值有限。     

Expression of survivin and of antigen detected by a novel monoclonal antibody, T332, is associated with outcome of diffuse large B-cell lymphoma and its subtypes

Although diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, it is both clinically and morphologically heterogenous. The present study investigates the significance of survivin and a novel monoclonal antibody (MAb), T332, immunohistochemically for predicting the prognoses of DLBCL and its subtypes classified as germinal center B-cell-like type (GCB) and non-GCB type (NGCB) based on the expression profiles of CD10, bcl-6, and MUM1. A total of 60 cases of DLBCL (GCB, n = 22; NGCB, n = 38) were examined for the expression of survivin and T332 antigen. Survivin(+) DLBCL had a significantly worse prognosis (P = 0.01) than survivin(-) cases, as already reported, while survivin(+) GCB or NGCB tended to have poor prognoses (P = 0.06 and 0.07, respectively). However, T332(+) DLBCL and NGCB had significantly more unfavorable prognoses than T332(-) cases (P = 0.01 and 0.02, respectively) while there was no significant survival difference between the T332(+) and T332(-) groups of GCB (P = 0.11). Interestingly DLBCL coexpressing survivin and T332 (n = 13) had a significantly worse prognosis (P = 0.009) than the remaining single positive and double negative cases (n = 31). In conclusion, survivin and the novel MAb, T332, might be a good predictor of DLBCL and its subtypes.     

ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.     

间变性淋巴瘤激酶阳性的大B细胞淋巴瘤病理形态学及分子遗传学研究

目的 探讨间变性淋巴瘤激酶(ALK)阳性的大B细胞淋巴瘤的临床病理及分子遗传学特点.方法 对3例ALK阳性的大B细胞淋巴瘤进行光镜观察,采用免疫组织化学EliVision法及分子遗传学方法检测,并结合文献进行分析和讨论.结果 3例患者均为成年男性,年龄32～42岁,平均年龄36.3岁,病变累及淋巴结.镜下观察:淋巴结结构破坏,可见淋巴窦侵犯,肿瘤细胞大,呈免疫母细胞样/浆母细胞样形态.免疫组织化学示肿瘤细胞CD45、CD138、上皮细胞膜抗原、ALK阳性,且ALK蛋白染色呈胞质内颗粒状阳性,CD3、CD20、CD79a和CD30均阴性.3例间期荧光原位杂交均检测到ALK基因易位.结论 ALK阳性大B细胞淋巴瘤是弥漫性大B细胞淋巴瘤的少见独立亚型,好发于中年男性,病变部位以淋巴结多见,具有特征性形态学、免疫表型和分子遗传学特点.

Abstract：

Objective To study clinicopathologic and genetic features of anaplastic lymphoma kinase (ALK)-positive large B-cell lymphoma (LBCL). Methods Light microscopy, EliVision immunohistocheimical method and fluorescence in-situ hybridization were used to evaluate three ALK + LBCL cases recently diagnosed accompanied with a literature review. Results All three cases were male adult patients ( mean age = 36.3 years) with nodal involvement by lymphoma. Histologic evaluation revealed a diffuse effacement of the nodal architecture by the infiltration of tumor cells. Sinusoidal infiltration was seen.The neoplastic cells were large and exhibited the immunoblastic/plasmablastic morphology. By immunohistochemistry, all the cases showed a cytoplasmic granular staining of ALK. They were positive for CD45, CD138, and epithelial membrane antigen ( EMA), but were negative for CD3, CD20, CD79a and CD30. Fluorescence in situ hybridization (FISH) demonstrated the presence of ALK gene translocation in all of the cases. Conclusions ALK + LBCL represents a distinct variant of diffuse large B-cell lymphoma,usually involving lymph node of middle-aged men. The tumor has a immunoblastic/plasmablastic morphology along with a distinct immunophenotypic profile and ALK gene rearrangement.     

Analysis of the immunoglobulin heavy chain gene variable region of CD5-positive diffuse large B-cell lymphoma.

To clarify the cell origin of CD5+ diffuse large B-cell lymphoma (DLBCL), we analyzed and compared the variable region of the immunoglobulin heavy chain gene (VH gene) in eight cases of CD5+ DLBCL and 23 cases of other CD5+ B-cell neoplasms; 10 cases of chronic lymphocytic leukemia (CLL), one case of small lymphocytic lymphoma, one case of hairy cell leukemia, and 11 cases of mantle cell lymphoma. CD5+ DLBCL were comprised of two cases of de novo lymphoma of nodal origin, five cases of de novo lymphoma of extranodal origin, and one case of Richter transformation. Whereas all cases of mantle cell lymphoma except one showed a germ line or low mutation frequency of the rearranged VH gene, the rearranged VH genes in both CD5+ CLL and CD5+ DLBCL were heterogeneous. The degree of somatic mutation of CD5+ CLL and CD5+ DLBCL ranged between approximately 0 to 15.0% and 0.7 to 12.9%, respectively. High frequency of expression of the VH4 family in both CD5+ CLL and CD5+ DLBCL was found. Moreover, none of the three cases of CD5+ DLBCL examined exhibited intraclonal diversity. These findings may be common characteristics of the rearranged VH gene of CD5+ CLL and CD5+ DLBCL and suggested that the cell origin of CD5+ DLBCL was the same as that of CD5+ CLL.     

Analysis of the immunoglobulin heavy chain gene of secondary diffuse large B-cell lymphoma that subsequently developed in four cases with B-cell chronic lymphocytic leukemia or lymphoplasmacytoid lymphoma (Richter syndrome)

The immunoglobulin heavy chain gene (IgH gene) was analysed in four cases of B-cell Richter syndrome, in order to determine whether a secondary diffuse large B-cell lymphoma (DLBCL) could arise from the same clone as the initial B-cell chronic lymphocytic leukemia (B-CLL) and lymphoplasmacytoid lymphoma (LPL) or be a de novo event, and whether secondary DLBCL shows an intraclonal microheterogeneity. Both the initial B-CLL and secondary DLBCL in two cases expressed CD5 antigen. Both samples of the initial B-CLL or LPL and the secondary DLBCL in three cases were examined for comparison. The polymerase chain reaction-amplified IgH gene of secondary DLBCL in two cases (CD5+ case and CD5- case) were different from those of the initial B-CLL, revealing a new malignant clone. The other case (CD5-) showed that secondary DLBCL had a sequence identical to the initial LPL, indicating the same clonal origin. The variable region of the IgH gene of secondary DLBCL (CD5+ two cases and CD5- two cases) exhibited a 0.5-9.0% somatic mutation range and no intraclonal microheterogeneity.     

De novo CD5 positive diffuse large B-cell lymphomas with bone marrow involvement in Korean

In CD5 positive (CD5+) mature B-cell lymphomas, newly recognized CD5+ diffuse large B-cell lymphoma (DLBCL) has been characterized by aggressive features. We studied twenty-five cases with CD5+ lymphomas involving bone marrow. Eleven cases were diagnosed as chronic lymphocytic leukemia, six cases were diagnosed as mantle cell lymphoma (MCL), and three cases with morphologic characteristics of MCL and without both the cyclin D1 expression and IGH/CCND1 rearrangement were unclassifiable. The remaining five cases, showing large to medium-sized lymphoid cells with prominent nucleoli and a moderate amount of cytoplasm, were diagnosed as DLBCL. Five DLBCL cases were positive for CD5, CD20, surface immunoglobulin, but negative for CD23. Patients with CD5+ DLBCL showed a high age of onset (median, 68 yr) and two patients expired one month after the diagnosis. Since CD5+ DLBCL forms a distinct subgroup of DLBCL, a study of CD5 expression in DLBCL would be helpful to predict prognosis and to determine future therapeutic strategy. To the best of our knowledge, this is the first report on de novo CD5+ DLBCL in Koreans.     

Primary cutaneous large B-cell lymphoma of the leg: histogenetic analysis of a controversial clinicopathologic entity

This study analyzes the pathologic and molecular features of 5 cases of primary cutaneous large B-cell lymphoma of the leg (PCLBCL-leg), recently included in the European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphoma. PCLBCL-leg accounts for 5% to 10% of all primary cutaneous B-cell lymphoma (PCBCL), usually affects elderly patients and carries a worse prognosis than other forms of PCBCL. It has been proposed that the malignant cells of PCLBCL-leg originate from germinal center (GC)-related cells, but their effective normal counterpart is unclear, and the rationale behind the inclusion of this lymphoma as a separate entity is based on its prognosis rather than on its proved histogenesis. All of our cases of PCLBCL-leg morphologically resembled diffuse large B-cell lymphoma (DLBCL), but to better define their histogenesis, we also analyzed various phenotypic and genotypic markers, including mutations of the Ig and of BCL-6 genes, as well as expression of the bcl-6, MUM1, and CD138/syndecan-1 proteins. Immunohistochemically, all of our cases stained for the L-26/CD20cy and CD79a antigens and expressed the bcl-2, bcl-6, and MUM-1 proteins but were negative for both the CD10/CALLA and CD138 antigens. With respect to molecular analysis, the lymphoma population of all PCLBCL-leg carried hypermutation of Ig genes, and all but 1 case also harbored mutations of the BCL-6 gene. Our results indicate that PCLBCL-leg are similar both under the morphofunctional and molecular profiles to most DLBCL of other sites. Thus, caution seems justified before definitely considering PCLBCL of the leg as a distinct entity.     

bcl-10蛋白异常表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤的诊断价值

目的探讨bcl-10蛋白表达对黏膜相关淋巴组织结外边缘区B细胞淋巴瘤（MALT淋巴瘤）的诊断价值。方法收集140例不同部位的MALT淋巴瘤,包括胃38例、眼眶35例、肠16例、皮肤15例、涎腺15例、肺14例、甲状腺3例、其他部位4例。对照：10例扁桃体反应性滤泡增生（RFH）、5例眼眶的淋巴组织增生和143例非MALT淋巴瘤、不同类型的非霍奇金淋巴瘤（NHL）,包括20例NK／T细胞淋巴瘤、20例滤泡性淋巴瘤（FL）、20例间变性大细胞淋巴瘤（ALCL）、20例淋巴结内弥漫大B细胞淋巴瘤（DLBCL）、10例原发胃DLBCL、13例淋巴结边缘区淋巴瘤（NMZL）、12例套细胞淋巴瘤（MCL）、11例脾脏边缘区淋巴瘤（SMZL）、6例血管免疫母细胞性T细胞淋巴瘤（AITL）、6例外周T细胞淋巴瘤（PTCL）、3例B．小淋巴细胞淋巴瘤（B-SLL）、1例淋巴浆细胞性淋巴瘤（LPL）和1例浆细胞瘤。免疫组织化学EnVision法检测bcl-10蛋白;免疫组织化学双标记法检测CD20与bcl-10的共表达。结果在扁桃体RFH中,bel-10蛋白呈中等强度表达于生发中心B细胞质中,套细胞不表达,边缘区细胞和副皮质区T细胞呈弱表达。在眼眶淋巴组织增生中,2例bel-10阴性,3例主要呈淋巴滤泡生发中心B细胞质阳性,与扁桃体RFH的表达类似。在非MALT淋巴瘤的其他类型NHL中,除3例（3／10）原发胃DLBCL呈胞核阳性外,其余均未见胞核表达;在不同NHL中的胞质阳性分别为：结内（12／20）和胃（7／10）DLBCL、FL和ALCL（16／20）、PTCL（5／6）、AILT（6／6）、NMZL（13／13）、SMZL（11／11）、B-SLL（3／3）和浆细胞瘤（1／1）,11例MCL呈胞质可疑阳性,20例NK／T细胞淋巴瘤和1例LPL阴性;在部分淋巴瘤中可见肿瘤性细胞表达而反应性小淋巴细胞不表达：MALT淋巴瘤之bcl-10的总表达率为92．1％（129／140）,其中54．3％（76／140）胞质阳性,37．9％（53／140）胞核阳性;但不同部位之胞核阳性率有所不同。在MALT淋巴瘤中,bcl-10蛋白核强表达最常见于眼眶（25．7％,9／35）;除出现异常bcl-10胞核表达外,约20％有反应性滤泡的病例呈生发中心失表达。双标记显示bcl-10阳性细胞为CD20阳性细胞,但CD20阳性细胞多于bcl-10阳性细胞。结论（1）淋巴细胞增生性病变中bcl-10蛋白普遍表达,细胞质表达可出现在多数NHL和反应性增生中,但在淋巴瘤中呈肿瘤细胞表达而反应性细胞不表达,提示bcl-10异常可能与部分淋巴瘤的形成有关;（2）细胞核内bcl-10异常表达主要见于MALT淋巴瘤;眼眶、肺等部位的胞核强阳性和生发中心阴性的特殊模式,对MALT淋巴瘤的诊断及其与反应性病变的鉴别诊断有一定辅助意义。