Diminished expression of CD19 in B-cell lymphomas

BACKGROUND: CD19 is expressed on most B-cell lymphomas; however, the frequency and types of B-cell lymphomas with low-level expression of CD19 are not well characterized. METHODS: We reviewed flow cytometric histograms specifically for decreased CD19 expression on 349 cases analyzed by the Flow Cytometry Laboratory at University Hospitals of Cleveland (Cleveland, Ohio). Results of flow cytometry were correlated with the morphologic diagnosis. RESULTS: Of the cases reviewed, 125 (36%) showed a visible decrease in CD19 expression compared with normal B lymphocytes. Decreased CD19 expression was noted in 79% of follicular lymphomas (27 of 34), 36% of small lymphocytic lymphomas/chronic lymphocytic leukemias (82 of 228), 31% of mantle cell lymphomas (4 of 13), 24% of diffuse large B-cell lymphomas (8 of 33), and 13% of marginal zone B-cell lymphomas/lymphoplasmacytoid lymphomas (4 of 30) and was not observed in any Burkitt lymphoma (0 of 5) or hairy cell leukemia (0 of 6). Decreased CD19 expression was significantly more frequent in follicular lymphomas than in other lymphoma subtypes (P < 0.001). No significant difference was observed in the frequency of decreased CD19 expression based on histologic grade of follicular lymphoma. CONCLUSIONS: Diminished expression of CD19 expression occurs frequently in B-cell lymphomas, in particular follicular lymphoma, and may be helpful in identifying B-cell lymphoma cells in complex cell mixtures such as bone marrow specimens.     

口咽部B细胞来源非霍奇金淋巴瘤的CT诊断

目的：分析口咽部B细胞来源非霍奇金淋巴瘤（NHL）的CT表现、特征,初步探讨不同病理类型B细胞来源NHL的CT表现特点,为临床诊断和治疗提供更为准确的信息。方法：对18例经病理证实的口咽部B细胞来源非霍奇金淋巴瘤的CT表现进行回顾性分析。结果：18例中,弥漫大B细胞淋巴瘤13例,占72．2％（13／18）,滤泡性淋巴瘤3例,占16．7％（3／18）,套细胞淋巴瘤1例,占5．6％（1／18）,结外边缘区淋巴瘤（MALT淋巴瘤）1例,占5．6％（1／18）。病变分布为：扁桃体NHL9例（弥漫大B细胞淋巴瘤8例、套细胞淋巴瘤1例）;舌根8例（弥漫大B细胞淋巴瘤5例、滤泡性淋巴瘤3例）;软腭1例,为结外边缘区淋巴瘤（MALT淋巴瘤）。18例病变均表现为肿块型。同时有淋巴结受累者12例（66．7％）,其中双侧受累者3例。结论：口咽B细胞来源NHL多发生于扁桃体及舌根。病理类型以弥漫大B细胞淋巴瘤为主,主要表现为肿块。CT对于B细胞来源NHL的鉴别诊断和病变范围的判断具有重要作用。     

肠道弥漫性大B细胞淋巴瘤患者的临床病理特征分析

目的:探讨肠道弥漫性大B细胞淋巴瘤(DLBCL)的临床病理特征.方法:回顾性分析2007年1月至2014年10月在山东第一医科大学附属济南人民医院确诊的136例DLBCL患者的临床特点、病理形态、免疫表型及EBER原位杂交等资料.共获取136例肿瘤样本,根据肿瘤部位分为十二指肠23例,回盲部63例,其他小肠29例,直肠...     

原发性甲状腺淋巴瘤的超声表现及病理特征

目的探讨原发甲状腺淋巴瘤(PTL)的超声表现及病理特征。方法回顾性分析28例经穿刺或手术病理证实的PTL患者的声像图表现,对病变的超声分型、形态特点、边界、回声及周围组织侵犯情况进行分析,并分析上述超声表现与其病理特征的关系。结果 28例PTL病例均为非霍奇金淋巴瘤,其中弥漫大B细胞淋巴瘤19例,结外边缘带B细胞淋巴瘤/低度恶性黏膜相关组织淋巴瘤6例,结外边缘带B细胞淋巴瘤伴大细胞转化3例。7例合并桥本甲状腺炎。超声示甲状腺弥漫性肿大,累及单侧或双侧,多呈不均匀极低回声,可有条索状强回声,后方回声增强,可伴数目不等的低回声结节,边界欠清,易侵犯颈部淋巴结,还可累及周围软组织、压迫气管。结论充分认识不同病理类型的PTL超声表现特点、结合病史及临床资料,有助于提高PTL的超声诊断准确率。     

原发扁桃体淋巴瘤的类型构成研究:213例会诊病例分析

目的探讨会诊病例中原发扁桃体淋巴瘤的病理类型、构成比率以及疑难会诊病例病种。方法收集北京友谊医院2005年1月至2013年11月213例原发扁桃体淋巴瘤的会诊病例,对其临床资料、病理组织学及免疫组织化学标记结果进行回顾性分析,按世界卫生组织(WHO,2008年版)分类标准进行病理诊断及分类,并与国内外原发扁桃体的淋巴瘤进行对比分析。结果 213例原发扁桃体淋巴瘤中,非霍奇金淋巴瘤(NHL)212例(99.5%),霍奇金淋巴瘤(HL)1例(0.5%)。NHL中B细胞来源183例(85.9%),T细胞或NK细胞来源29例(13.6%)。NHL中,检出率构成比居前5位的分别为弥漫大B细胞淋巴瘤-非特殊类型(DLBCL-NOS)138例(64.8%),滤泡性淋巴瘤(FL)12例(5.6%),黏膜相关淋巴组织边缘区B细胞淋巴瘤(MALT)12例(5.6%),结外NK/T细胞淋巴瘤11例(5.2%),外周T细胞淋巴瘤-非特殊类型(PTCL-NOS)9例(4.2%)。本组病例中HL仅1例(0.5%),为经典HL-混合细胞型。病变部位:左侧93例(43.7%),右侧96例(45.1%),双侧24例(11.2%)。结论 213例原发扁桃体淋巴瘤的会诊病例中,包括209例已明确分型和4例未能明确分型病例。已明确分型的病例共12种不同的病理类型。其中,NHL发病远多于HL,B细胞淋巴瘤中以DLBCL-NOS最多见,T细胞或NK细胞淋巴瘤中以结外NK/T细胞淋巴瘤最多见,HL罕见。     

T(11;18)及核bcl-10蛋白在胃肠MALT淋巴瘤中的表达

为了探讨t(11；18)(q21；q21)染色体易位及核bcl-10蛋白在胃肠粘膜相关淋巴组织淋巴瘤(MALT lymphoma)中的表达，用酸性酚氯仿法从石蜡组织中提取RNA；逆转录合成cDNA后用聚合酶链反应(PCR)扩增API2-MALT1融合基因；用免疫组织化学法检测石蜡切片中bcl—10蛋白的表达。结果表明：42例MALT淋巴瘤中，t(11；18)(q21；q21)染色体易位在低度恶性MALT淋巴瘤中的表达为14％，在伴高恶转化型MALT淋巴瘤中的表达为46％，在40例弥漫大B细胞淋巴瘤(diffuse 1arge B cell lymphoma，DLBCL)对照组中没有表达；43例MALT淋巴瘤中bcl-10蛋白在低度恶性MALT淋巴瘤的核表达为61％，在伴高恶转化型MALT淋巴瘤中的核表达为69％。结论：t(11；18)易位可能与高度进展MALT淋巴瘤有一定相关性，但与DLBCL无关;bcl-10蛋白的核表达在恶性程度不同的两组MALT淋巴瘤中无显著性差异，其原因有待进一步研究。     

155例非霍奇金淋巴瘤患者细胞遗传学分析

目的 了解非霍奇金淋巴瘤（NHL）患者染色体异常与WHO病理组织分型之间的关系，并与国外NHL染色体异常类型进行比较。方法 采用常规染色体G带分析和荧光原位杂交（FISH）方法对155例NHL患者的淋巴结组织进行细胞和分子遗传学研究。结果 155例NHL患者中常见的病理类型是弥漫大B细胞淋巴瘤（DLBCL）（59例，38．1％）、滤泡性淋巴瘤（27例，17．4％）、B小淋巴细胞淋巴瘤（16例，10．3％）、非特指周同T细胞淋巴瘤（13例，8．4％）、血管免疫母细胞性T细胞淋巴瘤（11例，7．1％）。155例NHL患者中染色体异常为119例，占76．8％。滤泡性淋巴瘤、B小淋巴细胞淋巴瘤、DLBCL、间变性大细胞淋巴瘤和前体T淋巴母细胞淋巴瘤染色体异常率较高，分圳为96．3％、87．5％、86．4％、83．3％、83．3％。DLBCL中复杂核型占86．3％，染色体结构异常累及最多的是3，6，14，1号染色体，41．2％为3q27异常，43．1％的病例有1号染色体异常。6q21、6q23和6q25异常占23．5％。DLBCL中典型t（14；18）的病例只有2例，明湿低于国外报道。用FISH方法检测DLBCL中IgH重排阳性率为40．1％。16例B小淋巴细胞淋巴瘤均未发现13q14缺失，只发现2例有13q10异常。11例血管免疫母细胞性T细胞淋巴瘤中只有3例核型异常。结论 我国淋巴瘤的病理类型分布与欧美国家有明显不同。尽管DLBCL染色体异常类型基本与国外相似，但t（14；18）较少见。与国外报道相比，B小淋巴细胞淋巴瘤和血管免疫母细胞性T细胞淋巴瘤染色体异常率较低，染色体异常类型也有差异。     

Clinicopathological features of malignant lymphoma in Japan: the Miyagi Study

The Miyagi Study is an epidemiological study of malignant lymphoma, including immunological and genetic analyses, constructed by a population-based registration system covering Miyagi prefecture, Japan. A total of 1,552 newly diagnosed cases in Miyagi between 2002 and 2008 were enrolled in this study; 75% were B-cell lymphomas, 19% were T-cell and natural killer-cell (T/NK-cell) lymphomas, and 5% were Hodgkin's lymphomas. The most frequent subtype of B-cell lymphoma is diffuse large B-cell lymphoma, followed by follicular lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (51%, 24% and 8%, respectively). Thus, follicular lymphoma accounts for 18.2% of newly diagnosed cases in Miyagi; unexpectedly, its frequency is similar to that reported in Western countries. The common subtypes of T/NK-cell lymphoma are peripheral T-cell lymphoma, angioimmunoblastic T-cell lymphoma, and adult T-cell leukemia/lymphoma (30%, 15% and 14%, respectively). Most of the data are similar to those reported in Asian countries, except for follicular lymphoma. We also analyzed the CD20 expression in B-cell lymphomas by flow cytometry for the cell membrane expression and by immunohistochemistry for the cytoplasmic expression. The cell membrane expression of CD20 protein may determine the susceptibility of B-cell lymphomas to anti-CD20 antibody therapy. The lack of CD20 expression was confirmed by both methods in 4 cases of 585 newly diagnosed cases (0.7%) and in 5 of 67 recurrent cases (7.5%). Furthermore, 23 cases (6.5%) showed the discrepancy of CD20 expression between both methods. The Miyagi Study has revealed the latest epidemiological features of malignant lymphoma in Japan.     

睾丸原发性恶性淋巴瘤6例报道并文献复习

目的 探讨原发性睾丸恶性淋巴瘤的临床及病理形态特征与预后的关系。方法 对6例原发性睾丸恶性淋巴瘤进行组织形态学和免疫组化染色观察，依据WHO新分类进行分型，并结合文献对其临床病理特点及随访资料进行分析。结果 患者年龄46～82岁。病程2周～1年，除2例伴有疼痛外均为单侧睾丸无痛性肿大。6例均为弥漫性大B细胞性淋巴瘤(DLBCL)，其中5例为中心母细胞性，1例为中心母细胞-中心细胞混合性。瘤细胞LCA、CD45RA和CD20均( )。随访4例，2例分别于首诊后5、10个月出现鼻咽部、胸膜累及；2例分别为13和18个月无瘤生存。结论睾丸原发性淋巴瘤以弥漫性大B细胞性非霍奇金淋巴瘤为主。老年人多见，预后与临床分期及组织学分型关系密切。     

滤泡树突状细胞表达模式变化 在淋巴瘤病理鉴别诊断中的应用价值

目的 探讨滤泡树突状细胞(follicular dendritic cell,FDC)网在各种类型淋巴瘤中的形态变化模式及其在鉴别诊断中的临床应用价值。方法 采用免疫组化方法对56例各种类型的淋巴瘤进行CD21免疫组化染色,观察FDC网的形态变化模式。其中包括弥漫大B细胞淋巴瘤8例、伯基特淋巴瘤2例、小淋巴细胞性淋巴瘤6例、浆细胞瘤6例、MALT淋巴瘤3例、外周T细胞淋巴瘤6例、间变性大细胞淋巴瘤5例、NK/T细胞淋巴瘤8例、滤泡性淋巴瘤4例、套细胞淋巴瘤3例、AITL 3例、FDC肉瘤2例。结果 FDC网在各种类型淋巴瘤中的形态变化可归为4种模式:①破坏消减型:绝大部分淋巴瘤FDC网完全或部分破坏,包括弥漫大B细胞淋巴瘤、伯基特淋巴瘤、小淋巴细胞性淋巴瘤、浆细胞瘤、外周T细胞淋巴瘤、间变性大细胞淋巴瘤、NK/T细胞淋巴瘤; ②存在型:FDC网存在,甚至有数量增多,包括MALT淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤; ③增生紊乱型:FDC网增多、变形、紊乱,如AITL; ④全表达型:FDC网在肿瘤组织中每个细胞表达,如FDC肉瘤。结论 FDC在各种类型淋巴瘤中存在不同的形态变化模式,在淋巴瘤鉴别诊断中具有重要的临床应用价值。     

Non-mediastinal grey zone lymphomas and report from the workshop

Grey zone lymphomas represent borderline lesions between classical Hodgkin lymphoma (cHL) and other morphologically and immunophenotypically related diseases and entities like nodular lymphocyte predominant HL, T-cell rich B-cell lymphoma, ALK-negative anaplastic large cell lymphoma (ALCL), diffuse large B cell lymphoma (DLBCL) anaplastic variant and primary mediastinal LBCL. The sharp definition of morphological, immunophenotypical and molecular features of the "text-book cases" of each disease and the comparison with grey zone cases has reduced most of the latter cases. Two reports in this workshop dealt with the problematic non-mediastinal grey zone lymphomas, one with a cHL of T cell-type presenting in the skin as a ALK-negative ALCL and the other with the grey zone between cHL of B-cell type and ALK-negative ALCL.     

Peripheral T-cell lymphomas: histologic, immunohistologic, and clinical characterization

A review of 40 cases of peripheral T-cell lymphoma identified at our institution between March 1983 and December 1985 revealed a clinically, histologically, and immunologically diverse group of neoplasms that were difficult to classify by conventional histomorphologic criteria for non-Hodgkin's lymphomas. These lymphomas were frequently extranodal at the time of initial manifestation (52%), and their clinical aggressiveness correlated with three major histologic categories--small lymphocytic, diffuse mixed, and large cell. Of the 40 lymphomas, 18 exhibited distinctive histologic features that allowed assignment of these cases into one of four subgroups: (1) angioimmunoblastic lymphadenopathy, (2) lymphomatoid granulomatosis, (3) Hodgkin's-like disease, and (4) Lennert's lymphoma (lymphoepithelioid lymphoma). Study of all our cases that fulfilled the morphologic criteria for lymphomatoid granulomatosis or angioimmunoblastic lymphadenopathy by using immunologic methods for identification of B-cell and T-cell antigens has shown these neoplasms to be peripheral T-cell lymphomas. Therefore, we now consider these earlier proposed entities to be distinct histologic variants of peripheral T-cell lymphoma.     

Benign, atypical and malignant lymphoproliferative disorders in rheumatoid arthritis patients

Lymphadenopathy, which may be associated with systemic symptoms, is frequently associated with rheumatoid arthritis (RA). Reactive non-neoplastic tissue comprises the majority of the lymph node lesions. However, several cohort studies have demonstrated that RA has an increased risk of non-Hodgkin's lymphomas (NHLs). Since the early 1990s, an atypical or malignant lymphoproliferative disorders (LPD) in patients immunosupressed with methtorexate (MTX) therapy for RA has been emphasized, namely MTX-associated LPDs. Epstein-Barr virus (EBV) has received attention in connection with the etiology of RA. The present review describes the clinicopathologic and immunohistochemical findings of reactive, atypical and malignant LPDs associated with RA along with the presence or absence of EBV in LPDs using the in situ hybridization (ISH) method. The majority of reactive lymph node lesions exhibit reactive follicular hyperplasia with interfollicular polyclonal plasmacytosis. Atypical LPDs rarely appears in RA patients. However, these cases occasionally pose difficult problems in the differential diagnosis from malignant lymphomas associated with RA or atypical and malignant LPDs showing RA-like clinicopathological findings. Clinicopathologically, three types of atypical LPDs have delineated, i.e. (i) resembling multicentric Castleman's disease (MCD); (ii) atypical paracortical hyperplasia with lymphoid follicles (APHLF) and; (iii) atypical lymphoplasmacytic immunoblastic proliferation. Malignant lymphoma associated with RA is characterized by; (i) predominance of elderly cases; (ii) usually female predominance, reflecting the sex ratio of RA; (iii) longstanding history of RA; (iv) relatively frequent advanced stage of disease; (v) majority of the patients had the B-cell phenotype; and (vi) an increased frequency of diffuse large B-cell lymphoma (DLBCL) in RA. It is unlikely that EBV is the causative agent of either reactive or atypical LPD. Among malignant lymphomas, EBV-associated lymphoma comprised only a small fraction of all NHLs in the general RA patient population.     

Sequential bcl-2 and c-myc oncogene rearrangements associated with the clinical transformation of non-Hodgkin''s lymphoma.

We report a case of untreated non-Hodgkin's lymphoma with histologic progression over 1 yr from a low-grade, small cleaved follicular center cell lymphoma to a high-grade, small noncleaved follicular center cell lymphoma. Both lymphomas had identical immunoglobulin (Ig) heavy-chain joining gene (JH), kappa light-chain joining gene, and bcl-2 gene rearrangements, indicating the clonal identity of the two tumors. The Ig heavy chain locus on one chromosome 14 was involved in an initial t(14; 18) translocation as shown by comigrating JH and bcl-2 rearrangements. However, the oncogene c-myc was in the germline configuration in the initial lymphoma but had one allele rearranged near the 3' end of exon I in the high-grade tumor; DNA sequence analysis was consistent with a chromosomal breakpoint at that site. The presence of the c-myc rearrangement in the high-grade tumor suggest a role for c-myc in the clonal evolution of the low-grade tumor into a more aggressive lymphoma. The coexistence of both bcl-2 gene and c-myc oncogene rearrangements in the same tumor is unusual, with only a few cases reported. Furthermore, this case is unique in the direct demonstration of the histologic and clinical progression of a human lymphoma associated with the sequential rearrangement of the bcl-2 gene and the c-myc oncogene.     

370例恶性淋巴瘤的WHO(1997)分类

目的：研究恶性淋巴瘤的临床、病理特点。方法：根据WHO(1997)分类标准对370例恶性淋巴瘤患进行临床、病理及免疫表型分析。结果：非霍奇金淋巴瘤(NHL)359例，占97．03％；霍奇金淋巴瘤(HL)11例，占2．97％。NHL中，B细胞淋巴瘤246例，占68．52％；T细胞淋巴瘤108例，占30．08％；组织细胞性淋巴瘤和滤泡树突状细胞肉瘤各1例，NK细胞性淋巴瘤3例。结外淋巴瘤(196例，占54．6％)多于结内淋巴瘤(163例，占45．4％)。NHL中发病率较高的淋巴瘤类型依次为：弥漫大B细胞淋巴瘤(173例，占48．2％)，外周非特殊T细胞淋巴瘤(54例，占15．0％)，黏膜相关淋巴组织细胞淋巴瘤(31例，占8．6％)，NK／T细胞淋巴瘤(25例，占7.0％)，滤泡性淋巴瘤(21例，占5．8％)，间变性T细胞淋巴瘤(12例，占3．3％)。结论：应用WHO(1997)分类对恶性淋巴瘤进行分析研究，具有重要的临床意义。     

Bcl-2与弥漫大B细胞淋巴瘤免疫学亚型及预后的关系

目的 从蛋白水平和基因水平研究Bcl-2在弥漫大B细胞淋巴瘤(DLBCL)的表达,分析其与DLBCL不同业型和预后的相关关系.方法应用免疫组化技术(Envision法)对73例DLBCL患者进行免疫学分型,标记抗体包括CD3、CD10、CD20、Bcl-6、Bcl-2、MUM-1.其中57例应用荧光原位杂交(FISH)技术检测t(14;18)和bcl-2基因的异常.结果肿瘤细胞CD10、Bcl-6、MUM-1、Bcl-2的阳性率分别为15.1%、38.4%、71.2%、79.2%,生发中心B细胞型(GCB型)16例(21.9%),非生发中心B细胞型(non-GCB型)57例(78.1%).FISH检测的57例中t(14;18)阳性16例(28.1%),其中GCB型5例(31.2%),non-GCB型11例(68.2%).Bcl-2蛋白表达与免疫学亚型存在相关性(P=0.035),与生存时间之间无相关性(P=0.253).t(14;18)阳性组与阴性组相比,生存时间差异有统计学意义(P=0.022),而t(14;18)与免疫学亚型无相关性(P=0.340).Bcl-2蛋白表达与t(14;18)无相关性(P=0.712).结论 Bcl-2蛋白表达町作为与DLBCL免疫学亚型相关的预后标志物,Bcl-2蛋白表达阳性的GCB型患者预后较差;t(14;18)可作为DLBCL独立的预后因素,阳性者预后较差.Bcl-2蛋白表达与t(14;18)无相关性.靶向治疗患者是否应检测t(14;18)尚待进一步探讨.     

Low-grade B-Cell lymphomas with plasmacytic differentiation lack PAX5 gene rearrangements

The chromosomal translocation t(9;14)(p13;q32) has been reported in association with lymphoplasmacytic lymphoma (LPL). Although this translocation involving the paired homeobox-5 (PAX5) gene at chromosome band 9p13 and the immunoglobulin heavy chain (IgH) gene at 14q32 has been described in approximately 50% of LPL cases, the actual number of cases studied is quite small. Many of the initial cases associated with t(9;14)(p13;q32) were actually low-grade B-cell lymphomas with plasmacytic differentiation other than LPL. Thus, we analyzed a series of low-grade B-cell lymphomas for PAX5 gene rearrangements. We searched records from the Department of Pathology, Stanford University Medical Center for low-grade B-cell lymphomas, with an emphasis on plasmacytic differentiation, that had available paraffin blocks or frozen tissue. We identified 37 cases, including 13 LPL, 18 marginal zone lymphomas (nodal, extranodal, splenic, and alpha-heavy chain disease), and 6 small lymphocytic lymphomas. A novel dual-color break-apart bacterial artificial chromosome probe was designed to flank the PAX5 gene, spanning previously described PAX5 breakpoints, and samples were analyzed by interphase fluorescence in situ hybridization. All cases failed to demonstrate a PAX5 translocation, indicating that t(9;14)(p13;q32) and other PAX5 translocations are uncommon events in low-grade B-cell lymphomas with plasmacytic differentiation. This study also confirms recent reports that found an absence of PAX5 rearrangements in LPL, suggesting the reassessment of PAX5 rearrangements in LPL.     

Concurrent lung adenocarcinoma and bladder diffuse large B-cell lymphoma: a case report and literature review

Lung adenocarcinoma is one of the most common solid tumors, and diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of adult non-Hodgkin’s lymphoma. Although extra-nodular lesions are frequently observed in patients with DLBCL, urinary bladder involvement is rare. We report the case of a 77-year-old woman with lung adenocarcinoma who was diagnosed with a second primary bladder DLBCL, 9 months after treatment with molecular targeted drugs. Simultaneous therapies for her lymphoma with lenalidomide and rituximab and a tyrosine kinase inhibitor therapy for her lung cancer were both effective. This result was consistent with previous reports suggesting that patients unable to tolerate intensive chemotherapy could benefit from targeted therapies. Current research into the use of lenalidomide for the treatment of lymphomas and solid tumors is promising in terms of exploring immunotherapy as an alternative option for patients with concurrent solid tumors and lymphomas who have poor tolerance to radiotherapy and chemotherapy.     

Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas

To investigate the possible relatedness of the subpopulations that make up so-called biclonal lymphomas, we examined five bigenotypic and biphenotypic follicular lymphomas using DNA probes specific for the t(14;18) chromosomal translocation, which is a characteristic feature of these neoplasms. On Southern blot analysis, both subpopulations from four of five lymphomas contained comigrating t(14;18) DNA rearrangements, confirming the single cell origins for these neoplasms. No comigrating t(14;18) DNA rearrangements were observed in the fifth lymphoma, but nucleotide sequence analysis of cloned, breakpoint DNA showed identical t(14;18) crossovers in the two subpopulations. The migration differences of both the Ig and chromosome 18 DNA rearrangements were shown to result from somatically acquired mutations of the Ig genes from the fifth lymphoma. These studies indicate that Ig gene rearrangements and idiotope expression are not consistently stable clonal markers since they are subject to variability as a result of somatic mutation. Although translocated chromosome 18 DNA rearrangements are more reliable, they may also vary among cells of some tumors since somatic mutation can affect, as well, DNA of translocated alleles in follicular lymphomas.