脾脏微结节性富于T细胞/组织细胞的B细胞淋巴瘤免疫表型及基因重排分析

目的探讨脾脏微结节性富于T细胞／组织细胞的B细胞淋巴瘤病理学特征。方法应用免疫组化、基因重排及激光捕获显微切割（LCM）等方法进行研究,并复习相关文献。结果光镜下见病变呈结节状,以大量增生的小淋巴细胞和组织细胞为主,其间可见散在分布的大细胞。免疫组化染色示大细胞表达CD20、CD30、EMA。背景细胞中小淋巴细胞表达CD3和CD20,但以CD3为主,组织细胞CD68阳性。免疫球蛋白K链呈阳性重排,LCM进一步研究发现阳性重排主要来自CD20阳性的小B淋巴细胞。结论脾脏微结节性富于T细胞／组织细胞的B细胞淋巴瘤中的大细胞伴间变大细胞淋巴瘤样分化,与文献报道的弥漫性大B细胞淋巴瘤不同。     

富于T细胞的B细胞淋巴瘤一例

患者男，６９岁，发现左腹股沟无痛性肿块２个月，不伴发热，腹痛于１９９８年８月就诊。体检：左腹股沟内侧可触及一直径３ｃｍ的肿块，质偏硬，活动尚可，无压痛，周围无红肿，全身其他部位未见肿大淋巴结或包块，胸腹部Ｂ超、ＣＴ示肝、胆、脾及双肾未见占位病变，腹膜后未见肿大淋巴结；前列腺Ｂ超无异常。临床诊断：淋巴瘤？行左腹股沟淋巴结活检术，术中见肿块直径２．５ｃｍ，包膜完整，色略红，小部分与周围组织轻度粘连。病理检查：灰红色椭圆形肿物一个，大小３．０ｃｍ×３．０ｃｍ×２．５ｃｍ，包膜完整，局部较粗糙，切面灰白…     

富于T细胞/组织细胞的大B细胞淋巴瘤

1.病例简介:患者男,65岁。左侧颌下淋巴结肿大1个月,于2004年8月2日入院行肿物切除术。术中所见:肿物大小约为3.5cm×2.5cm×2.0cm,灰白色,质硬,与周围组织粘连、固定,活动度较差。患者曾于9年前发现右颌下淋巴结肿大而行肿物切除术,术后病理诊断为非霍奇金淋巴瘤,B免疫母细胞型,高度恶性。在随后半年内应用CHOP方案化疗4疗程,放疗25次(总放射计量5000cGy),肿物消失。3年前右颌下淋巴瘤复发,予以CHOP方案化疗6疗程,肿物消失。1年前右颌下淋巴瘤再次复发,化疗效果不明显。2.病理检查:结节状肿物一个,大小3.5cm×2.5cm×2.0cm,切面灰粉、…     

富于T细胞/组织细胞的B细胞淋巴瘤的诊断

目的：探讨富于T细胞／组织细胞B细胞淋巴瘤（TCRBCL）的诊断。方法：用S－P石蜡免疫组化法检测22例依据形态学诊断的霍奇金淋巴瘤细胞和背景细胞的免疫表型。结果：4／22例是TCRBCL,3例富于T小淋巴细胞,1例富含组织细胞;瘤细胞3例呈中心母细胞样和免疫母细胞样。1例呈腔隙型细胞样,弥漫散在分布。免疫组化瘤细胞呈CD20（＋）、CD15（－）、CD30（－）、CD21（－）、vimentin(-)。背景细胞CD45RO（＋）／CD68（＋）细胞占绝对优势,为浸润细胞的70％－90％;CD20（＋）细胞散在,CD57（＋）稀少。16例为经典型霍奇金淋巴瘤（CHL）,瘤细胞为CD15（＋）（75％）、CD30（＋）（100％）、vimentin( )(19%)、CD21（－）、CD20（－）及CD45（－）,背景细胞CD45RO（＋）和CD20（＋）数量基本相等,CD57（＋）较少。1例为结节性淋巴细胞为主型霍奇金淋巴瘤（NLPHL）,瘤细胞呈CD20（＋）、CD45（＋）、CD30（－）、CD15（－）,而背景细胞中CD57（＋）较多。结论：石蜡免疫组化在TCRBCL诊断中起重要作用,而且也应用于CHL、NLPHL及TCRBCL间鉴别诊断。     

富于T细胞的大B细胞淋巴瘤1例

患者男性，７１岁，右颈部无痛性包块渐增大２年。体检：右颈部触及淋巴结２个，不活动，质地较硬，手术切除送病检。术中肿块质地脆，易碎，送检时淋巴结不完整，呈碎块状。病理检查淋巴结结构已破坏，可见两种细胞：①大细胞，胞浆丰富，嗜酸性，核大，染色质粗，靠近核...     

颈部淋巴结T细胞性淋巴瘤伴噬血细胞性综合征1例

患者男性,63岁,不规则发热月余伴畏寒,偶有轻咳,盗汗,咳少量黏性白痰。外院胸片示慢性支气管炎,经治疗（用药不详）症状无好转。查体：急性病容,发病以来体重下降5kg,T39.2℃,皮肤巩膜无黄染,全身浅表淋巴结肿大,部分粘连,质韧,无压痛,活动欠佳,     

结节性淋巴细胞为主型霍奇金淋巴瘤伴少见免疫结构变异1例并文献复习

目的观察结节性淋巴细胞为主型霍奇金淋巴瘤(nodular lymphocyte-predominant Hodgkin lymphoma, NLPHL)伴少见免疫结构变异即富于T细胞/组织细胞大B细胞淋巴瘤(T-cell/histiocyte-rich large B cell lymphoma, THRLBL)样转化的NLPHL的临床病理学特征,以提高对NLPHL免疫结构变异的认识、诊断及鉴别诊断。方法回顾性分析1例伴有THRLBL样转化的NLPHL的临床病理学特征及免疫表型。行EB病毒相关性和Ig/TCR基因克隆性检测,并复习相关文献。结果患者男性,58岁,腹股沟区无痛性淋巴结肿大。腹股沟淋巴结活检组织学观察可见淋巴结结构破坏,低倍镜下见浅染区和深染区交替分布,以浅染区为主,两种区域均可见散在分布的异型大细胞。免疫表型:大细胞一致强表达全B细胞标记(CD20、PAX5)、不表达CD30;CD21显示深染区内不规则滤泡树突细胞网结构,而浅染区内缺如。此外,两种结构背景细胞组成也存在明显差异。深染区背景细胞富于小B细胞,并可见PD1阳性细胞围绕大细胞形成花环样结构;浅染区背景细胞则以小T细胞和组织细胞为主,小B细胞基本缺如,且PD1阳性细胞量及强度均显著下降。EB病毒原位杂交检测两种结构内均无阳性细胞,Ig和TCR基因重排检测均未发现克隆性重排。结论伴有THRLBL样转化的NLPHL具有特殊形态学和免疫结构特征,易被误诊为原发性THRLBL,了解NLPHL免疫结构变异并结合细致全面的组织学观察和免疫组化检测有助于其诊断和鉴别诊断。     

富于T细胞/组织细胞的B细胞淋巴瘤病理形态、免疫表型及鉴别诊断

目的 探讨富于T细胞／组织细胞的B细胞淋巴瘤（TCRBCL）的组织学特点、免疫表型及鉴别诊断。方法 根据WHO淋巴瘤新分类（2001）回顾性研究245例霍奇金淋巴瘤,发现8例TCRBCL;另有5例会诊病例及3例外检诊断病例,共16例;应用免疫组织化学SP方法检测瘤细胞及背景细胞的免疫表型,所用抗体包括CD20、CD79a、CD3、CD8、CD45RO、CDl0、bcl-6、CD21、CD35、CD57、T细胞限制性细胞内抗原（TIA）-1、CD15、CD30、上皮膜抗原（EMA）、细胞周期蛋白（cyclin）D1、CD68、潜伏膜抗原（LMP）-1;4例行原位杂交检测EBER;4例应用聚合酶链反应技术检测瘤细胞IgH基因重排。结果 16例TCRBCL,男8例,女8例,男女比为1：1。年龄10～68岁,平均年龄40．3岁,中位年龄46．5岁。主要表现为淋巴结肿大,伴发热及肝脾肿大。临床分期Ⅱ期3例,Ⅲ期10例,Ⅳ期3例。组织学上见少数非典型性大细胞散在分布于小淋巴细胞和组织细胞背景中。免疫组织化学显示大细胞呈CD20、CD79a、EMA阳性,CD15、CD30阴性;背景小淋巴细胞呈CD3、CD45RO阳性,其中CD8、TIA-1阳性细胞多于CD57阳性细胞;组织细胞呈CD68阳性。CD21、CD35均为阴性反应。所检测的4例均为EBER1／2阴性,4例行IgH基因重排检测均可见单克隆条带。结论 TCRBCL有着独特的组织学和免疫表型特征,诊断应结合形态学和免疫表型特征。鉴别诊断包括霍奇金淋巴瘤、反应性淋巴组织增生、淋巴瘤样肉芽肿病等。     

淋巴结血管内T细胞淋巴瘤1例报道及文献复习

目的　探讨血管内淋巴瘤 (IVL)的临床病理特征。方法　对 1例腹股沟淋巴结IVL临床、病理组织学及免疫表型进行观察分析并复习文献。结果　男性 31岁 ,不明原因高热伴消瘦 5 0天 ,右腹股沟直径 1cm淋巴结 1枚 ,B超示肝脏轻度增大 ,血LDH明显升高伴ESR及转氨酶轻度升高 ,外周血WBC 3 3× 10 7/L ,骨髓像、多种病原及各肿瘤相关抗原检测均无异常。病理活检 :腹股沟淋巴结大部分破坏 ,代之以大量扩张的中小血管 ,腔内充满大量异型淋巴样细胞 ,局部伴管壁、管周浸润并累及结外脂肪组织。瘤细胞免疫表型CD4 5、CD4 5RO、CD3阳性 ,CK、CD6 8、CD79α、CD2 0均阴性 ,血管壁及内皮细胞CD31、CD34阳性。行CHOP化疗后症状缓解 ,现仍在随访中。结论　IVL是一罕见的非霍奇金淋巴瘤 ,好发于中枢神经系统及皮肤 ,其他部位少见 ,绝大数为B细胞型 ,T型罕见 ,以浅表淋巴结活检确诊者尚无报道。临床表现有一定提示性 ,确诊靠组织病理学检查 ,部分病例对化疗敏感 ,但多数病例预后差     

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma

A case showing the typical clinical and pathological features of splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is presented. Since the series recorded by Dogan et al (Am J Surg Pathol 2003;27:903-911), there have been very few reports on this lymphoma variant. Our case presents minor variations on the recorded features. Possible reasons for the scarcity of reports and for the confirmation of this lymphoma as a variant of T-cell-rich large B-cell lymphoma are discussed.     

CD5+ T-cell/histiocyte-rich large B-cell lymphoma.

CD5 expression in neoplastic large B-cells in T-cell/histiocyte-rich large B-cell lymphoma has not been reported, to the best of our knowledge. Here we describe the first case of CD5+ T-cell/histiocyte-rich large B-cell lymphoma that is well documented by histomorphology, immunohistochemistry, flow cytometry immunophenotyping and sorting, and immunoglobulin heavy-chain gene rearrangement study by polymerase chain reaction. The expression of CD5 in large neoplastic B-cells was demonstrated by immunohistochemistry and multicolor flow cytometry. The clonal nature of the CD5+ neoplastic B-cells was confirmed by rearranged immunoglobulin heavy (IgH) chain with polymerase chain reaction (PCR) of flow cytometry-sorted CD5+/CD19+/kappa+ cells. The CD5+ neoplastic large B-cells expressed bcl-6 and MUM1/IRF4 but not CD138 by immunohistochemistry. This suggests that the neoplastic cells may be of late germinal-center B-cell/ early post-germinal center B-cell origin. The patient responded to chemotherapy, CHOP (Cytoxan, doxorubicin, vincristine, and prednisone), and Rituxan very well and is currently in complete remission clinically. We propose that the current case, CD5+ T-cell/histiocyte-rich large B-cell lymphoma, represents a variant of recently reported de novo CD5+ diffuse large B-cell lymphomas. Our patient has had an excellent response to treatment; however, the clinical and biologic significance of CD5 expression in T-cell/histiocyte-rich large B-cell lymphoma requires further studies. Awareness of the CD5+ T-cell/histiocyte-rich large B-cell lymphoma variant will prompt pathologists to perform CD5 immunohistochemical stain in cases of T-cell/histiocyte-rich large B-cell lymphoma. This will lead to identifying more cases to understand the clinical and biologic characteristics of this variant.     

T-cell/histiocyte-rich large B-cell lymphoma associated with a near-tetraploid karyotype and complex genetic abnormalities

Cytogenetic data for T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) are scarcely available. We report here a case of THRLBCL with a near-tetraploid karyotype and complex chromosomal aberrations, without rearrangement of BCL2 or BCL6, and characterized pathologically by a variegated morphologic appearance with areas resembling nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL).     

T-cell/histiocyte-rich large B-cell lymphoma is a disseminated aggressive neoplasm: differential diagnosis from Hodgkin's lymphoma

AIMS: An accurate diagnosis of T-cell/histiocyte-rich large B-cell lymphoma needs to take into consideration those forms of Hodgkin's lymphoma also characterized by a predominance of small lymphocytes and histiocytes, i.e. nodular lymphocyte predominance Hodgkin's lymphoma and lymphocyte-rich classical Hodgkin's lymphoma. We have studied the clinical, phenotypic and genetic features of a series of 12 cases of T-cell/histiocyte-rich large B-cell lymphoma along with 18 cases of Hodgkin's lymphoma for comparative purposes. METHODS AND RESULTS: Of the Hodgkin's lymphoma cases, there were 11 lymphocyte predominance type and seven classic type. T-cell/histiocyte-rich large B-cell lymphomas presented usually in advanced stages (III or IV in 11/12 cases), frequently with 'B' symptoms (6/9 cases), and followed a more aggressive course than Hodgkin's lymphoma (4/8 patients died due to the tumour in T-cell/histiocyte-rich large B-cell lymphoma versus 0/15 in Hodgkin's lymphoma). T-cell/histiocyte-rich large B-cell lymphoma cases showed diffuse effacement of the nodal architecture by a proliferation of scattered large atypical B-cells obscured by a background of small T-lymphocytes (more CD8+, TIA1+ than CD57+). Five cases showed also a prominent histiocytic component. The large B-cells expressed CD45 and often EMA (6/10 cases). On the other hand, CD 30, CD15 and latent infection by Epstein-Barr virus (EBV) were generally lacking. bc l6 and CD10 were, respectively, detected in 6/6 and 1/5 cases. Conventional polymerase chain reaction (PCR) showed monoclonal immunoglobulin heavy chain (IgH) gene rearrangements in all T-cell/histiocyte-rich large B-cell lymphomas studied (5/5), but did not detect any case with t(14;18) involving the major breakpoint region (0/4). CONCLUSIONS: The differential diagnosis of T-cell/histiocyte-rich large B-cell lymphoma from Hodgkin's lymphoma is facilitated by the integration of different immunophenotypic, molecular and clinical findings. T-cell/histiocyte-rich large B-cell lymphoma is a monoclonal neoplasm of bc l6+ B-cells with a phenotypic profile similar to lymphocyte predominance Hodgkin's lymphoma, suggesting a germinal centre origin and a possible relation to this disease. Therefore, in order to distinguish it from lymphocyte predominance Hodgkin's lymphoma, characterization of the reactive background, IgH gene rearrangement studies by conventional PCR and clinical features are more useful. In contrast, T-cell/histiocyte-rich large B-cell lymphoma can be distinguished from classical Hodgkin's lymphoma thanks to the presence of monoclonal IgH rearrangement and the CD 30-CD15-CD45+EMA+ immunophenotypic profile of the neoplastic cells in T-cell/histiocyte-rich large B-cell lymphoma.     

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma: effect of prior corticosteroid therapy

We report on three patients who were treated with corticosteroids only prior to the diagnosis of splenic lymphoma. Corticosteroids were administered for different conditions, at different doses, and for various periods of time. The primary diagnosis was splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma in the three cases, and it was reached with variable difficulty. We suggest that the corticosteroid treatment was one of the causes for the complications in reaching a diagnosis. The morphologic appearance of the microscopic splenic nodules was the most variable feature and may possibly reflect the dose and duration of the corticosteroid therapy. However, the histopathologic changes are probably not related with Epstein-Barr virus-induced immunosuppression.     

T-cell/histiocyte-rich large B-cell lymphoma displays a heterogeneity similar to diffuse large B-cell lymphoma: a clinicopathologic, immunohistochemical, and molecular study of 30 cases.

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL), a proliferating peripheral B-cell neoplasm, is a morphologic variant of diffuse large B-cell lymphoma (DLBCL), which may be confused with Hodgkin's lymphoma, non-Hodgkin's lymphoma, and reactive lymphadenopathies. Though more recent studies suggested that it might be a distinct clinicopathologic entity and/or a heterogeneous entity with derivation from germinal center B cells, its histogenetic derivation remains controversial. The authors analyzed 30 cases of THRLBCL to further characterize the origin of the neoplastic cells using immunohistochemical and molecular studies for expression of Bcl-6, CD10, and CD138, as well as rearrangements of IgH/bcl-2 genes on paraffin-embedded tissue. Half of the cases (15/30) showed Bcl-6 expression and five cases (19%) showed CD10 expression, but none had CD138 expression (0/20). Only three cases showed coexpression of both Bcl-6 and CD10. Molecular studies performed in 21 cases detected rearrangement of immunoglobulin heavy gene in 18 cases, with none having detectable Bcl-2 gene rearrangement. These data indicate that similar to DLBCL, the cell origin of neoplastic cells in THRLBCL is composed of a heterogeneous group of proliferating peripheral B cells, with only some cases originating from germinal center B cells and others derived from heterogeneous origins. Lack of Bcl-2 gene rearrangements seems to argue against a possible progression from preexisting follicular lymphoma. Thus, the normal counterpart of the neoplastic cells cannot at this time be the sole basis for the subclassification of THRLBCL.     

Composite angioimmunoblastic T-cell lymphoma and diffuse large B-cell lymphoma: a case report and review of the literature

We report a rare case of composite angioimmunoblastic T-cell lymphoma (AILT) and diffuse large B-cell lymphoma occurring in a 48-year-old woman with generalized lymphadenopathy and hepatosplenomegaly. The patient initially sought care at a local hospital with a single enlarged left cervical lymph node. Histologic examination of the node was interpreted as an atypical immunoblastic proliferation. She developed generalized lymphadenopathy 10 months later and was referred to our institution for further evaluation. The recent biopsy of the cervical node showed typical features of AILT Flow cytometric immunophenotyping identified an aberrant CD4+ T-cell population that lacked surface CD3. Polymerase chain reaction analysis of the T-cell receptor gamma gene revealed a clonal rearrangement. In addition to the AILT, the lymph node showed partial involvement by a diffuse large B-cell lymphoma. The B lymphoma cells and admixed immnunoblasts and Reed-Sternberg-like B cells in the AILT were positive for Epstein-Barr virus (EBV) by in situ hybridization. Ourfindings raise the possibility that the EBV-associated large B-cell lymphoma is a secondary event in AILT via EBV infection or reactivation followed by clonal expansion of an immortalized EBV-infected B cell clone.     

Comparative genomic hybridization pattern distinguishes T-cell/histiocyte-rich B-cell lymphoma from nodular lymphocyte predominance Hodgkin's lymphoma

Several lines of evidences suggest that T cell/histiocyte-rich B-cell lymphoma (T/HRBCL) represents an aggressive variant of the clinically indolent entity nodular lymphocyte predominance Hodgkin's lymphoma (LPHL). Still, this view has not yet been supported by firm genetic evidence. In this study, we analyzed 17 T/HRBCL cases using comparative genomic hybridization (CGH) combined with microdissection of single CD20+ neoplastic cells and DNA amplification by degenerate oligonucleotide primed-polymerase chain reaction, an approach we previously used in LPHL. Genomic imbalances were detected in all cases (in total, 80 changes). The most common imbalances included gain of Xq, 4q13q28, Xp21p11, and 18q21, and loss of 17p. Of note, a partial gain of 4q, a rare change in lymphoma, is also among the genomic imbalances most frequently encountered in LPHL. On the other hand, the CGH profiles of T/HRBCL and LPHL showed several distinct features, in particular with respect to the number of genomic imbalances (average of 4.7 in T/HRBCL versus 10.8 in LPHL) and their distribution (usually 1 to 5 in T/HRBCL versus 6 to 22 in LPHL). Altogether, our CGH findings of shared as well as distinctive cytogenetic features in both diseases suggest that T/HRBCL constitutes a separate lymphoma entity, possibly originating from the same precursor cell as LPHL.