纵隔(胸腺)大B细胞淋巴瘤三例

例 1女, 18岁。因活动后心累 2年,胸骨后疼痛 1月余于 2004年 1月 5日入院。查体未见异常。血常规:白细胞9 05×109 /L,中性粒细胞 76 3%,淋巴细胞 13 6%。乳酸脱氢酶(LDH): 6 16μmol·s-1 /L。X线照片:前上纵隔明显增宽,双肺及心脏未见异常。CT检查示“前纵隔包块”。B超检查发现左肾先天性缺如,右肾代偿性增大,大小为13 5cm×4 5cm。入院后行“前纵隔包块切除术”。术中见肿瘤位于前上纵隔,分叶状,质硬,大小约 10cm×15cm×6cm,部分侵及右上肺及无名静脉,无名静脉壁明显增厚、变细。例 2男, 16岁。因胸前区胀痛不适 20余天于 200…     

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma without mediastinal disease: mimicking nodular sclerosis classical Hodgkin lymphoma

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma (BCLu-DLBCL/CHL), also known as gray-zone lymphoma, has overlapping clinical and biological characteristics of both diffuse large B-cell lymphoma and classical Hodgkin lymphoma (CHL). These lymphomas are typically associated with mediastinal disease, and extranodal involvement is rare. In the present report, we describe a case of a 78-year-old woman with BCLu-DLBCL/CHL found to have extranodal lesions and no evidence of mediastinal disease. Although biopsy specimens were histologically similar to nodular sclerosis CHL, the tumor cells were positive for CD30 and mature B-cell markers, such as CD20, CD79a, PAX5, BOB.1, and OCT-2, but negative for CD15. Furthermore, the patient had extranodal lesions and an increased level of soluble IL-2 receptor. These findings are unusual in CHL. Therefore, we diagnosed the patient with BCLu-DLBCL/CHL. She received adriamycin, bleomycin, vincristine, and dacarbazine therapy and exhibited partial response. Some cases without mediastinal disease, such as our case, have been reported; however, these cases are rare and further studies are required.     

The utility of CD83, fascin and CD23 in the differential diagnosis of primary mediastinal large B-cell lymphoma versus classic Hodgkin lymphoma

Primary mediastinal large B-cell lymphoma (PMBL) and classic Hodgkin lymphoma (CHL) are the most common large cell lymphomas arising in the mediastinum and are thought to be closely related histogenetically. Although the distinction between PMBL and CHL is usually straightforward, in some cases it is challenging and rarely these neoplasms have intermediate features and qualify for the diagnosis of mediastinal gray zone lymphoma (GZL). CD83 and fascin are markers of CHL and CD23 is a marker of PMBL. In this study we assess the utility of this combination of these immunohistochemical markers to distinguish CHL from PMBL. We retrospectively collected cases of PMBL, CHL and GZL from three centers. Tissue sections were stained with CD83, fascin and CD23. CD83 was expressed in the neoplastic cells of 100% of CHL (22/22), 93% of GZL (16/18) and 41% of PMBL (9/22). Similarly, fascin was positive in the neoplastic cells of 100% of CHL (22/22), 86% of GZL (18/21) and 32% of PMBL (7/22). CD23 was positive in 95% of PMBL (21/22), 67% of GZL (12/18) and 9% of CHL (2/22). CD83 and fascin are sensitive markers for CHL but not specific whereas CD23 is sensitive for PMBL and uncommon in CHL. The GZL cases in this study had an intermediate immunophenotype, but the results were closer to CHL than PMBL. A large panel of immunohistochemical studies is recommended to distinguish CHL from PMBL entities and we suggest that CD83, fascin and CD23 add value to panels designed for this differential diagnosis.     

Molecular profiling provides evidence of primary mediastinal large B-cell lymphoma as a distinct entity related to classic Hodgkin lymphoma: implications for mediastinal gray zone lymphomas as an intermediate form of B-cell lymphoma

Expanding on prior studies that have used molecular profiling to elucidate the heterogeneity of diffuse large B-cell lymphomas (DLBCLs), two recent studies (Rosenwald et al and Savage et al) have characterized a third molecularly distinct subtype of DLBCL, primary mediastinal (thymic) large B-cell lymphoma (PMLBCL). Both groups found distinct gene expression patterns that were able to reliably diagnose PMLBCL and distinguish it from other DLBCLs. Notably, the signature gene expression profile of PMLBCL was more closely related to classic Hodgkin lymphoma (CHL) than other DLBCL subtypes. These studies provide further evidence that PMLBCL and nodular sclerosis CHL may represent related tumors on either ends of a continuum, whose interface includes an intermediate form of disease, mediastinal gray zone (MGZL) lymphoma. MGZLs are tumors that have a transitional morphology and phenotype, combining features of both PMLBCL and nodular sclerosis CHL, and provide a diagnostic challenge to pathologists. These studies provide insights into the biology of PMLBCL and CHL and demonstrate the utility of genomic technologies in defining and diagnosing hematopoietic tumors. The ability to map specific pathologic signal transduction pathways regulating hematopoietic differentiation, proliferation, and apoptosis through genomic or proteomic technologies promises to provide the basis for the development of individualized molecularly targeted therapies for specific tumors.     

Myeloperoxidase-positive intravascular large B-cell lymphoma.

Intravascular large B-cell lymphoma (IVLBL) is an uncommon form of non-Hodgkin lymphoma that is also known as malignant angioendotheliosis, intravascular lymphomatosis, and angiotropic large-cell lymphoma. The disease is characterized by a bizarre population of neoplastic cells, which are found systemically within vascular lumina. Although originally thought to be a neoplastic process of the endothelial cells, it has since been demonstrated, by molecular techniques and immunohistochemistry, that the neoplastic cells are of lymphoid origin. The differential diagnosis of these lesions includes granulocytic sarcomas that can be distinguished from IVLBL or other lymphomas by the presence of immunohistochemical positivity for myeloperoxidase. We describe a patient with a history of a myelodysplastic syndrome who subsequently developed IVLBL, which demonstrated immunohistochemical positivity for myeloperoxidase. To our knowledge, this represents the first case of a malignant lymphoma to demonstrate such findings.     

Expression of c-FLIP in classic and nodular lymphocyte-predominant Hodgkin lymphoma.

Different molecular pathways are believed to be involved in the pathogenesis of classic Hodgkin lymphoma as opposed to non-Hodgkin lymphoma. Antiapoptotic mechanisms have been proposed for classic Hodgkin lymphoma, including expression of the cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (c-FLIP), which plays a critical role in resistance to CD95/Fas-mediated apoptosis. In this study, we compare the expression of c-FLIP in the neoplastic cells of classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma cases. Sixteen cases of classic Hodgkin lymphoma and 19 cases of nodular lymphocyte-predominant Hodgkin lymphoma were reviewed. Of 16 classic Hodgkin lymphoma cases, 13 cases (81%) were c-FLIP-positive, compared with 6 of 19 (32%) nodular lymphocyte-predominant Hodgkin lymphoma cases. Strong cytoplasmic staining was seen in 7 of 13 c-FLIP-positive classic Hodgkin lymphoma cases, in contrast with only 2 of 6 c-FLIP-positive nodular lymphocyte-predominant Hodgkin lymphoma cases. The 2 cases of nodular lymphocyte-predominant Hodgkin lymphoma with strong c-FLIP expression were associated with transformation to large B-cell lymphoma. An additional 15 cases of diffuse large B-cell lymphoma were studied for c-FLIP expression. All but 1 were c-FLIP-positive. In conclusion, we detected c-FLIP in a significantly lower proportion of nodular lymphocyte-predominant Hodgkin lymphoma cases compared with classic Hodgkin lymphoma cases. Therefore, c-FLIP expression may not be the major mechanism of pathogenesis in nodular lymphocyte-predominant Hodgkin lymphoma. However, strong c-FLIP expression in nodular lymphocyte-predominant Hodgkin lymphoma was associated with transformation to large B-cell lymphoma in 2 cases. c-FLIP expression is not limited to Hodgkin lymphoma, because the majority of diffuse large B-cell lymphoma cases tested were strongly c-FLIP-positive.     

Relationship between classic Hodgkin lymphoma and overlapping large cell lymphoma investigated by comparative expressed sequence hybridization expression profiling

There is a diagnostic grey zone between classic Hodgkin lymphoma (cHL) and some non-Hodgkin lymphoma (NHL), including primary mediastinal B cell lymphoma, diffuse large B cell lymphoma, and anaplastic large cell lymphoma. They all have some morphological and/or phenotypic features in common. To investigate this, we undertook an expression profiling study of these lymphomas using comparative expressed sequence hybridization. This technique detects chromosomal regions that are differentially expressed between a test and a reference tissue in a manner similar to comparative genomic hybridization, and is particularly suitable when the number of informative biopsies is limited. Using this approach, we identified a unique expression profile for all lymphoma types investigated. Unsupervised hierarchical cluster analysis of the acquired data showed that cHL separates from all investigated NHLs, including ALCL-like HL. Moreover, anaplastic lymphoma kinase (ALK)-negative ALCL clustered in a separate branch together with ALCL-like HL. Thus, analysing the neoplastic cells concurrently with their microenvironment, ALK-negative ALCL and ALCL-like HL seem to be related to each other, while cHL constitutes a separate lymphoma entity.     

免疫组织化学标记在鉴别结节性淋巴细胞为主型与富于淋巴细胞的经典型霍奇金淋巴瘤中的作用

霍奇金淋巴瘤（HL）分为结节性淋巴细胞为主型（NLPHL）和经典型（CHL）,因两者具有不同的免疫表型与临床特点必须加以区别。其中,NLPHL与富于淋巴细胞的经典型HL（LRCHL）的鉴别较困难。B细胞特异性激活蛋白（BSAP）和BOB.1（B-cell oct-binding protein 1）是目前研究较多的两种B细胞特异性转录因子,已有学者指出在NLPHL中的L＆H细胞表达这两种蛋白。目前国内对EB病毒在这两种病变中的表达情况研究较少,     

Diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma is the most common lymphoma worldwide. Both morphologically and prognostically it represents a diverse spectrum of disease. Traditional morphologic subclassification often results in poor interobserver reproducibility and has not been particularly helpful in predicting outcome. Recent gene expression profiling studies have classified diffuse large B-cell lymphoma into 2 main subtypes, germinal center B-cell and activated B-cell, with the germinal center type showing an overall better survival. Validation of these subtypes has become possible for the practicing pathologist with the use of surrogate immunohistochemical markers. Importantly however, these prognostic studies were performed on material from the pre-rituximab treatment era. With the now well-accepted addition of rituximab (anti-CD20 antibody) to the typical large B-cell lymphoma chemotherapeutic regimen, a revalidation of any survival differences between the large B-cell lymphoma subgroups is necessary. This short review covers the current clinical, morphologic, immunophenotypic, genetic, gene expression profiling, and prognostic (studies before and after the addition of rituximab) features of de novo diffuse large B-cell lymphoma.     

Intravascular large B-cell lymphoma

A rare type of diffuse large B-cell lymphoma, intravascular large B-cell lymphoma primarily affects the middle-aged to elderly population, with a slight predominance in men. By the time of presentation, most patients have advanced, disseminated disease, and often the diagnosis is made at autopsy. Patients may present with any of a myriad of symptoms, with any tissue potentially being infiltrated. Central nervous system and cutaneous involvement is common, as is the presence of B symptoms including fever, weight loss, and night sweats. Morphologically, growth of neoplastic cells is restricted to the lumen of small vessels. The cells are large, with 1 or more prominent nucleoli, scant cytoplasm, and frequent mitotic figures, and are commonly positive for cluster of differentiation markers 79a, 20, and 19, as well as MUM1/IRF4 and Bcl-2. Intravascular large B-cell lymphoma is aggressive, and without treatment is rapidly fatal.     

Diffuse large B-cell lymphoma

The recently published 4th edition of the WHO Classification of Tumours of Haematopoietic and lymphoid tissues has added significant new data into previous entities of large B-cell lymphoma as well as introducing some new categories and two borderline subtypes. This review discusses each of these issues in turn with an emphasis on providing a practical interpretation to assist the diagnostic pathologist in dealing with these lesions.     

CD56-positive large B-cell lymphoma.

CD56 (NCAM), a neural adhesion molecule, is normally expressed on natural killer cells and subsets of T cells and is commonly seen on hematolymphoid neoplasms such as plasma cell myeloma and acute myelogenous leukemia. It is uncommon in B-cell lymphoma. From 2001 to 2003 a cohort of 20 cases of CD56 B-cell lymphomas was identified by flow cytometry (<0.5% of all B-cell lymphomas studied) during a 2-year period. Most (90%) expressed CD10 and 5/5 tested cases were BCL6, suggesting a follicular origin. An extranodal disease presentation was seen in 45% and may be related to CD56 expression. These CD56 B-cell lymphomas may represent a new subset of large B-cell lymphoma. The relationship of cells with this antigenic profile to normal B-cell differentiation is explored.