Cavitary pulmonary involvement of diffuse large B-cell lymphoma transformed from extra nodal marginal zone B-cell lymphoma MALT type

We describe a case of pulmonary diffuse large B-cell lymphoma (DLBCL), which was thought to arise from extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). A 68-year-old woman presented with a 2-month history of cough and bloody sputum. The chest X-ray and computed tomography revealed a mass with cavitation in the right lower lobe. Transbronchial biopsy specimens revealed a granulomatous infiltration without malignant cells. However, diagnosis of MALT lymphoma was established from gastric biopsy specimen. Subsequently, a right lower lobectomy was performed because of hemoptysis. Examination of the resected specimen revealed a diffuse large B-cell lymphoma, which was considered to have transformed from MALT lymphoma, because both lung and stomach lesions had the chromosomal translocation t(11;18)(q21;q21) in common. In addition, there were no nodules, masses, alveolar or interstitial infiltrates in the lung fields, which are usually observed in the case of marginal zone B-cell lymphoma of bronchial mucosa-associated lymphoid tissue. These findings indicate that involvement of DLBCL have to be considered in patients with MALT lymphoma and cavitary lesion of the lung.     

Deletion 20q12 is associated with histological transformation of nodal marginal zone lymphoma to diffuse large B-cell lymphoma

The genetic and molecular abnormalities underlying histological transformation (HT) of nodal marginal zone lymphoma (NMZL) to diffuse large B-cell lymphoma (DLBCL) are not well known. While del(20q12) is commonly deleted in myelodysplastic syndrome it has not previously been associated with DLBCL. We recently described a case of DLBCL harboring del(20q12) in a patient with a history of MZL involving lymph nodes and skin. Here we report eight matched cases of transformed MZL(tMZL): six from nodal MZL (tNMZL) and two from splenic MZL (tSMZL). We found >20% del(20q12) in 4/6 tNMZL, but not in tSMZL, nor in unmatched DLBCL, MZL with increased large cells (MZL-ILC), or MZL cases. To examine whether transformation is associated with a specific gene signature, the matched cases were analyzed for multiplexed gene expression using the Nanostring PanCancer Pathways panel. The differential gene expression signature revealed enrichment of inflammatory markers, as previously observed in MZL. Also, tMZL and de novo DLBCL were enriched for extracellular matrix proteins such as collagen and fibronectin, vascular development protein PDGFRβ, DNA repair protein RAD51, and oncogenic secrete protein Wnt11. A subset of genes is expressed differentially in del(20q12) tMZL cases vs non-del(20q12) tMZL cases. These results suggest a specific pathway is involved in the histological transformation of NMZL, which could serve as an indicator of aggressive clinical course in this otherwise indolent neoplasm.     

IgG4-producing marginal zone B-cell lymphoma

IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. A chronic inflammatory state with marked fibrosis, which can often be mistaken for malignancy, especially by clinical imaging analyses, unifies these features. Little is known about lymphomagenesis in the context of IgG4-related disease, we recently first reported the ocular adnexal marginal zone B-cell lymphomas arising from IgG4-related disease. To the best of our knowledge, no existing study has ever established the neoplastic potential of IgG4-producing cells. In the present report, we describe the first IgG4-producing lymphoma. The patient was a 72-year-old male who was being followed for an asbestos-related pleural plaque. During follow-up, computed tomography revealed bilateral renal masses and multiple swollen retroperitoneal lymph nodes. A retroperitoneal lymph node biopsy was performed. Histologically, the interfollicular areas were expanded by medium to large plasmacytoid cells. These plasmacytoid cells showed nuclear pleomorphism and had prominent Russell bodies. Immunohistochemistry and double immunofluorescence staining of these cells revealed IgG4 positivity and monotypic lambda-light chain predominance. A portion of these cells were partially positive for CD20, negative for CD3, and somewhat faintly positive for CD138. In addition, serum IgG4 was elevated. Southern blot analysis of the lymph node specimen detected immunoglobulin heavy chain gene rearrangement. The present study indicates that, not only can malignant lymphomas occur in the setting of IgG4-related disease, but IgG4-producing cells can also be neoplastic.     

Treatment of diffuse large B-cell lymphoma

A review of new or emerging ideas concerning diffuse large B-cell lymphomas (DLBCL) is presented with particular emphasis on histologic classification, genetic prognostic factors, and first-line treatments. This lymphoma rests the most heterogeneous of all lymphomas for its clinical characteristics and outcome. This heterogeneity is probably secondary to the fact that a large proportion seems to occur from a transformation of an unknown indolent lymphoma. Current treatment is based on the combination of chemotherapy including cyclophosphamide, adriamycin, vincristine, prednisone (CHOP) or dose-intense CHOP-like regimen, and rituximab (R-CHOP).     

原发性胆汁性胆管炎合并胃弥漫性大B细胞淋巴瘤1例报告

1病例资料患者女性,40岁,因“乏力5年,伴间断腹胀、腹痛1年,加重3个月”于2014年11月1日来本院就诊。患者5年前因乏力就诊于解放军总医院第五医学中心,行相关检查后确诊为原发性胆汁性胆管炎(PBC),后口服熊去氧胆酸(UDCA)治疗。近1年反复腹水,伴间断腹胀、腹痛,3个月前上述症状加重,就诊于本院门诊,自带2014年9月解放军总医院第五医学中心化验结果,提示免疫三项:免疫球蛋白(Ig)G 13.97 g/L,IgA 4.33 g/L,IgM 2.6 g/L;肿瘤标志物:CA125224.30 U/ml。自身免疫性肝病系列:抗Sp100抗体(+++),抗gp210抗体(+++),抗52kD抗体(+)。     

Microarray-based classification of diffuse large B-cell lymphoma

OBJECTIVE: Hierarchical clusterings of diffuse large B-cell lymphoma (DLBCL) based on gene expression signatures have previously been used to classify DLBCL into Germinal Center B-cell (GCB) and Activated B-cell (ABC) types. To examine if it was feasible to perform a cross-platform validation on the Affymetrix HG-U133A oligonucleotide arrays and improve the classification, we determined the expression profiles of pretreatment, diagnostic samples from 52 primary nodal DLBCL. METHODS AND RESULTS: First, three previously published gene lists were converted to the HG-U133A probe sets and used for hierarchical clustering. In this way, three subtypes, including the GCB type (n = 20), the ABC type (n = 25) and an intermediate group, Type-3 (n = 5), were distinguished. The CD10 and Bcl-6 expression as well as t(14;18) translocation were prevalent, but not exclusive to the GCB type. By contrast, MUM1 was only expressed in the ABC and in Type-3 samples. The 5-year survival was similar between the groups, but GCB patients showed a better initial response to CHOP or CHOP-like regimens than the remaining patients and tended to have less advanced disease and lower IPI scores. As a next step, an improved set of classifier genes was generated by analysis of 34 patients that were consistently classified as GCB or ABC in the above analyses. Seventy-eight genes were selected and demonstrated on two previously published data sets (Shipp et al. Nat Med 2002;8:68-74 and Houldsworth et al. Blood 2004;103:1862-1868) to exhibit a higher specificity than the original gene lists. CONCLUSION: We conclude that gene expression profiling with Affymetrix Genechips is efficient to distinguish between GCB and ABC types of DLBCL and that these are likely to represent separate biological entities. The Genechip platform is highly standardised and therefore useful for future prospective investigations to establish the value of gene expression profiling in the clinical management of DLBCL.     

CD8-positive diffuse large B-cell lymphoma

In May, 1998, a 63-year-old woman was admitted for treatment of relapsed malignant lymphoma. In March 1997, a diagnosis of diffuse large B-cell lymphoma(DLBL), clinical stage IIISE A, was made from a biopsy specimen of the tumor in the left buccal mucosa. Six cycles of CHOP regimen were given, and complete remission was achieved. However, relapse of the lymphoma was suspected, and the patient was transferred to our hospital. On admission, a right tosillar mass, 8 mm in diameter, was found, and a biopsy showed DLBL. The immunophenotype of the lymphoma cells was CD3- CD4- CD5- CD8+ CD10- CD19+ CD20+ CD23- CD25+ IgL (lambda)+, and dual staining confirmed that the cells were CD8+ and CD19+. The patient was an HTLV-1 carrier, but monoclonal integration of HTLV-1 proviral DNA into the lymphoma cells was not detected. She was diagnosed as having CD8+ DLBL, clinical stage IA. Because she responded to salvage chemotherapy, autologous peripheral blood stem cell transplantation was performed and complete remission was obtained. To our knowledge, this is the first report of CD8+ DLBL.     

Drug resistance in diffuse large B-cell lymphoma

Despite significant advances in the treatment of diffuse large B-cell lymphoma (DLBCL), drug resistance remains a major cause of treatment failure. Early strategies to improve outcome were mostly empiric or relied on classical mechanisms of drug resistance and were largely unsuccessful. More recent approaches have been aided by an understanding of the molecular pharmacology of drug action and tumor biology. Microarray profiling in particular has provided important insights into the complex biology of DLBCL and has led to a molecular taxonomy based on cell of origin and pathways of lymphomagenesis. It is now recognized that drug resistance is a complex and dynamic process related to cell cycle and apoptotic pathways, cellular differentiation, and the microenvironment. Drugs that target potential pathways of drug resistance, such as nuclear factor kappaB (NFkappaB), cyclin-dependent kinases (CDKs), and BCL-2 have entered clinical trials. However, the complexity of drug resistance requires that future clinical trials incorporate molecular translational endpoints to help identify the biologic basis of treatment failure.     

Nodal marginal zone B-cell lymphoma: analysis of 36 cases. Clinical presentation and treatment outcomes of nodal marginal zone B-cell lymphoma

Nodal marginal zone B-cell lymphoma (NMZL) is a relatively uncommon type of lymphoma. Because of the rarity, the natural history and the optimal treatment modality have not been well defined. Therefore, we performed a retrospective analysis of the clinical features and treatment outcomes of NMZL. Thirty-six patients who were histologically diagnosed as NMZL were included in the analysis. Fifty-three percent of the patients had localized disease (stages I and II), and 21.2% (7/33) had bone marrow involvement at presentation. B symptom was present in only three patients (8.3%). Most patients were categorized as low or low-intermediate risk group by international prognostic index (IPI) (77.1%). Majority (94.4%) of the patients with localized disease achieved complete remission (CR) after the initial treatment. Of the seven patients with disseminated disease, who were treated with anthracycline-based chemotherapy, four patients achieved CR. Of the seven patients who received nonanthracycline-based chemotherapy, no patient achieved CR. After the median follow-up duration of 36 months, the median progression-free survival (PFS) was 3.9 (95% CI; 2.9–5.6) years, and the estimated 5-year PFS and overall survival rates were 47.2 and 82.7%, respectively. The significant predictive factors for PFS were performance status, advanced stage, and follicular lymphoma IPI (FLIPI) in this study. This clinical feature is similar to FL rather than to MZL-MALT type.