Lung transplantation for secondary interstitial pneumonitis caused by treatment for primary mediastinal diffuse large B-cell lymphoma

A 34-year-old woman was diagnosed as primary mediastinal diffuse large B-cell lymphoma, treated by cyclophosphamide, doxorubicin, vincrisitne, prednisolone (CHOP) chemotherapy and radiation therapy, and received high-dose ranimustine, cytarabine, etoposide, cyclophosphamide (MCVAC) chemotherapy with autologous peripheral blood stem cell transplantation. Seven years after complete remission was achieved, she recognized dyspnea and was diagnosed secondary interstitial pneumonitis caused by chemotherapy and/or radiotherapy. Because her symptoms and pulmonary function got worsen gradually, she underwent lung transplantation from a brain death donor when she was 47-year-old. She has successfully rehabilitated and returned to her life without oxygen inhalation therapy.     

Temporary mechanical circulatory support for Takotsubo cardiomyopathy secondary to primary mediastinal B-cell lymphoma

Abstract Background: Left heart mechanical circulatory support (MCS) through the left chest via the pulmonary vein and descending thoracic aorta is a good option for patients with an inaccessible anterior mediastinum and/or poor peripheral access. Materials and Methods: We report the case of a 19‐year‐old small female with a newly discovered bulky primary mediastinal diffuse large B‐cell lymphoma (PMBL) who developed refractory inverted Takotsubo cardiomyopathy (TC) with cardiogenic shock. Results: Temporary MCS was implemented in order to stabilize the patient and proceed with a chemotherapy treatment. Given the patient's oncologic “frozen” mediastinum and the presence of poor peripheral arterial access, the left heart temporary MCS was successfully implanted through a left mini‐thoracotomy via the left inferior pulmonary vein and descending thoracic aorta. Conclusions: This is the first report of temporary MCS to treat inverted TC and diffuse PMBL. (J Card Surg 2012;27:119–121)     

Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells?

Primary mediastinal large B-cell lymphomas (LBCLs) constitute a unique subtype of diffuse LBCLs, with distinct clinical, immunophenotypic, and morphologic features. These lymphomas are thought to originate from the thymus, and it has been hypothesized that they derive from a population of B lymphocytes normally present in the thymic medulla. Most diffuse LBCLs harbor somatic mutations in their immunoglobulin genes, suggesting that they have been exposed to the germinal center. To investigate the possible relationship of mediastinal LBCLs to germinal center B cells, we analyzed the expression of bcl-6 and CD10 in 19 mediastinal LBCLs, using an immunoperoxidase technique on formalin-fixed tissue. We found that 19 of 19 (100%) mediastinal LBCLs were bcl-6+ and 6 of 19 (32%) mediastinal LBCLs were CD10+. Because mediastinal LBCLs usually lack BCL-6 gene rearrangement or mutations, expression of bcl-6 and CD10 in these tumors tends to support a germinal center derivation.     

Aberrant expression of the dendritic cell marker TNFAIP2 by the malignant cells of Hodgkin lymphoma and primary mediastinal large B-cell lymphoma distinguishes these tumor types from morphologically and phenotypically similar lymphomas

Tumor necrosis factor-α-inducible protein-2 (TNFAIP2) is a protein upregulated in cultured cells treated with tumor necrosis factor α (TNF), but its expression in normal and neoplastic tissues remains largely unknown. Here, we use standard immunohistochemical techniques to demonstrate that TNFAIP2 is normally expressed by follicular dendritic cells, interdigitating dendritic cells, and macrophages but not by lymphoid cells in secondary lymphoid tissues. Consistent with this expression pattern, we found strong TNFAIP2 staining of tumor cells in 4 of 4 cases (100%) of follicular dendritic cell sarcoma and in 3 of 3 cases (100%) of histiocytic sarcoma. Although TNFAIP2 is not expressed by the small and intermediate-sized neoplastic B cells comprising follicular lymphoma, small lymphocytic lymphoma, mantle cell lymphoma, or marginal zone lymphoma, we observed strong TNFAIP2 staining of the large, neoplastic cells in 31 of 31 cases (100%) of classical Hodgkin lymphoma, in 12 of 12 cases (100%) of nodular lymphocyte-predominant Hodgkin lymphoma, and in 27 of 31 cases (87%) of primary mediastinal (thymic) large B-cell lymphoma. In contrast, TNFAIP2 was expressed by malignant cells in only 2 of 45 cases (4%) of diffuse large B-cell lymphoma, not otherwise specified, in 2 of 18 cases (11%) of Burkitt lymphoma, and in 1 of 19 cases (5%) of anaplastic large cell lymphoma. Further analysis indicates that TNFAIP2, as a single diagnostic marker, is more sensitive (sensitivity=87%) and specific (specificity=96%) than TRAF1, nuclear cRel, or CD23 for distinguishing the malignant B cells of primary mediastinal (thymic) large B-cell lymphoma from those of its morphologic and immunophenotypic mimic, diffuse large B-cell lymphoma, not otherwise specified. Thus, TNFAIP2 may serve as a useful new marker of dendritic and histiocytic sarcomas, the aberrant expression of which in the malignant cells of classical Hodgkin lymphoma and primary mediastinal (thymic) large B-cell lymphoma serves to distinguish these tumors from other large cell lymphomas in routine clinical practice.     

Enteropathy-type T-cell lymphoma after intestinal diffuse large B-cell lymphoma

A rare case of enteropathy-type T-cell lymphoma (ETL) developed in a 47-year-old Chinese male 6 years after the diagnosis of diffuse large B-cell lymphoma (DLBCL) in the small intestine. The patient initially presented with vague gastrointestinal complaints. Work-up demonstrated an ulcerated mass in the small intestine. Partial resection and histologic examination of the intestine showed a DLBCL, positive for CD20 and Bcl-2, involving the jejunum transmurally. Further staging work-up demonstrated mesenteric and retroperitoneal lymphadenopathy, splenomegaly, and ascites. The patient was treated aggressively with radiotherapy, chemotherapy, and autologous bone marrow transplant, and complete remission was obtained. Six years later, the patient presented with diarrhea and dehydration. Clinical work-up revealed thickening of the small intestinal wall, and biopsies demonstrated ETL based on morphology, immunohistochemistry, and polymerase chain reaction analysis. Celiac disease was diagnosed concurrently. The patient responded to chemotherapy, received allogeneic peripheral blood stem cell transplantation from an HLA-matched sibling donor, and remains in remission. To our best knowledge, this is the first reported case of metachronous ETL and DLBCL. Possible associations between the 2 types of lymphoma are discussed.     

Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma

Recent studies with cDNA microarrays showed that diffuse large B-cell lymphoma (DLBCL) cases with gene expression profiles similar to germinal center (GC) B cells had much better prognosis than DLBCL cases with gene expression profiles resembling activated B cells. The goal of the current study is to evaluate if using a panel of GC B-cell (CD10 and Bcl-6) and activation (MUM1/IRF4 and CD138) markers by immunohistochemistry defines prognosis in patients with de novo DLBCL. Immunohistochemical stains for the above markers were performed on paraffin-embedded tissues from 42 de novo DLBCL patients. Median follow-up in all patients was 41 months (range, 1-103 months) and in surviving patients was 65 months (range, 14-103 months). These cases could be classified into three expression patterns: GC B-cell pattern (pattern A) expressing CD10 and/or Bcl-6 but not activation markers; activated GC B-cell pattern (pattern B) expressing at least one of GC B-cell markers and one of activation markers; and activated non-GC B-cell pattern (pattern C) expressing MUM1/IRF4 and/or CD138 but not GC B-cell markers. Patients with pattern A had much better overall survival than those with the other two patterns (Kaplan-Meier survival analysis, P < 0.008, log rank test). Using multivariate Cox proportional hazards regression analysis, the international prognostic index scores and the expression pattern of these markers were independent prognostic indicators. Our results suggest that expression patterns of this panel of GC B-cell and activation markers by immunohistochemistry correlate with the prognosis of patients with DLBCL. Immunohistochemical analysis on paraffin-embedded tissues is more readily available than gene expression profiling by cDNA microarray and may provide similar prognostic information.     

Intravascular large B-cell lymphoma of the breast

The case of an 80-year-old woman with symmetrical breast engorgement and nonspecific systemic symptoms progressively developing over 3 months and confirmed on surgical biopsy to be due to an intravascular large B-cell lymphoma (ILBCL) is presented. To our knowledge, ILBCL has never been reported in the breast before and its mammography and ultrasound appearances are described.     

SIRT1 expression is associated with poor prognosis of diffuse large B-cell lymphoma

Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.     

原发性胃弥漫大B细胞淋巴瘤38例临床预后分析

目的探讨原发性胃弥漫大B细胞淋巴瘤(PG-DLBL)的外科手术治疗的意义。方法回顾性分析我院1996年1月至2007年12月经胃镜活检或手术病理证实的38例PG-DLBL患者的临床病理κ料,根据治疗情况分为手术联合化疗组㈦单纯化疗组,比较两组预后情况。结果手术联合化疗17例,单纯化疗21例。两组发病年龄、性别、肿瘤分期、肿瘤大小均无显著性差异,手术联合化疗组的5年生存率为56%,单纯化疗组为33%,差异无统计学意义(P=0.676)。单纯化疗组并发消化道出血1例。手术联合化疗组的完全缓解率为94.1%,单纯化疗组为81.0%(P=0.233)。结论手术不应是PG-DLBL的首选治疗措施。     

早期原发性胃弥漫大B细胞淋巴瘤的治疗与预后分析

目的探讨早期原发性胃弥漫大B细胞淋巴瘤（DLBCL）的预后影响因素及治疗方式的选择。方法回顾性分析天津医科大学附属肿瘤医院1993年1月至2008年8月间经胃镜活检或手术病理证实的75例早期DLBCL患者的临床病理资料。结果75例患者中接受单纯化疗20例．手术联合化疗55例：两组患者完全缓解率分别为65．0％（13／20）和83．6％（46／55），治疗有效率分别为75．0％（15／20）和92．7％（51／55），5年生存率分别为86．9％和78．7％，差异均无统计学意义（均P〉0．05）。单因素和多因素预后分析显示，国际预后指数（IPI）评分是DLBCL患者的独立预后因素（P〈O．05．HR=11．350，95％CI：1．011-127．371）。结论IPI评分是早期胃DLBCL中的独立预后因素：单纯化疗与手术联合化疗的疗效无显著差异。     

Primary large B-cell lymphoma of the thyroid. Apropos of 2 cases

Two cases of primary large B-cell non-Hodgkin's lymphoma are described. Both cases had typical symptoms: a sudden growth of thyroid in these female patients at their sixth decade of life. The differential diagnosis between undifferentiated carcinoma and lymphoma of the thyroid, uncertain with clinical and ultrasound examination, was defined by a fine needle biopsy (FNAB). Patients underwent a radical resection which permitted a correct cancer staging even in the presence of laterocervical lymph nodes swelling. Histological examination of the surgical specimen confirmed the presence of a large B-cell non-Hodgkin's lymphoma while the immunophenotypical analysis detected the expression of the common leukocytic antigen and B-correlated antigens CD20, CD74, CDW75 and CD79A. In both cases chemotherapy and radiotherapy were carried out.     

Primary non-Hodgkin large B-cell lymphoma of bladder. Report of a case

Introductionprimary genitourinary lymphomas are uncommon. Among them, bladder lymphomas are extremely unusual tumors, with clinico-radiological features similar to urothelial carcinomas of bladder. Histopathological, immunohistochemical and molecular studies are compulsory for the diagnosis. We report a case of this tumorClinical caseAn 80-year-old woman was admitted to our hospital with hematuria. Abdominal ultrasound and cystoscopy revealed an infiltrating bladder tumor involving the right lateral wall. After transuretral biopsy, a diagnosis of non-Hodgkin large B-cell lymphoma was made. Neither clinical symptoms nor radiological findings showed disseminated disease, indicating that the tumor was localized in the bladder. After chemotherapy, the patient is disease-free after 9 months follow-upCommentif a bladder tumor with uncommon histopathological features is found, lymphoma should be excluded, because chemotherapy avoids cystectomy     

Genetic aberrations in primary cutaneous large B-cell lymphoma: a fluorescence in situ hybridization study of 25 cases

In contrast to nodal large B-cell lymphomas, recurrent chromosomal aberrations have been studied only in a small number of cases of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL). We investigated 25 PCDLBCLs (classified according to the WHO-EORTC classification into PCDLBCL, leg-type, 8; and PCDLBCL, other, 17), using an interphase fluorescence in situ hybridization technique. All cases were analyzed for chromosomal aberrations commonly observed in nodal large B-cell lymphomas, including structural aberrations of the genes BCL2, BCL6, and c-MYC, and numerical aberrations of the chromosomes/genes 3, 7, 8, 11, 12, 13, 17, 18q, RB1, and p53. We observed genetic aberrations in 19 (76%) of 25 patients. The most frequent numerical aberrations were gains of chromosome 12 (7 of 25, 28%), 7 (5 of 25, 20%), 3 (5 of 25, 20%), 18q (3 of 25, 12%), 11 (3 of 25, 12%), X (3 of 25, 12%), and losses of chromosome/gene 17/p53 (3 of 25, 12%). BCL2, c-MYC, and BCL6 were rearranged with the IGH gene in 4 (16%), 1 (4%), and none (0%) of 25 cases, respectively. Most aberrations were homogeneously distributed among cases of PCDLBCL, leg-type and of PCDLBCL, other, cases located on the leg or at other body sites, cases with round and cleaved cell morphology, and Bcl-2+ and Bcl-2- cases. These results suggest that PCDLBCLs show similar chromosomal aberrations irrespective of classification, anatomic site, cell morphology, and Bcl-2 expression, and that many similarities between primary cutaneous and nodal diffuse large B-cell lymphomas can be observed.     

Primary diffuse large B-cell lymphoma of the sigmoid colon

IntroductionExtranodal lymphomas are commonly encountered in the gastrointestinal tract but lymphomas of colon and rectum are rare. Non-Hodgkin lymphoma is the most common type of colonic lymphoma and represents less than 0.5% of colorectal neoplasms. Chemotherapeutical agents are gateway to disease remission and sometimes cure in most patients but surgery may be necessary in emergent situations.Case presentationA 77-year-old male patient presented with abdominal discomfort, constipation, and obstructive defecation symptoms. Radiological imaging revealed a mass in the sigmoid colon extending towards the rectum. Colonoscopy was performed and biopsy of a nearly 10 cm ulcerovegetative lesion was obtained. Histological examination following biopsy revealed it to be a diffuse large B-cell lymphoma of the sigmoid colon. There was no indication for surgery and the patient was referred to medical oncology clinic for chemotherapy treatment.DiscussionNon-Hodgkin lymphoma is a lymphoproliferative disorder with the diffuse large B cell lymphoma (DLBCL) being the most common subtype. The DLBCL subtype is rarely observed in the colon and rectum. Chromosomal abnormalities are involved in the pathophysiology and gene rearrangements lead to adjustments in lymphocyte function and differentiation.ConclusionIn this case report, we present a rare presentation of a Non-Hodgkin lymphoma presenting in the sigmoid colon. The disease can present with nonspecific symptoms and various imaging modalities along with histopathological evaluation is necessary for the correct subtyping of lymphoma. Chemoradiotherapy is key for treatment, and surgery is usually reserved for cases of obstruction, perforation, or bleeding.