Primary testicular diffuse large B-cell lymphoma shows an activated B-cell-like phenotype

The most common type of primary testicular lymphoma is diffuse large B-cell type, which has a poor prognosis relative to other extra-nodal diffuse large B-cell lymphomas (DLBCL). These constitute a heterogeneous group of lymphomas with germinal center B-cell-like and activated B-cell-like subtypes. Such a distinction theoretically utilizes the immunohistochemical expression of CD10, Bcl-6, and MUM1. The purpose of this study was that we could stratify primary testicular lymphoma of diffuse large B-cell type according to this scheme, and further elucidate the reason why primary testicular diffuse large B-cell lymphoma possesses a poor clinical outcome. Seventeen Chinese patients with primary testicular DLBCL were examined by means of a 3-antibody panel (CD10, Bcl-6, MUM1). Among these 17 cases, 16 were assigned to the activated B-cell-like subtypes. One case was classified as germinal center B-cell-like type. Twelve of these 17 cases expressed high proliferative activity (≥40% Ki-67 labeling). The majority of primary testicular DLBCLs have activated B-cell-like subtype characteristics and high proliferative activity. These features might be a significant factor; moreover, they are associated with poor prognosis.     

Fine-needle aspiration biopsy for the primary diagnosis of lymphoproliferative disorders involving the spleen: one institution's experience and review of the literature

We report the fine-needle aspiration (FNA) biopsy findings for the primary diagnosis of lymphoproliferative disorders involving the spleen. We analyzed six cases of primary diagnosed lymphoma involving the spleen and out of these cases, identified one case of primary splenic lymphoma. We explore the potential pitfalls and difficulties encountered in making a primary diagnosis of lymphoma involving the spleen and how the preparation of the specimen for flow cytometric studies and/or cell block for immunohistochemical analysis can greatly aid in making a definitive diagnosis. To the best of our knowledge, this is the first report of T-cell rich B-cell subtype of diffuse large B-cell lymphoma and only the second report of primary splenic lymphoma of the spleen diagnosed by FNA biopsy. An extensive review and analysis of the literature involving FNA biopsy of the spleen is also discussed.     

Development of angioimmunoblastic T-cell lymphoma after treatment of diffuse large B-cell lymphoma: a case report and review of literature

Cases of diffuse large B-cell lymphoma (DLBCL) arising after the initial diagnosis of angioimmunoblastic T-cell lymphoma (AITL) and DLBCL synchronous with AITL have been reported. To date, there is no report on the subsequent development of AITL in patients with DLBCL. Here we presented a rare case of AITL developing six months after the initial diagnosis of DLBCL. In order to investigate the clinical and molecular features of patients with AITL and DLBCL, we also reviewed the literature on AITL patients developing DLBCL, and patients with composite AITL and DLBCL.     

CD23 expression in mediastinal large B-cell lymphomas

AIMS: Mediastinal large B-cell lymphoma (MLBCL) is a subtype of diffuse large B-cell lymphoma (DLBCL) in the WHO classification with peculiar features, such as female prevalence, young patient age and bulky presentation. It shows a B-cell phenotype with variable expression of surface immunoglobulin, negative CD21 and CD10 and positive CD30 in a large number of cases. An origin from activated thymic B cells has been suggested in several studies. A subpopulation of large, dendritic cells (asteroid cells) strongly expressing CD23 has been identified amongst thymic B cells and these could represent the normal cellular counterpart for this type of primary mediastinal large cell lymphoma. METHODS AND RESULTS: To explore this possibility, we immunostained 24 cases of primary mediastinal lymphomas and 100 cases of non-mediastinal, nodal and extranodal, DLBCLs for CD23 in routinely processed paraffin-embedded tissues. CONCLUSIONS: Our results show that a vast majority (70%) of mediastinal lymphomas strongly express CD23 whilst the same antigen is expressed in only 15% of non-mediastinal nodal DLBCLs and 9% of non-mediastinal extranodal DLBCLs. These results support the hypothesis that most cases of MLBCL arise from activated dendritic thymic B cells. We also suggest that CD23 should be included in the panel of antibodies currently used to characterize this subtype of DLBCL.     

Aggressive B-cell lymphomas with a primary bone marrow presentation

Aggressive B-cell lymphomas present as a heterogeneous spectrum of disease. A primary diagnosis in the bone marrow (BM) may be challenging in terms of diagnostic classification and clinical handling, owing to limited architectural information. Aggressive B-cell lymphomas can be subdivided into entities that typically present primarily in the BM, and cases with BM involvement in which the bulk of disease is present in other organs. One main topic at the 2018 BM workshop of the European Association of Haematopathology/Society of Hematopathology was therefore aggressive B-cell lymphomas with a primary BM presentation. The spectrum of cases submitted to this topic gave a good overview of commonly encountered problems, as well as unusual manifestations, and highlighted areas of imprecise disease definitions and diagnostic grey zones. The categories submitted to the workshop included cases of Burkitt lymphoma (BL) with unusual features, high-grade B-cell lymphomas (HG-BCLs) with and without so-called double/triple-hit, and diffuse large B-cell lymphomas (DLBCLs) with a primary BM presentation. Areas of difficulties included the morphological boundaries of HG-BCL not otherwise specified, cases with MYC and bcl-2 or bcl-6 translocations and terminal deoxynucleotidyl transferase (TdT) expression, which were categorised as B-cell lymphoblastic leukaemia/lymphoma if most cells showed TdT positivity, and the clinicopathological overlap between intravascular large B-cell lymphoma, CD5-positive DLBCL, and DLBCL with primary presentations in the BM, spleen, and liver. This review summarises our understanding of the main aggressive B-cell lymphoma categories with a common primary BM presentation and potential problem areas, and makes suggestions for the immunophenotypic and genetic work-up, illustrated by the interesting and challenging cases submitted to the workshop.     

Primary cutaneous B-cell lymphomas with large cell predominance–primary cutaneous follicle center lymphoma,diffuse large B-cell lymphoma,leg type and intravascular large B-cell lymphoma

In this review, we present clinical features and detailed histopathologic, immunologic, and molecular information regarding primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type which together represent two of the three most common types of primary cutaneous B-cell lymphoma recognized in the current WHO classification system.1, 2 Overall, B-cell lymphomas represent 19–27% of primary cutaneous lymphomas in most large European and American studies3, 4, 5, 6 and together, primary cutaneous follicle center lymphoma and primary cutaneous diffuse large B-cell lymphoma, leg type account for approximately 2/3 to ¾ of these cases.5, 7, 8, 9, 10, 11 Both subtypes can contain a high content of large B-lymphocytes, although most cases of primary cutaneous follicle center lymphomas exhibit a range in cell size and cytology. Intravascular large B-cell lymphoma, a less commonly-encountered EBV-negative primary cutaneous B-cell lymphoma composed of large cells, will be more briefly discussed in this report as well.     

Diffuse large B-cell lymphoma in the spinal epidural space: A study of the Osaka Lymphoma Study Group

Diffuse large B-cell lymphoma (DLBCL) involving spinal epidural space (SEDLBCL) is relatively rare, constituting 1.8% of DLBCLs in Osaka, Japan. The aim of this study was to analyze SEDLBCL cases for their clinical and histopathologic findings, including an association with Epstein-Barr virus (EBV) and immunohistochemical characteristics.     

Primary cutaneous B-cell lymphoma in Japanese patients

Primary cutaneous B-cell lymphoma (PCBCL) is a rare group of lymphoproliferative disorders. There have been few reports of Japanese patients with PCBCL, so the present study investigated the clinicopathological and immunological features and Bcl-2 gene rearrangement and protein expression in 28 Japanese patients with PCBCL. According to the Revised European-American Lymphoma (REAL) classification, there were 25 diffuse large B-cell lymphomas (DLBCL), one Burkitt type lymphoma, one lymphoblastic lymphoma and one marginal zone cell lymphoma. Of the 25 DLBCL, 17 were in males and eight in females, with an average age of 69.4 years. Follow-up data were available in 19 cases of DLBCL of which seven died and 12 were alive. The overall 5-year survival rate was 61%. Cases of DLBCL involving the legs were found to have poorer clinical outcomes; two of four cases with leg lesions died, with a mean survival of 13 months. Of 14 cases with non-leg lesions, four died, and the mean survival was 38.9 months. Only one case of Burkitt type lymphoma was CD10 positive. Bcl-2 rearrangement was not observed in 13 cases studied by polymerase chain reaction. Bcl-2 expression was observed in nine of 13 cases studied. All five cases with leg lesions exhibited Bcl-2 expression, but four of six cases with non-leg lesions also expressed the protein. These results show that DLBCL is the most frequent subtype of PCBCL in Japanese patients and that the prognosis of Japanese patients with DLBCL is worse than that of reported European cases. The study also found that PCBCL was frequently associated with Bcl-2 expression, which was not site-confined, and that there was no evidence for a follicular center origin of PCBCL.     

Extra-oral plasmablastic lymphoma: report of a case and review of literature

Plasmablastic lymphoma (PBL) of the oral cavity is classified as one subtype of diffuse large B-cell lymphoma that is most commonly seen in patients with human immunodeficiency virus infection. We report a rare case of PBL in the anal canal of a 33-year-old man with human immunodeficiency virus infection. The lymphoma cells were positive for CD138 and weakly positive for CD79a. In addition, these cells were also positive for CD10. The neoplastic cells were positive for Epstein-Barr virus and negative for human herpes virus 8. Review of the English medical literature revealed many more cases of extra-oral PBL. We propose that the term plasmablastic lymphoma of the oral cavity in World Health Organization classification be revised to simply plasmablastic lymphoma, which would include both oral and extra-oral PBLs, and the term to define the primary site of the lymphoma (ie, oral cavity) be dropped from the terminology used in World Health Organization classification.     

Diffuse large B-cell lymphoma with fibrillary matrix

Diffuse large B-cell lymphoma (DLBCL) with fibrillary matrix is an extremely rare variant of non-Hodgkin's lymphoma (NHL) whose pathological features are poorly known. Here, we report on our experience with such a condition arising in a 71-yr-old woman. Our findings not only demonstrate that DLBCL with fibrillary matrix actually represents a peculiar subtype of DLBCL, but they also illustrate that the cytologic and flow cytometric features in this disorder can be deceptive enough as to mislead even the most experienced cytopathologist.     

Diffuse large B-cell lymphoma of the uterus suspected of having transformed from a marginal zone B-cell lymphoma harboring trisomy 18: a case report and review of the literature

The patient was a 72-year-old female with the chief complaint of abdominal fullness. A giant primary myoma of the uterine cervix was suspected, and total hysterectomy was performed. Based on a postoperative histopathological examination of the tumor a diagnosis of diffuse large B-cell lymphoma (DLBCL) was made in the uterus and a mass in the greater omentum was diagnosed as a marginal zone B-cell lymphoma (MZBCL). No flow-cytometry studies or chromosome or gene examinations were performed on a fresh specimen. The results of an examination of a paraffin block histopathology specimen by fluorescence in-situ hybridization (FISH) showed no mucosa associated lymphoid tissue lymphoma translocation gene 1 (MALT1) (18q21.1), B-cell lymphoma 2 (BCL2) (18q21.3), or BCL6 (3q27) split signals in either the uterus or the greater omentum, however, trisomy 18 was detected in approximately 50%-70% of the tumor cells in both the uterus and the greater omentum. Trisomy 18 was present in around 15-33% of the DLBCL cells and MZBCL cells. These findings suggested a strong possibility that the tumor cells in the uterus and greater omentum were the same clone and that transformation from MZBCL to DLBCL had occurred. Since DLBCLs that result from a transformation usually have a worse outcome than de novo DLBCLs, even when a DLBCL seems to have originated in the uterus the surrounding tissue should always be examined, and caution should be exercised in regard to transformation from a low-grade B-cell lymphoma to a DLBCL.     

A reassessment of primary thyroid lymphoma: high-grade MALT-type lymphoma as a distinct subtype of diffuse large B-cell lymphoma

AIMS: Primary lymphoma of the thyroid gland (PTL) is a relatively rare disease. During an 18-year period, 53 cases of primary non-Hodgkin's lymphoma involving this extranodal site were seen at our institutions. The aims of this study were to evaluate the spectrum of PTLs using current lymphoma classification concepts and immunocytochemical markers, determine whether features of MALT-type lymphoma were evident in PTL, and if there was any clinical significance of such a finding. METHODS AND RESULTS: The cases were retrospectively studied clinically, histologically and immunohistochemically. The tumours were classified according to the Revised European-American Lymphoma Classification of lymphoid malignancies (REAL classification). Thirty-eight patients were females, 15 were males and mean age at diagnosis was 66.3 years (range 38-90). Three cases were low-grade marginal zone lymphomas (low-grade MALT-type lymphomas). There were 45 diffuse large B-cell lymphomas (DLBCL) of which there were 27 DLBCL-NOS and 18 high-grade MALT-type lymphomas. Within the diffuse large B-cell lymphoma (DLBCL) category, cases were subdivided into those without (DLBCL-NOS) and those with features of 'high-grade' MALT-type lymphoma based on presence of a low-grade component or large cell lymphoepithelial lesions (HG MALT-type lymphoma). In addition there were three follicle centre lymphomas, one anaplastic large cell lymphoma and one peripheral T-cell lymphoma. Twenty cases were stage IE, 18 stage IIE, and four stage IV. All patients with low-grade MALT-type lymphoma are alive without disease. The 5-year survivals for DLBCL-NOS and HG MALT-type lymphoma were 75% and 25%, respectively. Univariate analysis (log rank) among the DLBCLs showed stage (P < 0.001) and subtype (P = 0.005) were associated with survival. Stage was associated with type of DLBCL, 65% of DLBCL-NOS being stage IE compared to 20% of HG MALT-type lymphomas. CONCLUSIONS: We conclude that primary thyroid lymphomas occur most commonly in elderly women and are frequently present in clinical stage IE and IIE. Low-grade MALT-type lymphomas are relatively uncommon but appear to have a favourable prognosis. DLBCL is the most common lymphoma and features of MALT can be seen in over one-third of cases. As a group, HG MALT-type lymphomas had a worse outcome than DLBCL-NOS, primarily due to higher clinical stage at diagnosis. These two subtypes of DLBCL appear to be distinct clinical and histological entities.     

Expression of Histone Deacetylases in Diffuse Large B-cell Lymphoma and Its Clinical Significance

Background: Histone deacetylase inhibitors are a new class of drugs used in treatment of malignant tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common type of B-cell lymphoma, and it accounts for more than 40% of all B-cell lymphomas. In this study, we aimed to determine the expression patterns of histone deacetylases (HDACs) in DLBCL, to examine whether HDAC expression patterns differ among cases, and to assess whether these findings have clinical significance.Materials and methods: We selected 91 cases of DLBCL diagnosed at St. Vincent Hospital, The Catholic University of Korea, from 2001-2012. We performed a pathology slide review and collected clinical data including age, sex, tumor site, survival time, and mortality. Immunohistochemical analysis was performed using primary antibodies for HDACs, including HDAC1 and 2 of class I, HDAC4 and 5 of class IIa, and HDAC6 of class IIb. Expression site was determined to be nuclear, cytoplasmic, or both. Staining intensities were graded as low and high. We assessed correlations between HDAC expression levels and clinical data and survival analysis.Results: Of the 91 cases examined, 46 (50.5%) were men and 45 (49.5%) were women. Most of the patients were elderly, and 74 (81.3%) cases were older than 46 y. Forty-six (50.5%) cases showed lymph node involvement, and 45 (49.5%) cases showed lymphoma at extranodal sites. In nodal lymphoma, staining was strongly positive for HDAC2, whereas staining was weak or negative for HDAC4; however, there was no significant correlation with survival. But nodal lymphoma cases with high nuclear expression of HDAC2 and nodal lymphoma cases with high nuclear expression of HDAC2 and low nuclear expression of HDAC4 showed significantly shorter survival times compared with other cases.Conclusions: High nuclear expression of HDAC2 may play an important role in survival of DLBCL patients, especially in those with nodal lymphoma, which is associated with a shorter survival time. Our results may have important implications for treatment of DLBCL by epigenetic regulation.     

Diffuse large B-cell lymphoma showing an interfollicular pattern of proliferation: a study of the Osaka Lymphoma Study Group

Aims:  Diffuse large B-cell lymphoma (DLBCL) usually proliferates effacing lymph follicles. In occasional cases, tumour cells show an interfollicular pattern of proliferation preserving lymph follicles. The aim was to analyse clinicopathological findings in DLBCL showing an interfollicular pattern of proliferation to determine whether this type of lymphoma is a distinct entity of DLBCL.
Methods and results:  Clinicopathological findings in 12 cases of DLBCL showing an interfollicular pattern of proliferation [interfollicular group (IF)] were examined and compared with those in 30 cases of DLBCL with ordinary morphology [control group (CG)]. IF showed a significantly lower lactate dehydrogenase level and International Prognostic Index scores than CG ( P  = 0.023 and P  < 0.01, respectively). The frequency of localized disease, clinical stage 1 and 2, in IF was higher than that in CG ( P  = 0.016). A morphologically polymorphous pattern of proliferation was found in seven of 12 cases (58.3%) in IF, which was higher than that in CG, five (16.7%) of 30 cases ( P  < 0.01). Clonality analysis with the polymerase chain reaction method revealed that all 11 IF cases examined showed a monoclonal pattern. Immunohistochemically, the majority (11 of 12) of IF cases showed a non-germinal centre B-cell phenotype and the frequency was higher than that in CG ( P  = 0.021).
Conclusion:  Diffuse large B-cell lymphoma with an interfollicular pattern of proliferation shows distinct clinical and pathological findings from ordinary DLBCL.     

Primary platelet-derived growth factor-producing,spindle-shaped diffuse large B-cell lymphoma of the skull: a case report and literature review

A 39-year-old woman with a right frontal mass underwent a cranial bone tumor biopsy. Histopathologic examination of hematoxylin and eosin–stained slides showed spindle-shaped tumor cells in a storiform pattern, appearing somewhat like a sarcoma. However, the tumor cells were CD20-positive by immunohistochemical staining. Therefore, a diagnosis of spindle-shaped diffuse large B-cell lymphoma (Sp-DLBCL) was made. There have been at least 35 cases of Sp-DLBCL documented in the literature, and most were of the germinal center type, while the present case is the first report of a vimentin-positive primary Sp-DLBCL of the skull. The DLBCL in this case was immunohistochemically stained for six representative cytokines that might give rise to fibrosis, due to the evidence of fibroblastic proliferation. The DLBCL cells were positive for platelet-derived growth factor (PDGF), and some cells were also positive for tumor necrosis factor (TNF) α. Based on these findings, it was inferred that the PDGF and TNFα produced by DLBCL cells induced fibroblastic proliferation. The resultant conspicuous fibrosis caused interfibrous impingement on the DLBCL cells, which deformed them into a spindle shape. The present case is the first reported case of a PDGF-producing Sp-DLBCL.     

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting in nasal cavity: a case report and review of literature

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare subtype of non-Hodgkin’s lymphoma (NHL) with distinct morphologic and immunohistochemical features. We reported a 57-year-old female with ALK-positive DLBCL in her left nasal cavity. Histologically, the tumor cells were characterized by plasmablastic morphology and tested positive for ALK in a cytoplasmic granular staining pattern. The neoplastic cells were positive for CD38, CD4, MUM1, CD138 and Vimentin. However, they failed to express CD56, CD30, as well as mature B cells markers, such as CD79a, CD20 and T cells markers such as CD2, CD3, CD5, CD7 and CD8. The patient achieved complete response after four cycles of CHOEP (cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide) treatment. Then she received radiotherapy of the originally involved area. This case represented a rare ALK-positive DLBCL in the nasal region.     

弥漫性大B细胞淋巴瘤500例构成比及免疫表型分析

目的 按照WHO(2008版)造血与淋巴组织肿瘤分类,分析弥漫性大B细胞淋巴瘤(DLBCL)各亚型的构成比情况、免疫表型特点,及其总体生存率.方法 按照新分类,结合形态学观察,利用免疫组织化学、基因重排、原位杂交、荧光原位杂交(FISH)等技术对500例DLBCL,进行回顾性分析和归类,收集随访资料,并对生发中心B细胞(GCB)型和非GCB型组之间、老年人EB病毒(EBV)阳性的DCBCL亚型和非特殊型弥漫性大B细胞淋巴瘤(DLBCL-NOS)之间进行总体生存率比较.结果 500例中DLBCL-NOS约占77.2%(386/500),其次是老年人EBV阳性的DLBCL占9.4%(47/500),然后依次是原发中枢神经系统的DLBCL(4.4%,22/500)、原发纵隔(胸腺)的大B细胞淋巴瘤(2.8%,14/500)、富于T细胞/组织细胞的大B细胞淋巴瘤(2.6%,13/500),其余类型均属于比较罕见的.DLBCL-NOS按照形态学分类以中心母细胞性最为常见,约占95.1%(367/386);按免疫组织化学分型,非GCB型组在DLBCL-NOS中约占68.5%(219/320),GCB型组占28.4%(91/320),而CD5阳性DLBCL仅占3.1%(10/320).总体生存率比较,GCB型组和非GCB型组总体生存率差异无统计学意义(P=0.93),老年人EBV阳性的DLBCL组总体生存率与年龄匹配前、后的DLBCL-NOS组差异均无统计学意义(P值分别为0.13和0.28).对形态学表现为灰区的淋巴瘤病例进行FISH检测,发现了1例"双打击"(double-hit)淋巴瘤.结论 DLBCL-NOS在DLBCL中占绝大多数,其次是老年人EBV阳性的DLBCL和原发中枢神经系统的DLBCL,其他类型均属少见或罕见类型.按照Hans分类进行免疫组织化学分型,非GCB型占多数,GCB型和非GCB型分组总体生存率没有显著性差异.老年人EBV阳性的DLBCL组和用年龄匹配前后的DLBCL-NOS组的总体生存率均无显著性差异.

Abstract：

Objective To study the immunophenotype and overall survival of diffuse large B-cell lymphoma (DLBCL) classified according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Methods Five hundred cases of DLBCL were retrospectively analyzed with histologic review, immunohistochemistry, gene rearrangement study, in situ hybridization and fluorescence in situ hybridization. Follow-up data were collected. The overall survival rates of germinal center B-cell (GCB) and non-germinal center B-cell (non-GCB) subtypes, as well as those of DLBCL, not otherwise specified (NOS) and Epstein-Barr virus (EBV)-positive DLBCL of the elderly, were compared.Results DLBCL-NOS was the commonest subtype which accounted for 77.2% (386/500) of the cases.EBV-positive DLBCL of the elderly, primary DLBCL of central nervous system, primary mediastinal (thymic) large B-cell lymphoma and T cell/histiocyte-rich large B-cell lymphoma accounted for 9. 4%(47/500), 4. 4% (22/500), 2. 8% (14/500) and 2. 6% (13/500), respectively. 68. 5% (219/320) of DLBCL-NOS belonged to non-GCB subtype. The percentage of GCB subtype and CD5-positive subtype were 28.4% (91/320) and 3. 1% (10/320), respectively. Comparison of the overall survival, GCB and non-GCB immunophenotypic groups have no significant difference (P = 0. 93). And the same result in which of the EBV-positive DLBCL of the elderly and DLBCL-NOS group, before and after age matched (P =0. 13 and O. 28, respectively). A double-hit lymphoma was found by FISH detection, which presenting as gray zone lymphoma in morphology. Conclusions By using Hans algorithm, GCB and non-GCB subtypes show no significant difference in overall survival. EBV-positive DLBCL of the elderly and DLBCL-NOS also do not have significant difference in overall survival. Fluorescence in situ hybridization technique is helpful in identification of DLBCL with rare phenotypes.     

Diffuse large B-cell lymphoma involving the central nervous system

Lymphomas involving the central nervous system are recognized increasingly in immunocompetent as well as immunosuppressed individuals, and the majority of the cases are diffuse large B-cell lymphoma (DLBCL). The aim of this study was to compare the immunophenotype, clinicopathological features, and association with Epstein-Barr virus (EBV) of DLBCL of the central nervous system (CNS) in 3 different clinical situations: primary, in immunocompetent patients; "primary," in immunosuppressed patients; and in patients with secondary involvement by systemic lymphoma. The authors reviewed the clinicopathological features, morphology, immunophenotype (according to germinal-center B-cell-like and nongerminal B-cell-like subtypes), and association with EBV in 36 cases of DLBCL of the CNS, including 25 primary cases, 5 associated with immunosuppression, and 6 cases with secondary involvement. Survival was evaluated in 15 cases of primary CNS lymphomas. Of the 36 patients, 19 were male and 18 female. Only 2 cases of lymphomas were EBV-positive; both occurred in immunosuppressed patients. Separation into germinal-center and non-germinal center subtypes by an immunohistochemistry panel showed that 68% of primary, 80% of secondary, and 83% of the cases associated with immunosuppression were of non-germinal-center subtype, respectively. Patients with non-germinal-center immunophenotype showed significantly worse survival than those with CNS lymphomas of the germinal-center subtype.     

ALK-positive diffuse large B-cell lymphoma of the stomach associated with a clathrin-ALK rearrangement

ALK-positive diffuse large B-cell lymphoma is a rare, recently characterized lymphoma subtype that shows granular cytoplasmic ALK expression. This report describes a primary gastric ALK-positive B-lineage lymphoma in which a clathrin (CLTC)-ALK fusion was identified by RT-PCR and direct sequencing of the breakpoint. This confirmed the presence of t(2;17)(p23;q23) involving the CLTC gene and is only the 4th report of such a translocation in this lymphoma subtype and the first to describe this tumor within the stomach. As in previous reports, immunophenotyping showed the malignant cell to be a terminally differentiated B-lineage cell characterized by the absence of B-cell antigens and expression of antigens associated with plasma cell differentiation. This case confirms the existence of such a lymphoma subtype arising in extranodal locations and underscores the importance of detailed immunophenotyping and specialized molecular genetic investigations in confirming the diagnosis.