B-lymphoblastic Lymphoma Research Articles

Gastrointestinal B-cell lymphoma: a morphologic and immunohistochemical study of 194 cases

To study the morphologic and immunohistochemical features of gastrointestinal B-cell lymphomas. One hundred and ninety-four cases of gastrointestinal B-cell lymphoma were retrieved from the archival file. The clinical features and pathologic findings were reviewed. Immunohistochemical study for B-cell markers, T-cell markers, bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67 was carried out. The male-to-female ratio was 1.4:1. The age of patients ranged from 8 to 85 years. Amongst the 194 cases studied, 128 (66.0%) were diagnosed as diffuse large B-cell lymphoma, including 16 cases of large cell lymphoma associated with mucosa-associated lymphoid tissue (MALT) lymphoma component. There were also 40 cases (20.6%) of MALT lymphoma, 8 cases (4.1%) of follicular lymphoma, 5 cases of (2.6%) of lymphoplasmacytic lymphoma, 3 cases (1.6%) of mantle cell lymphoma, 1 case of (0.5%) of B-lymphoblastic lymphoma and 9 cases (4.6%) of indefinite type (including 5 biopsy cases). The site of involvement included stomach (100 cases, 51.5%), small intestine (43 cases, 22.2%), ileocecal junction (26 cases, 13.4%), appendix (1 case, 0.5%), colon (21 cases, 10.8%) and rectum (3 cases, 1.6%). Amongst the 163 cases which had undergone surgical resection, 20 cases (12.3%) cases had invasion down to the mucosa, 20 cases (12.3%) down to the superficial muscular layer, 19 cases (11.6%) down to the deep muscular layer and 104 cases (63.8%) with full-thickness involvement. Histologic examination showed lymphoepithelial lesions in 52 cases, residual lymphoid follicles in 29 cases, coagulative necrosis in 66 cases and nodular growth pattern in 30 cases. The lymphoma cells in all cases were immunoreactive for B-cell marker CD20. There was also various degrees of positivity for bcl-6, CD10, bcl-10, cyclin D1, TdT, MUM1 and Ki-67. Gastrointestinal B-cell lymphomas can be subdivided into two main groups: large B-cell lymphomas and small B-cell lymphomas. The latter group often poses diagnostic pitfalls. Accurate pathologic typing requires correlation with histologic and immunohistochemical findings.

Gall Bladder and Extrahepatic Bile Duct Lymphomas: Clinicopathological Observations and Biological Implications

Lymphomas of the gall bladder and extrahepatic bile ducts are exceedingly rare. We present the clinicopathological features of 19 cases from our files; 14 patients had primary lymphoma (13 involving gall bladder and 1 involving common hepatic duct), while 5 had systemic lymphoma on further work-up. Most patients presented with symptoms mimicking cholecystitis. The most common primary lymphoma types were diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, B-lymphoblastic lymphoma, and follicular lymphoma. Two cases had features of lymphomatous polyposis, one a case of follicular lymphoma and the second a case of mantle cell lymphoma, with disease limited to the mantle zones, so-called in situ mantle cell lymphoma. Other rare lymphoma subtypes not described earlier in this site included the extracavitary variant of primary effusion lymphoma and plasmablastic lymphoma. Patients with diffuse large B-cell lymphoma and extranodal marginal zone lymphoma were older (mean age 75.8 y) than those with other subtypes (mean age 47 y) and more likely to have gallstones (60% vs. 12.5%). A comprehensive literature review revealed 36 primary gall bladder and 16 primary extrahepatic bile duct lymphomas. When compared with primary gall bladder lymphomas, those involving the extrahepatic bile ducts present at a younger age (47 y vs. 63 y) usually with obstructive jaundice, and are less often associated with gallstones (17% vs. 50%) or regional lymph node involvement (6% vs. 31%). In conclusion, primary lymphomas of the gall bladder and extrahepatic bile ducts show a broad spectrum of disease types, but in many respects mirror the spectrum of primary lymphomas of the gastrointestinal tract.

Clinicopathological analysis of bone tumors with unknown primary site in adults.

e20525 Background: Bone is a frequent metastatic site in malignancy as well as brain, lung and liver. If the diagnosis of malignancy is not determined by any other method, bone biopsy of the involved lesion will be performed to make a diagnosis of malignancy and indicate its primary site. Objective: To pathologically classify bone tumors with unknown primary site. Design: Case-series study. Setting: Single institute patients: 1. Diagnosed as having a malignancy by bone biopsy during the past 10 years because of undetermined malignancy and unknown primary site. 2. More than 16 years old. 3. Patients who had suffered from malignancy in the past were excluded. 4. Patients with diffuse bone marrow invasion were also excluded. Methods: We reviewed clinical information from each medical record including age, sex, and biopsy site and classified according to pathological diagnosis. Primary outcome: Pathological diagnosis. Results: Among 89 patients receiving bone biopsy in the past decade, 27 patients (male 15pts, female 12pts) were eligible. Median age was 60 (± 13.1) years. Biopsy sites were as follows; lumbar vertebra in 5pts, thoracic and sacral vertebra in 4pts, iliac bone in 3pts, and pubic bone in 2pts, and others in 9pts, respectively. According to pathological diagnosis, 14 patients had a carcinoma (adenocarcinoma in 4pts, squamous cell carcinoma and small cell carcinoma in 1pt, carcinoma with not otherwise specified type in 8pts, respectively). Ten patients had a hematologic malignancy, consisting of 5pts of diffuse large B-cell lymphoma, 2pts of plasma cell neoplasm, 1pt of B-lymphoblastic lymphoma, 1pt of B-cell non-Hodgkin lymphoma, and 1pt of granulocytic sarcoma, respectively. The pathological diagnosis of the rest three patients were unclassifiable sarcoma, mesenchymal tumor and malignant tumor in each patient. Conclusions: Hematologic malignancy occupied in about 40% of bone tumor with unknown primary site. As hematologic malignancy is usually highly sensitive to chemotherapy, bone biopsy should be considered if primary site is unknown in suspected malignancy with bone lesion. No significant financial relationships to disclose.

上顎洞に生じたリンパ芽球性リンパ腫例

Lymphoblastic lymphoma is rare, accounting for 1% of adult malignant lymphoma cases, while lymphoblastic lymphoma derived from B cells comprise only 10% of malignant lymphoma. These lesions occur primarily in head and neck skin, and are frequently associated with bone lesions. We report a case of B-lymphoblastic precursor lymphoma developing in the maxillary sinus of a 29-year-old man initially seen for left buccal pain. Computed tomography showed a homogeneous shadow filling the left maxillary sinus. Based on a diagnosis of acute rhinosinusitis, conservative treatment failed to make any improvement. Suspecting a neoplastic lesion, we opened the maxillary sinus, finding trapped mucopurulent fluid and a granuloma-like lesion was found, which biopsy indicated was malignant lymphoma. More detailed examination yielded a diagnosis of B-lymphoblastic precursor lymphoma, treated as for acute lymphocytic leukemia. Following treatment, the lesion disappeared and no symptoms of recurrence have been seen.

Histopathologic classification of 171 cases of canine and feline non-Hodgkin lymphoma according to the WHO

A retrospective collection of 171 lymphoid neoplasms (123 dogs and 48 cats) was classified according to the Revised European-American Lymphoma (REAL) classification, adopted in 2002 by the World Health Organization (WHO), to evaluate the WHO system for categorization of canine and feline neoplasms. Microscopic examination was performed after standard hematoxylin-eosin staining and immunohistochemical labelling for B (CD79a) or T (CD3) cell phenotypes. B-cell lymphomas were prevalent in dogs and T-cell lymphomas in cats. B-Large cell lymphoma (B-LCL) frequently showed plasmacytoid differentiation; notably, two canine plasma cell tumours (PCT) expressed both CD79 and CD3. There were difficulties in differentiating B-lymphoblastic lymphoma (B-LBL) from Burkitt-type lymphoma. Furthermore, intestinal T-cell lymphoma (ITCL) exhibited a huge morphologic variability. Finally, multicentric mature small and thymic T-cell lymphomas were diagnosed, although these categories are not codified by the WHO classification.

A Comprehensive Identification of the Microrna Transcriptome and Its Application in B Cell Malignancies.

Abstract 2403Poster Board II-380 BackgroundMicroRNAs are 18-22 nucleotide-long RNA molecules that regulate expression of genes. We and others have previously demonstrated a role for microRNAs in the pathogenesis of B cell malignancies. Computational predictions suggest that the human genome encodes several thousand microRNAs. Thus far, about 700 microRNAs have been discovered in humans, including over 200 new microRNAs in the past year alone. The ongoing discovery of microRNAs makes it difficult to comprehensively study their role in a disease group. The advent of high throughput sequencing allows the simultaneous identification of millions of transcripts, thereby providing a sensitivity that is several orders of magnitude higher than conventional methods. We hypothesized that high throughput sequencing would be an effective tool to comprehensively identify microRNAs in normal and malignant B cells.While there is an overlap between diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma (BL) in morphology, immunophenotype and cytogenetics, distinguishing between BL and DLBCL is critical because there are important differences in their clinical management. We investigated whether microRNA expression could be used to reliably distinguish BL from DLBCL. Methods and ResultsWe carefully chose 31 human samples to represent the spectrum of normal and malignant B cells including FACS-sorted naive, germinal center, memory, plasma cells, EBV transformed and activated B cells. Samples derived from B cell malignancies included B-lymphoblastic lymphoma, chronic lymphocytic leukemia (immunoglobulin gene mutated and unmutated), mantle cell lymphoma, marginal zone lymphomas, HIV-related lymphoma, BL, DLBCL (activated and germinal center type), primary mediastinal B cell lymphoma, Hodgkin lymphoma, and multiple myeloma.We applied massively parallel, high-throughput sequencing of the 18-22 nt RNAs from these cases and generated a total of 255,624,785 sequences (∼5 billion bases). Using a computational approach that we have previously validated with normal B cells, we identified the expression of 429 known microRNAs in normal and malignant B cells, a number that is over three times higher than previously recognized in any tissue type. We also identified the expression of 302 novel microRNAs in normal and malignant B cells. The vast majority of these microRNAs were highly conserved in multiple species.As a proof of principle, we generated a custom microarray that included all the known human, and viral microRNAs, as well as 302 novel microRNAs identified by sequencing, and applied it to the clinically important distinction of BL from DLBCL. Biopsy samples were collected from 104 patients (BL, N=25, DLBCL, N=79) treated at 9 institutions that comprise an international consortium. All cases were reviewed for pathology diagnosis and profiled for microRNA expression. We constructed a Bayesian predictor to distinguish BL from DLBCL based on the microRNA expression. The predictor performance was tested using leave-one-out cross-validation. We also applied gene expression profiling to the cases of DLBCL to identify the molecular subsets of DLBCL: activated B cell like and germinal center B cell like DLBCL. The microRNA profiles of these cases were equally efficacious in distinguishing the DLBCL subsets.The predictor constructed based on microRNA expression was over 90% accurate in distinguishing BL from DLBCL, using pathology diagnosis as the gold standard. Further, microRNA-based predictor was also over 90% accurate in the distinction of the molecular subsets of DLBCL, compared to the gold standard of gene expression-profiling.As additional validation, we performed in situ hybridization of selected microRNAs to directly visualize their expression using methods that are easily accessible in conventional pathology laboratories. We found excellent concordance between the expression results derived from microarrays and in situ hybridization suggesting a ready path to clinical translation. ConclusionOur study represents the first comprehensive delineation of microRNA expression in B cell malignancies using high throughput sequencing. Our data suggest that microRNAs are a promising marker for the distinction of aggressive lymphomas. Disclosures:No relevant conflicts of interest to declare.

Intraocular Lymphoma: Diagnostic Approach and Immunophenotypic Findings in Vitrectomy Specimens

Diagnosis and classification of primary intraocular lymphoma can be challenging because of the sparse cellularity of the vitreous specimens. To classify and clinically correlate intraocular lymphoma according to the World Health Organization (WHO) classification by using vitrectomy specimens. Clinical history, cytologic preparations, flow cytometry reports, and outcome of 16 patients diagnosed with intraocular lymphoma were reviewed. The study group included 10 women and 6 men. The mean age of the patients was 63 years (range, 19-79 years). Eleven patients had central nervous system involvement and 6 patients had systemic involvement. All cases were adequately diagnosed and classified according to the WHO classification by using combination of cytologic preparations and 4-color flow cytometry with a limited panel of antibodies to CD19, CD20, CD5, CD10, and kappa and lambda light chains. The cases included 9 primary diffuse large B-cell lymphomas of the CNS type; 2 diffuse large B-cell lymphomas, not otherwise specified; 1 extranodal, low-grade, marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT); 1 precursor B-lymphoblastic lymphoma; and 3 peripheral T-cell lymphomas, not otherwise specified. Of note, all 11 cases of diffuse large B-cell lymphoma were CD10-. All the patients received systemic chemotherapy and radiation therapy. Only 4 patients were free of disease at last follow-up (range, 18 months to 8 years), with severe visual loss. Intraocular lymphoma cases can be adequately classified according to the WHO classification. Diffuse large B-cell lymphoma, CD10- and most likely of non-germinal center B-cell-like subgroup, is the most common subtype of non-Hodgkin lymphoma in this site, in contrast to ocular adnexal lymphoma for which MALT lymphoma is the most common subtype.

Primary cutaneous lymphoblastic lymphoma in children: series of eight cases with review of the literature

Primary cutaneous lymphoblastic lymphoma is a rare but well recognised tumour predominantly of childhood. In this study we examine eight cases of cutaneous lymphoblastic lymphoma in children, which is the largest series to date of tumours confined to the skin with or without local lymph nodes (stage I or II) but without systemic disease at diagnosis. The clinical history and histology from the eight cases were reviewed together with a panel of immunohistochemical stains to confirm lineage and diagnosis. Seven of the eight cases were confirmed as B-lymphoblastic lymphoma (B-LBL) of the skin, with the eighth case representing a CD4+/CD56+ plasmacytoid dendritic cell tumour. The cases were all stage I or II, and all patients received systemic chemotherapy after full staging investigations to exclude systemic disease at diagnosis. All patients remained in complete remission at the time of last follow-up of between 3 and 9 years from diagnosis. Lymphoblastic lymphoma may present primarily in the skin without systemic manifestation, with the majority of such cases representing B-LBL. A rare case of childhood CD4+/CD56+ plasmacytoid dendritic cell tumour with similar blastic morphology is also described. Full staging investigations are mandatory at diagnosis to exclude systemic disease. Cases confined to stage I or II at diagnosis carry an excellent prognosis with appropriate systemic chemotherapeutic treatment.

Clinical features and treatment outcomes of adult B- and T-lymphoblastic lymphoma: results of multicentre analysis in Korea

We performed a retrospective multicentre analysis to study the clinical features and treatment outcomes of B-lymphoblastic lymphoma (B-LBL) and T-lymphoblastic lymphoma (T-LBL) in Asian adult patients, and identify risk factors that predict relapse and poor prognosis. Fifty-five newly diagnosed patients (45 T-LBL and 10 B-LBL) were analysed. All patients were treated with intensive chemotherapy regimens including VPDL (vincristine, prednisolone, daunorubicin, L-asparaginase), CALGB (Cancer and leukemia group B), and Stanford/Northern California Oncology Group (NCOG). There was no difference of clinical features between B- and T-LBL except the frequent site of involvement. The overall response rate including complete response (28/55, 50.9%) and partial response (18/55, 32.7%) was 83.6%. Among 46 responders, 22 patients relapsed leading to 20 deaths. Partial responders showed more frequent relapse (10/18, 55.6%) than complete responders (11/28, 39.2%). The median progression-free survival (PFS) was 17 months (95% confidence interval, 11.5–22.5), and the 2-year overall survival was 52 ± 7% with a median follow-up of 50 months (range 8–152). Treatment outcome of T-LBL and B-LBL was not significantly different in terms of response and survival. The presence of pleural effusion was significantly prognostic for overall and PFS (p < 0.05). In conclusion, clinical features and treatment outcome of Asian adult LBL were comparable to previous results, and the prognosis is still poor despite intensive chemotherapy.

Histological characteristics of 21 Papua New Guinean children with high‐grade B‐cell lymphoma, which is frequently associated with EBV infection

The aim of the present study was to confirm the histopathological features of aggressive B-cell lymphoma in Papua New Guinea (PNG)-an EBV endemic region. The immunophenotypic features and expression of EBV-encoded proteins and RNA in B-cell lymphomas were analyzed in 21 PNG children, and compared to the corresponding features of 17 Japanese children with Burkitt lymphoma (BL). Histological diagnosis of the lymphomas from the PNG children was BL in nine patients; atypical Burkitt/Burkitt-like variant of BL (BLL) in three; diffuse large B-cell lymphoma (DLBCL) in four; and B-lymphoblastic lymphoma (B-LBL) in five. The lymphomas from the PNG children had a high positive rate on EBV-RNA in situ hybridization (EBV-ISH; 66.7%). With regard to the histological typing, 10 of 12 patients (83%) with BL/BLL, one of four (25%) with DLBCL, and three of five (60%) with B-LBL were positive for EBV-ISH. The findings of EBV-positive B-LBL were surprising because it is commonly considered that lymphoblastic lymphoma is not associated with EBV. EBV positivity was not detected in the 12 Japanese patients who were available for the EBV-ISH evaluation. It is concluded that it is possible that a proportion of DLBCL and B-LBL besides BL/BLL are associated with EBV in endemic region.

Primary Bone Lymphoma: A New and Detailed Characterization of 28 Patients in a Single-Institution Study

The incidence of primary bone lymphoma (PBL) is so rare that many of its aspects remain unknown. A number of studies have been reported from Western countries, but only a few reports are available from Asia. We retrospectively analyzed 28 consecutive patients diagnosed with PBL initially treated at our hospital between 1995 and 2004. All patients underwent chemotherapy with half receiving radiotherapy as their initial treatment. A log-rank test was used in a univariate analysis to identify factors affecting overall survival. Fifteen (54%) patients were male and 13 (46%) female with a median age of 47 (range: 5-81). Although 19 (68%) patients had diffuse large B-cell lymphoma (DLBCL), other histopathological subtypes (three B-lymphoblastic lymphoma, two anaplastic large cell lymphoma, two indolent B-cell lymphoma, one NK/T-cell lymphoma (NTCL) and one Hodgkin lymphoma) were also included. The pelvis was the most frequently involved site (54%). While 68% of patients had stage IV disease, none of them showed bone marrow involvement at their initial diagnosis. Despite 61% high intermediate-risk and high-risk patients based on the International Prognostic Index, the estimated 3-year overall and progression-free survival rates were 84% and 77%, respectively. Only 'histopathological subtype (immunoblastic variant of DLBCL or NTCL versus others)' and 'response to initial treatment (progression versus remission)' were factors significantly affecting overall survival. Although the total number of patients was relatively small, the detailed clinical data analyses presented here revealed several new characteristics of PBL and some aspects that may be unique to Japanese patients.

Precursor B-Lymphoblastic Lymphoma Presenting as a Solitary Bone Tumor Mimicking Osteomyelitis on MRI

Precursor B-Lymphoblastic Lymphoma Presenting as a Solitary Bone Tumor Mimicking Osteomyelitis on MRI

The impact of age and gender on biology, clinical features and treatment outcome of non‐Hodgkin lymphoma in childhood and adolescence

We analysed the impact of age and gender on biology and outcome of 2084 patients diagnosed with non-Hodgkin lymphoma (NHL) between October 1986 and December 2002 and treated according to the Berlin-Frankfurt-Münster (BFM) multicentre protocols NHL-BFM-86, -90 and -95. Median age at diagnosis was 8.0 years for 97 precursor B-lymphoblastic lymphoma (pB-LBL) patients, 8.8 years for 335 T-lymphoblastic lymphoma (T-LBL) patients, 8.4 years for 1004 Burkitt's lymphoma/leukaemia (BL/B-AL) patients, 11.4 years for 173 diffuse large B-cell lymphoma (centroblastic subtype) (DLBCL-CB) patients, 13.2 years for 40 primary mediastinal large B-cell lymphoma (PMLBL) patients and 10.8 years for 215 anaplastic large-cell lymphoma (ALCL) patients (P < 0.00001). The male:female ratio was 0.9:1 for pB-LBL and PMLBL, 1.7:1 for DLBCL-CB, 1.8:1 for ALCL, 2.5:1 for T-LBL and 4.5:1 for BL/B-AL (P < 0.00001). The probability of event-free survival at 5 years (5-year pEFS) was 85 +/- 1% for all 2084 patients [median follow-up 5.7 (0.1-15.9) years], and was significantly superior for male T-LBL and DLBCL-CB patients. Comparing age-groups 0-4, 5-9, 10-14 and 15-18 years, pEFS was inferior for the youngest patients only in the pB-LBL- and ALCL-groups. T-LBL and DLBCL-CB adolescent females had worse outcome than younger girls while age had no impact on pEFS for boys. We conclude that the distribution of age and gender differed between NHL-subtypes. The impact of gender on outcome differed between NHL subgroups. The prognostic impact of age differed not only by NHL-subtype but also according to gender in some subtypes.

Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody

BAFF-receptor (BAFF-R) is required for the successful maturation and survival of B-cells. We developed an anti-human BAFF-R monoclonal antibody (mAb), 8 A 7. The reactivity of 8 A 7 in normal and neoplastic tissue was examined by performing immunohistochemistry on paraffin-embedded sections. 8 A 7 reacted with lymphocytes in the mantle and marginal zones, but not with lymphocytes in the interfollicular area. Lymphocytes in the germinal centers were found to be negative or occasionally weakly positive for 8 A 7. BAFF-R expression was found only in B-cell lymphoma (44/80, positive cases/examined cases): B-lymphoblastic lymphoma 0/3, B-chronic lymphocytic leukemia/small lymphocytic lymphoma 4/4, mantle cell lymphoma 9/11, follicular lymphoma 10/14, diffuse large B-cell lymphoma (DLBCL) 11/25, marginal zone B-cell lymphoma 8/10, lymphoplasmacytic lymphoma 2/2, plasma cell myeloma 0/2, and Burkitt lymphoma 0/9, but not in T/NK cell lymphomas (0/19) or Hodgkin lymphoma (0/10). BAFF-R was expressed in most low-grade B-cell neoplasms and a small number of DLBCL, suggesting that BAFF-R may play an important role in the proliferation of neoplastic lymphoid cells. Thus, the mAb is very useful for further understanding of both healthy B-cell biology and its pathogenic neoplasms.

Coexpression of CD43 by Benign B Cells in the Terminal Ileum

Expression of CD43 by B cells is often used as a diagnostic criterion in favor of a B-cell lymphoproliferative disorder, including small lymphocytic lymphoma/chronic lymphocytic leukemia, mantle cell lymphoma, Burkitt lymphoma, precursor B-lymphoblastic lymphoma, and a subset of marginal zone B-cell lymphomas. Benign B cells generally do not coexpress CD43. The authors analyzed 20 biopsies of the terminal ileum for nonneoplastic disease for expression of CD43 and compared them with other sites and with CD20, CD138, and CD3 reactivity. The majority of cases (85%) showed strong coexpression of CD43 by benign perifollicular B cells. The presence of CD43 coexpression in B-cell populations of the terminal ileum, including those of Peyer's patches, should not be used as a diagnostic parameter to differentiate extranodal marginal zone B-cell lymphoma of MALT type from reactive processes.

Idiopathic hypereosinophilic syndrome: a case evolving in B-lymphoblastic lymphoma

Idiopathic hypereosinophilic syndrome (HES) is a rare disease characterized by tissue involvement and organ dysfunction due to abnormal eosinophil proliferation. Evolution of HES into myeloid or T-cell malignancies has been frequently reported. Here, we describe a case of HES that preceded the occurrence of a high-grade B-lymphoblastic lymphoma in which clonal evolution has been demonstrated at the molecular level.

Immunoreactivity of CD99 in Non-Hodgkin's Lymphoma: Unexpected Frequent Expression in ALK-positive Anaplastic Large Cell Lymphoma

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.

Immunohistochemical detection of ZAP-70 in 341 cases of non-Hodgkin and Hodgkin lymphoma

Using immunohistochemical methods, we evaluated zeta-associated protein (ZAP)-70 expression in 341 cases of non-Hodgkin and Hodgkin lymphoma. In B-cell NHL, ZAP-70 was positive in five of six (83%) precursor B-lymphoblastic lymphoma, 11 of 37 (30%) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), five of 39 (13%) mantle cell lymphoma, one of 12 (8%) Burkitt lymphoma, and one of 12 (8%) nodal marginal zone B-cell lymphoma. In 22 cases of CLL/SLL, seven of nine (78%) with unmutated IgVH genes expressed ZAP-70, compared with one of 13 (8%) with mutated IgVH genes (P=0.0015 Fisher's exact test). ZAP-70 expression was not detected in diffuse large B-cell lymphoma (n=26), extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (n=24), follicular lymphoma (n=21), plasma cell myeloma/plasmacytoma (n=10), lymphoplasmacytic lymphoma (n=10), or splenic marginal zone lymphoma (n=6). In T/NK-cell NHL, ZAP-70 was positive in all extranodal natural killer (NK) / T-cell lymphoma, nasal-type (n=6) and enteropathy-type T-cell lymphoma (n=4), four of five (80%) subcutaneous panniculitis-like T-cell lymphoma, six of eight (75%) mycosis fungoides, three of five (60%) precursor T-lymphoblastic lymphoma, 10 of 17 (59%) peripheral T-cell lymphoma, two of four (50%) blastic NK-cell lymphoma, one of three (33%) T-cell prolymphocytic leukemia, 13 of 52 (25%) anaplastic large cell lymphoma, and one of six (17%) angioimmunoblastic T-cell lymphoma. Seven of 12 (58%) cutaneous CD30-positive lymphoproliferative disorders were also ZAP-70-positive. In Hodgkin lymphoma, ZAP-70 was negative in neoplastic cells in all cases tested. ZAP-70 staining in B-cell lymphomas and reactive T cells was predominantly nuclear with variable cytoplasmic staining. By contrast, ZAP-70 staining in T/NK-cell lymphomas was heterogeneous, and a shift from predominantly nuclear to predominantly cytoplasmic staining was observed, particularly in those neoplasms with high-grade morphology. In summary, ZAP-70 is expressed by many lymphoma types, correlates with immunoglobulin heavy-chain variable region gene mutational status in CLL/SLL, and can be detected reliably using immunohistochemical methods.

Primary cardiac precursor B lymphoblastic lymphoma in a child: A case report and review of the literature

We describe an extremely rare case of primary cardiac precursor B lymphoblastic lymphoma (B-LBL) in a 10-year-old boy who presented with nonspecific complaints of fatigue and vomiting for 2 weeks and an episode of syncope. Chest X-ray showed cardiomegaly and echocardiography revealed a large right atrial mass, which was successfully resected. Pathology showed precursor B-LBL arising in the heart and there was no evidence of disease at any extracardiac site. A brief review of the literature is also presented.

DNA Polymerase μ Gene Expression in B-Cell Non-Hodgkin's Lymphomas: An Analysis Utilizing in Situ Hybridization

DNA polymerase mu (pol mu) is a novel error-prone DNA repair enzyme bearing significant structural homology with terminal deoxynucleotidyltransferase. Whereas other human error-prone DNA polymerases identified thus far show no preferential lymphoid tissue distribution, the highest levels of pol mu mRNA have been detected in peripheral lymphoid tissues, particularly germinal center B cells. Conceivably, up-regulation of the pol mu gene may be biologically significant in lymphomagenesis, especially in the development of B-cell non-Hodgkin's lymphomas (B-NHLs), because of enhanced error-prone DNA repair activities. To explore this possibility, we generated a digoxigenin-labeled riboprobe to pol mu mRNA and used the probe and in situ hybridization to examine the expression pattern of the pol mu gene in formalin-fixed, paraffin-embedded tissue sections of 37 B-NHLs. This included eight chronic lymphocytic leukemia/small lymphocytic lymphomas, six mantle cell lymphomas, seven follicular lymphomas, nine diffuse large B-cell lymphomas, three splenic marginal zone lymphomas, two Burkitt's lymphomas, and two precursor B-lymphoblastic lymphomas. We also correlated the pol mu mRNA expression levels with the tumor proliferation index, which was assessed in each case by image analysis of Ki-67 immunostained slides. Nineteen of 21 (90%) B-NHLs arising from postgerminal center B cells (follicular lymphomas, diffuse large B-cell lymphomas, splenic marginal zone lymphomas, and Burkitt's lymphomas) exhibited high expression of pol mu mRNA. In contrast, only 2 of 16 (13%) B-NHLs arising from pregerminal center B cells (chronic lymphocytic leukemia/small lymphocytic lymphomas, mantle cell lymphomas, and precursor B-lymphoblastic lymphomas) expressed significant levels of pol mu mRNA. Pol mu gene expression did not seem to correlate with the proliferation index, especially because a significant level of pol mu mRNA was not detected in either case of precursor B-lymphoblastic lymphomas. In conclusion, pol mu gene expression is highly associated with B-NHLs of postgerminal center B-cell derivation. Furthermore, the expression level is independent of the proliferation rate and thus is unrelated to the biological aggressiveness of the tumors. These findings, along with the error-prone nature of the enzyme, suggest that up-regulation of pol mu gene expression may be a contributing factor to the pathogenesis of a subset of B-NHLs through DNA repair-associated genomic instability.