Value of FDG-PET/CT Examinations in Different Cancers of Children, Focusing on Lymphomas

The aim of the study was to assess sensitivity and specificity of FDG-PET/CT in different forms of childhood cancer. We retrospectively evaluated the results dedicated of 162 FDG-PET/CT examinations of 86 children treated with: Hodgkin lymphoma (HL; n?=?31), non-Hodgkin lymphoma (NHL; n?=?30) and other high grade solid tumors (n?=?25). Patients were admitted and treated in two departments of pediatric hematology and oncology in Hungary. FDG-PET/CT was performed for staging (n?=?25) and for posttreatment evaluation (n?=?137). Imaging was performed in three FDG-PET/CT Laboratories, using dedicated PET/CT scanners. False positive results were defined as resolution or absence of disease progression over at least 1 year on FDG-PET/CT scans without any intervention. In some cases histopathological evaluation of suspicious lesions was performed. Fals negative results were defined as negative FDG-PET/CT results in case of active malignancy. Positive predictive values (PPV) and negative predictive values (NPV) were calculated. NPV was 100 %. The highest PPV was observed in high grade solid tumors (81 %), followed by HL (65 %) and NHL (61 %). There was a major difference of PPV in different histological types of HL (50 % in HL of mixed-cellularity subtype, 90 % in nodular sclerosing, and 100 % in lymphocyte-rich and lymphocyte depleted HL). We treated one patient with nodular lymphocyte predominant HL, who had 5 false positive FDG-PET/CT results. PPV of T- and B-lineage NHL were similar (60 % and 62 %, respectively). We observed an interesting difference of PPV in different stages of HL and NHL. In HL PPV was higher in early than in advanced disease forms: 66 % in stage II HL and 60 % in stage III HL, whereas there was an inverse relationship between PPV and disease stages in NHL 0 % in stage I and II patients, 67 % in stage III and 100 % in stage IV patients. PPV was lower in males (54 %) than in females (65 %). PPV were 64 % vs. 58 % in patients under vs. over 10 years of age. Negative FDG-PET/CT results during follow-up reliably predict the absence of malignancy. Positive FDG-PET/CT scan results in general have a low PPV. The relatively high PPV in patients with histologically proven high grade solid tumors, advanced stages of NHL and with nodular sclerosing, lymphocyte-rich and lymphocyte depleted subtypes of HL warrant a confirmation by biopsy, whereas the watch-and-wait approach can be used in other forms of childhood cancer patients with a positive FDG-PET/CT result in course of follow-up examinations.     

171例淋巴瘤病变组织中EB病毒表达情况的分析

目的:探讨不同类型淋巴瘤与EB病毒(Epstein-Barr virus,EBV)感染的关系。方法:收集淋巴瘤组织171例,包括弥漫大B细胞淋巴瘤(DLBC)106例;结外NK/T细胞淋巴瘤,鼻型22例;霍奇金淋巴瘤(HL)19例;血管免疫母细胞性T细胞淋巴瘤(AITL)13例;黏膜相关淋巴组织B细胞淋巴瘤(MALT)11例。应用EBV Lmp-1单抗免疫组化(IHC)和生物素标记的EBER1寡核苷酸探针原位杂交(ISH)分析EBV感染与淋巴瘤的关系。结果:淋巴瘤组织中EBV Lmp-1蛋白与EBER1 mRNA总阳性率分别为11.1%(19/171)、25.7%(44/171)。其中AITL为30.8%(4/13)、61.5%(8/13);HL为47.4%(9/19)、57.9%(11/19);结外NK/T细胞淋巴瘤为22.7%(5/22)、81.8%(18/22);DLBC为0.94%(1/106)、5.7%(6/106);MALT为0(0/11)、9.1%(1/11)。结果显示EBV在DLBC及MALT中的表达率低于AITL、HL及结外NK/T细胞淋巴瘤,差异有统计学意义(P0.05);且原位杂交检测EBER1 mRNA比免疫组化检测Lmp-1蛋白更为敏感(P0.01)。结论:EBV感染与淋巴瘤有密切关系,不同类型淋巴瘤与EBV感染的关系有差异。     

鼻腔鼻窦非霍奇金淋巴瘤免疫表型及其与EB病毒感染的关系

背景与目的:鼻腔鼻窦非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的患病率和免疫表型组成具有地域性差异.本研究探讨中国广州地区57例鼻腔鼻窦NHL免疫表型及其与EB病毒(Epstein-Barr virus,EBV)感染的关系.方法:收集2000年4月1日至2006年10月31日中山大学肿瘤防治中心病理科57例鼻腔鼻窦NHL标本.免疫组化染色确定免疫表型,EBER原位杂交及PCR检测EBV感染情况.结果:在同期诊断的1 412例NHL中,71例(5.03%)发生于鼻腔鼻窦,其中仅有57例适用于本研究.57例鼻腔鼻窦NHL患者中,男性38例,女性19例,年龄3～75岁,中位年龄50岁;44例(77.19%)为鼻型NK/T细胞淋巴瘤,其中37例(84.09%)为EBV /CD56 NK细胞肿瘤,7例(15.91%)为EBV /CD56-细胞毒性T细胞表型;11例(19.30%)为B细胞淋巴瘤,其中6例为弥漫大B表型,2例为Burkitt(Burkitt样)淋巴瘤(EBV ),1例为髓外浆细胞瘤(EBV ),1例为MALT淋巴瘤(EBV-),1例为小淋巴细胞性淋巴瘤(EBV-);2例(3.51%)为外周T细胞淋巴瘤(EBV-).37例适用DNA检测的病例中,25例(67.57%)感染缺失型LMP1(del-LMP1)EBV株,12例(32.43%)感染野生型LMP1(wt-LMP1)EBV株.结论:鼻腔鼻窦NHL最常见的类型为鼻型NK/T细胞淋巴瘤,可进一步分为EBV /CD56 NK细胞及EBV /CD56-细胞毒性T细胞表型.NK/T细胞淋巴瘤均感染了EBV,EBV株主要为del-LMP1型.     

Epstein-Barr virus in lymphoproliferative diseases in the sino-nasal region: Close association with CD56+ immunophenotype and polymorphic-reticulosis morphology

Association between Epstein-Barr virus (EBV) and nasal T-cell lymphoma (NTL) has been demonstrated. NTL has 2 types of histologic figures: one is ordinary non-Hodgkin's lymphoma (NHL) with monomorphous proliferation, and the other is polymorphic-reticulosis (PR) morphology. The presence of the EBV genome and its sub-types (A and B) were examined on paraffin-embedded specimens from 36 cases of sino-nasal lymphomas (SNL) collected from Seoul, Republic of Korea, where the frequency of NTL is high. Patients' ages ranged from 2 to 74 years (median 54 years) with a male-to-female ratio of 2.5:1. Immunophenotypically, 8 cases were B-cell type, 11 were T-cell type with CD56⁻, 14 were CD56⁺ type, and 3 were null-cell type. Five of 11 cases with ordinary NHL of T-cell type and 9 of 14 cases with PR were CD56⁺. The EBV genome was found by polymerase chain reaction (PCR) and in the tumor cells by in situ hybridization (ISH) in 1 of 4 B-cell type (25%), 5 of 10 T-cell type (50%), 11 of 13 CD56⁺ type (85%), and in both of null-cell type (100%). Of 16 cases with PR morphology, 15 (94%) were positive for the EBV genome. All of the 5 NTLs of ordinary NHL with CD56⁻ were negative for EBV. Concerning the sub-type of BV, 16 cases had type A, while none had type-B EBV. These findings suggest that NTL comprises 2 groups: EBV-positive NTLs are CD56⁺ and/or histologically PR, and EBV-negative NTLs are CD56⁻ and histologically ordinary NHL. The current results on Korean patients, together with earlier studies on Japanese and Malaysian patients, have shown the predominance of type-A EBV in sino-nasal lymphoma in Asia. © 1997 Wiley-Liss, Inc.     

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.     

不同类型淋巴瘤438例EB病毒分布特点

目的 探讨不同类型淋巴瘤中EB病毒(EBV)的分布特点.方法 选用免疫组织化学EnVision法标记ALK1、CD3、CD5、CD7、CD10、CD15、CD20、CD23、CD30、CD38、CD43、CD56、CD68、CD79、CD99、CyclinD1、EMA、TdT与EBV潜伏膜蛋白(LMP-1),原位杂交技术标记EBV编码的RNA(EBER).按照2008年WHO淋巴造血系统肿瘤分类标准对存档的438例淋巴瘤组织标本重新分类.结果 在B细胞非霍奇金淋巴瘤(B-NHL)、NK/T细胞淋巴瘤和霍奇金淋巴瘤(HL)中EBER阳性率分别是5.4％(14/261)、16.5％(19/115)和59.7％(37/62),LMP-1阳性率分别为5.4％(14/261)、5.2％(6/115)和59.7％(37/62).弥漫大B细胞淋巴瘤(DLBCL)患者中,EBER在60岁以上组中的阳性率(13.2％,7/53)明显高于60岁及以下组(1.2％,1/81)(P＜0.05);在NK/T细胞淋巴瘤中LMP-1蛋白表达与EBER表达具有不一致性,EBER阳性率明显高于LMP-1(P＜0.05);5例鼻型NK/T细胞淋巴瘤中全部表达EBER;在HL淋巴瘤中LMP-1蛋白表达与EBER表达具有一致性.结论 EBV感染与淋巴瘤类型相关,EBV在鼻型NK/T细胞淋巴瘤中表达率高,HL次之.鉴于EBER与LMP-1在HL中的一致性表达,出于经济学考虑,LMP-1可代替EBER用作EBV的检测.EBV可能在鼻型NK/T细胞淋巴瘤、HL等的发生、发展中有重要作用.     

Reproductive factors and lymphoid neoplasms in Europe: findings from the EpiLymph case–control study

Background

The study of lymphomagenesis has rarely focused on hormonal factors. Higher incidence rates are observed for many lymphoma subtypes in men compared with women suggesting an underlying association. Our goal was to investigate the association between reproductive factors and lymphomas.

Methods

The Epilymph study is a multicenter case?Ccontrol study carried out in six European countries from 1998 to 2004. Female cases of mature T-cell neoplasms (n?=?52), Hodgkin lymphoma (n?=?147), and mature B-cell neoplasms (n?=?795), including its common subtypes, and their respective controls (n?=?1,141) frequency matched by age, gender, and center were considered.

Results

An odds reduction of 29% (95% CI ?46 to ?6%) was observed for mature T-cell neoplasms for each child increase among parous women and of 13% (95% CI ?19 to ?7%) for mature B-cell neoplasms; while no association was observed for Hodgkin lymphoma. By B-cell neoplasm subtypes, these associations were found for chronic lymphocytic leukemia/small lymphocytic lymphoma (?21%, 95% CI ?31 to ?9%) and diffuse large B-cell lymphoma (DLBCL; ?14%; 95% CI ?23 to ?3%). Overall, no associations were observed with age at first and last pregnancy, and ever use of hormonal contraceptives and lymphoma. Higher odds ratios for a short-term use of hormonal contraceptives (<5?years), but not for a long-term use, were observed for mature B-cell neoplasms, DLBCL, and follicular lymphoma compared with never use.

Conclusion

These data support the hypothesis that increased parity confers a protective effect against lymphoma. Less clearly, our results also indicate that hormonal contraceptives could play a role.     

Epstein-Barr Virus-Associated Extranodal Non-Hodgkin's Lymphoma of the Sinonasal Tract and Nasopharynx in Thailand

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our ‍previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin’s lymphoma ‍(cHL), 51% of non-Hodgkin’s lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin’s lymphoma, B-cell (NHL-B) ‍were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin’s ‍lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin’s lymphoma of the nasopharynx ‍(e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ ‍hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in ‍NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and ‍immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant ‍lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP ‍were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) ‍of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-ã gene were detected ‍in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, ‍unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong ‍association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in ‍NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the ‍germline configuration of the TCR genes.     

Chewing of Betel,Areca and Tobacco: Perceptions and Knowledge Regarding their Role in Head and Neck Cancers in an Urban Squatter Settlement in Pakistan

Epstein-Barr virus (EBV) infection is highly associated with specific subtypes of malignant lymphoma. In our ‍previous report on nodal malignant lymphoma in Thailand, we found that 64% of classical Hodgkin’s lymphoma ‍(cHL), 51% of non-Hodgkin’s lymphoma, T-cell (NHL-T), and 13% of non-Hodgkin’s lymphoma, B-cell (NHL-B) ‍were EBV-related. In the present research, we conducted a retrospective study of primary extranodal non-Hodgkin’s ‍lymphoma of the sinonasal tract (e-NHL-ST) and primary extranodal non-Hodgkin’s lymphoma of the nasopharynx ‍(e-NHL-NP) in Southern Thailand, between 1997 and 2004. EBV-encoded RNA (EBER) expression by in situ ‍hybridization was performed in all cases and a T-cell receptor (TCR)-g gene rearrangement study was performed in ‍NHL-T cases. There were 18 cases of e-NHL-ST and 42 cases of e-NHL-NP detected by histologic and ‍immunohistochemistry examinations. The percentages of e-NHL-ST and e-NHL-NP as compared to nodal malignant ‍lymphoma were 3.7% and 6.8%, respectively. Sixteen cases (88.9%) of e-NHL-ST and 7 cases (16.7%) of e-NHL-NP ‍were NHL-T, and the remainder were NHL-B. All of the NHL-T cases in both sites were EBER-positive. Two (5.4%) ‍of the NHL-B cases in the nasopharynx showed EBER positive. Monoclonal bands of the TCR-ã gene were detected ‍in 71.4% of the extranodal NK/T-cell lymphomas, nasal type, patients; 50.0% of peripheral T-cell lymphoma, ‍unspecified, patients; and one case of angioimmunoblastic T-cell lymphoma. This study indicates a very strong ‍association of NHL-T in the sinonasal tract or nasopharynx with EBV infection, the link apparently being weaker in ‍NHL-B patients. The study also indicates that most cases of extranodal NK/T-cell lymphoma, nasal type, are not the ‍germline configuration of the TCR genes.     

Aggressive forms of non-Hodgkin's lymphoma in two patients bearing coinfection of Epstein-Barr and hepatitis C viruses

Although epidemiologic and experimental data suggest an etiopathogenetic role for both hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection in development of B-cell non-Hodgkin's lymphoma (NHL), potential interactions between EBV and HCV during progression of B-cell NHL have not yet been fully investigated. In the present study, tumor biopsy specimens from patients with both B-cell NHL and chronic HCV infection (HCV(+)) were analyzed for the presence of EBV-encoded RNA (EBER) by in situ hybridization (ISH). VH and VL gene segments were amplified from tumor biopsy specimen DNA by PCR. EBV infection (EBV(+)) was detected in tumors from 2 of 31 (6%) HCV(+) B-cell NHL patients. Clinical histories of these two EBV(+)/HCV(+) B-cell NHL patients indicated a particularly aggressive course of disease. Chemotherapy failed to induce long lasting remission for either of these EBV(+)/HCV(+) B-cell NHL patients. Amplification of CDR3 of the Ig heavy chain gene from DNA isolated from each EBV(+)/HCV(+) B-cell NHL indicated the presence of monoclonal B-cell expansion. Rearrangement of Ig genes in neoplastic B-cell clones from both EBV(+)/HCV(+) patients was similar to that previously reported for EBV(-)/HCV(+) B-cell NHL patients. Additionally, neoplastic B-cell clones from these two EBV(+)/HCV(+) B-cell NHL patients did not exhibit intraclonal variation. Previous studies have demonstrated that intraclonal variation is common among neoplastic B-cell clones from EBV(-)/HCV(+) patients. EBV infection may have prevented evolution of variant neoplastic B-cell clones by suppressing antibody affinity maturation. Together, these data suggest that EBV infection may cooperate with HCV infection during progression of B-cell NHL in immunocompetent individuals. Such an interaction may accelerate the course of disease in B-cell NHL patients.     

Epstein-barr virus is localized in the tumour cells of nasal lymphomas of NK,T or B cell type

Seven cases of nasal lymphoma were studied to identify the lineage of Epstein-Barr virus (EBV)⁺ cells using dual-labelling methods. Five cases were phenotypically and genotypically of natural killer cell (NK) type with germ-line configuration of T-cell receptor (TcR) β-chain gene and immunoglobulin heavy-chain joining region (lg/_H) gene, with one case each of T- and B-cell type showing rearranged TcRβ or lg/_H and Λ-light chain genes respectively. EBV genome was clonal in all these cases except in the B-cell case where its clonality was undeterminable. Using in situ hybridization (ISH) for EBV-encoded small nuclear RNA 1 and 2 (EBER), signal was detected in 45% to 88% of nucleated cells in the tumours. Immunostaining for EBV latent membrane protein-1 (LMP) also revealed numerous LMP⁺ cells in 3/5 NK-type cases and the T- and B-cell cases. Using ISH for EBER combined with immunostaining for CD markers and double immunohistochemistry for LMP and CD markers, the predominant lineage of the EBV⁺ cells was identified as: CD2⁺CD3^?CD19^?CD20- CD45R0⁺CD56⁺CD68- in the NK-type cases, CD2⁺CD3⁺CD19^?CD20^? CD45R0⁺CD56^?CD68^? in the T-cell case and CD20⁺CD45R0^?CD68- in the B-cell case, in agreement with the genotype and phenotype of each tumour. These results show that, in EBV⁺ nasal lymphomas of NK, T- or B-cell lineage, EBV was consistently associated with the tumour-cell population and support the view that EBV serves a promoting role in the pathogenesis of different types of EBV⁺ nasal lymphoma. © 1995 Wiley-Liss, Inc.     

Detection of Epstein-Barr Virus and Genotyping Based on EBNA2 Protein in Mexican Patients With Hodgkin Lymphoma: A Comparative Study in Children and Adults

BackgroundEpstein-Barr virus (EBV) is a member of the Herpesviridae family and is associated with Hodgkin lymphoma (HL). Isolates of EBV are classified according to sequence variation in the latency genes such as Epstein-Barr virus nuclear antigen (EBNA). EBNA2 contains the most divergent locus and is classified into type 1 and type 2 or EBNA2A and EBNA2B, respectively. We compared the frequency of EBV and the distribution of EBNA genotypes in Mexican children and adults with HL.Patients and MethodsLymph node biopsy specimens from children and adults with HL were embedded in paraffin. EBV was identified by LMP1 amplification and Epstein-Barr–encoded RNA EBER by in situ hybridization (ISH) and genotyped as EBNA2A or EBNA2B using nested polymerase chain reaction (PCR) and specific primers for the detection of subtype.ResultsSixty-six samples were obtained from 3 hospitals—42 (63%) from children and 24 (37%) from adults with HL. Thirty-two of the 42 samples (76.1%) were positive for EBV in children and 16 of 24 (66.6%) samples were positive in adults (P = .41). In both children and adults, EBV was found more frequently in male patients. Thirty-four of 48 cases could be typed (70.8%). EBNA2A was found in 7/21 (33.3%) children and in 4/13 (30.8%) adults (P = 1.0), and EBNA2B was found in 10/21 (47.6%) children and in 9/13 (69.2%) adults (P = .22). A mix of subtypes was found in 4/21 (19%) children.ConclusionEBV was found frequently in both children and adults with HL. EBNA2B was the most frequent subtype, and a high frequency of mixed subtypes was found in children.     

Blood Epstein–Barr virus DNA does not predict outcome in advanced HIV-associated Hodgkin lymphoma

In HIV-seronegative patients with advanced Hodgkin lymphoma (HL), Epstein–Barr virus (EBV) viraemia at diagnosis predicts a worse progression-free survival (PFS), independent of the International Prognostic Score. However, its role in HIV-associated HL is uncharacterised. We collected clinico-pathologic and treatment data from a prospective series of 44 HIV-associated HLs from 2000 to 2016. We evaluated circulating EBV DNA as a prognostic factor on uni- and multivariable analyses in relationship to the International Prognostic Index criteria. In 44 patients with HIV-associated HL, EBV was detected by in situ hybridisation in all diagnostic biopsies. Blood EBV DNA was detectable in 26 patients (59%) with a median of 600 copies/mL (range 0–161,000). EBV DNA was independent of CD4 cell count (p = 0.9) or HIV viral load (p = 0.6) and did not predict PFS (HR 1.6, 95% CI 0.39–6.7, p = 0.49). EBV DNA is not a prognostic trait in HIV-associated HL. Prognostication in HIV-associated HL should be solely based on the International Prognostic Index criteria.     

Contribution of flow cytometry to the diagnosis of malignant and non malignant conditions in lymph node biopsies

In order to assess the contribution of FC to the diagnosis of lymph node disorders we retrospectively compared the pathological and the FC diagnosis made in 118 consecutive lymph node biopsies. Pathological diagnosis included non malignant conditions (n = 43), B-cell Non Hodgkin lymphoma (NHL) (n = 30), T-cell NHL (1 case), carcinoma (n = 18), Hodgkin lymphoma (HL) (n = 15), melanoma (n = 2), chronic myelocytic leukemia (n = 12), miscellaneous non-lymphoid tissues (n = 6) and undetermined conditions (n = 2). Among the 116 assessable samples, FC was in agreement with histology in 102 cases (87.9%; 95%CI = 81-93) which included 38 benign conditions (90%; 95% CI = 77-97%), 29 NHL (96.7%; 95% CI = 83-100), 18 carcinomas (100%; 95% CI = 81-100), and 12 HL (80.0%; 95% CI = 52-96). Discrepancies (14 cases) included 3 HL undiagnosed by FC and 2 granulomatous adenitis with an erroneous FC diagnosis of HL. Finally, a malignant condition was suspected only by FC in 5 cases (1 carcinoma, 2 B-cell and 2 T-cell NHL) and subsequently demonstrated by additional diagnostic procedures. In conclusion, this study confirms that FC performed on fresh lymph node samples is a powerful diagnostic tool in patients with malignant lymphoma. A few cases left undiagnosed by classical pathological analysis can be recognized by FC. Carcinoma is readily identified by FC analysis, while some benign conditions and Hodgkin lymphoma can be misdiagnosed with the use of FC, although the potential of FC to properly recognize HL is improving compared to previously reported studies. FC is a useful adjunct to pathological analysis of lymph node specimens.     

A pathologic study of childhood lymphoma in Taiwan with special reference to peripheral T-cell lymphoma and the association with Epstein-Barr viral infection.

The authors retrospectively reviewed the clinicopathologic and immunologic features of 65 consecutive cases of childhood lymphoma reported between 1980 and 1989. Southern blot hybridization was also performed in 23 cases to study their association with Epstein-Barr virus (EBV) and human T-cell leukemia virus type 1 (HTLV-1). The 65 cases included 56 non-Hodgkin's lymphoma (NHL) (86%) and 9 Hodgkin's disease (HD) (14%). The NHL could be classified into the following groups: Group I, small noncleaved cell lymphoma (20 cases); Group II, lymphoblastic lymphoma (17 cases); Group III, large cell lymphoma (17 cases); and miscellaneous (2 cases). There was no follicular lymphoma case. Immunohistochemical study on paraffin sections and/or frozen specimens in 47 cases of NHL showed that all the Group I cases belonged to B-cell neoplasm (17 of 17 cases); most of the Group II cases belonged to T-cell neoplasm (9 of 14 cases); and most of the Group III cases were peripheral T-cell lymphoma (PTL) (8 of 16 cases), including 2 cases of Ki-1 lymphoma. The majority of childhood NHL belonged to high-grade malignancy with an aggressive clinical course (median survival time, 8 months). The EBV DNA could be detected from the tumor tissues in 4 of 6 PTL, but in none of the remaining 19 cases of NHL including 6 Burkitt's type lymphomas. HTLV-1 proviral genome was not detected in all specimens examined. The authors concluded that the distribution pattern and clinicopathologic feature of childhood lymphoma in Taiwan are comparable to that in Japan and western countries. The frequent association of EBV with aggressive PTL was unique and deserves additional investigation.     

Genetic variation in N-acetyltransferases 1 and 2, cigarette smoking, and risk of non-Hodgkin lymphoma

Cigarette smoke contains many carcinogens that are metabolically activated through xenobiotic metabolism by phase I and II enzymes, including N-acetyltransferases 1 and 2 (NAT1 and NAT2). We investigated non-Hodgkin lymphoma risk in general and by subtype in relation to NAT1 and NAT2 genotypes and cigarette smoking in a population-based case–control study in Connecticut. Of the 535 controls, 53.1% reported ever smoking, and of the 461 cases, 55.7% reported ever smoking. We found a two-fold increased risk of T-cell lymphoma among those possessing the NAT1*10 genotype compared to those with other NAT1 genotypes; including an OR of 2.0 (95% CI: 1.0–2.4) for those heterozygous or homozygous for NAT1*10 genotypes. Rapid acetylator NAT2 phenotype increased the risk of both T-cell lymphoma (OR = 3.2; 95% CI: 1.1–9.5) and marginal zone lymphoma (OR = 3.0; 95% CI: 1.0–8.7), though these results were based on a small number of cases. When smoking status and risk of NHL was stratified by NAT1 and NAT2 genotypes, an increased risk of NHL overall was observed in current (OR = 1.7; 95% CI: 1.2–2.4) smokers without the NAT1*10 genotype but not among smokers with the NAT1*10 genotype (p-interaction < 0.01). No association between history of cigarette smoking and risk of NHL overall was observed with any NAT2 genotype. Our results present modest evidence that acetylation rate is associated with risk of NHL for specific subtypes and that the NAT1*10 genotype is an “at-risk” allele. Additionally, our results suggest that the relationship between NHL and smoking status may be modified by common genetic variation in NAT1 but not NAT2. We conclude that these findings require replication in larger studies and ultimately in pooled analyses.     

EB 病毒与非霍奇金淋巴瘤——附180 例报道

 目的　探讨 NHL与 EBV感染的相关性。方法　用 ISH方法检测 1 80例 NHL中EBV编码的 RNA( EBER1 /2 )。结果　 ( 1 ) EBER1 /2感染率为 42 .8% ( 77/1 80 ) ,感染率依次为TCL64.8%、NK/T46.2 %、BCL9.5 %。其中 TCL、NK/T与 BCL相比 ,P≤ 0 .0 0 5 ;( 2 )结内、结外EBV感染率依次为 2 2 .2 %、5 3.8% ,有显著差异 ,P<0 .0 0 5 ;( 3)面中线 (鼻腔 /口咽环 ) EBER1 /2感染率 72 .4% ( 5 5 /76) ,多形细胞性 EBER1 /2感染率 70 .1 % ( 5 4 /77)。结论　本地区 NHL与 EBV感染关系密切 ,TCL、NK/T淋巴瘤感染率明显高于 BCL,而且有部位限制性和亚型倾向性.     

Incidence and pathology of primary brain lymphoma in Hong Kong Chinese patients

Primary brain lymphoma (PBL) is an uncommon extranodal lymphoma. Its incidence is rapidly increasing in both immunocompromised and immunocompetent patients in Western countries. Eighteen cases of PBL were identified during a 16-year period among HIV negative patients in Queen Mary Hospital, Hong Kong. One case of post-transplantation lymphoproliferative disease (PTLD) was positive for Epstein Barr virus (EBV) encoded RNA (EBER) by in situ hybridization. All the remaining 17 immunocompetent cases were classified as diffuse large B-cell lymphoma, except for one case of Burkitt's lymphoma. EBER expression was negative in all 13 cases tested. Immunostaining for bcl-2 and bcl-6 was positive in 8/11 and 6/11 cases tested, with heterogeneous combination of expression and intensity. The incidence rate of PBL in immunocompetent patients was stable at 1.03 per million per year. The incidence of PBL in post transplantation (0.16%) and HIV related setting (0.29%) is also low in Chinese. PBL in Chinese patients is almost uniformly represented by EBV negative, diffuse large B-cell lymphoma, confined to the brain. However, the molecular pathogenesis may be heterogeneous.     

High SUV uptake on FDG–PET/CT predicts for an aggressive B-cell lymphoma in a prospective study of primary FDG–PET/CT staging in lymphoma

BackgroundData assessing the role of positron emission tomography (PET)/computed tomography (CT) imaging in lymphoma staging is still being accumulated and current staging is based primarily on CT. This study aims to compare the value of PET/CT over conventional CT and bone marrow biopsy (BMB) in the initial evaluation of patients with lymphoma.MethodsData on 122 patients with PET/CT scans as part of their initial staging were prospectively collected and reviewed. All patients had complete staging, including BMB.ResultsAmong the 122 patients, 101 had non-Hodgkin's lymphoma (NHL) and 21 had Hodgkin's lymphoma (HL). Compared with conventional CT, PET/CT upstaged 21 (17%) cases [B-cell non-Hodgkin's lymphoma (B-NHL), 12; T-cell non-Hodgkin's lymphoma (T-NHL), 3; HL, 6]. Of significance, in 13 patients with 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-avid splenic lesions, four had normal CT findings. A maximum FDG uptake of >10 standardized uptake value (SUV) seems to significantly correlate with an aggressive B-cell lineage (odds ratio 2.47, 95% confidence interval 2.23–2.70). Overall, PET scan was concordant with BMB results in 108 (89%) and discordant in 14 (11%) cases. In HL, our data show that PET scan and marrow results agreed in 19 of the cases (90%), being concordantly negative in 18 cases and concordantly positive in one, giving a negative predictive value (NPV) of 100%, sensitivity of 100% and specificity of 90%. Of note, all 13 with early-stage HL had negative PET/CT scan and BMB. In NHL, all 17 cases of T-NHL had concordant PET and BMB results. In patients with aggressive B-NHL, BMB and PET/CT agreed in 58 patients (92%) and disagreed in five (8%), while the corresponding rates in indolent B-cell lymphoma were 14 (67%) and seven patients (33%), respectively. All seven were falsely negative.ConclusionsPET/CT upstages 17% of cases and detects occult splenic involvement. This may have potential therapeutic and prognostic implications. SUV >10 may predict for an aggressive histology. Except for indolent B-NHL, our data show that PET scans have a good overall NPV in excluding lymphomatous bone marrow involvement. This is particularly true of early-stage HL, suggesting that BMB may be safely omitted in this group.     

Household endotoxin levels and the risk of non-Hodgkin lymphoma

Objective

Endotoxin, a component of the outer membrane of gram-negative bacteria, elicits a strong innate and inflammatory immune response associated with the secretion of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α). Because TNF-α polymorphisms that increase TNF-α production are associated with an increased risk of non-Hodgkin lymphoma (NHL), we hypothesized that increased levels of household endotoxin would be associated with an increased NHL risk.

Methods

We evaluated this association in the National Cancer Institute/Surveillance, Epidemiology and End Results (NCI/SEER) NHL multicenter population-based case–control study. Used vacuum cleaner bags were collected from participants during a home interview. Dust samples from the bags of 594 cases and 442 controls were analyzed for endotoxin [endotoxin unit (EU)/mg of dust] using the kinetic chromogenic Limulus amebocyte lysate assay. Multivariable logistic regression was used to estimate the effect of endotoxin on NHL risk adjusted for age, sex, race, education, study center, and farm exposure.

Results

Endotoxin was not associated with NHL overall [odds ratio (OR) for highest quartile of endotoxin levels = 0.81, 95 % confidence interval (CI) = 0.55, 1.20; p for trend = 0.35] or with diffuse large B-cell lymphoma (OR = 0.63, 95 % CI = 0.34, 1.16; p = 0.31) or follicular lymphoma (OR = 1.07, 95 % CI = 0.61, 1.89; p = 0.73) subtypes. Both working and living on a farm were associated with higher household endotoxin levels compared to never working (p = 0.009) or living (p = 0.01) on a farm. Excluding farmers from the analysis did not change the results.

Conclusions

We found no evidence of a role for household endotoxin in NHL etiology.