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Objective: To determine the usefulness of fine needle aspiration cytology (FNAC) in combination with flow cytometry on the new World Health Organization (WHO) classification of malignant lymphoma., Study Design: Smears and flow cytometry reports of patients who underwent both methods at the same time were independently examined. Both methods were classified according to the new WHO classification of malignant lymphoma., Results: A group of 131 smears were examined. In 89 cases exact diagnosis was made by cytomorphology. Twenty-five cases were not classified exactly or were classified incorrectly, resulting in a sensitivity of 96.4% and a specificity of 85%. With flow cytometry, only 30 of 131 patients could be classified exactly, resulting in a sensitivity of 27% and specificity of 100%, respectively. The combination of methods showed a sensitivity of 85% and specificity of 100%., Conclusion: The combination of FNAC and flow cytometry obtained by FNAC can distinguish between benign and malignant lymphoid infiltrates and support a diagnosis of lymphoma.

Background: Primary lymphoma of genitourinary system is rare as these organs do not contain lymphoid tissue, however secondary involvement often occurs. The most commonly affected genitourinary organ is the kidney., Methods: Medical records of 901 patients with documented NHL seen at Shaukat Khanum Memorial Cancer Hospital & Research Center during 1995-2003 were studied for the incidence, histopathological, clinical and radiological correlation of renal involvement in NHL., Results: 19(2.1%) patients had renal involvement. Male to female ratio was 3.75:1. Histology was diffuse large cell lymphoma in 12(63%) patients. IPI was High, High intermediate and Low intermediate in 17(89.5%) patients. Radiologically, 5(26.5%) patients had the disease above the diaphragm, 2(10.5%) patients had disease below the diaphragm while 12(63%) had disease on both sides of the diaphragm. 11(58%) showed complete response, 1(5.5%) showed partial response while 7(36.8%) showed progressive disease., Conclusion: Majority of patients with renal involvement had low intermediate or higher IPI compatible with significant progression rate. The findings and disease behavior in our population is comparable to those quoted in English literature. Radiological tools have made it easier to monitor disease response and renal biopsy is seldom required.

Objective: To investigate the clinicopathology and immunophenotype of primary non-Hodgkin lymphoma (NHL) of the female genital system, and to analyze the prognosis of such tumors., Methods: Clinicopathologic features of 43 cases of primary NHL of the female genital system were studied retrospectively, with the histological classification based on the Classification of Haematopoietic and Lymphoid Tumors (WHO, 2001). Immunochemistry technique, in-situ-hybridization and polymerase chain reaction methods were used to detect the immunophenotype, epstein barrvirus (EB) virus infection status and immunoglobulin heavy chain gene rearrangement, respectively., Results: (1) Primary lesions: there were 24 cases of lymphoma originating in the ovary, 3 cases in the endometrium, 10 cases in the cervix, 2 cases in the vagina and 4 cases in the vulva. (2) Staging: 12 cases (28%) were in stage I, 9 cases (21%) in stage II, and 22 cases (51%) in stage III. (3) Histological classification: 37 cases (86%) were diffuse large B cell lymphoma (DLBCL), 3 cases were Burkitt lymphoma and the remaining 3 cases were unspecified peripheral T-cell lymphoma according to biopsy, immunophenotype analysis, in-situ-hybridization technique and IgH gene rearrangement detection. (4) Prognosis analysis: increase in the level of lactic acid dehydrogenase, stage III, DLBCL and single operation suggest poor prognosis., Conclusions: Establishment of the diagnosis of primary NHL of the female genital system is based on biopsy, immunophenotype analysis, in-situ-hybridization technique and IgH gene rearrangement detection, which play important roles in diagnosis and differential diagnosis of the tumor. Combined therapy is the first choice of therapeutic regimens.

In the last decades, considerable changes in the classification of lymphomas have been made. In addition to morphology and immunohistochemistry, the last WHO (2001) classification also utilizes cytogenetics and molecular biology. In many cases classification notices oncogenic mechanisms. The authors describe some differences in immunophenotype in certain entities: chronic lymphocytic leukaemia/small lymphocytic lymphoma--CLL/SLL, follicular lymphoma--FL, mantle cell lymphoma--MCL, diffuse large B-cell lymphoma--DLBCL, and anaplastic large cell lymphoma--ALCL, mainly with respect to prognosis. The authors point out to heterogeneity within the individual types of lymphomas from the point of view of morphology, immunohistochemistry and molecular biology. Recently it has been shown, that differences in prognosis are not limited to individual nosologic entities, but also may be found within the particular category of lymphoma. For example, CLL/SLL is divided in two different subunits according to mutational status of variable segment (VH) of the immunoglobulin heavy chain gene. The cases with unmutated VH segment display progressive disease which is in contrast to cases with the same morphology but with mutated VH segment. Similar differences were found in MCL. Attention is drawn to oncogenic and apoptosis-regulating mechanisms, such as gene p53 and the Bcl-2 family.

In France, adolescents (15-20 years) with non Hodgkin's lymphoma (NHL) are referred either to paediatric or to adult onco-haematological departments. According to data obtained from regional tumour registries (covering about 10% of France), their 5 year survival rate was 59% whereas it was 87% for children (< or =14 years) treated for NHL during a similar period of time. We reviewed the management of NHL either by the paediatricians or the onco-hematologists for adults. The categories of NHL that are reviewed and whose clinical and biological characteristics are presented are: Burkitt, lymphoblastic and large cell, either B or anaplastic. This review shows that, in most series, outcome was better in children than in adults. This raises the reasons of this difference: is it due to the different therapeutic approaches, to different tolerance of chemotherapy, to different biology within the same histological type ? Further studies specific to the adolescents are needed to better know the biology of their lymphoma and to determine the best therapeutic approach.

Data on 23 patients with low-grade non-Hodgkin lymphomas (NHLs), 4 mantle (MT), 4 marginal zone (MZ), and 15 follicular (FL), were analyzed and compared with 10 high-risk (HR) B-cell chronic lymphocytic leukemias (B-CLLs) with lymph node involvement and 4 diffuse large-cell lymphomas (DLCLs). A significant increase in circulating Vdelta1 T lymphocytes producing interleukin-4 (IL-4) was found in patients with FL, MT, and MZ NHL, at variance with DLCL and HR B-CLL. IL-4 was also detectable in the sera and lymph nodes of the same patients. In 19 of the 23 patients with NHL with increased circulating Vdelta1 T lymphocytes, B cells expressing the UL-16-binding proteins (ULBPs) ULBP2 or ULBP3 or both were found in peripheral blood, bone marrow, or lymph nodes. Of note, in HR B-CLL or in DLCL, where leukemic cells were negative for ULBPs, no Vdelta1 T-cell increase was found. Moreover, Vdelta1 T lymphocytes from patients with FL NHL proliferate in response to ULBP2+ and ULBP3+ lymphoma cells. Finally, patients with high expression of ULBPs, increased circulating Vdelta1 T lymphocytes, and high levels of serum IL-4 showed stable disease in a 1-year follow-up in contrast to patients with low circulating Vdelta1 T cells and undetectable IL-4 or ULBPs.

This retrospective study investigated a population of 96 dogs with newly diagnosed malignant lymphosarcoma that were treated with the commonly used University of Wisconsin-Madison (UW-M) chemotherapy protocol. Pretreatment characteristics were analyzed to determine prognostic factors. Dogs with higher World Health Organization (WHO) stages (including stage IV) and dogs with hypercalcemia were at significantly higher risk of relapse (P=0.018 and P=0.016, respectively). Dose reduction, treatment delays, and prior therapy with cortico-steroids were not associated with clinical outcome. First remission duration of 270 days was similar to historically reported data. Overall survival time of 218 days was much shorter than historical data.

A seasonal peak in hematologic malignancies may support hypotheses of infection-related precipitating events. Moderately increased incidence rates have been observed during the spring for leukemias and Hodgkin's disease but few studies have been conducted of non-Hodgkin's lymphoma (NHL). Our study consisted of 77,173 NHL patients in the Surveillance, Epidemiology, and End Results database diagnosed during 1973 - 99. Chi-square analyses showed excess observed-vs.-expected diagnoses during March, April, and June (P < 0.0001). B-cell origin subtype, but not T-cell/NK, was diagnosed more frequently in March. Controlling for age, sex, geographical location, and diagnosis year, multivariate Poisson regression revealed peaks in both March and April (P < 0.0001). Excluding cases in December, due to consistent troughs, regression uncovered greater-than-expected incidence during spring months for patients aged 20 - 39 years and 40 - 64 years (P = 0.043, P = 0.0001) but not among patients >or= 65 years. Future studies are needed to discern if a spring peak is due to diagnostic bias or other uncontrolled factors.

Based on the systematic improvements in treatment over recent decades, more than 70% of children and adolescents with non-Hodgkin lymphoma will survive at least 5 years with standard chemotherapy. This report highlights several advances in treatment for each histologic subtype of childhood non-Hodgkin lymphoma, focusing on published results of clinical trials from European and North American study groups.

Non-Hodgkin lymphoma (NHL), a malignancy that manifests in the lymphatic system, is one of the most commonly occurring hematologic disease types in the United States and other Westernized countries. NHL is divided into a range of subtypes with differing clinical features and outcomes. Depending on the type of NHL and the patient's overall clinical presentation, treatment varies from systemic combined chemotherapy regimens with or without immunotherapy, radioimmunotherapy, and transplants to investigational options. Oncology nurses play a vital role in implementing successful treatment and management of patients with NHL as oncology care moves into an era of novel targeted therapies.

Agranular CD4+/CD56+ hematodermic neoplasm is a distinct form of lymphoma with aggressive behavior and marked predilection for cutaneous involvement. Because of CD56 positivity, natural killer cells were initially suggested as the cell of origin in this tumor. In the recent World Health Organization-European Organization for Research and Treatment of Cancer classification, the term blastic natural killer cell lymphoma has been replaced with CD4+/CD56+ hematodermic neoplasm because of its derivation from a plasmacytoid dendritic cell precursor. Clinicopathologic features, immunohistochemical features, and differential diagnosis of this rare neoplasm with emphasis on the recent World Health Organization-European Organization for Research and Treatment of Cancer classification are discussed.

Objectives: To investigate the existence of quantum metabolic values in various subtypes of non-Hodgkin's lymphoma (NHL)., Methods: Fifty-eight patients with newly diagnosed NHL and positron emission tomography (PET) performed within three months of biopsy were included. The standardized uptake value (SUV) from PET over the area of biopsy and serum glucose [Glc] were recorded. The group glucose sensitivity(G) for indolent and aggressive NHL was obtained by linear regression with ln(SUV) = G x ln[Glc] + C, where C is a constant for the group. Finally, the individual's glucose sensitivity (g) was obtained by g = {ln(SUV)-C}/ln[Glc], along with their means in various subtypes of NHL. To further investigate the influence of extreme [Glc] conditions, the SUVs corrected by the individually calculated g at various glucose levels, [Glc'] using SUV' =SUV x {[Glc']/[Glc]}(g), were compared to the original SUVs for both indolent and aggressive NHL., Results: The averaged g (=G) for aggressive was significant different from that for indolent NHL (-0.94 +/- 0.51 vs. +0.13 +/- 0.10, respectively, p < 0.00005). There were significant differences in SUV for [Glc] < 80 or >110 mg/dl for both types of NHL. Unlike overlap among SUVs between NHL subtypes, the g value clearly categorized them into two distinct groups with positive (near-zero) and negative g values (around -1) for the indolent and aggressive NHLs, respectively., Conclusions: Distinct quantum metabolic values of -1 and 0 were noted in NHL. Aggressive NHL has a more negative value (or higher glucose sensitivity) than that of indolent and, thus, is more susceptible to extreme glucose variation.

The SEER (Surveillance, Epidemiology, and End Results) data for the years 1975-1998 show that children with non-Hodgkin lymphoma (NHL) have a better treatment outcome than do adults. Many factors may contribute to this age-related difference. Some factors are related to the patient (e.g., drug distribution and clearance, performance status, compliance, sex) whereas others pertain to tumor histology and biology. The spectrum of NHL subtypes is well known to differ in children and adults. From ages 5 through 14 years, Burkitt lymphoma is the predominant histologic subtype, whereas diffuse large B-cell lymphoma is most common in the 15- to 29-year age range. Because different treatment strategies are often used in children and adults with NHL, the choice of therapy for adolescents and young adults (ages 15 through 29 years) is challenging and somewhat controversial. It is reasonable to consider pediatric strategies for some adolescents and very young adults with NHL, and pediatric strategies are currently used to treat adults with certain subtypes of NHL (Burkitt lymphoma, lymphoblastic lymphoma). However, the use of pediatric strategies in adults does not guarantee a comparable outcome, as illustrated by trials for adult lymphoblastic lymphoma. There is clearly a need for further biologic study of NHL in children, adolescents, and young adults. Age-related differences in tumor biology have been demonstrated in anaplastic large-cell lymphoma (ALCL) and diffuse large B-cell lymphoma (DLBCL). Additional biologic data will not only improve prognosis and treatment stratification but, more important, will lead to the identification of specific molecular targets for therapy.

Background: The aim was to investigate whether 2 subgroups of Hodgkin lymphoma (Epstein-Barr virus-positive and Epstein-Barr virus-negative) are associated with smoking or alcohol., Methods: Patients with lymphoma diagnosed between age 16 and 69 years in geographically defined areas of England were recruited between 1998 and 2003. One control, matched to each lymphoma case on sex, date of birth, and area of residence, was randomly selected from population registers. Self-reported histories of tobacco and alcohol use were collected during face-to-face interviews with cases and controls., Results: Compared with lifelong nonsmokers, ever-smokers were at increased risk of Hodgkin lymphoma (odds ratio =1.4; 95% confidence interval = 1.1-1.9). This excess was among current smokers, defined as smoking 2 years before diagnosis (1.7; 1.2-2.3). An increasing trend was observed with rising numbers of years smoked. Risks fell as the number of years stopped smoking increased, becoming equivalent to that of a nonsmoker 10 or more years after quitting. Associations were suggested for Epstein-Barr virus-positive Hodgkin lymphoma, but less so for Epstein-Barr negative Hodgkin lymphoma. No associations between Hodgkin lymphoma and alcohol consumption were observed., Conclusions: The association between smoking and Hodgkin lymphoma in general, and Epstein-Barr-positive Hodgkin lymphoma in particular, is consistent with previous studies. Further exploration of the relationship between Hodgkin lymphoma and smoking and of the potential mechanisms by which smoking could interact with Epstein-Barr virus status to increase Hodgkin lymphoma risk are required.

Experimental animal model of tumor progression based on mice lymphosarcoma (LS) and resistant lymphosarcoma (RLS) has been developed. LS tumor displays high sensitivity to cyclophosphamide, which is widely used in anticancer therapy. RLS tumor was derived from LS by passaging in mice receiving low concentration of cyclophosphamide (20 mg/kg) and display resistance to cyclophosphamide (up to dose 150 mg/kg). The primary cultures of LS and RLS tumors display different expression levels of the genes related to apoptosis and multiple drug-resistant phenotype: in RLS tumor high levels of mdr1b and bcl-2 genes and low level of p53 gene expression were found. A total of 10% of cells in RLS primary culture display multiple drug-resistant phenotype and survive even at high dose of cytostatics. Cultivation of RLS primary culture in the presence of increasing vinblastine concentrations gives RLS(40) cell culture, which exhibits high levels of mdr1a/1b genes expression as compared to RLS and 20-fold increase of resistance to cytostatics. Drug-resistant RLS(40) cells were transplanted into CBA mice and sensitivity of the tumors to anticancer drugs was tested. RLS(40) tumors were resistant to a number of cytostatics used in anticancer therapy (cyclophosphamide, cysplatin, vinblastine, rubomycinum). Thus, RLS(40) tumor can be used as model, which corresponds to tumor status observed in patients after one or several courses of chemotherapy and can be useful for testing conventional therapy alone or together with newly developed gene-targeted therapeutics.

Profound disruption of immune function is an established risk factor for non-Hodgkin lymphoma. We report here a large-scale evaluation of common genetic variants in immune genes and their role in lymphoma. We genotyped 57 single nucleotide polymorphisms (SNP) from 36 candidate immune genes in 1,172 non-Hodgkin lymphoma cases and 982 population-based controls from a US multicenter study. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the association between individual SNP and haplotypes with non-Hodgkin lymphoma overall and five well-defined subtypes. A haplotype comprising SNPs in two proinflammatory cytokines, tumor necrosis factor-alpha and lymphotoxin-alpha (rs1800629, rs361525, rs1799724, rs909253, and rs2239704), increased non-Hodgkin lymphoma risk overall (OR, 1.31; 95% CI, 1.06-1.63; P = 0.01) and notably for diffuse large B cell (OR, 1.64; 95% CI, 1.23-2.19; P = 0.0007). A functional nonsynonymous SNP in the innate immune gene Fc gamma receptor 2A (FCGR2A; rs1801274) was also associated with non-Hodgkin lymphoma; AG and AA genotypes were associated with a 1.26-fold (95% CI, 1.01-1.56) and 1.41-fold (95% CI, 1.10-1.81) increased risk, respectively (P(trend) = 0.006). Among non-Hodgkin lymphoma subtypes, the association with FCGR2A was pronounced for follicular and small lymphocytic lymphomas. In conclusion, common variants in genes influencing proinflammatory and innate immune responses were associated with non-Hodgkin lymphoma risk overall and their effects could vary by subtype. Our results require replication but potentially provide important clues for investigating common genetic variants as susceptibility factors and in disease outcomes, treatment responses, and immunotherapy targets.

Objective: To assess the relative frequency of (primary and secondary) mammary lymphomas presenting to a tertiary care hospital, Pakistan and its categorization according to WHO classification of lymphoid neoplasms., Methods: All NHLs (nodal and extra nodal) diagnosed in the section of histopathology during 1992-2004 were retrieved and reviewed. All patients (n=30) diagnosed with lymphomatous involvement of the breast were selected. Distinction between primary and secondary breast lymphomas was not made owing to lack of availability of clinical information., Results: A total of 5637 breast malignancies were diagnosed in our department during the study period of 10 years and the total number of NHLs (Nodal and extra Nodal) was 2632. Thirty (n=30) patients accounting for 1.13% were diagnosed to have lymphomatous involvement of the breast. The Female to Male ratio was 13.5:1; age range was 12-92 years with a median age of 43 years (Mean age 46.5 years and Standard deviation of age was 16.88 years). The sites of the lesions were the right breast in 11 cases (37.93%), left breast in 9 cases (31.03%) and both breasts in 2 cases (6.89%), while the location of 8 masses (27.58%) was unknown. Immunohistochemical studies were negative for cytokeratins (MNF and Cam 5.2) in all cases. All cases of DLBCL expressed B cell lineage antigens and were positive for LCA and Pan B (CD20 and 79a)., Conclusion: We concluded that breast lymphomas represent 1.13% of all NHL and 0.5% of all breast malignancies in this study. The most frequent morphologic type was diffuse large B-cell lymphoma. As patients with primary breast lymphoma have a better prognosis than those with carcinoma of the breast or patients with extranodal lymphomas, a multidisciplinary approach including surgery, radiotherapy, and chemotherapy when needed would result in a more favourable outcome.

Objective: To investigate the relationship between histopathological subtype of non-Hodgkin' s lymphoma(NHL) and chromosomal abnormalities, and compare the difference of chromosomal abnormalities between China and the West., Methods: Routine G banding chromosome analysis and fluorescent in situ hybridization( FISH) were performed on lymph node specimens from 155 NHL patients., Results: Diffuse large B-cell lymphoma( DLBCL) constituted 38.1% of the cases followed by follicular lymphoma(FL) 17.4% , small lymphocytic lymphoma( SLL) 10.3% , peripheral T-cell lymphoma ( PTCL) ( unspecified) 8.4%, and angioimmunoblastic lymphoma 7.1%. One hundred nineteen patients (76. 8%) had clonal chromosomal abnormalities. The incidence of chromosomal abnormalities among FL, SLL, DLBCL, anaplastic large cell lymphoma (ALCL) and precursor T-cell lymphoblastic lymphoma (TLBL) was 96.3% , 87.5% , 86.4%, 83.3% and 83.3%, respectively. Complex karyotype was 86. 3% in DLBCL. The most frequent structural abnormalities in DLBCL involved chromosomes 3, 6, 14 and 1, with had high frequencies of 3q27 (41.2%) and 6q21, 6q23, 6q25 involvement (23.5%). But only 2 cases of DLBCL had classical t( 14; 18) (q32;q21) which was lower than that in the West (20%). The positive rate of IgH rearrangement was 40. 1% in DLBCL by FISH. No 13q14 deletion was found in 16 cases of SLL. Normal karyotype was observed in 8/11 cases with angioimmunoblastic T-cell lymphoma patients., Conclusions: The distribution of the histopathological subtypes of NHL is different among different geographical areas. The chromosomal abnormalities in DLBCL was comparable between China and the West, but t( 14; 18) was infrequent in the former. The chromosomal abnormalities in SLL was different from the West. The incidence of chromosomal abnormalities in angioimmunoblastic T-cell lymphoma was lower than that in the West.

Non-Hodgkin's lymphomas (NHL) are tumours of the lymphoid cells. During the process of development of lymphoid cells, neoplasia may evolve at any point. Neoplastic cells usually carry the imprint of cell of origin at the stage of origin. Various types of NHL may have similar morphology with wide variation in origin, immunophenotype and other biological features. Different ancillary laboratory techniques may help to overcome the limitations of morphology in this aspect. The commonly used ancillary techniques in lymphomas are immunocytochemistry (IC), flow cytometry, Southern blot (SB) technique, polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH). In addition, laser scanning cytometry (LSC) and DNA microarray technologies are in the research phase. Various laboratory techniques are used for immunophenotyping, demonstration of monoclonality, identification of chromosomal translocation, assessment of cell kinetics and expression of mRNA in the tumour cells. Flow cytometry helps in rapid immunophenotying of NHL and it has an added advantage over IC in recognizing the co-expression of CD markers. Fine needle aspiration cytology (FNAC) combined with flow immunophenotyping may help us to diagnose and subclassify certain NHLs, such as follicular lymphoma and mantle cell lymphoma, which were previously recognized as pure morphological entities. Loss of morphology is one of the important limitations of flow cytometry. LSC can overcome this limitation by studying morphology along with the immunophenotyping pattern of individual cells. Chromosomal changes in NHL can be identified by SB, PCR and FISH. Molecular diagnosis of NHL helps in diagnosis, subclassification, prognostic assessment and even in planning of therapy. DNA microarray is a relatively newer and promising technology. It gives information about the expression of several thousands of genes in a tumour in a single experiment. In the near future, FNAC combined with ancillary techniques may play a major role in diagnosis, subclassification and management of lymphomas.

Background: Very elderly patients (> or =80 years old) with non-Hodgkin's lymphoma (NHL) frequently have co-morbid conditions and are generally excluded from clinical trials or even from treatment. The optimal treatment of these patients is unknown., Patients and Methods: We reviewed the records of 109 patients > or =80 years at diagnosis of NHL (65 F/44 M; median age: 84 years, range; 80-95)., Results: Seventy-eight patients (72%) had aggressive NHL, 25 (23%) had indolent and NHL, eight had unclassified disease. Advanced-stage disease was noted in 54%. Forty patients (39%) had a poor ECOG performance status (PS), and 52 (49%) had an intermediate or high risk International Prognostic Index (IPI). Seventy-nine patients (72%) were treated with chemotherapy and 37 (34%) with radiotherapy. Initial chemotherapy consisted of chlorambucil in 15, oral etoposide in 2, and combination protocol in 62. Only 16% of patients received full-dose therapy, and only 50% completed > or =6 cycles of combination chemotherapy. The overall response rate for the 69 evaluable patients was 84% (complete 56.5%, partial 27.5%). Overall 5-year survival for the whole group was 39%, and median survival time was 26 months., Conclusion: A high response rate can be achieved in very elderly NHL patients despite aggressive histology, poor prognostic features, and reduced doses of chemotherapy. Age alone should not be a contraindication to treatment.

Molecular diagnostics for lymphoid malignancies has undergone substantial technical evolution during the past two decades, moving from labor-intensive investigations of individual abnormalities to high-throughput genome-wide analyses. Accordingly, its role has expanded to new fields such as monitoring of minimal residual disease and, more recently, outcome prediction in specific lymphoma subtypes. One novel technology that has had a major impact on the molecular diagnosis of lymphoid malignancies is gene expression profiling by DNA microarrays. It has provided robust and distinct molecular signatures for the most common types of lymphomas and has identified novel subsets that would not be identified by conventional methods. It also has led to the construction of molecularly defined prognostic models in these lymphoma subtypes and to a better understanding of the molecular mechanisms of lymphomagenesis. This development will undoubtedly transform diagnostic medicine in the near future and lead us into an era when tumor diagnosis will incorporate the information of critical molecular abnormalities that will have significant impact on disease outcome in each individual tumor sample. Future treatments are likely to be founded on effective, individualized, and mechanism-based therapies with the least toxicity.

Primary CNS lymphoma is an aggressive form of non-Hodgkin lymphoma whose growth is restricted to the central nervous system. We used cDNA microarray analysis to compare the gene expression signature of primary CNS lymphomas with nodal large B-cell lymphomas. Here, we show that while individual cases of primary CNS lymphomas may be classified as germinal center B-cell, activated B-cell, or type 3 large B-cell lymphoma, brain lymphomas are distinguished from nodal large B-cell lymphomas by high expression of regulators of the unfolded protein response (UPR) signaling pathway, by the oncogenes c-Myc and Pim-1, and by distinct regulators of apoptosis. We demonstrate that interleukin-4 (IL-4) is expressed by tumor vasculature as well as by tumor cells in CNS lymphomas. We also identify high expression in CNS lymphomas of several IL-4-induced genes, including X-box binding protein 1 (XBP-1), a regulator of the UPR. In addition, we demonstrate expression of the activated form of STAT6, a mediator of IL-4 signaling, by tumor cells and tumor endothelia in CNS lymphomas. High expression of activated STAT6 in tumors was associated with short survival in an independent set of patients with primary CNS lymphoma who were treated with high-dose intravenous methotrexate therapy.

The cutaneous environment hosts a number of hematopoietic neoplasms that are dominated by primary cutaneous (PC) T-cell lymphomas. Recent progress in molecular biology and immunology has provided tools to investigate the pathogenesis and the biology of these neoplasms. This review highlights newest findings concerning the immune biology of CD4+ CD56+ hematodermic neoplasms, and PC T-cell and B-cell lymphomas, speculating how these can be translated into more sophisticated, biology-based treatment approaches in the near future.

The recent WHO classification of non-Hodgkin's lymphoma is based on the morphology and immunohistochemical expression of the lymphoma cells and to a lesser extent, on the molecular and cytogenetic findings. Fifty-three cases of non-Hodgkin's lymphoma were included in the study. Of these, seven cases were primary extra nodal lymphomas. Twenty two patients had peripheral blood and/or bone marrow involvement. A detailed morphological assessment was done and classified using the International working formulation. The two most common types encountered were diffuse large cell lymphoma and small lymphocytic lymphoma. Immunohistochemistry was done using labeled streptavidin-biotin peroxidase complex with CD3, CD20, CD15, CD30, CD 45 (leukocyte common antigen), Cyclin D1, EMA (epithelial membrane antigen). 38 cases (72%) showed B cell expression and 12 cases (22.5%) showed T cell expression. Three cases did not express either marker. B-cell diffuse large cell lymphoma (26%) was found to be the predominant B cell non-Hodgkin's lymphoma. The commonest T-cell lymphoma was T lymphoblastic lymphoma (67%) followed by peripheral T cell angioimmunoblastic lymphoma (25%). Immunohistochemistry is a useful and necessary diagnostic modality and helps subdivide prognostically different types of non-Hodgkin's lymphoma.

Objective: To analyze the prevalence of lymphoma subtypes in Shanxi according to the latest World Health Organization (WHO) classification, and to compare the figures with those in other parts of the world., Methods: The hematoxylin and eosin-stained sections of 447 lymphoma cases from the archive files of Shanxi Tumor Hospital were reviewed. Immunohistochemical study was performed using a panel of antibodies, including ALK1, bcl-6, CD (1a, 3, 4, 5, 7, 8, 10, 15, 20, 23, 30, 43, 56, 68, 79a and 99), cyclin D1, EMA, IgD, kappa, lambda, LMP1, PAX5, TdT and Vs38C. In addition, in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER) was carried out. All cases were then reclassified according to the latest WHO classification of lymphoma., Results: Of the 447 cases studied, 385 cases (86.1%) were confirmed to be non-Hodgkin lymphoma (NHL), while 62 cases (13.9%) belonged to classic Hodgkin lymphoma (HL). Of the NHL cases, 68.3% were of B-cell lineage and 30.6% were of T and/or NK-cell lineage. Histiocytic neoplasm accounted for only 0.8% (3 cases). As for the subtyping of NHL, diffuse large B-cell lymphoma was commonest (35.1%), followed by peripheral T-cell lymphoma, NOS (12.0%), extranodal marginal zone B-cell lymphoma (MALT lymphoma) (11.7%), follicular lymphoma (8.6%), T-lymphoblastic lymphoma (7.0%), anaplastic large cell lymphoma (4.2%), B-small lymphocytic lymphoma (3.6%) and mantle cell lymphoma (2.6%). Amongst the 263 cases of B-cell lymphoma, 105 cases (39.9%) expressed immunoglobulin light chain (kappa in 52 cases and lambda in 53 cases) in paraffin sections. Regarding markers for EB virus infection, 14 cases of the B-cell lymphoma gave positive findings with both EBER in-situ hybridization and LMP-1 immunohistochemistry, while 6 of the T/NK-cell lymphoma expressed LMP-1 and 19 showed positive signals for EBER. In NHL, there was discordance in EBER in-situ hybridization and LMP-1 immunohistochemical results. As for HL, EB virus positivity was noted in 37 of the 62 cases (59.7%), including 7 cases of lymphocyte-rich HL, 11 cases of mixed cellularity HL and 19 cases of nodular sclerosis HL. In classic HL, there was complete concordance of results by both EBER in-situ hybridization and LMP-1 immunohistochemistry., Conclusions: The prevalence of diffuse large B-cell lymphoma in Shanxi is similar to that in America, Australia, Japan and Korea. The incidence of follicular lymphoma however is much lower than America and Australia.

Evidence for balanced cell growth where protein and RNA content rise at a constant relative rate with respect to DNA content with increasing grade of cancer and with malignant transformation, is derived from analysis of infrared spectra of malignant lymphoma and transformed fibroblasts within the literature. This evidence is consistent with flow cytometry derived RNA-protein relationships, and supports the biosynthetic connection proposed here between the RNA/DNA ratio as calculated from the absorbance pulse at 1121 cm(-1), and the protein/nucleic acid ratio as measured by the absorbance ratio A1650 cm(-1)/A1084 cm(-1). The present analysis is the first to explain and show evidence for a simple unifying biomolecular content theory for interdependent changes seen within the fingerprint region (900 cm(-1)-1750 cm(-1)) of the infrared spectrum of cells. Structural changes to lipids and proteins in the wavenumber range 2800 cm(-1)-3000 cm(-1), seen as increasing CH3/CH2 ratio and decreasing symmetric CH2/asymmetric CH2 ratio, are found for the first time to occur with increasing cancer (lymphoma) grade as well. These lipid/protein structural changes (2800-3000 cm(-1)) may reflect an increasing protein/lipid content ratio with malignant grade, and are the same as those shown recently for benign to malignant transformation, further supporting their cellular metabolic basis. Rising ribose content (1121 cm(-1)) is seen to correlate with rising 996 cm(-1)/966 cm(-1) ratio (another index of RNA/DNA) with increasing malignant lymphoma grade as well, The proposed spectral connections have a high signal/noise ratio with respect to clinically meaningful information. They may potentially be applied to clinical cancer grading, or in vitro cancer treatment sensitivity testing.

Non-Hodgkin lymphoma (NHL) represents one of the most rapidly growing malignancies in childhood and adolescence. About 80% of patients now are cured with adequate treatment. Serious complications at presentation due to tumor lysis syndrome or local tumor effects are commonly observed. Thus, a rapid diagnosis with the least invasive procedure enabling the initiation of early and specific therapy is necessary to diminish early fatality or persistent impairment. In 56 centrally registered patients with NHL, cytomorphologic analyses (FAB criteria) of May-Grünwald-Giemsa-stained touch imprints or malignant effusions and flow cytometric immunophenotyping (EGIL criteria) of fresh cell suspensions with a standardized panel of monoclonal antibodies were performed. The authors identified 23 patients with Burkitt lymphoma by the combination of FAB L3 morphology and a mature B-cell phenotype and 22 patients with lymphoblastic lymphoma by FAB L1/L2 morphology and a T-/B-cell precursor phenotype. They also found 11 patients with large cell lymphomas, 3 of them with anaplastic large cell lymphoma (T-cell phenotype; NPM/ALK-positive). In the remaining 8 patients diffuse large B-cell lymphoma was suspected by the combined use of cytologic and immunophenotypic findings (mature B-cell phenotype). In all cases with available solid tumor material (n = 42/56) the preliminary diagnosis was confirmed by histopathology. Burkitt lymphoma, lymphoblastic lymphoma, and, in a few cases, some large cell lymphomas could be classified reliably by cytomorphology and immunophenotyping of freshly obtained tumor cell material, enabling an early start of specific lymphoma treatment.

The past 20 years have brought significant advances in our ability to manage patients with non-Hodgkin's lymphoma. More precise classification systems, improvements in diagnosis and staging, and effective new treatments have improved outcomes and made cure a reasonable goal for many patients with these disorders. In this overview of the progress seen in the field over the past 2 decades, we describe a variety of advances for specific lymphomas, including diagnostic methods such as gene array studies and immunophenotyping and new treatment approaches.

Although the small B-cell lymphomas show major morphologic overlapping, they have been recently shown to be distinct entities with several biologic and clinical differences. Therefore, the utility of a panel of paraffin-reactive antibodies in differentiating these neoplasms was investigated. Using clinical data and morphologic criteria, 134 cases of small B-cell lymphomas were grouped as those with (1) one strongly suggested diagnosis, (2) differential diagnosis between two types of lymphomas, and (3) small B-cell lymphoma without hints for further subclassification. With a panel of antibodies including CD5, CD10, CD23, CD43, bcl-2, and cyclin D1, most but not all cases could be precisely categorized. This panel confirmed the diagnosis in 96.5% of the cases from group 1. In group 2 it confirmed one of the two diagnoses in 81.5% of the cases. In group 3 it established a definitive diagnosis in 55% of the cases. When all groups were considered, a correct diagnosis could be established for 88.1% of cases; for 6.7% of them the authors remained with two possible diagnosis, and the broad "small B-cell lymphoma" was the only diagnosis for 5.2% of cases. CD10 separated most follicular lymphomas from other small B-cell lymphoid neoplasms. CD23 separated small lymphocytic lymphoma/chronic lymphocytic leukemia. Cyclin D1 separated mantle cell lymphoma. The present study selected CD10, CD23, and cyclin D1 as a minimal panel for the classification of small B-cell lymphomas, yielding a final diagnosis in 88.1% of the cases.

The etiology of non-Hodgkin lymphoma, as well as its global dramatic rise in incidence during the past decades, remains largely unexplained. However, there is increasing awareness that this group of malignancies may entail not only clinical, morphological and molecular heterogeneity, but also considerable variations in terms of etiologic factors. In this review, epidemiologic patterns are summarized as well as current evidence of associations between various known or suspected risk factors for non-Hodgkin lymphoma overall or for any of its subtypes. Central pathogenetic mechanisms include immunosuppression, especially in relation to T-cell function and loss of control of latent EBV infection, and chronic antigen stimulation. Some degree of familiar aggregation also implies a role for genetic susceptibility. A number of recent investigations of non-Hodgkin lymphoma etiology will hopefully lead to a better understanding of the causes of these malignancies.

The authors present the true incidence of non-Hodgkin's lymphomas basing on the cases diagnosed in Małopolska district during one-year period. The data point to higher lymphoma morbidity than the incidence of them reported by National Cancer Register. Noteworthy is also the distribution of lymphoma types in Polish population being different from that one reported in majority of other Europe countries. The present report indicate the lymphomas become growing diagnostic and clinical challenge, as they place among the most frequent neoplasms in population.

Background and Purpose: Primary central nervous system lymphomas (PCNSLs) are usually high-grade and are rarely low-grade non-Hodgkin lymphomas (NHLs). On MR imaging, PCNSLs typically present as contrast-enhancing lesions in contact with the subarachnoid space without evidence of necrosis. We evaluated the radiologic morphology and clinical characteristics of low-grade PCNSLs, hypothesizing that they may differ from high-grade PCNSLs., Methods: Records were reviewed from 332 patients screened for inclusion in 3 multicenter prospective trials. MR imaging scans were obtained from all patients and were centrally reviewed by 2 consultant neuroradiologists., Results: Ten patients (3%) with low-grade PCNSLs (7 men and 3 women; median age, 59 years; age range, 19-61 years) were identified. Four patients had one lesion, 2 patients 2 lesions, and 4 patients had multiple lesions. The following radiologic features infrequently seen in high-grade PCNSLs were found in a substantial proportion of patients: location in deep structures or spine (n = 6); lack of periventricular location (n = 5); hyperintensity on T2-weighted images (n = 10); moderate or absent contrast enhancement (n = 6); and heterogeneous contrast enhancement (n = 5). In 8 patients, >2 of these features were present in at least one lesion, and, thus, the radiologic appearance was assessed atypical of high-grade PCNSLs. The atypical radiologic appearance in combination with atypical or mild symptoms resulted in a false or delayed diagnosis., Conclusion: Low-grade PCNSLs may have a variable and atypical radiologic morphology compared with high-grade PCNSLs with the risk of false or delayed diagnosis.

Progressive disease is the major cause of treatment failure after autologous hematopoietic stem cell transplantation for relapsed or refractory non-Hodgkin's lymphoma. An augmented high-dose regimen of cyclophosphamide 7,200 mg/m2, carmustine 300 - 400 mg/m2, and etoposide 2,400 mg/m2 (CBV) was developed in an attempt to improve disease control post-transplant. Sixty-seven adult patients received augmented CBV followed by infusion of unpurged autologous peripheral blood stem cells. Thirty seven patients had relapsed after standard chemotherapy, 28 patients had primary refractory disease, and 2 patients had transformed lymphoma in first partial response. Treatment-related mortality was 4%. Actuarial four year overall survival and progression-free survival were 46+/-8% and 36+/-6%, respectively. Risk factors for disease progression were histologic involvement of marrow by lymphoma and infusion of increased numbers of CD34 + cells per kg in the stem cell autograft. The outcome for patients with relatively chemorefractory disease (defined as 25 - 49% reduction in tumor volume after salvage chemotherapy) was no different than that for patients with chemosensitive disease. Compared to standard high-dose CBV regimens, augmented CBV does not appear to have substantially improved disease control. Prospective study of the association between inferior progression-free survival and infusion of higher CD34 + cell doses in stem cell autografts is warranted.

The clinicopathologic features of malignant lymphomas had not been documented in the Niger Delta region of Nigeria, which is known for its petrochemical industries and gas flare sites. Cases of lymphomas that presented to the University of Benin Teaching Hospital (UBTH), a major referral centre in the region, from January 1990 to December 2003 were reviewed. Demographic and clinical information were obtained from the case files. Diagnosis was established based on the histological examination of an accessible biopsy lymph node and classified according to the Working Formulation (WF). Haematological parameters were done using an automated Coulter counter. Non-Hodgkin's lymphoma (NHL) occurred predominantly in young adults (20-39 years). A majority of the patients presented in the advanced stage of the disease (Stages III-IV) according to the Ann Arbor system and a performance status (PS) scale of 2-4. The intermediate grade NHL (41.2%) formed the largest group of which diffuse large cell lymphoma (DLCL) was the most commonly observed histopathologic type followed by the large cell immunoblastic type.

Purpose of Review: Therapeutic vaccines targeting B cell lymphoma idiotype have reached an advanced stage of clinical development, with three multicenter randomized clinical trials ongoing. This review describes the rationale and development of this immunotherapeutic approach, the design of current phase III trials, and other active vaccination approaches likely to move forward into clinical testing for lymphomas., Recent Findings: Several groups have achieved promising results in phase II trials of patient-specific idiotype vaccines, with very few side effects noted. Anti-idiotype antibodies, in addition to cytotoxic T cells, are now believed to be important effectors of antitumor immunity after idiotype vaccination. The manufacturing of autologous tumor idiotype proteins is being rapidly refined by the use of molecular technologies. Two trials involving more than 1000 patients are now under way, which use idiotype vaccination after induction chemotherapy; one trial completed accrual in early 2004. A third trial opened in 2004, using rituximab followed by idiotype vaccine with maintenance booster vaccines continuing throughout the period of normal B cell recovery. In accordance with the United States Food and Drug Administration, progression-free survival serves as the accepted primary efficacy endpoint in these studies., Summary: Lymphoma idiotype vaccination represents a promising immunotherapeutic approach targeting a patient-specific tumor antigen. The results of pivotal phase III trials for three first-generation idiotype vaccines will become available in the next several years. Advanced manufacturing techniques should permit application of this tailor-made treatment to large numbers of non-Hodgkin's lymphoma patients.

In a previous criterion-based pathology report review of 717 cases of non-Hodgkin's lymphoma in an Australian population-based epidemiologic study, a WHO category could be assigned in 91% of cases, but confidence in this classification was high in only 57.5%. Given this lack of confidence, a pathology review was done in a subset of 315 cases, with the aims of assigning a WHO classification category and the corresponding International Classification of Diseases for Oncology, Third Edition code in all cases previously unclassified or classified with low confidence and testing the accuracy of report review in assigning a confident WHO classification. After pathology review, 10 cases were ineligible (not non-Hodgkin's lymphoma, 3.2%) and 99% (301 of 305) of the remainder were assigned a WHO classification, with high confidence in 87% (261 of 301). There was 78% overall agreement between the WHO classification assigned by report review and pathology review, with 92% agreement when there was high confidence in the report review classification and 69% agreement when there was low confidence. Eighteen percent of follicular lymphomas and 23% of diffuse large B-cell lymphomas were reclassified. The pathology review increased the accuracy of WHO classification by an estimated 12.5% in the 694 cases who were still eligible in the study. Although a potential error rate of 7.5% remained, reviewing more cases, or not reviewing any cases classified with high confidence, would have produced only a small change in accuracy. Criterion-based pathology report review of all cases followed by selective pathology review in cases classified with low confidence is recommended as a cost-saving and accurate strategy for pathology review in large epidemiologic studies.

Background: Most studies describing the subtypes of lymphoma in Jordan were carried out in the 1980s at a time when immunohistochemical facilities were unavailable. Using a database established after immunohistochemical studies were introduced, we determined the frequency of the various types of nodal and extranodal lymphomas in the adult and paediatric Jordanian population. We also assessed the incidence of bone marrow involvement at the initial presentation for each lymphoma type., Methods: A retrospective analysis of the histopathological subtypes of various lymphomas was conducted on all primary lymphoma cases diagnosed during a 3-year period between January 2001 and December 2003., Results: Of 347 patients included in the study, 78.4% had non-Hodgkin's lymphoma (NHL) and 21.6% had Hodgkin's lymphoma (HL). In the NHL group, diffuse large B-cell lymphoma was the most common (28.2%) followed by follicular lymphoma (15.6%). In the HL group, the nodular sclerosis variant was the most frequent (7.8%) followed by the mixed cellularity type (5.5%). Of all the lymphoma cases, the highest incidence of marrow involvement was seen in patients with lymphoplasmacytic lymphoma. Forty-nine patients were children (age <15 years) in whom Burkitt's lymphoma (15 cases) and HL (14 cases) were the commonest subtypes. One-hundred six patients with primary extranodal lymphomas (ENL) accounted for 30.5% of all lymphomas., Conclusions: There is a higher incidence of NHL in Jordan compared with other series in the Middle East. Among the various lymphomas, diffuse large B-cell lymphoma is the most commonly encountered lymphoma in adults. Burkitt's lymphoma and Hodgkin's disease are the most frequent childhood lymphomas, followed closely by lymphoblastic lymphoma.

Aim: To evaluate the value of CT-guided core-needle biopsy in diagnosis and classification of malignant lymphomas., Methods: From January 1999 to October 2004, CT-guided core-needle biopsies were performed in 80 patients with suspected malignant lymphoma. Biopsies were performed with an 18-20 G biopsy-cut (CR Bard, Inc., Covington, GA, USA) needle driven by a spring-loaded Bard biopsy gun., Results: A definite diagnosis and accurate histological subtype were obtained in 61 patients with a success rate of 76.25% (61/80). Surgical sampling was performed in 19 patients (23.75%) with non-diagnostic core-needle biopsies. The success rate of CT-guided core-needle biopsy varied with the histopathologic subtypes in our group. The relatively high success rates of core-needle biopsy were noted in diffuse large B-cell non-Hodgkin's lymphoma (NHL, 88.89%) and peripheral T-cell NHL (90%). However, the success rates were relatively low in anaplastic large cell (T/null cell) lymphoma (ALCL, 44.44%) and Hodgkin's disease (HD, 28.57%) in our group., Conclusion: CT-guided core-needle biopsy is a reliable means of diagnosing and classifying malignant lymphomas, and can be widely applied in the management of patients with suspected malignant lymphoma.

Non-Hodgkin lymphomas are a heterogeneous group of malignancies of the lymphoid system. Based on the World Health Organization classification of hematological and lymphoid tumors, these diseases have been classified as B-cell and T-cell neoplasms. B-cell lymphomas account for approximately 90% of all lymphomas, and the 2 most common histological disease entities are follicular lymphoma and diffuse large B-cell lymphoma. Approximately 55,000 to 60,000 new cases of non-Hodgkin lymphoma are diagnosed annually in the United States, a number that has nearly doubled during the past 3 decades. The Ann Arbor Staging Classification is used routinely to classify the extent of disease, and the International Prognostic Index has been used to define prognostic subgroups. Also, recent data have identified molecular and genetic markers of prognosis that may be used in the future to further refine treatment decisions. Treatment of these diseases is based on the histology and extent of disease. Patients with follicular lymphomas with early-stage disease generally are treated with radiation therapy, whereas those with stage III and IV disease requiring treatment usually are treated with chemotherapy, Immunotherapy, or radioimmunotherapy. These patients generally experience long survival, but only a minority are cured. For patients with diffuse large B-cell lymphoma, treatment of limited-stage disease generally includes doxorubicin-based chemotherapy combined with rituximab followed by involved field radiation therapy. Those with extensive disease are treated with rituximab combined with chemotherapy alone. Disease relapse is a problem, and high-dose therapy with stem cell support is the treatment of choice for chemosensitive relapsed aggressive lymphomas. Patients with chemoresistant disease or whose disease relapses subsequently should be treated with novel experimental therapies.

Non-Hodgkin lymphoma (NHL) consists of a heterogeneous group of tumors. Population-based data on the familial risk for specific histopathologic subtypes have not been established. Such data are useful for clinical counseling and for searching tumor subtypes sharing common genetic pathways. We used the Swedish Family-Cancer Database to calculate standardized incidence ratios (SIRs) for histopathology-specific subtypes of NHL in 4455 offspring with NHL whose parents or siblings were affected with different types of lymphoproliferative malignancies. A familial history of NHL significantly increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings. Our study provides the first quantification of the familial risks for NHL by histopathology. The present findings give evidence for a strong familial association of NHL, with little differences in the magnitude of risks for various histopathologic subtypes. The patterns of risks in parents and siblings support the hypothesis of an autosomal-dominant component for diffuse large B-cell NHL and a recessive one for follicular NHL.

In 2004, new cases of non-Hodgkin's lymphoma in the United States were estimated at 54,370, representing 4% of all cancers and resulting 4% of all cancer deaths, and new cases of Hodgkin's lymphoma were estimated at 7,880. The appropriate staging and management of lymphomas greatly depend on an accurate pathological diagnosis and classification. The recently established Revised European-American Classification of Lymphoid Neoplasms (REAL) and the subsequently adopted and updated World Health Organization (WHO) classification include modern cytogenetic, molecular, and immunologic techniques and knowledge and reach an international consensus on the classification of lymphomas. This classification scheme represents an advance in our understanding of lymphomas and serves as an operative guideline for studying and diagnosing lymphomas. Imaging techniques always have served as staging and monitoring tools for the clinical management of lymphomas. The understanding and adoption of the current classification system is important in refining the role of imaging modalities in the management of specific lymphoma. To help one understand the current classification, this current review gives a brief history of lymphoma classifications and summaries the recent classification schemes, including new entities, clinical staging methods, and clinical prognostic criteria.

Grey zone lymphomas represent borderline lesions between classical Hodgkin lymphoma (cHL) and other morphologically and immunophenotypically related diseases and entities like nodular lymphocyte predominant HL, T-cell rich B-cell lymphoma, ALK-negative anaplastic large cell lymphoma (ALCL), diffuse large B cell lymphoma (DLBCL) anaplastic variant and primary mediastinal LBCL. The sharp definition of morphological, immunophenotypical and molecular features of the "text-book cases" of each disease and the comparison with grey zone cases has reduced most of the latter cases. Two reports in this workshop dealt with the problematic non-mediastinal grey zone lymphomas, one with a cHL of T cell-type presenting in the skin as a ALK-negative ALCL and the other with the grey zone between cHL of B-cell type and ALK-negative ALCL.

New therapies have enhanced treatment of non-Hodgkin's lymphoma (NHL), but extent of treatment use in community practice is unknown. We conducted a population-based study of NHL patients diagnosed in 1999 with histologically confirmed NHL (n = 947) residing in areas covered by the Surveillance, Epidemiology, and End Results program. We performed analyses to study factors associated with receipt of chemotherapy, radiation, and rituximab, and examine factors associated with mortality. Most patients presented with B-cell lymphoma (n = 828). Approximately 20% of patients received no therapy, over 60% received chemotherapy, and 12% received rituximab, alone or in combination. Patients aged 75 +, and males were less likely to have received chemotherapy (p = 0.01). There were no significant associations between receipt of rituximab and the factors analyzed. Patients who presented with B-symptoms or unknown B-symptom status were less likely to receive radiation (OR = 0.32 and 0.47, respectively, p = 0.0002) than asymptomatic patients. Cause-specific and all-cause mortality were significantly associated with patient age, race/ethnicity, gender, marital status, co-morbid conditions, and histological subgroup. Hispanic and African-Americans, patients age 75 +, males, unmarried patients, or patients with B-symptoms had higher risk of death from NHL and all-cause (p < 0.01). This is the first population-based study examining therapy received for many histological subtypes of NHL.

Non-Hodgkin lymphomas (NHLs) are often present outside the lymph nodes. Although primary extranodal NHLs (PE-NHL) form a substantial part of all NHLs, reports on oral PE-NHLs are rare. Forty patients with PE-NHL of the oral cavity have been studied for the distribution of gender, age, oral subsite and presenting complaint, histological subtype according to the WHO classification, clinical stage, treatment, and follow-up. The data are reviewed against the background of the literature. Furthermore, the International Prognostic Index has been taken into consideration. All patients had a lymphoma of B-cell lineage. Two-thirds of patients presented with locoregional disease. Mean survival time was 38 months, with a mean recurrence-free survival time of 31 months. There was no statistically significant difference in survival time between patients with bone versus soft tissue localisation of the PE-NHL. In view of the rarity of PE-NHL involving the oral region multicenter studies are needed for evaluation of the usefulness of the International Prognostic Index for non-Hodgkin lymphoma in this particular part of the body.

Purpose: To analyze the influence of radiotherapy doses, chemotherapy doses, and clinical parameters on in-field disease control to assess the optimal radiation doses for treatment of non-Hodgkin's lymphoma according to the newly proposed WHO classification., Patients and Methods: Subjects consisted of 35 extranodal marginal-zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type, 75 diffuse large B-cell lymphomas (DLBCL), 14 follicular lymphomas, 17 extranodal natural killer (NK)/T-cell lymphomas, nasal type, eight unclassified peripheral T-cell lymphomas, four anaplastic large-cell lymphomas, T/null cell type, and five others. 59 patients received radiotherapy alone. 98 patients received CHOP, modified CHOP, or more intensive chemotherapy, and six patients were treated with other combination., Results: No patients with MALT lymphoma had in-field local recurrence. There were no recurrences in DLBCL patients who received chemotherapy in which the doses of adriamycin were > 200 mg/m(2), nor in DLBCL patients who were treated with > 45 Gy. Only nine of 15 patients with T-cell lymphoma treated with < or = 50 Gy and three of five patients treated with > 50 Gy had local control. The dose of adriamycin had no influence on local control of T-cell lymphoma., Conclusion: T/NK-cell lymphomas were more radioresistant than B-cell lymphomas. The prognosis for peripheral T/NK-cell lymphomas is poor even when treated by irradiation combined with chemotherapy.