Classification Of Malignant Lymphomas Research Articles

The Lymphocyte Subsets Activation Profiles in Peripheral Blood May Contribute to the Diagnosis of Natural Killer/T-Cell Lymphoma-Associated Hemophagocytic Lymphohistiocytosis

The lymphocyte subsets activation profiles in peripheral blood may contribute to the diagnosis of natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis Background: Hemophagocytic lymphohistiocytosis (HLH) is a rampant and potentially fatal systemic hyperinflammation characterized by dysfunction of macrophages and cytotoxic T cells. Natural killer/T-cell lymphoma (NKTCL) has been reported to be one of the most common etiologies of HLH among hematologic neoplasms. Although, the diagnosis of natural killer/T-cell lymphoma-associated hemophagocytic lymphohistiocytosis (NK/T-LAHS) refers to the HLH-2004 diagnostic guidelines for primary HLH, most of them are based on non-specific clinical features. Identification of the immunophenotype characteristics is important for the diagnosis of NK/T-LAHS. In this study, we investigated the lymphocyte subsets activation profiles of peripheral blood mononuclear cells (PBMC) from NKTCL patients, and preliminarily screened molecular marker with potential diagnostic value for NK/T-LAHS. Methods: This study retrospectively collected peripheral blood samples from 58 patients diagnosed with NKTCL in Sun Yat-sen University Cancer Center from September 2020 to December 2022. Among them, 29 patients had HLH at the time of enrollment, and peripheral blood samples from 10 healthy people were collected as the control group. NKTCL was diagnosed according to the 2016 WHO classification of malignant lymphoma. All HLH patients met HLH-2004 diagnostic criteria and primary HLH was excluded. Flow cytometric staining of PBMC was performed on BD Fortessa according to the manufacturer's instructions. All samples were analyzed by Flowjo（V10）software. The ROC curve was drawn according to the percentage of lymphocyte subsets to determine the optimal cutoff threshold. RStudio 4.2.1 was used to calculate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and likelihood ratio (LR) of the related indicators. Graphpad prism 8.0.1 and SPSS 26.0 (IBM) was used for drawing and statistical analysis. All statistical tests were two-sided, and p＜0.05 were considered statistically significant. Results:The median age of 58 patients was 41 (range, 18-83) years old, and 10 patients (17.2%) had poor performance status (ECOG PS≥2). Forty-two patients (72.4%) were stage III-IV, and 26 patients (44.8%) had PINK-E score≥3. Firstly, we compared the immune cell activation profiles between healthy donors, NKTCL patients with or without HLH. We observed that the proportion of functionally activated T cells, NK cells, NKT cells that expressed CD86, CD69, or HLADR was significantly higher than healthy donors ( p＜0.05), except for CD86+NK cell levels was no significance between the three groups (Figure1). In addition, the percentage of CD86+NK/T cells, CD69+NK cells, HLADR+NK cells and HLADR+NKT cells were significantly higher than NKTCL patients without HLH and healthy controls( p＜0.05), and no significant difference of these immune cells subsets between those non-HLH patients and healthy controls was observed (Figure1). Based on the significance of these lymphocyte subsets in NKTCL patients with and without HLH, we evaluated the diagnostic value of CD86+NKT cells, CD69+NK cells, HLADR+NK cells, and HLADR+NKT cells in NK/T-LAHS patients by ROC analysis to determine the optimal diagnostic threshold. We observed that HLADR+NK > 15.9% could better distinguish NK/T-LAHS from non-HLH patients, with a sensitivity of 0.759 (95%CI: 0.603-0.914) and specificity of 0.828(95%CI:0.690-0.965), and the AUC was 0.775 (95%CI:0.647-0.904) (Table 1). HLADR+NK cells may have potential application value for the diagnosis of NK/T-LAHS. Conclusions: These activated T cells, NK cells, and NKT cells that express functional activation markers was increased in NK/T-LAHS patients. Among them, HLADR+NK > 15.9% could better distinguish NK/T-LAHS from NKTCL patients without HLH and healthy donors, which may be a potential biomarker for the diagnosis of NK/T-LAHS patients and contribute to better management.

Comparison of 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma using endoscopic ultrasound fine-needle aspiration.

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML). Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles. Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group. Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Update on the WHO classification of malignant lymphomas

With the current 2008 WHO monograph on the classification of malignant lymphomas about 6 years old, work on a significant update has begun. A meeting of the Clinical Advisory Committee was already held, where the editors, selected authors and internationally prominent clinicians held wide-ranging discussions concentrating on areas where new validated data exists that would impact on the classification or on the characterization and criteria for specific entities. Although publication of the update is not expected until Fall, 2015, areas in need of updating are established. On the B-cell side, there is great interest in dealing with the borders of lymphoma and clonal proliferations that are not overtly malignant as well as in learning how to best deal with the extra-aggressive B-cell lymphomas. New molecular discoveries have also had a major impact such as BRAF V600E mutations in hairy cell leukemia and MYD88 L265P mutation in lymphoplasmacytic lymphomas. We are also learning more about the complexity of the mature T-cell lymphomas and how to deal with the spectrum of T-cell lymphomas derived from T follicular helper cells and gamma delta type T-cells. Indolent clonal T- and NK-cell proliferations, such as those in the GI tract, have also received increased attention.

Evaluation of a panel of expert pathologists: review of the diagnosis and histological classification of Hodgkin and non-Hodgkin lymphomas in a population-based cancer registry

Correct histological classification of malignant lymphomas is important but has always been a difficult challenge. Since 2001 the World Health Organization (WHO) classification has been used, which should make it easier to define distinct disease entities. The purpose of this study was to evaluate the usefulness of a panel of expert hematopathologists in reviewing the diagnosis of malignant lymphomas and to examine whether the discordance between primary and panel diagnoses has declined throughout the years. All patients with a primary malignant lymphoma diagnosed between 2000–2001 and 2005–2006 were identified through the population based cancer registry. All diagnoses were reviewed by a panel of three expert pathologists. In 2000–2001, 344 patients were included, and in 2005–2006, 370 patients. The overall discordance rate decreased from 14% in 2000–2001 to 9% in 2005–2006 (p = 0.06). We were able to identify lymphoma subgroups with the highest discordance rates and lowest discordance rates (mantle cell lymphoma and classical Hodgkin lymphoma), which remained unchanged throughout the years. Based on these results we would propose to review all cases of malignant lymphoma with the exception of mantle cell lymphoma and classical Hodgkin lymphoma, when the initial pathologist has no doubt about the diagnosis.

Grauzonenlymphome

Grey zone lymphomas are lymphatic tumors that cannot be assigned to a defined lymphoma entity due to morphological, clinical or genetic reasons. As a defining criterion they present with features of two overlapping entities or features that are intermediate. Such lymphomas may represent a grey zone in the differentiation between indolent and aggressive lymphomas. Often they may show morphological features of one entity but be more related to another entity with respect to the immunophenotype and/or genetic constitution, such as lymphomas in the grey zone between primary mediastinal large B-cell lymphoma and primary nodal diffuse large B-cell lymphoma. The B-cell lymphoma, unclassified, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma has recently been recognized as a provisional category in the updated WHO 2008 classification of malignant lymphomas. This corresponds to a practical lymphoma category that obviously contains several entities with a Burkitt-like appearance and aggressive clinical behavior. Genetically, tumors in this category are frequently characterized by an atypical MYC translocation and complex karyotypic alterations. As yet, no adequate therapy concept exists.

Translationale Forschung und Diagnostik beim Lungenkarzinom

Lung cancer is the most common malignant disease leading to death worldwide. Histologically, it is broadly subcategorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), with the latter mainly consisting of the major entities adenocarcinoma and squamous cell carcinoma. However, molecular profiling of various lung cancer entities has revealed major molecular differences within distinct histological tumor entities, resulting in the integration of molecular alterations in the subclassification of lung cancers. These findings can only estimate the genetic complexity of lung tumors. Large scale molecular profiling has the potential to identify novel diagnostic, prognostic and predictive markers as well as therapeutic targets. Importantly, this recently arising categorization of lung carcinomas can be regarded as an example for the characterization of malignomas of other organ systems. The pioneer model for this molecular subcategorization is the classification of malignant lymphomas.

Diagnosis and subclassification of lymphomas and non‐neoplastic lesions involving mediastinal lymph nodes using endobronchial ultrasound‐guided transbronchial needle aspiration

The value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been established for staging mediastinal lymph nodes in lung carcinoma patients with radiologically enlarged lymph nodes, but its utility for evaluation of primary lymph node disorders is not well defined. The objective of this study was to evaluate the usefulness of EBUS-TBNA with on-site assessment and triage of sample for multiple ancillary techniques, for the diagnosis and subclassification of lymphomas and non-neoplastic lesions involving mediastinal lymph nodes. One hundred and twenty consecutive patients who underwent EBUS-TBNA between January 2008 and August 2009 were reviewed. The final cytological diagnosis was based on air-dried Romanowsky and alcohol-fixed Papanicolaou stained direct smears, immunohistochemistry, immunophenotyping, and fluorescence in situ hybridization (FISH). A total of 38 cases were included in this study consisting of eight reactive lymphoid hyperplasia, 20 granulomatous lymphadenitis (17 non-necrotizing and 3 necrotizing granulomatous inflammations), 3 Hodgkin lymphomas and 7 non-Hodgkin lymphomas (1 small lymphocytic lymphoma (SLL), 1 SLL with scattered Reed-Sternberg cells, 1 marginal zone lymphoma, and 4 large B cell lymphomas). Cultures performed in 13 cases were negative for AFB and fungi. Immunophenotyping and immunohistochemistry for MIB1 in six cases, and FISH in five cases provided necessary information for subclassification. EBUS-TBNA is a minimally invasive procedure which provides sufficient sample for definitive primary diagnosis and classification of malignant lymphoma and granulomatous inflammation in patients with mediastinal lymphadenopathy. Rapid on-site specimen assessment is invaluable for appropriate assignment of sample to ancillary studies.

WHO Classification of Malignant Lymphomas in Korea: Report of the Third Nationwide Study

Background: The aim of study was to determine the relative frequency of malignant lymphoma according to World Health Organization (WHO) classification in Korea. Methods: A total of 3,998 cases diagnosed at 31 institutes between 2005 and 2006 were enrolled. Information including age, gender, pathologic diagnosis, site of involvement and immunophenotypes were obtained. Results: The relative frequency of non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) was 95.4% and 4.6%, respectively. B-cell lymphomas accounted for 77.6% of all NHL, while T/ natural killer (T/NK)-cell lymphomas accounted for 22.4%. The most frequent subtypes of NHL were diffuse large B-cell lymphoma (42.7%), extranodal marginal zone B-cell lymphoma (MZBCL) of mucosa-associated lymphoid tissue (19.0%), NK/T-cell lymphoma (6.3%) and peripheral T-cell lymphoma (PTCL), unspecified (6.3%), in decreasing order. The relative frequency of HL was no dular sclerosis (47.4%), mixed cellularity (30.6%), and nodular lymphocyte predominant (12.1%) subtypes. Compared with a previous study in 1998, increase in gastric MZBCL and nodular sclerosis HL, and slight decrease of follicular lymphoma, PTCL, and NK/T-cell lymphoma were observed. Conclusions: Korea had lower rates of HL and follicular lymphoma, and higher rates of extranodal NHL, extranodal MZBCL, and NK/T-cell lymphoma of nasal type compared with Western countries. Changes in the relative frequency of lymphoma subtypes are likely ascribed to refined diagnostic criteria and a change in national health care policy.

The WHO Classification of Lymphomas: Cost-effective Immunohistochemistry Using a Deductive Reasoning “Decision Tree” Approach

The 2008 World Health Organization Classification of Tumors of the Haematopoietic and Lymphoid Tissues defines current standards of practice for the diagnosis and classification of malignant lymphomas and related entities. More than 50 different types of lymphomas are described. Faced with such a broad range of different lymphomas, some encountered only rarely, and a rapidly growing armamentarium of 80 or more pertinent immunohistochemical (IHC) "stains," the challenge to the pathologist is to use IHC in an efficient manner to arrive at an assured and timely diagnosis. This review uses deductive reasoning following a decision tree or dendrogram model, combining basic morphologic patterns and common IHC markers to classify node-based malignancies by the World Health Organization schema. The review is divided into 2 parts, the first addressing those lymphomas that produce a follicular or nodular pattern of lymph nodal involvement appeared in the previous issue of AIMM. The second part addresses diffuse proliferations in lymph nodes. Emphasis is given to the more common lymphomas and the more commonly available IHC "stains" for a pragmatic and practical approach that is both broadly feasible and cost-effective. By this method, an assured diagnosis may be reached in the majority of nodal lymphomas, at the same time developing a sufficiency of data to recognize those rare or atypical cases that require referral to a specialized center.

Investigation of the Safety and Usefulness of Computed Tomography-Guided Percutaneous Needle Biopsy of Paraaortic Lymph Nodes.

Abstract 5027 BackgroundVarious factors such as malignant lymphoma cause abdominal lymph node enlargement. A histological diagnosis of malignant lymphoma is important in planning therapy, and although superficial lymph node biopsies are often obtained, target lesions occasionally arise only around the abdominal aorta. These require surgical, or more recently, endoscopic biopsies. To intraoperatively determine whether target lymph nodes are correctly resected during a surgical biopsy can be difficult, and therapy could be delayed due to postoperative complications. ObjectiveTo assess the safety and effectiveness of percutaneous biopsy of paraaortic lymph nodes under computed tomography (CT) fluoroscopic guidance. Subjects and MethodsWe retrospectively investigated puncture success rates based on findings of diagnostic imaging, size of target lymph nodes, rate of confirmed diagnosis, frequency of changes in therapeutic plans and incidence of complications among 36 patients after percutaneous needle biopsy using an 18G cutting needle between September 2002 and March 2009. ResultsThe pre-biopsy diagnoses for the 36 subjects who underwent percutaneous needle biopsy included: malignant lymphoma (n = 26), lymph node metastasis of esophageal cancer (n = 3), lymph node metastasis of lung cancer (n = 3), lymph node metastasis of pancreatic cancer (n = 3) and unknown (n = 3). The median size of the target lymph nodes was 25 mm (range: 9–102 mm). The results of diagnostic imaging indicated that all punctures were successful. The diagnoses were confirmed in 33 of the 36 patients (91.7%). Histopathological findings confirmed malignant lymphoma (n = 21; Follicular Lymphoma in 11 patients, Diffuse Large B cell Lymphoma in 8, T-Cell Lymphoma in 1, Hodgkin Disease in 1), squamous cell carcinoma (n = 2), poorly differentiated adenoma (n = 2), other malignancies (n = 5), benign lesions (n = 3) and unknown in 3. Therapeutic strategies were altered based on the results of CT-guided percutaneous needle biopsies in 12 of the 36 patients (33.3%). Three patients developed 4 adverse events comprising grade 1 radiation dermatitis (n = 1), grade 1 hematoma (n = 2) and grade 1 pneumothorax (n = 1). ConclusionsTarget paraaortic lymph nodes can be accurately punctured using CT-guided percutaneous needle biopsy, and the specimens were too small to examine the flowcytometry or chromosome analysis, however it was enough to confirmed the diagnosis according to WHO classification of malignant lymphoma. Percutaneous biopsy of paraaortic lymph nodes under CT fluoroscopic guidance is useful for confirming diagnoses with a low risk of serious deep organ damage. DisclosuresNo relevant conflicts of interest to declare.

IHC and the WHO Classification of Lymphomas

The 2008 World Health Organization Classification of Tumors of the Hematopoietic and Lymphoid Tissues defines current standards of practice for the diagnosis and classification of malignant lymphomas and related entities. More than 50 different types of lymphomas are described, combining fine morphologic criteria with immunohistochemical (IHC), and sometimes molecular, findings. Faced with such a broad range of different lymphomas, some encountered only rarely, and a rapidly growing, ever changing, armamentarium of approximately 80 pertinent IHC "stains", the challenge to the pathologist is to employ IHC in an efficient manner, to arrive at an assured diagnosis as rapidly as possible. This review uses deductive reasoning, after a decision tree or dendrogram model that relies upon recognition of basic morphologic patterns for efficient selection, use and interpretation of IHC markers to classify node-based malignancies by the World Health Organization schema. The review is divided into 2 parts, the first addressing those lymphomas that produce a follicular or nodular pattern of lymph nodal involvement; the second addressing diffuse proliferations in lymph nodes. It is accepted that only specialized centers are able to apply all of the technical resources and experience necessary for definitive diagnosis of unusual cases. Emphasis therefore is given to the more common lymphomas and the more commonly available IHC "stains", for a pragmatic and practical approach that is both broadly feasible and cost effective. By this method an assured diagnosis may be reached in the majority of nodal lymphomas, at the same time developing a sufficiency of data to recognize those rare or atypical cases that require referral to a specialized center.

Klassifikation und Pathogenese der malignen Lymphome

The classification of malignant lymphomas according to the WHO scheme of 2001 is based on modern knowledge of B- and T-cell differentiation, the immunophenotype and genetic alterations of the neoplastic cells, as well as on clinical features. Conventional histology does not suffice for a reliable diagnosis of lymphoma diseases and the application of additional methods is required. Immunophenotyping by means of immunohistochemistry is indicated in practically all instances. In a number of cases, the analysis of clonality by PCR and cytogenetic alterations by FISH also need to be applied. A high risk cause of B-cell lymphomagenesis involves rearrangements at the immunoglobulin locus and events occurring during the germinal centre reaction (somatic mutations and immunoglobulin heavy chain class switch) which may result in molecular accidents in the form of chromosomal translocations and/or gain or loss of functional mutations. This may disrupt B-cell homeostasis resulting in increased proliferation, inhibition of apoptosis or both. Clinical behaviour may be influenced by the microenvironment, e.g. T-cells, cytokines and pathogenic microorganisms.

Das mediastinale (thymische) großzellige B-Zell-Lymphom

Mediastinal B-cell lymphoma is a locally highly aggressive tumour which was first described in the early 1980s. The incidence is about 2-3% of all non-Hodgkin's lymphomas. The conceptional evolution of this lymphoma entity was hampered by its low incidence and the broad spectrum of morphological variants present. However, since mediastinal B-cell lymphoma has distinct morphological, immunological, genetic, and clinical features, it has been listed in the revised European-American Classification of Lymphoid Neoplasms (REAL-Classification) since 1994 as a variant of diffuse large B-cell lymphoma. In the World Health Organization classification of malignant lymphomas, mediastinal B-cell lymphoma is now listed with an own disease code (ICD-9679/3).

Establishment of liver metastasis model of human primary colonic lymphoma by orthotopic transplantation

To provide an ideal animal model for exploring pathogenesis and experimental treatment of primary colonic lymphoma. Primary colonic and liver metastatic lymphoma tissues were obtained from the surgical specimens,and transplanted into colonic mucosa of nude mice respectively. The tumorigenesis, invasion, metastasis and morphology of the transplanted tumor were observed. Karyotype was analyzed and DNA content was measured. According to the new WHO classification of malignant lymphoma, two high metastatic models (HCBL-0303 from primary lymphoma and HCBL-0304 from live metastatic lesion) of human primary colonic non-Hodgkin's B cell lymphoma in nude mice were established successfully by orthotopic transplantation. Pathological examination showed poorly differentiated non-Hodgkin's B cell lymphoma of the transplanted tumors, and immunohistochemical staining showed positive expressions of CD19, CD20 and CD22, and negative expressions of CD3 and CD7. The number of chromosome ranged from 55 to 59, and DNA index (DI) was 1.59 - 1.71 (i.e. heteroploid). In HCBL-0303,liver metastasis rate was 63.7% and lymph node metastasis rate was 56.4%. However, in HCBL-0304, both metastasis rates of liver and lymph node were 100%. The transplanted tumors grew autonomously and invasively in nude mice, and further developed hematogenous, lymphatic metastasis and intraperitoneal seeding. HCBL-0303 and HCBL-0304 are the first established high metastatic models of primary colonic lymphoma, and can be applied to the research on pathogenesis, invasion,metastasis and experimental therapy of human primary colonic lymphoma.

Efficacy of CT-guided percutaneous needle biopsy in the diagnosis of malignant lymphoma at first presentation

Purpose The aim of this study was to evaluate retrospectively the accuracy and reliability of CT-guided percutaneous biopsy as an alternative to surgical biopsy in a selected population of patients without superficial enlarged lymphnodes and a final diagnosis of malignant lymphoma at first presentation. Methods The results of 145 CT-guided needle biopsies in 137 patients with malignant lymphoma at its first presentation and without superficial enlarged lymphnodes were analyzed retrospectively. Biopsies were performed in 24 patients with Hodgkin's disease (HD) and 113 with non-Hodgkin lymphoma (NHL). Factors such as patient's sex, age, type of lymphoma and biopsy site were evaluated to detect factors that could influence the success rate of the procedure. Results Biopsy specimens were diagnostic in 101 of the 113 patients with NHL and in 18 of the 24 patients with HD. Repeating of a previously nondiagnostic biopsy was successful in 7 out of 13 patients with NHL. No positive results were obtained, repeating the inconclusive biopsy in six patients with HD. Conclusions Our results suggest that percutaneous CT-guided biopsy is a useful and reliable tool in the diagnosis and classification of malignant lymphomas in patients without superficial lymphadenopathy and can be considered as an alternative to surgical sampling. However, little advantages were obtained, repeating previously inconclusive biopsies: In these cases, surgical sampling is mandatory.

Value of CT-guided core-needle biopsy in diagnosis and classification of malignant lymphomas using automated biopsy gun

To evaluate the value of CT-guided core-needle biopsy in diagnosis and classification of malignant lymphomas. 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. 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. 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.

Immunophenotypic and Molecular Studies in the Diagnosis and Classification of Malignant Lymphoma

Immunophenotypic and molecular studies play an increasingly important role in the diagnosis and classification of lymphoid neoplasms. These studies are not yet a substitute for expert histopathologic evaluation, but are a valuable adjunct to the examination of the hematoxylin and eosin-stained slide. Major applications include determination of lineage, determination of B and T cell monoclonality, detection of oncoprotein expression, and detection of oncogene rearrangements and chromosomal translocations. The recognition of the lymphomas as distinct biologic entities with specific immunophenotypic and genotypic features, as embodied in the Revised European-American Lymphoma (REAL) and World Health Organization (WHO) classifications, is a key to the future development and application of targeted biologic and molecular therapies. In the future, application of gene expression array analysis to the lymphoid neoplasms will permit classification of the lymphomas at a molecular level.

Chromosomal translocations involved in non-Hodgkin lymphomas.

The discovery that recurrent chromosomal translocations are involved in the pathogenesis of non-Hodgkin lymphomas has greatly improved our understanding of these diseases and revolutionized their diagnosis. To review the mechanisms by which chromosomal translocations occur and contribute to the pathogenesis of various types of non-Hodgkin lymphomas and to review the utility of molecular genetic methods for the assessment of these translocations. Primary research studies and reviews published in the English language that focus on chromosomal translocation and non-Hodgkin lymphomas. Chromosomal translocations, which usually result in oncogene activation, occur in many types of B- and T-cell lymphoma, and their detection is helpful for establishing an accurate diagnosis and monitoring disease following therapy. However, the precise mechanisms that explain how translocations occur remain unknown, although for some types of translocations a clear relationship has been established with immunoglobulin gene rearrangement mechanisms. In recent years, a number of genes deregulated by chromosomal translocations have been identified, and the detailed molecular mechanisms by which chromosomal translocations contribute to the pathogenesis of non-Hodgkin lymphoma are beginning to be elucidated. Molecular genetic analysis has played a major role in improving our understanding of B- and T-cell non-Hodgkin lymphomas and has allowed more precise definition of lymphoma types. Molecular genetic tests to detect these translocations are important ancillary tools for the diagnosis and classification of malignant lymphomas.

Epstein-Barr Virus-Associated Anaplastic Large Cell Variant of Diffuse Large B-Cell-Type Non-Hodgkin’s Lymphoma with Concurrent P53 Protein Expression

In the new World Health Organization (WHO) classification of malignant lymphoma, anaplastic large cell lymphoma of B-cell phenotype is classified either as the anaplastic large cell variant of diffuse large B-cell lymphoma or as Hodgkin's lymphoma. A 71-year-old Japanese man developed fever and generalized lymphadenopathy. Biopsy of the right axillary node revealed morphology of malignant lymphoma in which large cells with abundant cytoplasm and pleomorphic nuclei were scattered among small lymphocytes. Immunostaining with various monoclonal antibodies revealed the large cells to be CD79+, CD20/L26+, CD45RO/UCHL-(1-), CD3-, CD10-, CD30+, NPM/ALK-, EMA-, CD15-, and bcl-(2-). Amplification of the J region of the immunoglobulin heavy chain by polymerase chain reaction revealed a single rearranged band. Therefore the diagnosis of anaplastic large cell variant of diffuse large B-cell lymphoma, stage IIIB, was made from the standpoint of the new WHO classification of malignant lymphoma. Biopsy led to findings of Epstein-Barr virus (EBV)-associated lymphoma with positive in situ hybridization results for EBV small RNAs, positive results of immunostaining with EBV latent membrane 1 antibody, and negative results of immunostaining with Epstein-Barr nuclear antigen 2. Results of immunostaining of the mass with p53 antibody also were positive for lymphoma cells. The findings in this case may suggest a close relationship between p53 expression and latent EBV infection.

Nodal marginal zone B-cell lymphoma with a novel t(X;5)(q28;q22): conventional and molecular cytogenetic analysis

Cytogenetic studies provide important information for the diagnosis and classification of malignant lymphomas that in some cases also has prognostic significance. Furthermore, the investigation of isolated novel cytogenetic findings in malignant lymphoma has led to the discovery of many important oncogenes and tumor suppressor genes. For this reason, a case of nodal marginal zone B-cell lymphoma in a 72-year-old woman is described in which analysis by conventional and molecular cytogenetic techniques demonstrated the presence of a t(X:5)(q28;q22) as the sole chromosomal abnormality. This translocation has not been previously reported in the literature.