Revised European-American Classification Of Lymphoid Neoplasms Research Articles

ADC Thresholds in the Discrimination of Indolent and Aggressive Orbital Adnexal Lymphoma

Aim: This study aims to determine whether ADC measurements allow discrimination of indolent (group A) from aggressive orbital lymphoma (group B) and how much ADC value can predict lymphoma subtype. Methods: A retrospective two-armed cohort study including 32 Orbital Adnexal Lymphoma (OAL) lesions evaluated by conventional magnetic resonance image (MRI) and Diffusion Weighted Image (DWI) examination preceding histopathological lesion confirmation. DWI using single-shot echo-planar imaging with b factors of 0,400 and 800 sec/mm2 were performed on 3 Tesla MRI unit. Lymphomas were grouped into indolent or aggressive histopathological subtypes according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). The groups minimum, maximum and percentiles of ADC values of indolent were compared to those of aggressive lymphoma subtype. Multiple receiver operating characteristic curve (ROC) analysis was performed for predicting aggressive OAL. Results: Of the 32 (OAL) cases, 23 (71.9%) were indolent and 9 (28.1%) were aggressive OAL subtypes. In general, ADC values were significantly higher in the indolent compared to the aggressive OL subtypes. (P<0.001). Extra-ocular muscles (P = 0.69) and globe involvement (P = 0.9) were not significant confounders for association of ADC to histological type. The area under curve (AUC) for ADC minimum was 94.4% and for ADC maximum was 81.6%. ADC minimum showed higher sensitivity and specificity than ADC maximum in revealing (OAL) subtypes. Conclusions: ADC measurements are higher in indolent than in aggressive (OAL). ADC minimum has higher sensitivity and specificity than ADC maximum in (OAL) lesions. These concepts confirm and expand the knowledge on (OAL), revealing the importance of ADC minimum in discriminate indolent from aggressive OAL. DWI can be used to characterize (OAL) based on ADC values, having higher sensitivity and specificity to point the (OAL) subtypes.

Classificação de 86 casos de linfoma em bovinos de acordo com a Working Formulation (WF) of Non-Hodgkin's Lymphomas for Clinical Usage e a Revised European-American Classification of Lymphoid Neoplasms (REAL)

Resumo Por meio de um estudo retrospectivo, realizou-se avaliação fenotípica (histologia) e imunofenotípica (imuno-histoquímica [IHQ]) de 86 casos de linfoma bovino. Quanto ao padrão de distribuição, todos os linfomas foram incluídos como difusos. Em relação à dimensão dos linfócitos neoplásicos, 83,8% dos linfomas foram considerados como de grandes células e 11,6% como de pequenas células. Linfomas mistos, ou seja, constituídos por grandes e pequenas células, representaram apenas 4,6% dos casos. Quanto ao número de mitoses, 84,9% dos linfomas foram incluídos como de grau intermediário, 10,5% como de baixo grau e 4,6% como de alto grau. No que se refere à morfologia do núcleo, linfomas em que predominavam linfócitos não clivados (58,2%) ou linfócitos clivados (37,2%) foram mais frequentes do que aqueles em que havia uma mistura igualmente proporcional de linfócitos clivados e não clivados (4,6%). Com base nestes resultados, os 86 linfomas foram assim distribuídos utilizando-se a classificação proposta pela Working Formulation (WF) of Non-Hodgkin's Lymphomas for Clinical Usage: difuso de grandes células não clivadas (46,5%), difuso de grandes células clivadas (33,7%), difuso de pequenas e grandes células (4,6%), difuso de pequenas células - tipo plasmocitoide (7%), imunoblástico (3,5%), difuso de pequenas células - tipo intermediário (2,3%), difuso de pequenas células não clivadas (1,2%) e difuso de pequenas células não clivadas - tipo Burkitt (1,2%). Na imuno-histoquímica, 27 dos 86 (31,4%) linfomas foram positivos para o anticorpo monoclonal CD79αcy, utilizado para detecção de linfócitos B, e nenhum caso foi positivo para o anticorpo policlonal CD3, utilizado para detecção de linfócitos T. Com base nestes resultados, os 27 linfomas B foram assim distribuídos utilizando-se a Revised European-American Classification of Lymphoid Neoplasms (REAL): linfoma difuso de grandes células B (81,5%), linfomas imunoblásticos de grandes células (11,1%) e linfomas linfoplasmocíticos (7,4%). Os resultados aqui apresentados permitem concluir que à semelhança do que vem sendo descrito em outras partes do mundo, os linfomas bovinos são basicamente difusos e predominantemente de grau intermediário, de grandes células, com núcleos clivados ou não clivados. Esses linfomas são decorrentes da proliferação neoplásica de linfócitos B e correspondem, em sua quase totalidade (92,6%), ao que atualmente é incluído na REAL como linfoma difuso de grandes células B.

Immunohistochemical (IHC) Analysis of Non-Hodgkin's Lymphoma (NHL) Spectrum According to WHO/REAL Classification: A Single Centre Experience from Punjab, India.

The distribution of the major subtypes of non-Hodgkin's lymphoma (NHL) differs across geographic regions. This study, from the north Indian state of Punjab, has incorporated immunophenotypic findings while investigating the distribution of NHL subtypes based on World Health Organization (WHO)/ Revised European-American Classification of Lymphoid Neoplasms (REAL) system of classification. Over all seventy seven cases of lymphoma over a period of one year (between April 2012 and April 2013) were diagnosed in the Department of Pathology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar (Punjab). Of these 30 cases (39%) were of Hodgkin's Lymphoma (HL) and 47 cases (61%) were of Non Hodgkins lymphoma NHL. Of the total of cases of lympho-proliferative disorders, the diagnosis of NHL was done by light microscopy alone. All the cases diagnosed provisionally as NHL were taken up for immunophenotyping with Immunohistochemical (IHC) studies. There was 100 % concordance between the light microscopy and IHC studies. The individual NHL cases were classified according to the WHO/REAL classification according to the positive or relevant negative immonophenotypic expression and tabulated to ascertain the morphological spectrum of NHL in this part of the country. B-cell lymphomas formed 89.3%, whereas T-cell lymphomas formed 10.7% of the NHLs. Diffuse Large B-Cell Lymphoma (DLBCL) was the most common subtype (46.8% of all NHLs). B-cell small lymphocytic lymphoma, Mantle-Cell Lymphoma (MCL), marginal zone B-cell lymphomas (including MALT lymphomas), Diffuse, mixed small cleaved cell and large-cell type and Follicular centre-cell lymphomas amounted to 17%, 12.8%, 2.1%, 2.1% and 4.3%, respectively. Among the T-cell lymphomas, T-cell lymphoblastic lymphoma, anaplastic large-cell lymphomas of T/null-cell type, and Angioimmunoblastic T-cell lymphoma (AITL) accounted for 6.4%, 2.1%, and 2.1% of all NHL cases, respectively. The distribution of NHL subtypes in India shows disparity with those from the rest of the world. Follicular Lymphoma (FL) and MCL are less common in India compared to Europe and the USA. Peripheral T-cell lymphomas and T/NK-cell lymphomas of nasal and nasal types, which are common in many other Asian countries, are also less prevalent. T-cell lymphoblastic lymphoma and anaplastic large T/null cell lymphoma are more prevalent in India.

Update on classification of lymphomas

Lymphomas constitute approximately 5% of all malignant neoplasms of the head and neck. They are divided into two major subtypes, Hodgkin's lymphomas and non-Hodgkin's lymphomas, depending on the presence or absence of Reed-Sternberg cells. Controversy in the classification of lymphomas dates back to the first attempts to formulate such classifications. Much of this controversy arose from the assumption that there must be a single guiding principle, a gold standard for classification. Earlier classifications of lymphomas were based on the morphology, treatment response, and survival and some were based on cell lineage and differentiation. The International Lymphoma Study Group (I.L.S.G.) developed a consensus list of lymphoid neoplasms, which was published in 1994 as the Revised European-American Classification of Lymphoid Neoplasms (REAL). The classification was based on the principle that a classification is a list of real disease entities, which are defined by a combination of morphology, immunophenotype, genetic features, and clinical features and there cannot be a single gold standard.

Incidence and Histologic Patterns of Bone Marrow Involvement of Malignant Lymphoma Based on the World Health Organization Classification- A Single Institution Study

Working Formulation and Revised European American Classification of Lymphoid Neoplasms (REAL) have mainly been used in the studies for bone marrow involvement of malignant lymphoma in Korea. We investigated the incidence and histologic patterns of malignant lymphoma according to the WHO classification. This study included 507 cases of malignant lymphoma that were requested for bone marrow study for the staging during the period January 1999-December 2005 in Korea Cancer Center Hospital. Medical records, peripheral blood smears, bone marrow aspiration smears, biopsy sections, and histopathologic findings were analyzed retrospectively. Of the 507 cases of malignant lymphoma, 473 (93.3%) were non-Hodgkin lymphoma (NHL) and 34 (6.7%) were Hodgkin lymphoma (HL). The overall incidence of bone marrow involvement by NHL and HL was 12.5% (59/473) and 11.8% (4/34), respectively. Among NHL cases, the incidence of bone marrow involvement by B-cell and T-cell neoplasms was 11.4% (43/377) and 16.7% (16/96), respectively. Although the incidences of bone marrow involvement by several B-cell neoplasms were more than 30%, diffuse large B cell lymphoma showed a relatively low incidence of bone marrow involvement (4.6%). Of bone marrow involvement patterns, diffuse infiltration pattern was the most common (40.0%). Peripheral blood involvement by lymphoma was observed in 35.6% of cases with bone marrow involvement. We used WHO classification in the study for the bone marrow involvement of malignant lymphoma, and this single-institution study should give a useful, up-to-date histopathologic information.

Changes in Cancer Registry Coding for Lymphoma Subtypes: Reliability Over Time and Relevance for Surveillance and Study

Because lymphoma comprises numerous histologic subtypes, understanding the reasons for ongoing increases in its incidence requires surveillance and etiologic study of these subtypes. However, this research has been hindered by many coexisting classification schemes. The Revised European American classification of Lymphoid Neoplasms (REAL)/WHO system developed in 1994 and now used in clinical settings was not incorporated into the International Classification of Diseases-Oncology (ICD-O), used by cancer registries, until the release of the third edition (ICD-O-3) in 2001. Studies including patients diagnosed before 2001 may have codes from earlier ICD-O versions that must be converted to ICD-O-3 and have higher proportions of unclassified (e.g., lymphoma and not otherwise specified) cases. To better understand (a) the agreement of computer-converted ICD-O-3 codes to ICD-O-3 codes generated directly from diagnostic pathology reports and (b) the reproducibility of unclassified status, we reviewed a population-based series of diagnostic pathology reports for lymphoma patients diagnosed before (1988-1994; n = 1,493) and after (1998-2000; n = 1,527) the REAL/WHO scheme was introduced. Overall, computer- and coder-assigned ICD-O-3 codes agreed for 77% of patients in both groups and improved slightly (82%) when codes were grouped. The most common lymphoma subtypes, diffuse large B cell and follicular, had relatively good reliability (84-89%) throughout the study period. T-cell and natural killer cell lymphomas had worse agreement than B-cell lymphomas, even when grouped. Many (42-43%) lymphomas reported as unclassifiable could be assigned a subtype upon pathology report review. These findings suggest that the study of lymphoma subtypes could be improved by (a) use of more standardized terminology in pathology reports, (b) grouping individual ICD-O-3 codes to reduce misclassification bias, and (c) routine secondary editing of unclassified lymphomas by central cancer registries.

Avances en el diagnóstico de los tumores otorrinolaringológicos

In the present study we review ENT tumor pathology in childhood. Only the most salient aspects are emphasized and the variety of entities reviewed was restricted. Molecular biology techniques reveal infection by human papilloma virus (types 6 and 11) in 50 % of papillomas, while immunohistochemical techniques are less effective in papilloma virus detection. The myofibroblastic nature of nasal angiofibroma has been demonstrated and its incidence is 25 times more frequent in patients with familial polyposis of the colon. Overexpression of p53 occurs in the initial stages of nasopharyngeal carcinoma, while overexpression of c-myc is correlated with an unfavorable prognosis. Recently, olfactory neuroblastoma has been shown not to express the protein product of the MIC-2 gene (antibody 12E7), thus the hypothesis that it could be a member of the Ewing tumor family (neuroectodermal peripheral tumors) has not been confirmed, although it is a primitive neural tumor. The head and neck rhabdomyosarcoma with the best prognosis is that located in the orbit, and cytogenetic studies have shown chromosomic translocation t(2;13) in 50 % of these childhood tumors when they are of the alveolar-type, while trisomy of chromosome 2 or 20 is more characteristic of the embryonic-type. Currently, any classifying features of ENT lymphomas must be based on the Revised European-American Classification of Lymphoid Neoplasms (REAL). Papillary and medullary carcinomas are the most common histological types of thyroid carcinoma in childhood. Alterations in ret/PTC play a significant role in the pathogenesis of both.

Who is WHO and what was REAL?

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.

Who is WHO and what was REAL?

The principles of the new WHO classification of haematopoietic and lymphoid tumours are based on those defined in the Revised European American classification of Lymphoid neoplasms (REAL), published by the International Lymphoma Study Group (ILSG) in 1994. Thus, the new WHO classification may be considered an updated version of the REAL classification rather than of the old WHO classification published in 1976. Disease entities are defined on the basis of morphological, phenotypic, genotypic, and clinical data. The relative impact of these characteristics varies among different diseases and there is "no gold standard". Thus, the strict hierarchy among diagnostic criteria, headed by morphology and followed by immunohistochemistry and genetics, has been discontinued. The WHO classification not only encompasses lymphoid tumours but extends to myeloid, mast cell and histiocytic/dendritic cell malignancies. Neoplasms are primarily stratified according to their tumour cell lineage. For each neoplasm a cell of origin is postulated. The classification of lymphoid malignancies recognises three major categories, B-cell neoplasms, T-/NK-cell neoplasms, and Hodgkin lymphomas. B-cell and T-cell lymphomas are further divided into precursor neoplasms and mature neoplasms, the latter being subdivided according to their clinical manifestation into disseminated/leukaemic, extranodal and nodal malignancies. In contrast to previous classifications, the neoplasms are grouped neither according to their histological grade (Kiel classification) nor according to their clinical aggressiveness (International Working Formulation). However, the histological grade is considered a prognostic factor which enters into the description of each disease entity. Hodgkin's disease, now more appropriately termed Hodgkin lymphoma, comprises nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphomas of nodular sclerosis, mixed cellularity, lymphocyte-depleted and lymphocyte-rich subtype. For practical purposes this minireview disregards the description of myeloid, macrophage/histiocytic, dendritic cell and mast cell disorders. Furthermore, the present paper is restricted to those lymphoid tumours that are not already identically described in the REAL classification, in order to focus on what is really new in the WHO classification.

Localized aggressive non-Hodgkin’s lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group

Purpose: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin’s lymphomas (NHL) originating in the nasal cavity. Methods and Materials: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992. Results: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22–66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% ( p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0–1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively ( p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2–3. The 5-year local control rates of the patients who received >46 Gy ( n = 22) and ≤46 Gy ( n = 20) were 95% and 76% ( p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma. Conclusions: Patients with nasal lymphomas (m-IPI 0–1) should be treated with combined therapy. For the patients with high risk (m-IPI 2–3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.

Long-term clinical and molecular remission after allogeneic stem cell transplantation (SCT) in patients with poor prognosis non-Hodgkin's lymphoma.

From 1987 to 1999 35 patients with poor prognosis non-Hodgkin's lymphoma (NHL) underwent allogeneic stem cell transplantation (SCT) at the University Hospitals of Vienna and Graz. Initial biopsy specimens were reclassified according to the Revised European-American Classification of Lymphoid Neoplasms (REAL). All patients surviving 28 days engrafted. Twenty-eight of them (93%) attained clinical remission. At the last follow-up 14 patients were alive and disease-free at a median of 5.0 (range, 2.3-12.9) years after allogeneic SCT. The actuarial overall survival is 35%. Five patients relapsed 1.8 to 27.6 months after transplant, the probability of relapse is 23%. Of the 21 deaths following SCT, seven were due to relapse/refractory disease and 14 due to transplant-related causes. The probability of treatment-related mortality is 48%. After SCT, minimal residual disease (MRD) was monitored by polymerase chain reaction (PCR) in seven patients with a BCL-2/IgH translocation and in 13 with a clonal immunoglobulin heavy chain (IgH) rearrangement. All 20 patients attained clinical remission rapidly and converted to PCR negativity. In the follow-up nine of these patients are in long-term clinical and molecular remission, six PCR-negative patients died of transplant-related causes and five patients relapsed. In summary, allogeneic stem cell transplantation has a curative potential for patients with refractory and recurrent non-Hodgkin's lymphoma. In our series long-term disease-free survival was associated with molecular disease eradication after SCT. Treatment-related mortality rate was high, thus earlier referral of selected patients to allogeneic SCT should be considered.

Pattern of Malignant Lymphoma in the United Arab Emirates - A Histopathologic and Immunologic Study in 208 Native Patients

The aim of this study was to analyze the distribution of the various pathologic types of lymphoma in a native Arab population of the United Arab Emirates (UAE). Two hundred and eight patients with malignant lymphoma diagnosed over a 12-year period (1988?1999) were retrospectively studied morphologically and immunohistochemically with a panel of monoclonal antibodies and classified according to the revised European?American classification of lymphoid neoplasms (REAL). Of the 208 patients in the study, 41% had Hodgkin's disease (HD) and 59% had non-Hodgkin's lymphoma (NHL). The distribution of HD showed a predominance of nodular sclerosis and mixed cellularity types. Among NHLs, the most frequent type was diffuse large B cell (59% of all NHLs) followed by the Burkitt's type (13%). The proportion of primary extranodal NHL was 29%. Immunologically, the percentages of NHL with B-cell and T-cell phenotypes were 83 and 11, respectively. When the International Working Formulation was used, 34% of NHLs were classified as high grade, 59% as intermediate grade and only 7% as low-grade lymphomas.

Principles behind definitions of diseases--a criticism of the principle of disease mechanism and the development of a pragmatic alternative.

Many philosophers and medical scientists assume that disease categories or entities used to classify concrete cases of disease, are often defined by disease mechanisms or causal processes. Others suggest that diseases should always be defined in this manner. This paper discusses these standpoints critically and concludes that they are untenable, not only when 'disease mechanism' refers to an objective mechanism, but also when 'mechanism' refers to a pragmatically demarcated part of the total "objective" causal structure of diseases. As an alternative to principles that use the concept of disease mechanism or analogous concepts, a pragmatic approach is suggested and described. This approach has been suggested before, but in problematic or inadequate versions. This paper proposes a version compiled of two "pragmatic principles" and shows that they are much more adequate than the principle of disease mechanism. With reference to a case study of a still ongoing international discussion of various candidates for a classification system for malignant lymphomas, including REAL (Revised European-American Classification of Lymphoid Neoplasms) in which the concept of disease mechanism or analogous concepts plays a very small part, it is shown just how pivotal these two pragmatic principles can be in actual discussions of definitions of diseases. Finally, it is pointed out that with regard to modern philosophy of language it may, at least in some cases, be problematic to distinguish between the two pragmatic principles as they stand.

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

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

Anaplastic large cell lymphoma arising in bone: report of a case of the monomorphic variant with the t(2;5)(p23;q35) translocation.

Anaplastic large cell lymphoma (ALCL) represents approximately 2% of all non-Hodgkin lymphomas according to the recent Non-Hodgkin Lymphoma Classification Project. As defined in the revised European-American classification of lymphoid neoplasms (REAL), ALCL is a neoplasm of T-cell or null-cell lineage; 20% to 60% of cases are associated with the t(2;5)(p23;q35) translocation. ALCL commonly involves nodal as well as a wide variety of extranodal sites, although primary or secondary involvement of bone is rare. We describe the case of a 71-year-old man with stage IE T-cell ALCL, monomorphic variant, arising in the left anterior fifth rib and involving adjacent soft tissue without other sites of disease. The monomorphic histologic features hindered the initial recognition of this neoplasm as ALCL. However, strong uniform CD30 antigen expression and subsequent demonstration of the t(2;5)(p23;q35) translocation and anaplastic lymphoma kinase (ALK) immunoreactivity led to the correct diagnosis. We identified only 5 reported cases of T-cell and null-cell ALCL arising in bone and only 2 of these cases involved a single bone site. All 5 previously reported cases were ALCL of the classic type. We report a case of ALCL that is unique to our knowledge. This case of monomorphic ALCL was localized to bone and tumor cells contained the t(2;5)(p23;q35) translocation.

Burkitt's lymphoma: historical background and recent insights into classification and pathogenesis.

In this paper, the authors evaluate the historical evolution of the definition of Burkitt's lymphoma (BL) and of its clinicoepidemiological (endemic, sporadic, and acquired immunodeficiency syndrome-associated BL) and morphological variants. On the basis of the morphological, immunologic, genetic, and clinical characteristics of these tumors, the authors also emphasize the importance of precise disease definitions for biological and epidemiological studies. These principles were used in accordance with the Revised European-American classification of lymphoid neoplasms (REAL), which proposed that disease entities should be defined by a constellation of pathobiological and clinical features.

Diagnosis of lymphoma by fine-needle aspiration cytology using the revised European-American classification of lymphoid neoplasms.

Recent changes in the classification of non-Hodgkin lymphoma (NHL) emphasize the diagnostic importance of cytomorphology, immunophenotyping, and molecular findings in addition to histology. These changes have allowed for a greater role of fine-needle aspiration cytology (FNA) in the diagnosis of NHL. A review of the English language literature regarding the use of FNA in the cytodiagnosis of lymphoma was performed. The revised European-American classification of lymphoid neoplasms (REAL) was reviewed in the context of its adaptability to the cytologic diagnosis of lymphoid neoplasms. FNA is being used more frequently in the diagnosis, staging, and follow-up of lymphoma whenever supportive studies are readily available. Cytomorphologic, immunophenotypic, and molecular criteria as well as pitfalls in the diagnosis of lymphoma by FNA have been delineated. Information was compiled into tables to facilitate correlation of criteria with the proposed REAL system. Many cases of NHL can be diagnosed and subclassified by FNA when there is adequate immunophenotypic information. Cancer (Cancer Cytopathol)

Mantle Cell Lymphoma Molecular and Immunophenotypic Diagnostic Aids

○ Objective.-This article summarizes the most useful ancillary immunohistochemical and molecular assays for use in the diagnosis of mantle cell lymphoma. Data Sources.-The English language literature was surveyed, with an emphasis on recent publications, for articles presenting key advances in the molecular characterization of mantle cell lymphomas and for series of cases testing the utility of molecular diagnostic tests. The authors' series of 26 small B-cell lymphomas, analyzed for the cyclin D1 protein by paraffin immunohistochemistry and for t(11;14) by polymerase chain reaction, is included. Conclusions.-Mantle cell lymphoma, a B-cell lymphoma now recognized in the 1994 Revised European-American Classification of Lymphoid Neoplasms (REAL) classification, is a relatively aggressive lymphoma with a poor prognosis. Its characteristic t(11;14)(q13;q32) translocation has a role in oncogenesis and has been exploited for molecular diagnostic tests, but these tests vary in sensitivity, specificity, and ease of use. Improved immunohistochemical tests are sufficient to confirm the diagnosis in most cases. Conventional cytogenetics and molecular diagnostic tests for t(11;14)-Southern blot and polymerase chain reaction analysis-may be helpful in selected cases, but are laborious or of limited sensitivity. Other methods, such as fluorescence in situ hybridization, need further development to provide faster, more sensitive diagnosis.

Mantle Cell Lymphoma

Abstract Objective.—This article summarizes the most useful ancillary immunohistochemical and molecular assays for use in the diagnosis of mantle cell lymphoma. Data Sources.—The English language literature was surveyed, with an emphasis on recent publications, for articles presenting key advances in the molecular characterization of mantle cell lymphomas and for series of cases testing the utility of molecular diagnostic tests. The authors' series of 26 small B-cell lymphomas, analyzed for the cyclin D1 protein by paraffin immunohistochemistry and for t(11;14) by polymerase chain reaction, is included. Conclusions.—Mantle cell lymphoma, a B-cell lymphoma now recognized in the 1994 Revised European-American Classification of Lymphoid Neoplasms (REAL) classification, is a relatively aggressive lymphoma with a poor prognosis. Its characteristic t(11;14)(q13;q32) translocation has a role in oncogenesis and has been exploited for molecular diagnostic tests, but these tests vary in sensitivity, specificity, and ease of use. Improved immunohistochemical tests are sufficient to confirm the diagnosis in most cases. Conventional cytogenetics and molecular diagnostic tests for t(11;14)—Southern blot and polymerase chain reaction analysis—may be helpful in selected cases, but are laborious or of limited sensitivity. Other methods, such as fluorescence in situ hybridization, need further development to provide faster, more sensitive diagnosis.

Clinicopathological analysis of 501 non-Hodgkin's lymphomas in Korea according to the revised European-American classification of lymphoid neoplasms.

The clinical relevance of the Revised European-American Classification of Lymphoid Neoplasms (REAL) is still debated. To test the clinical validity of the REAL classification in Korea, where the incidence of T-cell lymphoma is higher, we investigated the clinicopathological features of non-Hodgkin's lymphoma (NHL) from Korea Cancer Center Hospital. Five hundred and one patients with NHL were reclassified according to the REAL classification and clinicopathologically analysed. Immunophenotypically, B-cell lymphoma accounted for 67.9% and T- and NK-cell type for 30.5%. Approximately 48.5% of cases were forms of diffuse large B-cell lymphoma (DLBCL), while only 5.4% were follicular lymphoma. Peripheral T-cell lymphoma unspecified (PTCL-U; 10.8%) and angiocentric lymphomas (11.8%) comprised the majority of T-cell lymphomas. Most of the angiocentric lymphomas presented with localized nasal/nasopharyngeal or tonsillar primaries. All peripheral T-cell lymphomas (PTCL) showed a significantly low overall survival compared to DLBCL (P = 0.02, log rank). Overall survival rates for DLBCL and PTCL-U were also significantly different (P = 0.0043, log rank), though for DLBCL and angiocentric lymphoma there was no significant difference (P = 0.2142, log rank). Angiocentric lymphoma, however, was characterized by a shorter median survival time than DLBCL (54 months vs. 96 months). Among DLBCL patients according to the REAL classification, overall survival was significantly better in nonimmunoblastic type (intermediate-grade, WF-F,G) as compared to large cell immunoblastic type (high-grade, WF-H) (log rank, P < 0.001). The morphological distinction of the immunoblastic and nonimmunoblastic among DLBCL of the REAL classification bears significant prognostic relevance worthy of further consideration. We conclude that lineage assignment (T vs. B) in the REAL classification is a clinically important distinction, but that it is necessary to subdivide the broad category of DLBCL.