European-American Classification Of Lymphoid Neoplasms Research Articles

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee

AbstractSince the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

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.

Guidelines for the investigation and management of mantle cell lymphoma.

The guideline group was selected to be representative of UK-based medical experts and patients representatives. Ovid MEDLINE, EMBASE and NCBI Pubmed were searched systematically for publications in English from 1980 to 2011 using the MeSH subheading 'lymphoma, mantle cell' and 'lymphoma, mantle cell' as a keyword, as well as all subheadings. In addition, all references to mantle cell lymphoma in the World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissue (Swerdlow et al, 2008) and the British Committee for Standards in Haematology (BCSH) Guideline: Best Practice in Lymphoma Diagnosis and Reporting (Parker et al, 2010) have been included. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Haemato-oncology Task Force of the BCSH. The guideline was then reviewed by a sounding board of approximately 50 UK haematologists, the BCSH and the British Society for Haematology Committee and comments incorporated where appropriate. The 'GRADE' system was used to quote levels and grades of evidence, details of which can be found in Appendix I. The objective of this guideline is to provide healthcare professionals with clear guidance on the investigation and management of patients with mantle cell lymphoma. The guidance may not be appropriate to patients with other lymphoma sub-types and in all cases individual patient circumstances may dictate an alternative approach.

Low-dose methotrexate in PAH related to T-cell large granular lymphocyte leukaemia

To the Editors: The classification of pulmonary hypertension (PH) has recently been updated and PH associated with haematological disorders is classified as category V [1]. T-cell large granular lymphocytes (LGLs) are a morphologically distinct subset of normal peripheral blood mononuclear cells classified into two major lineages based on the presence of the CD3 receptor: CD3+ lymphocytes and CD3- natural killer cells. The revised European-American classification of lymphoid neoplasms [2] considers clonal proliferation of these cells, or LGL leukaemia (as proved by a cytogenetic study of the rearrangement of the T-cell receptor), as a distinct type of peripheral T-cell neoplasm. In the vast majority of cases, LGL leukaemia has a CD3+, αβ+, CD4-, CD8+, CD16+, CD57+ and CD56- phenotype and an indolent course [3]. Overexpression of some natural killer receptors (NKRs) of the killer immunoglobulin-like receptor family, such as CD94 and CD158b, is sometimes observed [4–6]. T-cell LGL leukaemia is frequently associated with various autoimmune diseases, particularly rheumatoid arthritis (30% of cases) and haematological disorders ( e.g. neutropenia) [3]. PH associated with T-cell LGL leukaemia has been described in rare cases and an aetiopathological link between the diseases has been suggested [4–8]. In this context, the efficacy of immunosuppressive agents in association with standard treatment (oral anticoagulants±diuretics±oxygen) with or without vasodilatory drugs has been investigated [4, 6, 7]. Herein, we describe a new case of PH associated with T-cell LGL leukaemia that responded to immunosuppressive therapy. Possible aetiopathological mechanisms are discussed on the basis of literature data. A 50-yr-old female without significant medical history was admitted to hospital because of rapidly progressive New York Heart Association (NYHA) functional class …

Double-Hit Lymphoma at Second Relapse of Burkitt-Like Lymphoma : A Case Report

Double-hit lymphoma (DHL) is a rare and extremely unfavorable type of lymphoma with concurrent chromosomal translocations of BCL2 and MYC. It is considered that BCL2 translocation precedes MYC events in lymphomagenesis of DHL. In fact, most cases of DHL arise de novo or following FL. We describe a very rare case of DHL arising from Burkitt-like lymphoma according to the revised European-American classification of lymphoid neoplasms. A 67-year-old Japanese male presented with persistent fever. [(18)F]-fluorodeoxyglucose positron emission tomography revealed multiple abnormal accumulations in the bone marrow, pancreas, and periphery of the left kidney. The patient was diagnosed with Burkitt-like lymphoma according to a bone marrow biopsy. At the disease onset and the first relapse, chemotherapy was effective and the patient experienced sustained and complete remission. At the second relapse, however, the clinical presentation and morphology of lymphoma cells were nearly identical, but a high level of chemoresistance was acquired, and the patient succumbed almost 1 month after hospitalization. Chromosomal analyses revealed a complex karyotype with concurrent t(14;18) and t(8;22) translocations, which have not been previously detected. It is therefore important to note that DHL cannot be diagnosed without chromosomal analysis. Cytogenetic analyses should thus be performed for patients with high-grade B-cell lymphoma and who experience a recurrence of this lymphoma.

Follicular lymphoma of the extrahepatic bile duct mimicking cholangiocarcinoma

We report a case of a 33-year old man who presented with symptoms and signs of an acute biliary tract obstruction with jaundice and abdominal pain. Diagnostic imaging studies revealed a biliary stricture of the hepatic confluence, and a mass at the hepatic hilum which obstructed the extrahepatic bile duct from the outside. At laparotomy, there was 3-cm-size nodule at the hilum which presented with a rubbery consistency. We performed extrahepatic bile duct resection and right and left hepaticojejunostomy. Histological examination of the resected specimen revealed follicular lymphoma, which consisted of medium cleaved follicle-like cells, grade 1 of 3 according to the revised European-American classification of lymphoid neoplasms proposed by International Lymphoma Study Group. Postoperative follow-up of more than 1 year has been completely uneventful, without any symptoms or signs of disease recurrence. This is the second case report of follicular lymphoma of the extrahepatic bile duct.

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).

Lymphoproliferative Disease of the Ocular Adnexa: A Clinical and Pathologic Study With Statistical Analysis of 69 Patients

To evaluate the clinical features, treatment, and outcomes of a cohort of patients with ocular adnexal lymphoproliferative disease classified according to the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms and to perform a robust statistical analysis of these data. Sixty-nine cases of ocular adnexal lymphoproliferative disease, seen in a tertiary referral center from 1992 to 2003, were included in the study. Lesions were classified by using the World Health Organization modification of the Revised European-American Classification of Lymphoid neoplasms classification. Outcome variables included disease-specific survival, relapse-free survival, local control, and distant control. Stage IV disease at presentation, aggressive lymphoma histology, the presence of prior or concurrent systemic lymphoma at presentation, and bilateral adnexal disease were significant predictors for reduced disease-specific survival, local control, and distant control. Multivariate analysis found that aggressive histology and bilateral adnexal disease had significantly reduced disease-specific survival. The typical presentation of adnexal lymphoproliferative disease is with a painless mass, swelling, or proptosis; however, pain and inflammation occurred in 20% and 30% of patients, respectively. Stage at presentation, tumor histology, primary or secondary status, and whether the process was unilateral or bilateral were significant variables for disease outcome. In this study, distant spread of lymphoma was lower in patients who received greater than 20 Gy of orbital radiotherapy.

Association of celiac disease and intestinal lymphomas and other cancers

Celiac disease (CD) is associated with intestinal lymphoma and other forms of cancer, especially adenocarcinoma of the small intestine, of the pharynx, and of the esophagus. Enteropathy-associated T-cell lymphoma (EATL) is a rare form of high-grade, T-cell non-Hodgkin lymphoma (NHL) of the upper small intestine that is specifically associated with CD. This NHL subtype arises in patients with either previously or concomitantly diagnosed CD. In a subgroup of patients, there is progressive deterioration of a refractory form of CD. EATL derives from a clonal proliferation of intraepithelial lymphocytes and is often disseminated at diagnosis. Extraintestinal presentations are not uncommon in the liver/spleen, thyroid, skin, nasal sinus, and brain. The outlook of EATL is poor. Recent studies indicated that (1) CD is associated with a significantly increased risk for NHL, especially of the T-cell type and primarily localized in the gut (EATL); (2) the CD-lymphoma association is less common than previously thought, with a relative risk close to 3; (3) CD screening is not required in patients with NHL of any primary site at the onset, unless suggested by specific findings (T-cell origin and/or primary gut localization). The risk of NHL associated with clinically milder (or silent) forms could be lower than in typical cases of CD. Several follow-up studies suggest that the GFD protects from cancer development, especially if started during the first years of life. Strict adherence to the GFD seems to be the only possibility of preventing a subset of rare but very aggressive forms of cancer.

Combined therapy with rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) for Sjögren's syndrome-associated B-cell aggressive non-Hodgkin's lymphomas.

To determine the safety and therapeutic response of a regimen consisting of cyclophosphamide/doxorubicin/vincristine/prednisone (CHOP) plus rituximab in patients with Sjögren's syndrome (SS) and aggressive non-Hodgkin's lymphoma (NHL). Four SS patients with aggressive marginal zone NHL were enrolled in this trial. All patients were classified according to the newly proposed revised European-American classification of lymphoid neoplasms. Three out of four patients also had mixed cryoglobulinaemia (MC) of type II. They were treated every 3 weeks for eight cycles of CHOP. Patients also received rituximab, at a dose of 375 mg per square metre, on day 1 of each of the eight cycles of CHOP. Four weeks after completion of the eighth course of CHOP plus rituximab and every 6 months thereafter, patients were re-evaluated for response. Complete remission of lymphoma was achieved in all four patients. The lymphoma patients remained in remission for a period of 23, 15, 12 and 10 months respectively, while certain signs and symptoms of MC type II (purpura, peripheral neuropathy and arthralgias) significantly improved with treatment. In addition, the titres of circulating cryoglobulins and RF decreased, while C4 levels returned to normal. CHOP plus rituximab was well tolerated and proved effective in SS patients with aggressive NHL. Our observations may warrant a larger controlled trial to assess the effectiveness of this regimen in such patients.

Overview of non-Hodgkin's lymphoma: Biology, staging, and treatment

The Revised European-American Classification of Lymphoid Neoplasms was recently developed to address the shortcomings of the National Cancer Institute Working Formulation and to establish a common classification system that could be used internationally. The Revised European-American Classification of Lymphoid Neoplasms classification is a major improvement over previous systems and has been shown to define “real” clinical entities that can be diagnosed by expert hematopathologists. Important advances also have recently been made in the staging of lymphomas with the development of the International Prognostic Index, which accurately defines prognostic subgroups and can be used to identify patients who may benefit from more aggressive experimental treatment. With respect to treatment, there remains considerable controversy over the most effective options for patients with indolent lymphomas. However, several novel approaches appear very promising, including monoclonal antibody-based therapy, particularly radioimmunotherapy and purine analogues. In patients with aggressive lymphomas, the treatment options are less controversial. Combination chemotherapy remains the standard of care, but relapse with the development of drug resistance continues to be a problem. Recent data suggest that high-dose therapy with stem cell support may be the treatment of choice for patients with relapsed aggressive lymphomas that remain chemosensitive. Semin Oncol 30 (suppl 4):3-9. © 2003 Elsevier Inc. All rights reserved.

Overview of non-Hodgkin's lymphoma: biology, staging, and treatment.

The Revised European-American Classification of Lymphoid Neoplasms was recently developed to address the shortcomings of the National Cancer Institute Working Formulation and to establish a common classification system that could be used internationally. The Revised European-American Classification of Lymphoid Neoplasms classification is a major improvement over previous systems and has been shown to define "real" clinical entities that can be diagnosed by expert hematopathologists. Important advances also have recently been made in the staging of lymphomas with the development of the International Prognostic Index, which accurately defines prognostic subgroups and can be used to identify patients who may benefit from more aggressive experimental treatment. With respect to treatment, there remains considerable controversy over the most effective options for patients with indolent lymphomas. However, several novel approaches appear very promising, including monoclonal antibody-based therapy, particularly radioimmunotherapy and purine analogues. In patients with aggressive lymphomas, the treatment options are less controversial. Combination chemotherapy remains the standard of care, but relapse with the development of drug resistance continues to be a problem. Recent data suggest that high-dose therapy with stem cell support may be the treatment of choice for patients with relapsed aggressive lymphomas that remain chemosensitive.

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.

Immunodeficiency-related lymphoproliferative disorders: prospective data from the United Kingdom Children's Cancer Study Group Registry.

Clinical data and biological samples were prospectively collected in 42 children with lymphoproliferative disease (LPD) secondary to organ/bone marrow transplant-related immunosuppression (30: 11 liver, 10 heart/lung, 8 kidney and 1 bone marrow), other drug-induced immunosuppression (2), congenital immunodeficiency (8) or human immunodeficiency virus (HIV)-related immune dysfunction (2). Ages ranged from 10 months to 17 years and there were 15 girls. Pathology was centrally reviewed and showed polymorphic features in 5 cases, monomorphic in 23, mixed pattern in 5 patients and 9 other types. Using the Revised European-American Classification of Lymphoid Neoplasms, 5 were B lymphoblastoid, 24 were high-grade B and 14 were other subtypes. Using the Pittsburgh classification, 9 were lymphadenopathic, 10 were systemic, 25 were lymphomatous and, with the Murphy grouping for non-Hodgkin's lymphoma (NHL), 10 were localized and 32 non-localized. Twenty-four out of 38 evaluable cases were Epstein-Barr virus positive. Thirty-five patients were evaluable for clonality; 24 were monoclonal and 11 were polyclonal. Reduced immunosuppression in solid organ transplant patients resulted in resolution of disease in 14/24, which was sustained in 11. Nineteen patients received chemotherapy, 14/18 evaluable responded, which was sustained in 8 cases. Seven out of 29 solid organ transplant and 10/13 other immune-deficient patients died. In the largest group of patients, solid organ transplants, no significant clinical or biological characteristics that predicted outcome were identified. In the transplant group close monitoring of response during reduction in immunosuppression is essential and the early use of B NHL chemotherapy may be effective.

High frequency of MALT lymphoma in a series of 14 cases of primary breast lymphoma.

This article reports the clinicopathologic and immunohistochemical findings of 14 cases fulfilling the criteria of Wiseman and Liao for primary lymphoma of the breast (PBL), with emphasis on the frequency of mucosa-associated lymphoid tissue (MALT) lymphomas. The tumors were reclassified according to the revised European-American classification of lymphoid neoplasms. Immunohistochemistry was used to assist in the classification and subtyping of PBL, to demonstrate lymphoepithelial lesions (LEL), and to assess estrogen/progesterone receptor expression. Nine tumors were classified as MALT lymphomas (seven low grade and two high grade), four as diffuse large cell lymphomas and one as follicle center lymphoma. Extensive lymphoid cell infiltration of mammary ducts and acini was also found in non-MALT lymphoma cases. None of the 14 cases expressed hormonal receptors. Primary lymphoma of the breast is a rare and morphologically heterogeneous entity. There is similarity on the clinicopathologic overall profile of the current series of patients and those previously reported, but we recorded a higher incidence of MALT lymphoma (64.3%). Immunohistochemistry is mandatory to identify "true" LEL because epithelial permeation by lymphoid cells can also be found in non MALT-type lymphomas.

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.

Angiotropic Lymphoma: An Immunophenotypically and Clinically Heterogeneous Lymphoma

Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated.Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5−, CD10− (11 cases); CD5+, CD10− (3 cases), and CD5−, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission.Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.