Linfoma Hodgkin clássico de apresentação incomum. Relato de caso / An unusual presentation of a classic Hodgkin lymphoma. Case report

O linfoma é uma neoplasia originária do sistema linfático, a partir de células linfocitárias. A sintomatologia mais comum é febre, tosse, sudorese noturna, perda de peso, fraqueza e linfoadenopatia indolor. A etiologia ainda permanece desconhecida, tendo sido relacionada ao vírus Epstein-Barr. O diagnóstico se baseia na visualização das células de Reed-Sternberg. O esquema adriamicina, bleomicina, vinblastina e dacarbazina (ABVD) ainda é o tratamento preconizado, associado ou não à radioterapia. Relatamos um caso de linfoma de Hodgkin de apresentação atípica, cujo diagnóstico só foi possível por esplenectomia.(AU)

The lymphoma is a cancer of the lymphatic system originating from lymphocyte cells. The most common symptoms are fever, cough, night sweats, weight loss, weakness, and painless lymphadenopathy. The etiology remains unknown, having been related to the Epstein Barr virus. The diagnosis is based on visualization of Reed Sternberg cells. The adriamycin, bleomicin, vinblastine and dacarbazine (ABVD) regimen is still the preferred treatment, with or without radiation therapy. We report a case of Hodgkin's lymphoma of atypical presentation, the diagnosis of which was only possible through splenectomy.(AU)

Dermatoscopia do nevo de Spitz pigmentado / Dermatoscopy of the pigmented Spitz nevus

O nevo de Spitz pigmentado consiste em uma lesão melanocítica benigna com características peculiares. Geralmente, melanoma é considerado no diagnóstico diferencial desta lesão, bem como o nevo de Reed. A dermatoscopia representa uma parte relevante da abordagem diagnóstica e, portanto, ela permite um estudo mais eficiente dessas lesões dermatológicas. O presente relato de caso é sobre uma paciente com dois nevos de Spitz pigmentados de localização no tronco e história familial de melanoma, no qual a dermatoscopia associada à histopatologia foram cruciais para o diagnósticos das lesões.

Clinicopathologic analysis of angioimmunoblastic T-cell lymphoma with Hodgkin/Reed-Sternberg-like cells / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the clinicopathologic features and pathologic diagnosis and differential diagnosis of angioimmunoblastic T-cell lymphoma with HRS-like cells.</p><p><b>METHODS</b>Six cases of angioimmunoblastic T-cell lymphoma with HRS-like cells were examined histologically and immunohistochemically (EliVision method) and in-situ hybridization for Epstein-Barr virus-encoded RNA (EBER), and the literature was reviewed.</p><p><b>RESULTS</b>The cytologic and microscopic features of these imprints and lymph node samples showed a heterogeneous population of hematolymphoid cells, including small to intermediate lymphoid cells, immunoblasts, plasma cells, dendritic cells, and eosinophils, as well as small vessels that were surrounded by some of the abnormal cells. The neoplastic T-cells expressed CD3 and CD5 and partly positive for CD10 and bcl-6, CD21 showed expanded and irregular follicular dendritic cell (FDC) meshworks that surrounding the high HEV. The HRS-like cells were positive for MUM-1 and Ki-67, variable intensity positive for CD30, CD20, and PAX-5, but negative for CD15. EBV-positive cells included HRS-like cells and small to large-sized neoplastic T-cells, which formed small clusters or scattering in the background of the disease.</p><p><b>CONCLUSIONS</b>The clinical course of angioimmunoblastic T-cell lymphoma with HRS-like cells is aggressive. Which present with histomorphology overlap with classical Hodgkin lymphoma (CHL), similar to CHL in EBER and immunophenotype, however, it is easy to misdiagnosis as HL. Thus, angioimmunoblastic T-cell lymphoma pathology diagnosis should comprehensive analysis of different kinds of materials, including clinical features, and histological structure, and EBER, and immunophenotype, and gene rearrangement.</p>

Nevus de Spitz- variedad de Reed en una niña de 10 años / Spitz Nevus - Reed's variety on a 10 year old girl

Presentamos el caso de una niña de 10 años de edad, con antecedentes personales de nevos atípicos, que consultó en el Servicio de Dermatología de nuestro hospital por una lesión papuloide, hiperpigmentada, localizada en la región anterior de la pierna izquierda compatible con Nevus de Spitz variedad de Reed. Se revisaron las formas de presentación clínica, los métodos diagnósticos (histopatología y dermatoscopía), el diagnósticodiferencial con melanoma y el algoritmo terapéutico...

Epstein-Barr virus and the origin of Hodgkin lymphoma / 癌症

Although Epstein-Barr virus (EBV) is present in the malignant Hodgkin/Reed-Sternberg (HRS) cells of a proportion of cases of classical Hodgkin lymphoma (cHL), how the virus contributes to the pathogenesis of this disease remains poorly defined. It is clear from the studies of other EBV-associated cancers that the virus is usually not sufficient for tumor development and that other oncogenic co-factors are required. This article reviews what is known about the contribution of EBV to the pathogenesis of cHL and focuses on emerging evidence implicating chronic inflammation as a potential oncogenic co-factor in this malignancy.

Factores que participan en la interacción huésped-agente patógeno en el riesgo de Linfoma de Hodgkin inducido por el virus Epstein Barr / Factors involved in host-pathogen interaction for the risk of Hodgkin lymphoma induced by Epstein Barr virus

El linfoma de Hodgkin (LH) es una neoplasia del sistema linfático. La incidencia mundial anual del LH es de 3-10/100,000 habitantes. El mecanismo mediante el cual se lleva a cabo la transformación celular no es completamente claro; sin embargo, algunas evidencias parecen indicar que ciertos virus oncogénicos como el virus Epstein Barr (VEB), pueden tener alto impacto en la patogénesis de la linfoproliferación. También algunos factores genéticos y ambientales pueden estar involucrados, pues se ha encontrado una alta incidencia de casos de LH entre individuos de una misma familia que comparten características genéticas y conviven en un mismo ambiente. En México se han realizado estudios encaminados a conocer la prevalencia del VEB en pacientes con LH y se ha encontrado la presencia de este virus hasta en el 64,2%. El VEB ha sido detectado en las Células Reed Sternberg (CRS) y en Células de Hodgkin (CH) en el 50% de los casos de LH clásico. No se ha dado hasta ahora una explicación satisfactoria, pero se ha propuesto que la variabilidad geográfica y la variabilidad inmunológica desempeñan un papel determinante en la positividad del VEB en LH. A pesar de los avances que hasta ahora se tienen, no existen suficientes evidencias que permitan establecer una clara asociación entre los factores del huésped, el medio ambiente y el agente patógeno en el riesgo de la linfoproliferación que conduce al desarrollo de LH. La presente revisión tiene como objetivo analizar algunos de los factores de riesgo que influyen durante la interacción huésped, agente patógeno y medio ambiente en la etiología del LH.

Hodgkin lymphoma (HL) is a neoplasm characterized by malignant cells called Reed Sternberg and Hodgkin’s cells in the lymphatic system. Such cells comprise 1% of the tumor while the remainder is made up of lymphocytes, histiocytes, eosinophils and plasma non-neoplastic cells. The annual global incidence of HL is 3-10/100,000 inhabitants and is most commonly found in young adults. The mechanism by which cell transformation is accomplished is not entirely clear; however, some evidences suggest that oncogenic viruses like the Epstein Barr virus (EBV) may have a high impact on the pathogenesis of lymphoproliferation. Genetic and environmental factors could be involved, since it has been found a high incidence of HL among members of the same family. In Mexico, there have been studies to determine the prevalence of EBV in patients with HL and found the presence of this virus in up to 64.2% of the cases. EBV has been detected in the Reed Sternberg cells and Hodgkin cells in 50% of cases of classical HL. There is not a satisfactory explanation for this, but it has been proposed that geographic and immunological variabilities play a role in the positivity of EBV in HL. However, despite recent advances in the field, there is insufficient evidence to show a clear association between host factors, environment and pathogens, and the risk of lymphoproliferation leading to the development of HL. This review aims to give an overview about the risk factors that influence the interaction of host, pathogens and environment in the etiology of HL.

Estudo do valor preditivo e prognóstico de marcadores imunológicos no linfoma de Hodgkin clássico, no Ceará – Brasil / Study of the predictive and prognostic value of immunological markers in the classic Hodgkin’s lymphoma, in Ceará - Brazil

O linfoma de Hodgkin clássico (LHc) apresenta desafios terapêuticos com fatores preditivos e prognósticos pouco confiáveis. A análise imunohistoquímica é valiosa para o diagnóstico e, provavelmente, também para o prognóstico desta doença. O objetivo deste estudo é avaliar a importância preditiva e prognóstica da expressão do CD15, CD20, LMP-1, p53 e Bcl-2 nos pacientes com LHc no que se refere à refratariedade ao tratamento, à recidiva, à sobrevida câncer específica e à sobrevida livre de doença. Foi realizada uma coorte retrospectiva dos pacientes diagnosticados entre 01/2000 e 12/2009, com acompanhamento médio de 65,4 meses (1 – 141 meses). Foram estudados 273 pacientes tratados homogeneamente com o esquema ABVD, com ou sem radioterapia. Setenta e oito pacientes (28,6%) foram refratários ao ABVD e ocorreu recidiva em 19 (9,7%) dos 195 pacientes que atingiram remissão completa. Trinta e oito pacientes (13,9%) morreram. A prevalência do marcador CD15 foi 77,0%; do CD20, 18,7%; do LMP-1, 42,5%; do p53, 96,0% e do Bcl-2, 22,1%. Os casos que apresentaram CD15 positivo apresentaram menor associação com a refratariedade (p=0,038). Nenhum dos imunomarcadores estudados apresentou associação com a recidiva. O p53 apresentou-se como um indicador de melhor prognóstico em relação à sobrevida livre de doença (p=0,016) e à sobrevida câncer específica (p=0,041) na análise univariada. Contudo, ele perdeu a significância estatística na análise multivariada.

Linfoma de Hodgkin con depleción linfocítica e infiltración difusa de médula ósea / Hodgkin's lymphoma with lymphocyte depletion and diffuse bone marrow infiltration

Se presenta el caso clínico de un paciente varón de 38 años de edad, agricultor, natural de Lamas, San Martín (selva peruana), quien desde hacía 8 meses presentaba diarreas, fiebre intermitente, dolor abdominal, pérdida ponderal y anemia severa. Aunque lúcido, a su ingreso el paciente exhibía mal estado general, palidez y adenopatías generalizadas de menos de 0,5 cm, hepatoesplenomegalia y matidez desplazable. La tomografía computarizada abdominal reveló hepatoesplenomegalia y múltiples adenopatías retroperitoneales, mesentéricas y otras. La biopsia de ganglio mostró células de Reed Sternberg, células mononucleares, eosinófilos y escasos linfocitos. La inmunohistoquímica ganglionar fue positiva para anticuerpos CD15 y CD30. La biopsia de hueso señaló fibrosis difusa, células mononucleares y marcada escasez de linfocitos. La hibridización in situ para EBV-virus de Epstein Barr fue positiva en las células neoplásicas.

We present the case of a 38 year-old male, farmer, born in Lamas, San Martin (Peruvian jungle), who for the past 8 months suffered of diarrhea, intermittent fever, abdominal pain, weight loss and severe anemia. On admission the patient was lucid and exhibited malaise, pallor and generalized lymphadenopathy (size less than 0.5 cm) hepatosplenomegaly and abdominal displaceable dullness. Abdominal computed tomography showed hepatosplenomegaly and retroperitoneal, mesenteric and other adenopathies. Node biopsy revealed Reed-Sternberg cells, mononuclear cells, eosinophiles and scarce lymphocytes. Immunohistochemical node staining was positive for CD15 and CD30 antibodies. Bone biopsy showed diffuse fibrosis, mononuclear cells and scarcity of lymphocytes. In situ hybridization for EBV Epstein Barr virus was positive in neoplastic cells.

Análise do perfil de expressão gênica em amostras de linfoma de Hodgkin clássico: estudo da patogênese com ênfase no papel da infecção pelo vírus de Epstein-Barr / Gene expression analysis in classical Hodgkin lymphoma: a pathogenetic study emphasizing the role of Epstein-Barr virus infection

O linfoma de Hodgkin clássico é uma neoplasia linfóide monoclonal caracterizada pela presença de raras células de Hodgkin e Reed-Sternberg em meio a um infiltrado inflamatório abundante constituído por linfócitos, eosinófilos, plasmócitos, macrófagos e neutrófilos. Aspectos específicos da patogênese desta neoplasia, particularmente as alterações que impedem a entrada das células neoplásicas em apoptose, não são ainda totalmente conhecidos... Material e métodos. Foram utilizadas 3 linhagens celulares negativas para o EBV (L428, L1236 e KM-H2) e uma linhagem positiva (L591), gentilmente cedidas pelo Prof. Dr. Harald Stein, e 10 amostras de tecido fresco congelado envolvidas por linfoma de Hodgkin clássico, fornecidas pelo Banco de Tumores do Hospital A C Camargo... Blocos de parafina contendo material conservado em formalina de 148 casos de LHC foram selecionados do arquivo do Departamento de Patologia do Centro de Tratamento e Pesquisa Hospital A C Camargo, São Paulo, Brasil, no período de 1970 a 2005... Resultados. Foi observada expressão diferencial de 756 genes, que após análise funcional se agruparam em diversos grupos relevantes, incluindo os grupos de genes relacionados à sinalização célula-célula, ao desenvolvimento do sistema imune, envolvidos na regulação da via de NFkB, e quimiotaxia... Conclusões. Os resultados do presente estudo sugerem a capacidade das CHRS de explorarem diversas vias de sinalização para alterar seu ciclo-celular e controle mitótico, assim como evadir ao sistema de imunovigilância do organismo...

Background. Classical Hodgkin lymphoma is a monoclonal lymphoid neoplasm whose hallmark is the Reed-Sternberg cell and its variants, which are surrounded by an inflamatory background. Although extensively studied, many aspects of its pathogenesis, especially those involving the programmed cell death pathway, are still not understood. The role of Epstein-Barr virus (EBV), which is detected in approximately 50% of Hodgkin lymphomas, is also not well established. Although data on EBV association with clinical outcome of Hodgkin lymphoma patients are controversial, some studies suggest that the cases in which EBV is detected follow a different pathway leading to apoptosis blockage.This can stimulate the search for new treatments based on the presence or absence of EBV. Studies employing differential gene expression techniques can add new information to help solving these questions. Objective. This study analyzed the gene expression pattern of Hodgkin cell lines and tissues involved by classical Hodgkin lymphoma, comparing the differences related to the presence or absence of Epstein-Barr virus infection. Additionally, a Tissue Microarray containing cases of classical Hodgkin lymphoma was constructed to validate the protein expression of some of the genes observed in the analysis, comparing the results with Epstein-Barr status and clinical outcome of the patients. Materials and methods. Three EBV-negative Hodgkin cell lines (L428, L1236 e KM-H2), one EBV-positive Hodgkin cell line (L591), and 10 classical Hodgkin lymphoma frozen tissue samples were used in the gene expression analysis study. Following total RNA extraction, cRNA probes were hybridized in oligoarray glass slides. Data from the image acquisition were submitted to quality control pre-analysis prior to bioinformatic statistical analysis for gene clustering experiments and functional analysis. Paraffin-blocks from 148 retrospective cases of classical Hodgkin Lymphoma, diagnosed between 1970 and 2005, were retrieved from the archives of the Department of Pathology. Cases without enough formalin-fixed and paraffin-embedded tissue to run the immunohistochemical (IHC) reactions, relapse biopsies and HIVassociated HL were excluded. Histological diagnosis was revised, with the use of immunostains when necessary. A tissue microarray was built and immunostains performed with antibodies against Aurora-B, Caspase-1, Caveolin-1, CCL20, CDC2, MMP9 and LMP-1. Cases were also tested for EBV using "in situ" hybridization for "EBV early RNAs" (EBER-1). The reactions were analyzed and the results submitted to statistical analysis. Results. We observed that 756 genes are differentially expressed between EBV-positive and EBV-negative Hodgkin cell lines. These genes are functionally related to many relevant groups, such as cell-cell signaling, immune system development, NFkB regulation and chemotaxis. Some genes belonging to these groups were selected for immunoistochemical validation (Aurora-B, Caspase-1, Caveolin-1, CCL20, CDC2 and MMP9), whose protein expression was detected in 58,78%, 38,51%, 25,68%, 49,32%, 75,68% e 52,03% of the cases, respectively. CCL20 protein expression was specifically associated with EBV-infection (p<0,0001). Disease-specific survival rates of patients between 15 and 45 years who expressed Caspase-1 and MMP9 in neoplastic cells were significantly lower than those who did not express these markers. The expression of MMP9 by neoplastic cells was an independent prognostic factor is this group of patients. Conclusions. The results of this study suggest the ability of Hodgkin-ReedSternberg cells to explore different signaling pathways to control their cell-cycle and mitotic activity, as well as evade immunosurveillance, regulating different genes according to EBV infection status. CCL20 protein expression is associated with EBV infection in Hodgkin lymphoma cases. We also observed the expression of new proteins by Hodgkin-Reed-Sternberg cells, such as Caspase-1 and Caveolin-1. The expression of Caspase-1 and MMP9 by Hodgkin-Reed-Sternberg cells associates with a poor outcome in Hodgkin lymphoma patients between 15 and 45 years. MMP9 expression by neoplastic cells is an independent prognostic factor in this group of patients.

Clonality analysis and mutational status of IgVH gene in Hodgkin variant of Richter syndrome / 中华病理学杂志

<p><b>OBJECTIVE</b>To detect the clonal relationship, the rearrangement, and the mutational status of IgVH gene; the influence of these molecular characteristics on the clinical outcome in Hodgkin variant of Richter syndrome; and the possible molecular pathogenesis in this transformation.</p><p><b>METHODS</b>The clonal rearrangements and mutational status of IgVH genes were analyzed in Hodgkin variant of Richter syndrome and B-CLL with Reed-Stemberg (R-S)-like cells by GeneScan analysis and sequencing. Semi-nest PCR based on laser capture microdissection was utilized to compare the clonal relationship between B-CLL and R-S/R-Slike cells. Immunohistochemical staining was used to detect the different expressions of ZAP70, p53, IRF-4 and LMP1 in the two components.</p><p><b>RESULTS</b>(1) 5/6 B-CLL cases transformed to Hodgkin lymphoma (HL)/R-S-like cells carried the mutated IgVH genes; (2) 2 cases of R-S cells and 1 case of R-S-like cells were clonally distinct from B-CLL clone and express LMP1, whereas 1 case of R-S-like cells was relating to the surrounding B-CLL cells and did not express LMP1; (3) 2/6 B-CLL cases transformed to HL convey VH4-34 and VH3-48 respectively.</p><p><b>CONCLUSIONS</b>(1) Richter transformation to HL/R-S-like cells evolves from the B-CLL which originates from the germinal center or post germinal center B cells, indicating that different lymphoma cells of different subtypes in Richter syndrome come from different B cell lineage and possibly involve a different pathogenesis and pathway; (2) HL and R-S-like cells evolve from either the B-CLL clone or may develop as a clonally unrelated lymphoma, the independent secondary malignancies are appear to be EBV-positive, possibly as a consequence of the underlying immunodeficiency; (3) The biased usage of IgVH genes suggested a role of antigens involved in the HL variant of Richter syndrome.</p>

A Case of Cutaneous Hodgkin's Disease Presented with a Maculopapular Rash / 대한피부과학회지

Hodgkin's disease (HD) is a lymphoproliferative disorder that presents as a clinically asymptomatic mass or painless lymph node swelling. Cutaneous HD is a very rare manifestation in patients with HD. A 66-year-old man complained of a maculopapular rash waxing and waning for one year. A painful mass had developed on his left axilla 7 weeks prior to presenting. The biopsy specimens of both skin and lymph node revealed Hodgkin's lymphoma with atypical lymphoid cells and Reed-Sternberg cells. We report a case of cutaneous involvement of HD, which had been presented as a maculopapular rash for one year.

Proliferating cell nuclear antigen (PCNA), p53 and MDM2 expression in Hodgkins disease

CONTEXT AND OBJECTIVE: Tumor cells in Hodgkins disease (HD) express cell proliferation markers that are evaluated according to the oncogenes involved or the expression of their proteins. Correlations between the protein expression grade and clinical data are now important for disease prognosis. DESIGN AND SETTING: This was a retrospective analysis on proliferating cell nuclear antigen (PCNA), p53 and MDM2 (murine double minute-2) expression using immunohistochemistry, on formalin-fixed, paraffin-embedded tissues from diagnostic biopsies on 51 patients with HD. The study was conducted at the Division of Hematology and Transfusion Medicine, Hospital São Paulo, Universidade Federal de São Paulo. METHODS: Antigen expression was evaluated as the proportions of positive Hodgkin and Reed-Sternberg (HRS) cells and reactive lymphocytes (L), which were compared using Spearman correlation coefficients. The Friedman test was used for comparisons between the markers. The Pearson test was used to investigate associations between marker expression and clinical and laboratory parameters, marrow involvement, complete remission (CR) and overall survival (OS) rates. RESULTS: There was overexpression of antigen proteins in HRS, in relation to L (p < 0.001). In HRS, MDM2 was higher than p53 and PCNA (p < 0.003), while the latter two were equivalent. In L, p53 was lower than MDM2 and PCNA (p < 0.001), while the latter two were equivalent. There was no relationship between protein expression and clinical and laboratory variables or outcome. CONCLUSIONS: PCNA, p53 and MDM2 are tumor markers for HD, but showed no clinical or prognostic significance in our analysis.

CONTEXTO E OBJETIVO: As células tumorais da doença de Hodgkin (HD) são positivas para marcadores de proliferação celular que são analisados por seus genes e respectivas proteínas. A correlação entre a expressão destas proteínas e os parâmetros clínico-laboratoriais são, no momento, de importância para o prognóstico da doença. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo da expressão do antígeno de proliferação celular (PCNA) e da p53 e MDM2 em tecidos obtidos ao diagnóstico, fixados por formol, embebidos em parafina de 51 pacientes com HD. O trabalho foi realizado na Divisão de Hematologia e Transfusão, Hospital São Paulo, Universidade Federal de São Paulo. MÉTODOS: As expressões antigênicas foram analisadas através da proporção de células de Hodgkin e células de Reed Sternberg (HRS) e linfócitos reacionais (L) positivos. A intensidade de expressão de cada proteína foi comparada entre L e HRS através do coeficiente de Spearman. A comparação da PCNA, p53 e MDM2 em L e HRS se fez pelo teste de Fiedman. As correlações entre variáveis clínico-laboratoriais, comprometimento da medula óssea, taxas de sobrevida geral e remissão clínica com as proteínas em HRS se fizeram pelo coeficiente de Pearson. RESULTADOS: Houve superexpressão das três proteínas em células HRS comparadas aos L (p < 0,001). Nas células HRS, a MDM2 foi maior que a p53 e a PCNA (p < 0,003), que foram equivalentes. Nos L, a p53 foi menor que a MDM2 e a PCNA (p < 0,001), que foram equivalentes Não houve relação entre as expressões das proteínas com as variáveis clínico-laboratoriais e sobrevida. CONCLUSÕES: PCNA, p53 e MDM2 são marcadores tumorais na HD, porém não mostraram significado clínico-prognóstico em nossa análise.

Primary Cerebellar Hodgkin's Lymphoma

Authors report a very rare case of primary Hodgkin's lymphoma limited to the cerebellum. A 64-year-old female patient presented with headache, nausea, and vomiting. Magnetic resonance imaging of the brain revealed a nodular enhancing mass in the left cerebellar hemisphere. Tumor was removed totally with retromastoid suboccipital approach. Diagnosis was Hodgkin's lymphoma of mixed cellularity type, consisting of a dense mixed inflammatory infiltrate containing scattered large atypical mononuclear Hodgkin cells and multinucleated Reed-Sternberg cells. Systemic work-up for the Hodgkin's lymphoma was followed with negative result. Postoperative radiation therapy was given and the patient is disease-free at 16 months after the operation.

Central nervous system involvement in Hodgkin's lymphoma associated with Epstein-Barr virus in a patient with AIDS: case report and review of the literature

Intracranial and intraspinal involvement is a rare complication of Hodgkin's disease. We report a case of a patient with diagnosis of AIDS and Hodgkin's lymphoma who developed brain and spinal involvement at the time of the relapse of the neoplasm disease. Mixed cellularity histology was the subtype of Hodgkin's disease in our patient; we identified the Epstein-Barr virus genome in the Reed-Sternberg cells by immunohistochemistry and in situ hybridization.

Immunophenotyping of Hodgkin's disease--an aid to its classification.

Based on morphological, phenotypic, genotypic and clinical findings, Hodgkin's disease has recently been classified into two subtypes: Nodular lymphocyte predominant and classical Hodgkin's disease. Forty-two cases of Hodgkin's disease were subjected to detailed morphological assessment and immunophenotyping. The commonest subtype was Nodular Sclerosis seen in 27 cases. The panel of antibodies used was CD 15, CD 30, CD 3, CD 20, CD 45 and Epithelial Membrane Antigen. Immunophenotyping was done by Streptavidin Biotin Peroxidase complex technique. CD 30 was expressed in 86% and CD 15 in 76% cases. Immunophenotype helped reclassify two cases, according to the WHO classification scheme. Although morphology remains the gold standard in the diagnosis of Hodgkin's disease, immunophenotype is a useful adjunct in differentiating prognostically distinct subtypes.

Interfollicular Hodgkin's disease: an uncommon pattern that may cause diagnostic difficulty.

Interfollicular Hodgkin's Disease is characterised by reactive follicular hyperplasia with involvement of the interfollicular area of lymph node by Hodgkin's lymphoma. It represents a peculiar pattern of focal involvement of lymph node and does not constitute a classical subtype. Its importance rests in the fact that it can be misinterpreted as one of the many causes of reactive hyperplasia of lymph node and not as Hodgkin's disease. Eleven cases of interfollicular Hodgkin's disease were diagnosed in a period of five years. Majority of the patients were less than twenty years and all had localised lymphadenopathy. Lymph node biopsy showed follicular hyperplasia with expanded interfollicular area. Careful search of the interfollicular area showed infiltration by inflammatory cells and scattered Reed-Sternberg and Hodgkin's cells. Immunohistochemistry with CD 15 and CD 30 highlighted the atypical cells. This report emphasises on the problems in diagnosis of interfollicular Hodgkin's disease.

Expression of fragile histidine triad (FHIT) protein and its significance in diagnosing classical Hodgkin lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of FHIT protein and its potential application in diagnosing classic Hodgkin lymphoma.</p><p><b>METHODS</b>Immunohistochemical study using EnVision method for FHIT tumor suppressor protein, hematopoietic stem cell markers CD133/AC133 and CD34, B-cell marker CD20, T-cell marker CD3 and oncoprotein c-erbB2 was performed on 33 cases of classic Hodgkin lymphoma.</p><p><b>RESULTS</b>Thirty-three of the Hodgkin lymphoma cases (90.9%) expressed FHIT protein. The antigen was mainly located in the cytoplasm, nucleus and membrane of classic Reed-Sternberg and Reed-Sternberg-like cells. Normal B and T lymphocytes, as well as their malignant counterparts, were negative for FHIT protein; whereas monocytes, histiocytes and dendritic cells were positive. All the cases studied were negative for CD133/AC133, CD34, CD3 and c-erbB-2. Two of the 33 cases showed positive staining for CD20 in some of the Reed-Sternberg cells.</p><p><b>CONCLUSION</b>The expression of FHIT protein can be used as a useful adjunct in diagnosing classic Hodgkin lymphoma.</p>

[ frequency of Epstein-Barr Virus [EBV] expression in various histological subtypes of Hodgkin's lymphoma]

The incidence of Hodgkin's Lymphoma [HL] shows marked heterogenecity according to age, gender, race, geographical state, socioeconomic position and histological subtypes. Recently, multiple studies in different countries have been applied by newer technologies such as Immunohistochemistry [IHC] and polymerase chain reaction [PCR], being more familiar with the pathogenesis of this neoplasm. The Epstein-Barr virus [EBV] is detected with high incidence in HL cases, approximately 40-50% in developed countries and much more [up to 95% of cases] in developing countries. There is evidences that mixed cellularity [MC] Hodgkin's Lymphoma is more likely to be EBV-associated which is against association of nodular sclerosis [NS] subtype. With regard to the geographical location of Iran and absence of similar documented research in our knowledge, it is needed to perform studies like this. This study was done by IHC method with antibody against latent membrane protein-1 [LMP-1] antigen of EBV for assessment of relationship between EBV infection and parameters such as age, gender and histological subtype. We collected 30 paraffin section samples of classic HL and positive cytoplasmic reactivity of Reed-Steinberg [RS] cells was evaluated. From 30 cases surveyed in this study only 2 cases were not immunoreactive for EBV marker of which both were NS subtype in two adult males. We confirm frequency of 93% EBV associated HL in our cases, and also confirm the above histological subtype distribution, and that childhood cases are more likely to be EBV-associated than adult cases. There is possible female predominance of EBV associated HL. This survey as a pilot study needs further studies with more cases for distinct confirmation. It seems that EBV is a strong etiologic factor especially in developing countries like Iran and in childhood cases