Presence of B-cell clones in angioimmunoblastic T cell lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the significance of B-cell clones in angioimmunoblastic T cell lymphoma (AITL) and the correlation with Epstein-Barr virus (EBV) and prognosis.</p><p><b>METHOD</b>The histopathologic features, T cell clonality and EBV positivity in 33 cases of AITL and 10 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) collected from May 2010 to February 2014 were analyzed by immunohistochemistry, PCR gene rearrangement and in situ hybridization. Follow-up data were also collected.</p><p><b>RESULTS</b>Of the 33 cases with AITL, seven cases (21.2%) exhibited clonal rearrangement of Ig genes; 21 cases (63.6%) were EBV positive. Seven cases had B-cell clones and all (7/7) were EBV positive; 14 of the 26 (53.8%) cases without B-cell clones were EBV positive. The difference between the two groups was statistically significant (P = 0.032). Four levels were made according to the number of EBV-labeled cells, Ig gene rearrangements, but there was no significant difference among levels 1, 2 and 3. There was no correlation between B-cell clones and prognosis (P = 0.263).</p><p><b>CONCLUSION</b>Clonal rearrangement of Ig genes is a common finding in AITL, and it is highly associated with EBV positivity, but not with the number of EBV-labeled cells. The clinical significance remains unclear; further study with more samples is warranted.</p>

Linfomas plasmoblásticos del tracto gastrointestinal en pacientes con sida / Plasmablastic lymphoma of the gastrointestinal tract in AIDS patients

Los pacientes con infección por el virus de inmunodeficiencia humana (HIV) tienen 200 veces más riesgo de desarrollar un linfoma no Hodgkin (LNH) con respecto a la población general. El linfoma plasmoblástico (LP) representa menos del 3% de todos los LNH asociados con el HIV. El objetivo de este estudio es informar las características clínico-patológicas de 5 pacientes con enfermedad HIV/sida y LP del tracto gastrointestinal. Se revisaron de forma retrospectiva los casos de LP del tracto gastrointestinal diagnosticados en el Instituto Nacional de Cancerología de la Ciudad de México en el periodo comprendido entre los años 2000 al 2009. Se analizaron las características clínico-patológicas y se realizaron cortes de bloques de tejidos embebidos en parafina para reacciones de inmunohistoquímica. La presencia del virus de Epstein Barr (VEB) se examinó por reacción en cadena de la polimerasa (PCR) in situ. De los cinco pacientes, cuatro fueron hombres y una mujer, con una mediana de edad de 29 años. Tres tumores se localizaron en la región anorrectal, uno en colon ascendente y el restante en el estómago. Histológicamente, todos los tumores se caracterizaron por una proliferación difusa de células grandes de aspecto plasmoblástico. Las células neoplásicas fueron CD 138/MUM-1 positivas y CD 20 / PAX-5 negativas. En cuatro pacientes se detectó el genoma del VEB en las células neoplásicas mediante PCR in situ. La mediana de seguimiento fue 18 meses; tres pacientes estaban vivos con enfermedad y dos sobreviven sin evidencias de la neoplasia. El diagnóstico precoz de LP como una entidad clínico-patológica es importante para establecer el tratamiento correcto y mejorar el pronóstico de estos pacientes.

The risk of developing non-Hodgkin lymphoma (NHL) is 200 times higher in HIV-positive patients than otherwise healthy persons. Plasmablastic lymphoma (PL) represents < 3% of all NHL associated with HIV infection. The aim of this study was to review the clinical-pathologic features of PL of the gastrointestinal tract in 5 patients with HIV/aids disease. We performed a retrospective study of PL of the gastrointestinal tract diagnosed at the National Institute of Cancer at Mexico City, from 2000 to 2009. Clinical and pathological information was obtained and immunohistochemical studies were performed in paraffin-embedded tissue sections. The presence of Epstein-Barr Virus (EBV) was examined by in situ polymerase chain reaction (PCR). Four male and 1 female were included with a median of age of 29 years. Three tumors involved the ano-rectal area, one tumor the ascendant colon and one tumor the stomach. All tumors were histologically characterized by a monotonous proliferation of large lymphoid cell with plasmablastic features. Tumor cells were CD 138 / MUM-1positive and CD 20 / PAX-5 negative in all cases. EVB genome was detected by in situ PCR in 4 cases. The median of follow-up was 18 months, and revealed that three patients are alive with neoplasm disease and two patients are still alive with no evidence of the neoplasm. Recognition of this entity by pathologists and clinicians is important in order to establish the correct diagnosis and the early treatment of these patients.

Coexistencia de linfoma plasmablástico, sarcoma de Kaposi y enfermedad de Castleman en un paciente con infección por virus de inmunodeficiencia humana / Coexistence of plasmablastic lymphoma, Kaposi sarcoma and Castleman disease in a patient with HIV infection

El linfoma plasmablástico (LP) es un linfoma de células B poco común que está fuertemente asociado con la infección por el virus de inmunodeficiencia humana (VIH), y muestra una afinidad característica de presentación extra-ganglionar en la cavidad oral. Informamos el caso de un LP afectando el estómago en un paciente masculino de 36 años de edad con infección por VIH, asociado con sarcoma de Kaposi (SK) en áreas adyacentes al linfoma. Tenía el antecedente de enfermedad de Castleman y SK en una biopsia de ganglio linfático.

Plasmablastic lymphoma (PL) is an uncommon B-cell lymphoma that is strongly associated with human immunodeficiency virus (HIV) infection, and displays distinctive affinity for extranodal presentation in the oral cavity. We report the case of a PL involving the stomach in a 36 year-old man HIV+ patient, associated with Kaposi sarcoma (KS) in sections adjacent to lymphoma. He had a positive history of Castleman disease and KS in a lymphoid node biopsy.

A Case Report with Plasmablastic Lymphoma of the Jejunum

Plasmablastic lymphoma (PBL) is a recently identified entity that is considered to be a type of diffuse large B-cell lymphoma with a unique immunophenotype and a predilection for the oral cavity of patients with the human immunodeficiency virus (HIV). Although its clinical features may help in the differential diagnosis, an extraoral location in a patient without HIV makes it more difficult to suspect clinically. This case report is the first to describe a patient with PBL originating from the jejunum in a 60-yr-old, HIV-seronegative man. Computed tomography of the face, chest and abdomen showed about a 9.4x9.0 cm mass of the proximal jejunum, multiple masses in the musculoskeletal soft tissue, and multiple lymphadenopathies. The histological examinations demonstrated a large cell lymphoma with plasmablastic differentiation. The neoplastic cells were diffusely positive for MUM1, epithelial membrane antigen and lambda light chains, and focally positive for CD79a; but negative for CD3, CD20, CD30, CD34, CD45RO, CD56, CD99, and CD117. The proliferation index by Ki-67 immunohistochemistry was approximately 70%. These findings were compatible with the diagnosis of PBL. The findings in this case suggest that PBL should be included in the differential diagnosis of a small bowel mass even in a HIV-negative patient.

Morphological spectrum of AIDS-related plasmablastic lymphomas.

We have had a recent spurt in cases of AIDS-related lymphoma (ARL) at our centre. Most of these cases are aggressive mature B cell lymphomas, mainly plasmablastic lymphoma (PBL) and diffuse large B-cell lymphoma (DLBCL). Most of the PBL are extranodal in location and are mucosa-based. We reviewed the morphological features of 34 cases of PBL. Diagnosis was based on morphology, immunohistochemistry, proliferation index, HIV positive status and its preference to extranodal sites (mostly mucosa based). We classified PBL into three morphological subtypes (immunoblastic - 25, Burkitt's - 7, plasmacytic - 2). Tumor cells expressed as leucocyte common antigen (LCA) in 60%, CD138 in 100%, EMA in 45% and light chain restriction in 86% cases. CD20 was negative in all cases. Pathologists need to be aware of PBL and its various morphological subtypes as the identification of this entity from its close differentials carries major therapeutic implications.

Distribución de ß-galactosidasa por transferencia adenoviral como modelo de terapia génica intralinfonodal en perros con linfosarcoma multicéntrico espontáneo / Distribution of ß-galactosidase by adenoviral transfer as a model for intralymphonodal gene therapy in dogs with spontaneous multicentric lymphosarcoma

La terapia génica en cáncer se administra principalmente por vía intravenosa e in situ mediante el empleo de vectores virales y no virales. La administración sistémica del vector transfiere el gen terapéutico al tejido neoplásico, pero también a otros órganos. El objetivo de este estudio fue evaluar la distribución de expresión del gen reportero Lac Z insertado en un vector adenoviral y administrado vía intralinfonodal (ILN) en perros con linfosarcoma multicéntrico espontáneo. La distribución de la expresión de la proteína ßgalactosidasa de un adenovirus no replicativo recombinante (Adßgal) fue evaluada 72 h después de su administración ILN en 6 perros con linfosarcoma multicéntrico espontáneo mediante la exposición al sustrato cromogénico X-gal. Se emplearon dosis de 0 (control), 1,35 X 10 a la 10, 2,53 X 10 a la 10, 6,10 X 10 a la 10, 18,38 X 10 a la 10, y 153,85 X 10 a la 10 partículas virales (PV)/kg. La expresión se presentó en un 100 por ciento del tejido linfocítico neoplásico que incluye, linfonodos y bazo, con menor intensidad se expresó en órganos infiltrados con linfocitos neoplásicos: hígado, médula ósea y pulmones. La expresión de ßgal fue exclusiva en tejido linfocítico neoplásico y en sitios de metástasis.Esto permite mejorar la eficiencia en la transferencia del gen terapéutico con menores dosis y reducir los riesgos detoxicidad y también potencialmente menos inmunogénico. La terapia génica adenoviral vía intralinfonodal tiene un elevado potencial para su aplicación en animales y humanos con linfosarcoma y también para metástasis linfonodales.

Gene therapy administration in cancer is mainly performed by intravenous, oral, and in situ routes, with viral or nonviral delivery vector systems. Systemic administration frequently transfers the therapeutic gene to neoplastic tissue and as well as to other organs. The objective of this study was to evaluate the distribution expression of Lac Z reporter gene by adenoviral transfer administered by intralymphonodal route (ILNR) in dogs with lymphosarcoma. The distribution of b-galactosidase protein expression by a non replicative recombinant adenovirus (Adb-gal) delivery was determined in six dogs with spontaneous multicentric lymphosarcoma, 72 h after ILNR administration using X-gal chromogenic substrate. The doses administered were 0 (control), 1.35 X 1010, 2.53 X 1010, 6.10 X 1010, 18.38 X 1010 and 153.85 X 1010 viral particles (VP) /kg. The expression was manifested in 100% of lymphocytic tissue, including lymph nodes and spleen. The infiltrated organs with neoplastic lymphocytes: liver, bone marrow and lungs were positive but with lower intensity. Conclusion. The expression of b-gal was restricted to neoplastic lymphocytic tissue and metastatic sites. The ILNR would enhance gene therapy efficacy to a specific cell type and permit the delivery of lower doses, which result in reduced toxicity and may also potentially be less immunogenic. This suggests that adenoviral gene therapy by ILNR is a potential model of administration in animals and human beings with lymphosarcoma and also for metastasis to lymph nodes.

A Case of Anaplastic Myeloma: Role of Immunophenotyping in Initial Diagnosis / 대한진단검사의학회지

Anaplastic myeloma has various synonyms such as dysplastic myeloma, aggressitve phase myeloma, or immunoblastic sarcoma. This is known to be an extremely aggressive subentity of plasma cell myeloma, and the diagnosis can usually be delayed because of the lack of the typical morphologic characteristics of myeloma. We describe here a 45-year-old man with anaplastic myeloma, whom we had difficulties with in initial diagnostic workup. The patient was admitted to the hospital due to gum bleeding for 2 weeks. A few abnormal cells were found in the peripheral blood. In bone marrow aspiration smears, the normal hematopoietic cells were replaced by numerous anaplastic cells. An immunophenotype study showed only a dim expression of CD56 antigen, while other routine surface antigens as well as CD45 were all negative. Additional studies showed a moderate positivity of CD38 and cytoplasmic lambda light chain. Serum immunoelectrophoresis confirmed monoclonal lamda light chain production, which led to the diagnosis of anaplastic myeloma. Because the morphologic feature is confused with other lymphoproliferative disorders, the diagnosis of anaplastic myeloma could be delayed unless a high degree of suspicion is made. Cytoplasmic light chains as well as CD56 will be helpful in initial immunophenotyping workup when the neoplastic cells show anaplastic features.

Model of B immunoblastic lymphomas in the Hu-PBL-SCID mice / 中国医学科学院学报

<p><b>OBJECTIVE</b>To constitute a model of B immunoblastic lymphomas in the Hu-PBL-SCID mice.</p><p><b>METHODS</b>The SCID mice were reconstituted by intraperitoneal injection (i.p.) of 5 x 10(7) human lymphocytes from Epstein-Barr virus (EBV) seronegative individuals. After one week, the SCID mice were inoculated with EBV by i.p. injection, and subjected to the investigation of whether there was any tumor in the abdomen of such SCID mice four weeks later. The characteristics of the found tumor was observed by the methods of Hematoxylin-eosin (HE) stain, immunohistochemical staining and polymerase chain reaction (PCR).</p><p><b>RESULTS</b>Compared with the control groups, all the EBV-infected Hu-PBL-SCID mice had abdominal solid tumors [(32 +/- 12.5) mm3] developed, often located in the liver. HE staining and immunohistochemical staining showed the tumors were human B cell lymphomas. EBV DNA could be detected in the tumors by the PCR.</p><p><b>CONCLUSIONS</b>The model of B immunoblastic lymphomas in the Hu-PBL-SCID mice is successfully constituted, and may well be useful to the human tumor immunological study.</p>

A Case of Posttransplant Lymphoproliferative Disease (PTLD) Following Renal Transplantation in a Child

Posttransplant lymphoproliferative disease (PTLD) represents a diverse lymphoproliferative disorder ranging from nonspecific reactive hyperplasia to malignant immunoblastic sarcoma developed in a setting of immunosuppression following organ or cellular transplantation. It is often associated with Epstein-Barr virus (EBV) infection and high dose immunosuppression. PTLD after renal transplantation was reported at first in adult in Korea in 1997. In children there have been several cases of PTLD after liver transplantation but PTLD after renal transplantation has not been reported. This is a case report of PTLD developed 4 months after renal transplantation in a 9-year-old boy. The major clinical manifestations were fever, multiple lymph nodes enlargement and blood-tinged stool. EBV was detected by in-situ hybridization in the enlarged cervical lymph node and the colonic tissue. Histological examination revealed B-cell lineage. Use of ganciclovir and reduction of the immunosuppression level resulted in complete remission of PTLD. This is the first pediatric case report of PTLD following renal transplantation in Korea.

Linfomas cutáneos de células T, CD30 (+) / Cutaneous T-cells lymphomas, CD30 (+)

El aspecto de desórdenes linfoproliferativos cutáneos primitivos CD 30 (ki-1) positivos está constituido por la papulosis linfomatoide, el linfoma de células grandes anaplásico y los linfomas inmunoblásticos y pleomórfico de células medianas y grandes. Durante el período enero de 1995 a septiembre de 1998, nuestro Servicio evaluó 7 casos, representados por 3 casos de papulosis linfomatoide (una de las cuales luego de remitir evolucionó a un linfoma de alto grado), 4 casos de linfomas de células grandes anaplásicas, uno de ellos se desarrolló sobre una micosis fungoidea previa. Los estudios de inmunohistoquímica confirmaron CD 30 (+) en todos los casos, 6 presentaron inmunofenotipo T CD 4(+) y 1 tipo null cel. Se observaron remisiones espontáneas parciales en varios casos y recidivas en la zona con aspecto clínico, similar a la lesión previa. Fueron sensibles a la radioterapia y no recidivaron luego de cirugía. Nuestra casuística confirma el buen pronóstico que la CD 30 positividad otorga a estos linfomas cutáneos, a diferencia de la localización cutánea secundaria de un linfoma de origen nodal que tiene mal prónostico

Linfoma imunobláatico primário do corpo uterino - metástases em mama e sistema nervoso central: relato de caso e revisäo da literatura / Primary limphoma of uterine body - immunoblastic metastasis of mammma and central nervous system -case report and literature review

O diagnóstico diferencial entre lesöes benignas e malignas do útero, embora difícil, constitui um instrumento fundamental para a definiçäo de conduta nas doenças do trato genital feminino. Relatamos o caso de uma paciente de 42 anos, com história de metrorragia há dois meses, aumento de volume abdominal e dor em hipogástrio. A investigaçäo ginecológica, por exame clínico e ultra-sonografia abdominal, identificou um tumor no corpo uterino. A paciente foi submetida a pan-histerectomia. O exame histológico do útero revelou um Linfoma Näo-Hodgkin de grandes células, tipo imunoblástico. A revisäo de cavidade cirúrgica evidenciou linfonodos regionais acometidos, configurando estádio I-E, pelo critério Ann Arbor. Dois meses após o diagnóstico, houve aparecimento de metástases em mamas e hemiface esquerda, seguida de metástases em Sistema Nervoso Central (SNC). O linfoma imunoblástico primário genital constitui uma entidade rara, com pobre resposta ao tratamento e prognóstico reservado. Por ser infreqüente a patologia, foi realizada uma breve revisäo dos LNH acometendo o aparelho reprodutor feminino. Säo apresentadas as freqüências da moléstia, localizaçäo, dados epidemiológicos de acometimento dos Linfomas. É apresentada uma detalhada descriçäo, baseada em observaçöes anatomopatológicas com descriçäo microscópica dos aspectos histológicos e citológicos dos subtipos de linfomas mais frequentes que acometem o aparelho reprodutor feminino. Säo descritos os resultados observados na literatura com estudos imunológicos, de imunohistoquímica e discutidos os resultados dos tratamentos empregados nas diversas modalidades de Linfomas Näo-Hodgkin. Com este relato, os autores pretendem trazer mais elementos para o reconhecimento, diagnóstico precoce e tratamento das lesöes linfoproliferativas primárias no trato genital feminino.

Posttransplant Lymphoproliferative Disease(PTLD) following Renal Transplantation / 대한이식학회지

Posttransplant lymphoproliferative disease(PTLD) represents a diverse lymphoproliferative disorder ranging from non-specific reactive hyperplasia to malignant immunoblastic sarcoma developed in a setting of immunosuppression following organ or cellular transplantation. It is often associated with Epstein-Barr virus infection and high dose immunosuppression. EBV detection and immunotyping including immunoglobulin clonality is crucial for prediction of prognosis and treatment modality. We report one case of PTLD developed 5 months after renal transplantation in 33 year-old man. Clinical manifestion was submandibular mass, and EBV was detected by in situ hybridization. Histology and immunotyping revealed immunoblastic lymphoma andl lambda chain monoclonality. He has been treated with reduction of immunosuppression, acyclovir and radiotherapy, and is in stable condition with normal renal function at postoperative 11months without evidence of disease reccurrence.

Linfomas no Hodgkin en el niño: aspectos histopatológicos / Non-Hodgkin lymphomas in children: histopathology

Se realiza una puesta al día en aspectos histopatológicos de los linfomas no-Hodgkin en pediatría. El interés de esta comunicación es poner a disposición del pediatra los aspectos prácticos de estas entidades desde el punto de vista de la anatomía patológica con especial referencia al empleo de la inmunotipificación

Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I

Este artículo describe el caso clínico de un enfermo con SIDA coinfectado por HTLV-1 que desarrolló un linfoma B del recto, variedad sarcoma inmunoblástico con diferenciación plasmacitoide. Las células malignas mostraron arreglo clonal de los genes de las CP (Jh) y CLk. La infección por el VEB fue demostrada serológicamente y por hibridación de un monitor específico con el ADN genómico de las células cancerosas. No se detectaron secuencias de HTLV-1 en el seno del tumor. Una remisión clínica completa, pero temporal, se obtuvo con siete ciclos de VACO-B. El enfermo abandonó el tratamiento y la sobrevida se desconoce.

Peripheral T-cell lymphomas-clinicopathologic and immunophenotypic analysis of 25 cases

The clinicopathologic and immunophenotypic findings of 25 cases of peripheral T-cell lymphoma in Korea were analysed. Seventeen cases (68%) of the 25 T-cell lymphomas presented in the extranodal sites including the nasal mucosa, tonsil, oral cavity, skin and rarely bone, mediastinum and breast. Immunologic studies showed that 12 cases (48%) of the lymphomas were of T-helper phenotype, 5 cases (20%) were of cytotoxic/suppressor phenotype, 1 case (4%) expressed both helper and cytotoxic/suppressor markers, and 7 cases (28%) lacked detectable markers for subsets. Histologically, fourteen cases (56%) showed histologic features suggestive of peripheral T-cell lymphoma. The more frequently seen histologic types by Working Formulation (WF) included large cell type and immunoblastic type. Classification by WF was straightforward in most cases of large cell, immunoblastic type. However, with some cases of small cell, large cell and mixed types, there were problems fitting the morphology seen into the WF category. We hope that the establishment of a world wide immunologic and clinicopathologic classification for peripheral T-cell lymphoma will be made in the near future.

Linfoadenopatía angioinmunoblástica y linfoma de colon / Angioimmunoblastic lymphadenopathy and colonic lymphoma

La linfoadenopatía angioinmunoblástica (LAAI), descripta por primera vez en la década el 70, es una enfermedad infrecuente y generalmente fatal en corto tiempo. Se caracteriza por prersentar linfoadenopatías, hepatoesplenomegalia, fiebre y rash. Los hallazgos més frecuentes en el laboratorio son anemia con test de Coombs positivo, leucocitosis con linfopenia e hipergammaglobulinemia policlonal. A pesar de estar considerada como una enfermedad no neoplásica, produce importantes trastornos inmunes que predisponen al paciente a infecciones graves frecuentemente fatales. Con el transcurso del tiempo estos enfermos tienen una elevada posibilidad de desarrolar linfomas malignos u otros tumores. En el presente trabajo se comunica el caso de una paciente que presentó proliferación ganglionar y síntomas generales, diagnosticándose por biopsia ganglionar LAAI. Se trató con corticosteroides lográndose remisión completa luego de 8 meses de tratamiento; 3 meses después, reingresó por enterorragia y franco deterioro del estado general. Se demostró la presencia de un tumor en el colon y la ausencia de adenomegalias en las zonas afectadas anteriormente por la LAAI. Se extirpó el colon derecho y el examen anatomopatológico confirmó la presencia de un linfoma inmunoblástico que comprometí en forma parcial los ganglios regionales. Los linfomas son infrecuentes en el colon, sólo del 1 al 4%. Se los relaciona con enteropatías crónicas como enfermedad de Crohn, colitis ulcerosa, síndoromes ...