Resumen Introducción: El linfoma de Hodgkin clásico presenta escasas células de Reed Sternberg/Hodgkin inmersas en un abundante microambiente tumoral. Los desbalances genómicos del locus 9p24.1 han sido asociados con alteraciones en la expresión de los genes del ligando de muerte celular 1 y 2, ambos reguladores de la respuesta inmune. Objetivo: Evaluar desbalances genómicos del locus 9p24.1 en células de Reed Sternberg/Hodgkin y del microambiente tumoral en biopsias de pacientes con linfoma de Hodgkin clásico y correlacionarlo con la expresión del ligando de muerte celular 1 y la presentación de la enfermedad. Materiales y Métodos: Se efectuó hibridación in situ en biopsias de 22 pacientes con linfoma de Hodgkin clásico dirigida a los genes del ligando de muerte celular 1 y 2. Las alteraciones se clasificaron en: amplificación, ganancia y polisomía. La expresión se evaluó mediante inmunohistoquímica. Resultados: Todos los pacientes mostraron alteraciones del número de copias. Se diferenciaron dos grupos: con amplificación (32%) y sin amplificación (68%); este último subdividido en: rico en ganancia (53%) y rico en polisomías (47%). El grupo rico en polisomías mostró mayor edad (p=0,027). El 40% de los pacientes con amplificación y rico en ganancias no presentó masa bulky. La expresión proteica mostró score +3 sólo en estos últimos. El title% de los casos ricos en polisomías presentaron monosomía del cromosoma 9 en los linfocitos circundantes respecto al 36,4% de los otros dos grupos. Conclusiones: Nuestros datos constituyen un aporte a la caracterización biológica del LHC, de interés en el marco de las nuevas modalidades terapéuticas. MÉD.UIS.2020;34(1):35-44.

Abstract Background: Classical Hodgkin lymphoma shows scarce tumor Reed-Sternberg/Hodgkin cells surrounded by a dense immune microenvironment. Genetic alterations at the 9p24.1 locus result in genomic imbalances in the copy number of PD-L1/PD-L2 genes, both of them being immune response regulators. Aim: To characterize genomic imbalances at the 9p24.1 locus in Reed-Sternberg/Hodgkin cells and immune microenvironment in biopsies of patients with Classical Hodgkin lymphoma and correlate it with PD-L1 protein expression and disease presentation. Material and Methods: Paraffin embedded biopsies of 22 patients with CHL were retrospectively evaluated by fluorescence in situ hybridization using SPEC CD274/PDCD1LG2/CEN9 DNA probe. The frequency of 9p24.1 alterations, amplification, copy gain and polysomy, were determined taking into account the number of gene copies with respect to the centromere. PD-L1 protein expression was evaluated by immunohistochemistry. Results: All cases presented alterations in the number of copies of PD-L1 / PD-L2, which are differentiated in two groups: with amplification (32%) and without amplification (68%). The latter was subdivided into rich in gains (RG) (53%) and rich in polysomies (RP) (47%). Groups with amplification and RG were younger than the RP group (p = 0.027). The latter was not associated with bulky disease, a fact observed in 40% of patients with amplification and RG. Protein expression showed score +3 only in the latter. All RP cases presented chromosome 9 monosomy in the surrounding lymphocytes, compared to 36.4% of the other two groups. Conclusions: Our data contributes to the biologic characterization of CHL, of interest in the context of new therapeutic modalities. MÉD.UIS.2020;34(1):35-44

Intestinal intussusception rarely occurs in the adult population and accounts only for 1% to 5% of all the causes of intestinal obstruction. This complication is more frequent in the small bowel and can be due to different aetiologies, including inflammatory, infectious or neoplastic diseases. Malignancies account for 50% to 60% of all cases of colon invagination. The gastrointestinal (GI) tract is the most common site for extra-nodal non-Hodgkin lymphomas (NHL), representing 5% to 20% of all the cases. However, primary NHL of the GI tract is a very infrequent clinic-pathological entity and accounts only for 1% to 4% of all the neoplasms of the GI tract. Primary NHL of the colon is a rare disease and it comprises only 0.2% to 1.2% of all colonic malignancies. Here we describe a case of an AIDS adult patient who developed an intussusception secondary to a primary large B cell lymphoma of the transverse colon. English and Spanish literature was reviewed.

La invaginación (intususcepción) intestinal es una complicación poco frecuente en la población adulta, representando sólo del 1% al 5% de todas las causas de obstrucción intestinal. Es más frecuente en el intestino delgado, donde puede responder a causas inflamatorias, infecciosas o neoplásicas, y rara en el colon, en donde en el 50%-60% de los casos se origina en neoplasias subyacentes. El aparato digestivo es el sitio más común de localización de los linfoma no Hodgkin (LNH) extranodales, incluyendo del 5% al 20% del total de los mismos. Sin embargo, los LNH primarios del tracto gastrointestinal son entidades clínico-patológicas muy raras y representan sólo del 1% al 4% de todas las neoplasias del tubo digestivo. Los LNH primarios de colon son tumores muy infrecuentes y representan del 0,2% al 1,2% del total de las neoplasias colónicas. Se describe el caso de un paciente adulto con sida, que desarrolló una invaginación colónica secundaria a un linfoma difuso de grandes células B primario del colon transverso. Se revisan los hallazgos clínicos, imagenológicos e histopatológicos y se realiza una revisión de la literatura inglesa y española sobre este tema.

Introduction Plasmablastic lymphoma is a rare entity that was first described in the jaws and the oral cavity of patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Plasmablastic lymphoma is considered as a diffuse, large, B-cell lymphoma with a unique phenotype and a predilection for the oral cavity. Objectives The authors describe a case of an aggressive plasmablastic lymphoma of the oral cavity as the primary manifestation of AIDS. Resumed We report a case of plasmablastic lymphoma involving only the oral cavity as the first manifestation of AIDS. Diagnosis was confirmed by the oral lesion biopsy and the histopathologic examination that showed a dense infiltrate composed of atypical lymphocytes with numerous plasmocytes that expressed the plasma cell markers MUM-1 and CD138 and that were negative for the B-cell markers CD3, CD20, and CD45. Immunohistochemical and in situ hybridization revealed the Epstein-Barr virus genome in the atypical cells. Polymerase chain reaction was also positive for human herpesvirus-8 RNA. Conclusion The HIV serologic status should be evaluated in all patients with plasmablastic lymphoma of the oral cavity or extraoral sites.

Non-Hodgkin lymphomas (NHL) are a heterogeneous group of diseases with a high prevalence in human immunodeficiency virus (HIV) infected patients. The immunosuppression associated with AIDS predisposes to develop NHL, including Burkitt's lymphoma (BL). BL is an uncommon and aggressive subtype of NHL that occurs with increased frequency among patients with AIDS. BL is associated with a high proliferative rate (Ki67 index) and compromises extranodal sites as the clinical presentation of the disease. Here we report a case of a primary BL of the oral cavity in an AIDS female patient, and a review the literature on the characteristics of oral cavity lymphomas in AIDS patients.

Los linfomas no Hodgkin (LNH) son un grupo heterogéneo de enfermedades linfoproliferativas con elevada prevalencia en pacientes infectados por el virus de la inmunodeficiencia humana (VIH). La inmunodeficiencia asociada al sida predispone al desarrollo de LNH, incluyendo el linfoma de Burkitt (LB). El LB es un subtipo infrecuente y agresivo de LNH con elevada frecuencia en pacientes con sida. Se asocia a una alta tasa de replicación celular (determinada por el índice Ki67) y con alta frecuencia de compromiso extranodal como forma de presentación clínica de la neoplasia. Se presenta una paciente con sida que desarrolló un LB primario de la cavidad oral y se realiza una revisión de la literatura sobre el tema.

Introduction  Extranodal non-Hodgkin lymphomas (NHLs) are commonly described in patients with acquired immunodeficiency syndrome (AIDS) and are related with an atypical morphology and aggressive clinical course. AIDS-associated lymphomas are characterized by their rapid progression, frequent extranodal manifestations, and poor outcome. Objective  The aim of this article is to remake the clinical features of head and neck (HN) NHL in patients with AIDS to facilitate early diagnosis and treatment. Methods  We evaluated the epidemiologic, clinical, immunologic, virologic, and histopathologic characteristics of 24 patients with human immunodeficiency virus (HIV)/AIDS with primary HN NHL treated at a single institution between 2002 and 2012. Histopathologic diagnosis was made according to the criteria of the World Health Organization Classification of Tumors of Hematopoietic and Lymphoid Tissues. Additional immunohistochemical stains were applied in all cases. Results  Eighteen patients (75%) were men and the median of age was 39 years. The gingiva and the hard palate were the most common sites of the lesions (15 patients, 62.5%). Lactate dehydrogenase levels were elevated in 16 cases (84%). Bone marrow infiltration was detected only in 4 cases (16.6%). The median CD4 T-cell count was 100 cells/µL. According to the histopathologic evaluation, the most common subtype was diffuse large B-cell lymphoma (12 cases, 50%), followed by plasmablastic lymphoma (9 cases, 37.5%) and Burkitt lymphoma (3 cases, 12.5%). Conclusion  HN NHL is a severe complication of advanced HIV/AIDS disease. Early diagnosis followed by chemotherapy plus highly active antiretroviral treatment is necessary to improve the prognosis and the survival of these patients.

Os linfomas Não-Hodgkin primários de tecidos moles são muito raros e responsáveis por somente 0,1% dos casos. Geralmente, os linfomas Não-Hodgkin de tecidos moles se apresentam como massas subcutâneas sem evidência de comprometimento dos nódulos ou da pele. Descrevemos aqui quatro casos de linfomas Não-Hodgkin primário de tecidos moles em pacientes infectados pelo vírus da imunodeficiência humana. O local mais comum de comprometimento foi a parede torácica em todos os pacientes; os exames histopatológico e imunofenotípico do esfregaço da biópsia revelaram dois casos de linfoma plasmablástico, um linfoma de Burkitt e um linfoma difuso de grandes células B. O linfoma Não-Hodgkin deve ser incluído no diagnóstico diferencial de massas de tecidos moles nos pacientes soropositivos para vírus da imunodeficiência humana.

Primary soft tissue Non-Hodgkin lymphomas are very rare and account only for 0.1 % of the cases. Generally, Non-Hodgkin lymphomas of the soft tissue present as large subcutaneous masses without evidence of nodal or skin involvement. We describe four cases of primary Non-Hodgkin lymphomas of the soft tissue in patients infected with the human immunodeficiency virus. The most common site of involvement was the chest wall in all the patients; histopathological and immunophenotypic examination of the biopsy smears revealed two cases of plasmablastic lymphomas, one Burkitt and one diffuse large B-cell lymphoma. Non-Hodgkin lymphomas should be included in the differential diagnosis of soft tissue masses in human immunodeficiency virus - seropositive patients.

Non-Hodgkin lymphomas (NHL) of the B-cell type are the second most common neoplasm among patients with human immunodeficiency virus (HIV) infection and AIDS. Here, we evaluated 48 cases of AIDS-related lymphomas (ARL) diagnosed at the Histopathological Division of the Instituto de Investigaciones Hematológicas of the National Academy of Medicine. Five were females and 43 were males with a median of age of 37 years at the time of the diagnosis. Micrometer sections were prepared and stained with hematoxilin-eosin; immunohistochemical examination for the presence of Epstein-Barr virus (EBV) was carried out in 48/48 cases. Additionally, biotinilated oligonucleotides were used to determine the presence of DNA of the Human Herpes virus type-8 (HHV-8) in 14/14 biopsy smears corresponding to plasmablastic lymphomas (PL). All were fenotype B cell lymphomas with an aggressive course and advanced neoplasm disease at the time of diagnosis. Virological findings showed the strong association between EBV and AIDS-related NHL. According to the histopathological subtype, the EBV genome was detected in 16/21 (76%) diffuse large B cell lymphomas, 1/3 Burkitt lymphoma and 3/4 (75%) of primary central nervous system lymphomas. Globally, EBV genome was detected in 20/28 NHL of this series. Detection of HHV-8 was negative in all cases of PL. Hodgkin lymphoma were more frequent in males 18/20 (90%), with an aggressive clinical course and a significant predominance of the subtypes associated with worse prognosis (90% of cases). We detected a significant association between EBV and HL (90% of cases). We consider that all cases of AIDS related lymphomas should be assessed for the presence of EBV because its presence may play a role in the prognosis.

Los linfomas no Hodgkin (LNH) constituyen la segunda neoplasia definitoria de Sida más frecuente. En el presente trabajo se evaluaron 48 casos de linfomas asociados con la enfermedad debida al virus de la inmunodeficiencia humana (HIV) diagnosticados en la División Histopatología del Instituto de Investigaciones Hematológicas de la Academia Nacional de Medicina. Se incluyeron en la investigación 5 mujeres y 43 hombres con una mediana de edad al momento del diagnóstico de la neoplasia de 37 años. La evaluación morfológica se realizó en cortes coloreados con hematoxilina-eosina, estudio inmunohistoquímico para la detección del virus de Epstein Barr (VEB) en 48/48 casos, y mediante sonda oligonucleotídica biotinilada para la detección del ADN del Herpes virus humano tipo-8 (HHV-8) en 14/14 linfomas plasmoblásticos (LP). Todos fueron linfomas de fenotipo B, con un curso clínico agresivo y enfermedad neoplásica avanzada al momento del diagnóstico. Se pudo demostrar la fuerte asociación del VEB con los linfomas asociados al sida, con frecuencias que variaron según el subtipo histológico: 16/21 (76%) para los linfomas difusos de grandes células; 1/3 casos (33%) de linfomas de Burkitt y 3/4 (75%) en los linfomas primarios del sistema nervioso central. Globalmente, el genoma del VEB se detectó en 20/28 (71%) de las muestras de biopsias de LNH de esta serie. La detección del HHV-8 resultó negativa en los 14 LP. Los linfomas de Hodgkin fueron más frecuentes en varones,18/20 (90%), con un curso clínico agresivo y franco predominio de los subtipos histológicos de peor pronóstico (90% de casos). En estas neoplasias también se comprobó una frecuente asociación patogénica con el VEB (90% de casos).

Cutaneous B cell lymphoma (CBCL) is a lymphoproliferative disorder of neoplastic B cell of the skin with a wide range of clinical manifestations. Commonly, the clinical features of CBCL are plaques, nodules, or ulcerative lesions. Skin is one of the common sites for extra-nodal lymphomas in patients with AIDS and B cell type is less common than T cell type. Only recently, the existence of B cell lymphomas presenting clinically in the skin without evidence of extra-cutaneous involvement has been accepted as primary CBCL. Here, we are presenting 5 patients with cutaneous involvement in the setting of HIV/AIDS disease. Two of them were primary cutaneous non-Hodgkin lymphomas. All were CBCL; 3 were immunoblastic, 1 was plasmablastic, and the other was a Burkitt lymphoma. We analyzed the epidemiological, clinical, virological, and immunological characteristics of this group of patients.

Neoplasmas da musculatura lisa são mais freqüentes em crianças infectadas pelo vírus da imunodeficiência humana do que em adultos HIV-soropositivos. Leiomioma endobronquial é um tumor benigno em pacientes adultos infectados por HIV. Vírus Epstein-Barr (EBV) tem sido implicado na patogenia destes tumores. Descrevemos paciente adulto infectado pelo HIV com atelectasia do lobo pulmonar superior esquerdo como primeira manifestação clínica de leiomioma intrabronquial. Neste caso não pudemos demonstrar a associação com EBV. Nosso relato sugere que tumores de musculatura lisa como leiomioma deveriam ser incluídos no diagnóstico diferencial de massas endobronquiais em pacientes com AIDS.

Smooth muscle neoplasms are more frequent in human immunodeficiency infected children than in HIV seropositive adults. Endobronchial leiomyoma is a rare benign tumor in HIV infected adult patients. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of these tumors. Here we describe an adult patient with HIV infection with atelectasis of the left upper pulmonary lobe as the first clinical expression of an intrabronchial leiomyoma. In this case, we can not show the association with EBV. Our report suggests that smooth muscle tumors as leiomyoma should be included in the differential diagnosis of endobronchial masses in AIDS patients.

O linfoma não-Hodgkin de células B é a segunda neoplasia mais comum em pacientes com infecção pelo vírus da imunodeficiência humana depois do sarcoma de Kaposi. A maioria dos casos de linfoma não-Hodgkin associados com a síndrome da imunodeficiência adquirida envolve locais extraganglionares, especialmente o trato digestivo e o sistema nervoso central. Nós relatamos um caso de linfoma primário do duodeno em um paciente com AIDS. Uma endoscopia digestiva alta mostrou massas pseudopolipóides encontradas na segunda porção do duodeno. Um estudo diagnóstico completo incluindo exames histológicos, imunohistoquímicos e virológicos mostrou um linfoma de células B tipo Burkitt. Detectou-se genoma do vírus Epstein-Barr em biópsias por hibridização in situ e imuno-histoquímica.

Non-Hodgkin's lymphoma of B-cell type is the second most common neoplasm after Kaposi's sarcoma, among patients with human immunodeficiency virus infection. Most non-Hodgkin's lymphoma cases that are associated with acquired immunodeficiency syndrome involve extranodal sites, especially the digestive tract and the central nervous system. We report a case of primary lymphoma of the duodenum in a patient with AIDS. Upper gastrointestinal endoscopy revealed pseudopolypoid masses found in the second portion of the duodenum. A complete diagnostic study including histological, immunohistochemical and virological analyses showed high-grade B-cell Burkitt's lymphoma. The Epstein-Barr virus genome was detected in biopsies by immunohistochemical and in situ hybridization.

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.

Extranodal involvement is common in lymphomas associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). However, primary pulmonary AIDS-related non-Hodgkin's lymphoma is very rare and only few reports were published in the medical literature. Clinical presentation is nonspecific, with "B" and respiratory symptoms. Also, patients were with advanced immunodeficiency at the time of diagnosis. Generally, chest radiography showed peripheral nodules or cavitary masses. Primary pulmonary lymphoma associated with AIDS is generally a high-grade B-cell non-Hodgkin lymphoma and Epstein-Barr virus is strongly associated with the pathogenesis of these tumors. We report a patient with AIDS and primary pulmonary lymphoma which clinical presentation was a total atelectasis of the left lung.

El compromiso extranodal es frecuente en los linfomas asociados con la enfermedad debida al virus de la inmunodeficiencia humana y su consecuencia, el síndrome de inmunodeficiencia adquirida. Sin embargo, el linfoma pulmonar primario es muy raro y solo existen pocos casos publicados en la literatura. La presentación clínica de esta complicación es inespecífica, con síntomas "B" y manifestaciones respiratorias. Generalmente, la radiografía de tórax muestra nódulos periféricos o masas que pueden cavitarse y los pacientes presentan inmunodeficiencia severa al momento del diagnóstico. El linfoma pulmonar primario asociado con el sida es un tumor de alto grado, de células B y asociado en su patogenia con el virus de Epstein-Barr. Se relata un caso de linfoma primario de pulmón que se presentó bajo la forma radiológica de una atelectasia global del pulmón izquierdo.

Telomeres are essential for maintaining chromosomal integrity and stability. We studied here telomere length (TL) in bone marrow and/or lymph node from 36 patients: 29 with follicular lymphoma (FL) at diagnosis and 7 with diffuse large B cell lymphoma secondary to FL (S-DLBCL). TL was evaluated using terminal restriction fragments (TRF) assay. BCL-2 gene rearrangement was analyzed by nested and long distance PCR. Mean TRF values showed significant telomere shortening in FL (4.18±0.18 Kb) and S-DLBCL (3.31±0.25 Kb) respect to controls (8.50±0.50 Kb) (p<0.001). Differences between both histological subtypes (p=0.036) were also detected. Moreover, the samples positive for BCL-2 rearrangements showed longer TL (4.25±0.19 Kb) than the negative ones (3.39±0.30 Kb) (p=0.023). A trend to telomere shortening was observed when Major Breakpoint Region (MBR-J H), minor cluster region (mcr-J H) and BCL-2 negative patients were compared (4.35±0.21 Kb; 3.84±0.45 Kb and 3.39±0.30 Kb, respectively). Our results show a TL reduction in FL and S-DLBCL, with significant short TRFs in the last group, suggesting the participation of telomere shortening in tumor progression. Furthermore, the differences detected between BCL-2 positive and negative FL support the involvement of diverse pathogenic mechanisms.

Los telómeros son estructuras esenciales para el mantenimiento de la integridad cromosómica y la capacidad replicativa de la célula. La reducción de la longitud telomérica (LT) aumenta la probabilidad de producir errores capaces de generar cambios genómicos importantes para el desarrollo neoplásico, determinando desbalances de material genético. En este trabajo se evaluó la LT mediante el análisis de fragmentos de restricción terminal (TRF) en médula ósea y/o biopsia ganglionar de 36 pacientes (edad media: 54.2 años; rango 29-77 años; 21 varones): 29 con linfoma folicular (LF) al diagnóstico y 7 con linfoma B difuso a células grandes secundario a LF (LBDCG-S). Se efectuó el análisis del rearreglo molecular del gen BCL-2 por PCR anidada y de larga distancia. Las medias de TRF en LF (4.18±0.18 Kb) y LBDCG-S (3.31±0.25 Kb) resultaron significativamente menores que en controles (8.50±0.50 Kb) (p<0.001), encontrándose diferencias entre ambos subtipos histológicos (p=0.036). Las muestras negativas para el rearreglo BCL-2 mostraron LT menores (3.39±0.30 Kb) que las positivas (4.25±0.19 Kb) (p=0.023), observándose una tendencia a valores menores en pacientes negativos para el rearreglo BCL-2, intermedios en positivos para mcr, minor cluster region, (3.84±0.45 Kb) y mayores en los positivos para MBR, Major Breakpoint Region, (4.35±0.21 Kb). Nuestros resultados muestran una reducción de la LT en LF y LBDCG-S, con TRFs significativamente más cortos en estos últimos, sugiriendo la participación del acortamiento telomérico en la progresión tumoral. Asimismo, las diferencias detectadas entre los casos BCL-2 positivos y negativos sustentarían la presencia de diferentes mecanismos patogénicos propuestos para estos distintos LF.