Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients.

Diffuse large B-cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult non-Hodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein-Barr virus (EBV)+ DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV+ DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T-cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T-cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV+ DLBCL, with ≥20% of EBERs+ cells. These findings suggest that EBV+ DLBCL in our series was similar to the previously described in Asia and Latin-America, displaying latency II or III expression profile and no age-specific characteristics. Finally, EBV+ DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal.

MALT lymphoma in labial salivary gland biopsy from Sjögren syndrome: importance of follow-up in early detection.

Mucosa-associated lymphoid tissue (MALT) lymphomas are known to occur in Sjögren syndrome (SS) patients, but reported cases in labial salivary glands (LSG) are rare. We report a case of 60-year-old female patient with SS who developed MALT lymphoma in the labial salivary glands during a 2-year time interval when she was participating in the Sjögren's International Clinical Collaborative Alliance, an ongoing longitudinal multisite observational study funded by the National Institutes of Health of the United States. At follow-up exam, LSG biopsy showed atypical diffuse infiltration by mononuclear cells of variable size and atypical nuclei affecting the whole specimen with destruction of glandular architecture, leading to a diagnosis of B-cell MALT lymphoma. Computerized tomography and bone marrow biopsy failed to show additional evidence of disease. Clinical, serologic, ocular, histologic and immunohistochemical findings are presented. A "watch and wait" policy was adopted with regular examinations.

Oral cavity and extra-oral plasmablastic lymphomas in AIDS patients: report of five cases and review of the literature.

Plasmablastic lymphoma (PBL) is a distinct disease entity of the diffuse large B-cell lymphoma, which often occurs in HIV-positive patients. The immunophenotype of this lymphoid neoplasm is characterized by the presence of plasma cell-associated markers VS38c and CD138 antigens and the absence of B-cell markers such as CD20 and CD45. The most frequent site of involvement is the oral cavity and the jaw, while several reports describe the development of PBL in extra-oral sites including the lymph nodes, the anal canal, the soft tissue, the skin and the gastrointestinal tract as less frequent. Epstein-Barr virus is often associated with PBL pathogenesis and the neoplastic cells contain this virus genome. Here we review the epidemiological, clinical, immunological, histopathological and virological characteristics and their prognosis and outcome in a series of five patients with diagnoses of HIV/AIDS and PBL.

Vulvar plasmablastic lymphoma in a HIV-positive child: a novel extraoral localisation.

Plasmablastic lymphoma (PBL) has been characterised by the World Health Organization as a new entity. This report describes an unusual case of PBL in a 3-year-old HIV-infected patient showing a cutaneous vulvar lesion with 9 months of evolution and prolapsed vulvovaginal mucosa. Histopathological examination of a biopsy sample showed diffuse submucosal infiltration by large cells with a cohesive growth pattern, and round and vesicular nuclei with fine chromatin centrally or eccentrically placed with one or more prominent nucleoli. Immunohistochemical staining in neoplastic cells was positive for multiple melanoma oncogene (MUM1), CD138, CD45 and epithelial membrane antigen (EMA). The diagnosis was PBL, stage III. Epstein-Barr virus (EBV) expression was positive by EBV encoded RNAs in situ hybridisation. This is believed to be the third case of paediatric HIV-associated PBL reported in the literature, and the first with vulvar localisation, which is a new anatomical location for this entity.

Mantle cell lymphoma with aberrant expression of CD10.

AIMS: Morphological, immunophenotypic and genetic heterogeneity amongst mantle cell lymphomas (MCLs) can lead to difficulties in diagnosis and management. The aim was to describe the clinical and pathological features of MCLs with aberrant expression of CD10. METHODS AND RESULTS: Of 17 specimens from 13 patients, 14 expressed CD10 and three (presenting before or after a CD10+ specimen) did not. All expressed cyclin D1 and carried the t(11;14)(q13;q32)/CCND1-IGH translocation. Similar to non-selected MCL patients, most patients had disseminated disease and an adverse clinical course. Five specimens showed pleomorphic blastoid morphology and blastoid transformation was associated with a change in phenotype, including gain or loss of CD10. Additional phenotypic variations likely to cause diagnostic difficulty were present in eight specimens: five were CD5- and five (all CD10+) expressed Bcl-6. One Bcl-6+ case carried a BCL-6 translocation and three others had extra copies of the BCL-6 gene. Sequence analysis of the immunoglobulin heavy chain variable region in five cases showed only one to have low-level somatic mutation, indicating that they did not arise from germinal centre B cells. CONCLUSIONS: Expression of CD10 by MCL is often associated with other variant morphological, immunophenotypic or genetic features, but does not reflect derivation from germinal centre B cells.

Catastrophic antiphospholipid syndrome and Kikuchi-Fujimoto disease: the first case reported.

The case of a man with diagnosis of Kikuchi-Fujimoto disease (KFD) and catastrophic antiphospholipid syndrome (CAPS) is reported. He presented prolonged fever, lymphadenopathies, arthralgia, weight loss, hepatosplenomegaly and positive IgM for cytomegalovirus. While he was empirically treated with tuberculostatic drugs, he suddenly developed systemic inflammatory response syndrome, multiple organ failure and distal necrosis. On suspicion of severe sepsis, antibiotics, corticoids and recombinant human activated protein C (XIGRIS) were administrated. Exhaustive laboratory searching was negative. Histopathologic examinations of lymph node first disclosed malignant lymphoma but later KFD was confirmed. One month later, laboratory tests showed the presence of antiphospholipid antibodies (aPL). The patient was discharged after two months of hospitalization. This case exhibits a KFD complicated by definite CAPS. Cytomegalovirus could be involved in the development of both CAPS and KFD. Because of the severity of the case, we believe that XIGRIS noticeable improved the altered coagulation profile associated with CAPS.

Análisis molecular de la longitud telomérica en linfomas foliculares: Su participación en la progresón tumoral / Molecular analysis of telomere length in follicular lymphomas: Its participation in tumor progression

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 em 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.

Análisis molecular de la longitud telomérica en linfomas foliculares: Su participación en la progresón tumoral / Molecular analysis of telomere length in follicular lymphomas: Its participation in tumor progression

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 em 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. (AU)

Linfoma primario de esofago en una paciente con SIDA / Primary esophageal lymphoma in a patient with AIDS

Primary esophageal lymphomas are extremely rare. We report a primary esophageal T cell lymphoma of a diffuse large cell phenotype B in a patient with AIDS. Also we reviewed other published cases. The diagnosis of this complication should be considered in HIV seropositive patients with progressive displagia and endoscopic findings of masses, polyps or ulcerations and, specially in those unresponsive to antifungal or antiviral therapy. Biopsy and histopathologic studies are needed to confirm the diagnosis.

Linfoma primario de esofago en una paciente con SIDA / Primary esophageal lymphoma in a patient with AIDS

Primary esophageal lymphomas are extremely rare. We report a primary esophageal T cell lymphoma of a diffuse large cell phenotype B in a patient with AIDS. Also we reviewed other published cases. The diagnosis of this complication should be considered in HIV seropositive patients with progressive displagia and endoscopic findings of masses, polyps or ulcerations and, specially in those unresponsive to antifungal or antiviral therapy. Biopsy and histopathologic studies are needed to confirm the diagnosis. (AU)

[Primary esophageal lymphoma in a patient with AIDS]. / Linfoma primario de esófago en una paciente con SIDA.

Primary esophageal lymphomas are extremely rare. We report a primary esophageal T cell lymphoma of a diffuse large cell phenotype B in a patient with AIDS. Also we reviewed other published cases. The diagnosis of this complication should be considered in HIV seropositive patients with progressive displagia and endoscopic findings of masses, polyps or ulcerations and, specially in those unresponsive to antifungal or antiviral therapy. Biopsy and histopathologic studies are needed to confirm the diagnosis.

Linfoma primario de esófago en una paciente con SIDA. / [Primary esophageal lymphoma in a patient with AIDS]

Primary esophageal lymphomas are extremely rare. We report a primary esophageal T cell lymphoma of a diffuse large cell phenotype B in a patient with AIDS. Also we reviewed other published cases. The diagnosis of this complication should be considered in HIV seropositive patients with progressive displagia and endoscopic findings of masses, polyps or ulcerations and, specially in those unresponsive to antifungal or antiviral therapy. Biopsy and histopathologic studies are needed to confirm the diagnosis.

Nonhepatosplenic gamma delta T-cell lymphoma with initial testicular compromise.

We report here a case of nonhepatosplenic gammadelta T-cell lymphoma with undescribed initial localization in testis, without hepatosplenomegaly or adenopathies, and subsequent development in the maxillary sinus. The maxillar mass biopsy revealed a T-cell infiltration, and its immunologic characterization by flow cytometry showed a gammadelta T-cell phenotype (CD45+, CD3+, CD2+, TCR gammadelta+), without expression of CD7, CD5, CD1a, TdT, CD4, CD8, TCR alphabeta, or NK antigens (CD16, CD56, and CD57). Clonal gamma-chain gene rearrangement by polymerase chain reaction (PCR) was detected in testicular and maxillar biopsies. Epstein-Barr virus type 1 (EBV) sequences were detected by molecular biology in the biopsy material, suggesting that this oncogenic virus may play a role in the genesis of the clonal expansion of gammadelta T-cells. The patient was initially treated with standard chemotherapeutic protocols, with poor response and aggressive course.

Bcl-2 molecular analysis in paraffin-embedded biopsies from diffuse large B-cell lymphomas.

Translocation t(14; 18) has been observed in 50-85% of follicular and in 30% of diffuse non-Hodgkin lymphomas. About half of follicle center lymphoma (FCL) undergo histological conversion at relapse to more aggressive diffuse large B-cell lymphoma (DLBCL). This report correlates the molecular bcl-2/IgH rearrangement by PCR and Bcl-2 immunohistochemical (IHC) expression in a series of high grade DLBCLs with and without FCL remnant. Twenty-three paraffin-embedded lymph nodes from DLBCL patients were analyzed. Eleven patients showed FCL remnant (Group A) and 12, did not (Group B). Single PCR from paraffin extracted DNA followed by Southern transfer of products, hybridisation with internal oligoprobes for the MBR/JH and MCR/JH bcl-2 rearrangements and IHC analysis of Bcl-2 expression, were performed. PCR analysis was positive in 34.8% of patients. Bcl-2/IgH gene rearrangements were observed in 8 (34%) cases and 7 (30%) showed Bcl-2 expression on large noncleaved B-cells (centroblasts). All patients from Group A showed IHC positive reaction on FCL remnant (small cleaved cells) but only 2 (18%) were positive in DLBCL areas, suggesting either the loss of the bcl-2 expression on the transformed lymphoma, or, alternatively, the development of a second disease when the first lymphoma transforms. Group B patients showed a clear correlation between PCR and IHC studies. Our results suggest a similar frequency of t(14; 18) in DLBCLs to that reported in Europe and USA series. The discordance observed between PCR and IHC, particularly in Group A, points out the necessity to perform both studies in order to detect bcl-2 gene involvement in DLBCLs.

[Hairy cell leukemia. An alternative method for the detection of minimal residual disease using flow cytometry]. / Leucemia de células vellosas. Un método alternativo para la detección de enfermedad minima residual por citometría de flujo.

In patients with hairy cell leukemia (HCL) who received chemotherapeutic treatment and achieved complete remission (CR), minimal residual disease (MRD) can be detected in bone marrow biopsies using immunohistochemical (IHC) techniques. In this study, we investigated the value of flow cytometry (FCM) and IHC to detect MRD and to establish whether MRD+ could predict relapse. A total of 15 HCL patients in CR were studied. Samples of bone marrow (BM) and peripheral blood (PB) were processed by FCM with triple staining of the following monoclonal antibodies (mAbs): CD20, CD22, CD11c, CD103, CD25, anti-Kappa and anti-Lambda light chains. Reference values were obtained from normal samples of peripheral blood and bone marrow. FCM detected MRD in 64% of the patients. BM samples were more demonstrative than peripheral blood for MRD detection in HCL. IHC was performed in paraffin-embedded BM biopsies using CD20 and DBA44 mAbs. MRD+ was detected in 46% of patients. Although not statistically significant, FCM appeared more sensitive compared with IHC. Detection of MRD by either of these methods in our series did not predict hematological relapse. The results show that FCM is a useful alternative method to detect MRD in HCL and that a longer, follow-up is required to establish the predictive outcome of MRD+ patients.