Classification and diagnostic evaluation of nodal T- and NK-cell lymphomas.

Nodal T- and NK-cell lymphomas are among the most frequent T-cell malignancies and most subtypes have aggressive clinical behavior. Evolving understanding of the biology and molecular characteristics of these lymphomas, as well as the development of new precision therapy approaches, underscores the importance of ongoing updates to the classification and diagnostic evaluation of this group of malignancies. Here, we discuss the classification of nodal T- and NK-cell lymphomas based on the 2022 International Consensus Classification of Mature Lymphoid Neoplasms (2022 ICC). Lymphomas of T-follicular helper cell origin are now grouped into a single entity, follicular helper T-cell lymphoma (TFH lymphoma), with three subtypes (angioimmunoblastic-type, follicular-type, and not otherwise specified), reflecting their common cellular origin and shared molecular and clinical characteristics. Classification of anaplastic large cell lymphoma (ALCL) remains essentially unchanged; DUSP22-rearranged cases are now considered a genetic subtype of ALK-negative ALCL. Primary nodal EBV-positive T-/NK-cell lymphoma is introduced as a new provisional entity; these cases were previously considered a variant of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS). PTCL, NOS remains a diagnosis of exclusion, with evolving molecular data indicating the presence of distinct subgroups, including PTCL-TBX21, PTCL-GATA3, and EBV-negative cytotoxic PTCLs. We also discuss diagnostic strategies to facilitate the 2022 ICC classification among nodal T- and NK-cell lymphomas and the distinction from nodal involvement by extranodal neoplasms.

Enfermedad de Castleman multicéntrica en pacientes HIV positivos. Reporte de dos casos y revisión de la literatura / Multicentric Astleman disease in HIV positive patients. Two cases. Report and literature review

La enfermedad de Castleman (EC) es un proceso linfoproliferativo poco frecuente que se caracteriza por hiperplasia de los ganglios linfáticos. Existen dos variedades histológicas bien diferenciadas la hialino-vascular y la plasmocelular, que a su vez pueden ser localizadas o multicéntricas. La forma hialino-vascular suele ser asintomática y localizada en mediastino mientras que la plasmocelular se presenta frecuentemente con signo-sintomatología sistémica y suele ser difusa o multicéntrica. En el contexto de la enfermedad debida al virus de la inmunodeficiencia humana (VIH), la EC se asocia en su patogenia a la infección por el herpes virus humano tipo-8 (HHV-8). La mayoría de los casos corresponden a la variante hialino-vascular (80/90%) en tanto un pequeño porcentaje (10/20%) son de la variante plasmocelular. En algunos pacientes, el patrón histopatológico puede ser mixto. Se describen dos casos de enfermedad de Castleman multicéntrica HHV8- positiva en pacientes con enfermedad HIV/SIDA.

Castleman's disease (CD), is a rare hematological condition of uncertain etiology, involves a massive proliferation of lymphoid tissues and typically presents as mediastinal masses. This is considered as a distinct type of lymphoproliferative disorder associated with inflammatory symptoms. In the context of human immunodeficiency virus (HIV) infection, CD is associated with human herpesvirus-8 (HHV8) infection. Most cases of CD represent either the hyaline vascular variant (80­90% of cases) or the plasma cell variant (10­20%); a small percentage present with a mixed histologic appearance. Two cases of Castleman's disease associated with HHV-8 and HIV/AIDS infection are described

CD5-negative mantle cell lymphoma: clinicopathologic features of an indolent variant that confers a survival advantage.

Conventionally, mantle cell lymphoma (MCL) is an aggressive CD5-positive B-cell malignancy with poor prognosis and limited survival. However, a small subset of patients presents with indolent disease and can be managed on a 'watch and wait' approach. CD5-negative MCL has recently been recognized as a more favorable variant of MCL, but its clinical and biological implications remain ill-defined. We performed the most extensive review to-date of all reported cases of CD5-negative MCL and included unpublished cases diagnosed at our institutions to further characterize this disease subset. Based on our analysis of 356 cases of CD5-negative MCL, we conclude that median overall survival exceeds 14 years and is independent of favorable prognostic markers such as leukemic non-nodal disease, absence of SOX11, and low Ki-67.

Desbalances genómicos del locus 9p24.1 en pacientes argentinos con linfoma de Hodgkin clásico / Genomic imbalances at 9p24.1 locus in Argentine patients with classical Hodgkin lymphoma

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

Mutational profile and EBV strains of extranodal NK/T-cell lymphoma, nasal type in Latin America.

Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus (EBV) associated lymphoma, prevalent in Asia and Latin America. Studies in Asian cohorts have identified some recurrent gene mutations in ENKTL; however, the mutational landscape of ENKTL in Latin America is unknown. In this study, we investigated the mutational profile and EBV strains of 71 ENKTL cases from Latin America (42 from Mexico, 17 from Peru, and 12 from Argentina) and compared it with Asian cohorts. The mutational analysis was performed by next generation sequencing (NGS) using an Ion AmpliSeq™ custom panel covering for the most frequently mutated genes identified in ENKTL. STAT3 was the most frequent mutated gene (16 cases: 23%), followed by MSN (10 cases; 14%), BCOR (9 cases; 13%), DDX3X (6 cases; 8%), TP53 (6 cases; 8%), MGA (3 cases; 4%), JAK3 (2 cases; 3%), and STAT5B (1 case; 1%). Mutations in STAT3, BCOR, and DDX3X were nearly mutually exclusive, suggesting different molecular pathways involved in the pathogenesis of ENKTL; whereas mutations in MGA, MSN, and TP53 were concomitant with other mutations. Most cases (75%) carried Type A EBV without the 30-bp LMP1 gene deletion. The overall survival was significantly associated with serum LDH level, Eastern Cooperative Oncology Group (ECOG) performance status, International Prognostic Index (IPI) score, and therapy (p < 0.05), but not associated with any mutation, EBV strain or deletion in EBV LMP1 gene. In conclusion, mutational analysis of ENKTL from Latin America reveals frequent gene mutations leading to activation of the JAK-STAT pathway (25%), mostly STAT3. Compared to Asian cohorts, BCOR, DDX3X and TP53 mutations were also identified but with different frequencies. None of these mutations were associated with prognosis.

Primary cutaneous lymphoma in Argentina: a report of a nationwide study of 416 patients.

BACKGROUND: The aim of this study was to determine the relative frequency of primary cutaneous lymphoma (PCL) in Argentina according to the new World Health Organization (WHO)-European Organization for the Research and Treatment of Cancer (EORTC) classification system. METHODS: A total of 416 patients from 21 dermatology services were included during a 5-year period (2010-2015); these patients were classified using WHO-EORTC criteria. RESULTS: There were 231 (55.2%) males and 185 (44.8%) females; the male-to-female ratio was 1.35. The median age of the patients was 57 years (range, 0-90 years). Most patients were Caucasian (79%), and only 16% of patients were registered as Amerindian. Most patients (387/416, 93%) had cutaneous T-cell lymphoma (CTCL); 28 patients (6.7%) were diagnosed with cutaneous B-cell lymphoma (CBCL). The most frequent CTCL subtypes, in decreasing order of prevalence, were mycosis fungoides (MF), including its variants (75.7%); CD30+ primary cutaneous lymphoproliferative disorders (7.2%); and Sézary syndrome (SS) (3.1%). Cutaneous follicle center lymphoma was the most common CBCL subtype (2.9%). In the subset of patients ≤20 years of age, the most common condition was MF (57%), followed by extranodal NK-T nasal-type lymphoma (14%). CONCLUSIONS: This study revealed relatively higher rates of MF and lower rates of CBCL in Argentinean patients that have been reported in American and European countries.

Alta incidencia de patologías neoplásicas en biopsias ganglionares de pacientes asistidos en un hospital de enfermedades infecciosas / High incidence of neoplasmic diseases in lymph node biopsies in assisted patients in an infectious diseases hospital

La presencia de adenopatías periféricas con rango adenomegálico es un hallazgo clínico frecuente, tanto en los pacientes con serología reactiva como en los no infectados por el VIH. En este estudio retrospectivo se analizaron 132 muestras de biopsias quirúrgicas ganglionares obtenidas de pacientes internados en un hospital de referencia en Enfermedades Infecciosas del GCABA, Argentina, en el período comprendido entre enero de 2011 y diciembre de 2015. La mayoría de los pacientes (100/132, 75,8%) tuvieron serología reactiva para VIH; en este subgrupok de sujetos, la mediana del recuento de linfocitos T CD-4 positivos fue de 141 cél/µL. El diagnóstico histopatológico más frecuente resultó la infiltración ganglionar por neoplasias linfoides primarias (linfomas) o metástasis de carcinomas (41%). Entre las patologías infecciosas predominaron las micobacteriosis, en especial la tuberculosis. Solo en 3 de 132 (2,3%) muestras de biopsias los hallazgos histológicos fueron normales. En conclusión, la biopsia quirúrgica de adenopatías periféricas resulta un método muy valioso y mínimamente invasivo para el diagnóstico de patologías infecciosas y tumorales. Una alta incidencia de enfermedades neoplásicas se detectaron en este estudio realizado en un hospital de Enfermedades Infecciosas.

Peripheral lymphadenopathy is a common clinical condition in both HIV-infected and non-HIV patients and has a wide spectrum of differential diagnoses. In this retrospective study, we carried out a cross-sectional study of peripheral lymph node biopsies performed from January 2011 to December 2015 in a reference hospital of Infectious Diseases in Argentina. We include a 132 patients underwent excisional lymph node biopsies during the time of study. The majority of patients were HIV-seropositive (100/132; 75,8%); the median of CD4 T-cell count was 141 cell/µL. The most common histopathological diagnosis was primitive or secondary neoplasms (54/132; 40,9%). In 51/132 biopsies the diagnosis corresponded to infectious pathologies, especially mycobacterial diseases, including tuberculosis. Only 3 of 132 biopsies (2,3%) included in the evaluation had only with normal findings. Peripheral lymph node biopsy is a simple and useful tool to diagnose opportunistic diseases and neoplasms in HIV and non-HIV infected patients. A high incidence of neoplasm diseases (41%) were obtained in this retrospective study

Clinicopathologic Features and Prognostic Impact of Lymph Node Involvement in Patients With Breast Implant-associated Anaplastic Large Cell Lymphoma.

Breast implant-associated anaplastic large cell lymphoma (BI-ALCL) is a rare T-cell lymphoma that arises around breast implants. Most patients manifest with periprosthetic effusion, whereas a subset of patients develops a tumor mass or lymph node involvement (LNI). The aim of this study is to describe the pathologic features of lymph nodes from patients with BI-ALCL and assess the prognostic impact of LNI. Clinical findings and histopathologic features of lymph nodes were assessed in 70 patients with BI-ALCL. LNI was defined by the histologic demonstration of ALCL in lymph nodes. Fourteen (20%) patients with BI-ALCL had LNI, all lymph nodes involved were regional, the most frequent were axillary (93%). The pattern of involvement was sinusoidal in 13 (92.9%) cases, often associated with perifollicular, interfollicular, and diffuse patterns. Two cases had Hodgkin-like patterns. The 5-year overall survival was 75% for patients with LNI and 97.9% for patients without LNI at presentation (P=0.003). Six of 49 (12.2%) of patients with tumor confined by the capsule had LNI, compared with LNI in 8/21 (38%) patients with tumor beyond the capsule. Most patients with LNI achieved complete remission after various therapeutic approaches. Two of 14 (14.3%) patients with LNI died of disease compared with 0/56 (0%) patients without LNI. Twenty percent of patients with BI-ALCL had LNI by lymphoma, most often in a sinusoidal pattern. We conclude that BI-ALCL beyond capsule is associated with a higher risk of LNI. Involvement of lymph nodes was associated with decreased overall survival. Misdiagnosis as Hodgkin lymphoma is a pitfall.

Epstein-Barr virus lytic cycle involvement in diffuse large B cell lymphoma.

Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed lytic transcripts, being transcribed at the BZLF1, BHRF1, and BLLF1 locus, by real-time quantitative polymerase chain reaction. This lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and a positive correlation between lytic and latent genes was confirmed, revealing a close link between their expressions in EBV+ DLBCL pathogenesis. Remarkably, BZLF1 displayed a negative correlation with CD4 cell counts, and this could be in part justified by the restriction of antigen presentation previously reported. The direct correlation for the late lytic gene BLLF1 and IFNγ in this series could represent a specific response directed towards this antigen. Interleukin 10 transcripts also displayed a positive correlation with lytic expression, indicating that regulatory mechanisms could be also involved on EBV-associated DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive tumours could potentially kill EBV-positive malignant cells, providing a tool to promote tumour cell killing mediated by EBV as a complementary treatment strategy.

Implicancia pronóstica de características basales en trombocitopenia esencial / Prognostic implication of basal characteristics in essential thrombocythemia

OBJETIVO: evaluar asociación entre características basales de Trombocitemia Esencial (TE) y eventos. Materiales-métodos: estudio observacional retrospectivo, datos capturados prospectivamente. Población: adultos con TE confirmada seguidos en CH del IIHEMA. Resultados: 67 pacientes evaluables. Md 68 años. Femenino 44, Masculino 23. Seguimiento Md 6 años. Score riesgo Alto 40, Intermedio 15, Bajo 12. Hematocrito Md 41%. Hemoglobina Md 13.4 g/dL. Leucocitos Md 9.7x109/L. Plaquetas Md 852x109/L. Esplenomegalia 12. Cariotipo normal 40, alterado 5. JAK2 V617F positivo 29/41. BCR/ABL1 negativo 45/45. FRV 40. Eventos: 67. Sangrado, 21 pacientes, presentó asociación con leucocitosis: Md 12.2x109/L en el grupo con sangrado y 8.8x109/L en el grupo sin evento (p=0.003). El 76% del grupo con sangrado y el 36,96% del grupo sin evento tenían leucocitos >10.0x109/L (p= 0.003). Trombocitosis Md 1.204x109/L en el grupo con sangrados y 814.5x109/L en el grupo sin evento (p=0.0098), no alcanzó significación estadística al comparar proporción de pacientes con recuento normal (p=0.46). Tromboembolia, 16 pacientes, se asoció con leucocitosis (Md 11.9x109/L en el grupo con tromboembolia y 9.2x109/L en el grupo sin evento (p=0.02). 75% del grupo con eventos y 41% del grupo sin eventos tenían leucocitos >10.0x109/L (p=0.018)) y con trombocitosis (Md 1.182x109/L en el grupo con tromboembolia y 809x109/L en el grupo sin evento (p=0.04), pero no alcanzó significación estadística al comparar proporción de pacientes con recuento normal (p=0.5)). CONCLUSIÓN: la asociación entre trombocitosis extrema/leucocitosis y sangrado coincidió con la literatura; leucocitosis se asoció a tromboembolia. El JAK2 V617F no mostró asociación: analizaremos prospectivamente aumentando la población para esclarecer asociación y posible rol de terapias dirigidas en esta entidad. (AU)

OBJETIVE: asses association basal characteristics of Essential Trombocitemia (ET) and events. MATERIALS-METHODS: retrospective observational study, data captured prospectively. Population: adults with confirmed ET treated in CH of IHEMA. RESULTS: 67 evaluable patients. Md 68-years-old. Female 44, Male 23. Follow up Md 6 years. Risk Score High 40, Intermeddle 15, Low 12. Hematocrit Md 41%. Hemoglobin Md 13.4 g/dL. Leukocytes Md 9.7x109/L. Platelets Md 852x109/L. Splenomegaly 12. Normal karyotype 40, abnormal 5. JAK2V617F positive 29/41. BCR-ABL1 negative 45/45. Vascular risk factors 40. EVENTS: 67. Bleeding, 21 patients, showed association with leukocytosis: Md 12.2x109/L in the group with bleeding and 8.8x109/L in the group without event (p=0.003). Leukocytes >10.0x109/L was seen in 76% of the group with bleeding versus 36.96% of the group without event (p= 0.003). Thrombocytosis Md 1.204x109/L in the group with bleeding and 814.5x109/L in the group without event (p=0.0098), but did not reach statistical significance when comparing with the proportion of patients with normal counts (p=0.46). Thromboembolism, 16 patients, showed association with both leukocytosis (Md 11.9x109/L in the group with thromboembolism and 9.2x109/L in the group without event (p=0.02). Leukocytosis >10.0x109/L was seen in 75% of the group with events and 41% of the group without event (p=0.018)) and with thrombocytosis (Md 1.182x109/L in the group with thromboembolism and 809x109/L in the group without event (p=0.04), but did not reach statistical significance when comparing with the proportion of patients with normal counts (p=0.5)). CONCLUSION: the association between extreme thrombocytosis/leukocytosis and bleeding was consistent with literature; leukocytosis was associated also with thromboembolism. JAK2 V617F mutated did not show association, we will prospectively analyze increasing the population to clarify its association and possible role of target therapies in this disease. (AU)

Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: clinical features and survival impact.

Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.

Invaginación intestinal como forma de presentación de linfoma no Hodgkin primario de colon en un paciente VIH positivo / Intussusception as clinical presentation of primary non-Hodgkin lymphoma of the colon in a HIV-patient

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 (AU)

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 (AU)

Genomic imbalances and microRNA transcriptional profiles in patients with mycosis fungoides.

Mycosis fungoides is the most common type of primary cutaneous T cell lymphoma. We have evaluated CDKN2A losses and MYC gains/amplifications by FISH analysis, as well as expression of miR-155 and members of the oncogenic cluster miR-17-92 (miR17, miR18a, miR19b, and miR92a) in MF patients with advanced disease. Formalin-fixed paraffin-embedded skin biopsies from 36 patients at diagnosis, 16 with tumoral MF (T-MF), 13 in histological transformation to a large T cell lymphoma (TR-MF), and 7 cases with folliculotropic variant (F-MF), were studied. Twenty cases showed genomic alterations (GAs): 8 (40 %) had CDKN2A deletion, 7 (35 %) showed MYC gain, and 5 (25 %) exhibited both alterations. GAs were more frequently observed in F-MF (p = 0.004) and TR-MF (p = 0.0001) than T-MF. GAs were significantly higher in cases presenting lesions in head, neck, and lower extremities compared to those observed in trunk and upper extremities (p = 0.03), when ≥25 % neoplastic cells were CD30 positive (p = 0.016) as well as in cases with higher Ki-67 proliferation index (p = 0.003). Patients with GAs showed bad response to treatment (p = 0.02) and short survival (p = 0.04). Furthermore, MF patients showed higher miRNA expression compared to controls (p ≤ 0.0223). T-MF showed higher miR17 and miR-18a expression compared to F-MF and TR-MF (p ≤ 0.0387) while miR19b, miR92a, and miR-155 showed increased levels in F-MF and TR-MF with respect to T-MF (p ≤ 0.0360). Increased expression of miR17 and miR19b in GA group compared to cases without alterations (p ≥ 0.0307) was also detected. Our results add new information about genomic imbalances in MF patients, particularly in F-MF, and extend the present view of miRNA deregulation in this disease.

SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P ≤ 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5(+) (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology. © 2016 Wiley Periodicals, Inc.

Intussusception as clinical presentation of primary non-Hodgkin lymphoma of the colon in a HIV-patient.

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.

Linfoma primario del sistema nervioso central como primera manifestación de sida. Presentación de un caso y revisión de la literatura / Primary central nervous system lymphoma as first manifestation of AIDS. Report of a case and literature review

El linfoma primario del sistema nervioso central (LPSNC) es una neoplasia infrecuente que comprende solo el 5% del total de los linfomas de localización extranodal. El LPSNC se define como un linfoma de tipo No Hodgkin (LNH) que solo infiltra el eje cerebro espinal sin compromiso sistémico. Esta neoplasia es más frecuente en sujetos con inmunodeficiencias congénitas y adquiridas. En los pacientes con SIDA, el LPSNC ocurre con igual incidencia en todos los grupos de riesgo y edades pero con una mayor prevalencia en aquellos con recuentos de linfocitos T CD4 + de < de 50 células/µL. Se trata de un linfoma de células grandes, de alto grado de malignidad, y fuertemente asociado en su patogenia al virus de Epstein Barr (VEB) cuyo genoma se detecta en las células linfoides atípicas. La presencia del genoma del VEB se detecta en el 100% de los casos de LPSNC asociado al SIDA pero esto no ocurre en otras clases de pacientes con esta misma neoplasia. En pacientes con SIDA y lesiones de masa cerebral ocupante, la detección del genoma del VEB en el líquido cefalorraquídeo (LCR) a través de la reacción en cadena de la polimerasa (PCR) tiene una sensibilidad del 83% a 100% y una especificidad > del 90% para el diagnóstico. El uso difundido de la terapia antirretroviral de gran actividad (TARGA) se asoció con una declinación en la incidencia de LPSNC. El pronóstico de esta neoplasia en pacientes con SIDA es pobre y se asocia con una mediana de supervivencia de 2 a 3 meses en la era previa a la TARGA con una discreta prolongación en la supervivencia con la TARGA. Se presenta un paciente que desarrolló un LPSNC como primera manifestación de SIDA y se efectúa una actualización de la literatura sobre el tema.

An Aggressive Plasmablastic Lymphoma of the Oral Cavity as Primary Manifestation of Acquired Immunodeficiency Syndrome: Case Report and Literature Review

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.(AU)

An Aggressive Plasmablastic Lymphoma of the Oral Cavity as Primary Manifestation of Acquired Immunodeficiency Syndrome: Case Report and Literature Review.

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. Objective The authors describe a case of an aggressive plasmablastic lymphoma of the oral cavity as the primary manifestation of AIDS. Resumed Report 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.

Linfoma B primario cutáneo difuso de células grandes / Primary diffuse large B-cell lymphoma of the skin

Los linfomas B primarios cutáneos difusos de células grandes corresponden al 6% de los linfomas cutáneos, presentan un comportamiento agresivo y un pronóstico intermedio. La variante de las piernas es la más frecuente. Se presenta generalmente en los miembros inferiores, aunque puede presentarse en otros sitios. Existe un subgrupo de linfomas B difusos de células grandes que por sus características morfológicas no pueden ser incluido en el tipo de las piernas y se los llama la variante otros. Presentamos dos casos clínicos de pacientes con diagnóstico de linfoma B cutáneo difuso de células grandes, uno variante de las piernas con localización en la cara y otro variante no especificada localizado en el antebrazo. La clínica, la histopatología y la inmunohistoquímica son fundamentales para arribar al diagnóstico correcto e iniciar de manera temprana el tratamiento correspondiente...