New concepts in EBV-associated B, T, and NK cell lymphoproliferative disorders.

EBV-associated lymphoproliferative disorders (LPD) include conditions of B, T, and NK cell derivation with a wide clinicopathological spectrum ranging from indolent, self-limiting, and localized conditions to highly aggressive lymphomas. Since the 2016 World Health Organization (WHO) lymphoma classification, progress has been made in understanding the biology of the EBV-associated LPDs. The diagnostic criteria of EBV+ mucocutaneous ulcer and lymphomatoid granulomatosis have been refined, and a new category of EBV-positive polymorphic B cell LPD was introduced to encompass the full spectrum of EBV-driven B cell disorders. The differential diagnosis of these conditions is challenging. This report will present criteria to assist the pathologist in diagnosis. Within the group of EBV-associated T and NK cell lymphomas, a new provisional entity is recognized, namely, primary nodal EBV+ T or NK cell lymphoma. The EBV + T and NK cell LPDs in children have undergone major revisions. In contrast to the 2016 WHO classification, now four major distinct groups are recognized: hydroa vacciniforme (HV) LPD, severe mosquito bite allergy, chronic active EBV (CAEBV) disease, and systemic EBV-positive T cell lymphoma of childhood. Two forms of HV LPD are recognized: the classic and the systemic forms with different epidemiology, clinical presentation, and prognosis. The subclassification of PTLD, not all of which are EBV-positive, remains unaltered from the 2016 WHO classification. This review article summarizes the conclusions and the recommendations of the Clinical Advisory Committee (CAC), which are summarized in the International Consensus Classification of Mature Lymphoid Neoplasms.

Apuntes actualizados sobre la neurocisticercosis

Introducción: La neurocisticercosis es una infección parasitaria prevenible, producida por los quistes larvarios de la Taenia solium (solitaria), que pueden infectar cualquier parte del cuerpo, en este caso, el cerebro, siendo la forma más grave de la enfermedad y en ocasiones puede ocasionar convulsiones e incluso llegar a ser mortal. Objetivo: Sistematizar la información acerca de esta patología. Método: Se realizó una búsqueda bibliográfica actualizada en bases de datos como PubMed, Google Scholar, Medline, Web of Science, Cochrane Library y ClinicalKey, así como en revistas de alto impacto en SciELO, Scopus, complementada la información con revisiones sistemáticas, estudios clínicos aleatorizados y enfoques de metaanálisis, en los cuales se indagaron palabras claves para facilitar la búsqueda como: "Neurocisticercosis", "Fisiopatología", "etiología", "manifestaciones clínicas", "prevalencia", "morbimortalidad", "diagnostico", "tratamiento". Desarrollo: La investigación permitió reconocer el arduo trabajo que se precisa en el diagnóstico de esta enfermedad, debido a la dificultad que requiere su tipificación Se destacó la importancia de los estudios de neuroimagen como herramientas para calificar la gravedad de la neurocisticercosis y, de esta manera, escoger el tratamiento adecuado. Se desarrollaron acápites de: epidemiología, etiopatogenia, ciclo de vida, manifestaciones clínicas, clasificación, estadio evolutivo de las lesiones, diagnóstico, criterios diagnósticos, y tratamiento. Conclusiones: Ecuador es considerado como un país endémico para la Taenia solium. Implementar la prevención debe ser un pilar fundamental del ministerio de salud debido a la persistencia de los factores de riesgo para la infección de este parásito y el conjunto de aspectos asociados a la precaria calidad de vida en muchos sitios del país.

Introduction: Neurocysticercosis is a preventable parasitic infection caused by larval cysts of Taenia solium (tapeworm), which can infect any part of the body, including the brain and is the most severe form of the disease, sometimes lead to seizures and even be fatal. Objective: To synthesize information concerning this pathology. Method: An updated bibliographic search was carried out in databases such as PubMed, Google Scholar, Medline, Web of Science, Cochrane Library and ClinicalKey, as well as in high impact journals like SciELO, and Scopus. The information gathered was complemented with the use of systematic reviews, randomized clinical studies and meta-analysis approaches, in which to facilitate the search process various key words were used: "neurocysticercosis", "pathophysiology", "etiology", "clinical manifestations", "prevalence", "morbimortality", "diagnosis", and "treatment". Development: The research allowed the researchers to recognize the arduous work required for the diagnosis of this disease, assuming as well how difficult is to typify it. The importance of neuroimaging studies as tools to qualify the severity of neurocysticercosis and, thus, to choose the appropriate treatment was highlighted. The following sections were developed: epidemiology, etiopathogenesis, life cycle, clinical manifestations, classification, and evolution of lesions, diagnosis, diagnostic criteria, and treatment. Conclusions: Ecuador is considered an endemic country for Taeniasolium. The implementation of preventive actions should be regarded as a fundamental task of the Ministry of Health due to the permanent surrounding risk factors, which have an influence for getting infection and the set of aspects associated with the precarious quality of life in many parts of the country.

Introdução: A neurocisticercose é uma infecção parasitária evitável, produzida pelos cistos larvais da Taenia solium (tênia solium), que pode infectar qualquer parte do corpo, neste caso, o cérebro, sendo a forma mais grave da doença, podendo por vezes causar convulsões e podem até ser fatais. Objetivo: Sistematizar as informações sobre esta patologia. Método: Foi realizada busca bibliográfica atualizada em bases de dados como PubMed, Google Scholar, Medline, Web of Science, Cochrane Library e ClinicalKey, bem como em revistas de alto impacto no SciELO, Scopus, complementando as informações com revisões sistemáticas, análises clínicas estudos randomizados e abordagens de meta-análise, em que foram investigadas palavras-chave para facilitar a busca como: "Neurocisticercose", "Fisiopatologia", "etiologia", "manifestações clínicas", "prevalência", "morbidade e mortalidade", "diagnóstico" , "tratamento". Desenvolvimento: A pesquisa permitiu reconhecer o árduo trabalho que é exigido no diagnóstico desta doença, pela dificuldade que a sua tipificação exige, destacou-se a importância dos estudos de neuroimagem como ferramentas para qualificar a gravidade da neurocisticercose e, neste maneira, escolher o tratamento adequado. Foram desenvolvidas seções sobre: epidemiologia, etiopatogenia, ciclo de vida, manifestações clínicas, classificação, estágio evolutivo das lesões, diagnóstico, critérios diagnósticos e tratamento. Conclusões: O Equador é considerado um país endêmico para Taenia solium. A implementação da prevenção deve ser um pilar fundamental do Ministério da Saúde devido à persistência de fatores de risco para infecção por este parasita e ao conjunto de aspectos associados à precária qualidade de vida em muitas partes do país.

GATA-3 is a proto-oncogene in T-cell lymphoproliferative neoplasms.

Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.

Notch Signaling Promotes Mature T-Cell Lymphomagenesis.

Peripheral T-cell lymphomas (PTCL) are agressive lymphomas that develop from mature T cells. The most common PTCLs are genetically, molecularly, and clinically diverse and are generally associated with dismal outcomes. While Notch signaling plays a critically important role in both the development of immature T cells and their malignant transformation, its role in PTCL is poorly understood, despite the increasingly appreciated function of Notch in regulating the proliferation and differentiation of mature T cells. Here, we demonstrate that Notch receptors and their Delta-like family ligands (DLL1/DLL4) play a pathogenic role in PTCL. Notch1 activation was observed in common PTCL subtypes, including PTCL-not otherwise specified (NOS). In a large cohort of PTCL-NOS biopsies, Notch1 activation was significantly associated with surrogate markers of proliferation. Complementary genetically engineered mouse models and spontaneous PTCL models were used to functionally examine the role of Notch signaling, and Notch1/Notch2 blockade and pan-Notch blockade using dominant-negative MAML significantly impaired the proliferation of malignant T cells and PTCL progression in these models. Treatment with DLL1/DLL4 blocking antibodies established that Notch signaling is ligand-dependent. Together, these findings reveal a role for ligand-dependent Notch signaling in driving peripheral T-cell lymphomagenesis. SIGNIFICANCE: This work demonstrates that ligand-dependent Notch activation promotes the growth and proliferation of mature T-cell lymphomas, providing new therapeutic strategies for this group of aggressive lymphomas.

Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice.

PURPOSE: Peripheral T-cell lymphoma (PTCL) includes heterogeneous clinicopathologic entities with numerous diagnostic and treatment challenges. We previously defined robust transcriptomic signatures that distinguish common PTCL entities and identified two novel biologic and prognostic PTCL-not otherwise specified subtypes (PTCL-TBX21 and PTCL-GATA3). We aimed to consolidate a gene expression-based subclassification using formalin-fixed, paraffin-embedded (FFPE) tissues to improve the accuracy and precision in PTCL diagnosis. MATERIALS AND METHODS: We assembled a well-characterized PTCL training cohort (n = 105) with gene expression profiling data to derive a diagnostic signature using fresh-frozen tissue on the HG-U133plus2.0 platform (Affymetrix, Inc, Santa Clara, CA) subsequently validated using matched FFPE tissues in a digital gene expression profiling platform (nCounter, NanoString Technologies, Inc, Seattle, WA). Statistical filtering approaches were applied to refine the transcriptomic signatures and then validated in another PTCL cohort (n = 140) with rigorous pathology review and ancillary assays. RESULTS: In the training cohort, the refined transcriptomic classifier in FFPE tissues showed high sensitivity (> 80%), specificity (> 95%), and accuracy (> 94%) for PTCL subclassification compared with the fresh-frozen-derived diagnostic model and showed high reproducibility between three independent laboratories. In the validation cohort, the transcriptional classifier matched the pathology diagnosis rendered by three expert hematopathologists in 85% (n = 119) of the cases, showed borderline association with the molecular signatures in 6% (n = 8), and disagreed in 8% (n = 11). The classifier improved the pathology diagnosis in two cases, validated by clinical findings. Of the 11 cases with disagreements, four had a molecular classification that may provide an improvement over pathology diagnosis on the basis of overall transcriptomic and morphological features. The molecular subclassification provided a comprehensive molecular characterization of PTCL subtypes, including viral etiologic factors and translocation partners. CONCLUSION: We developed a novel transcriptomic approach for PTCL subclassification that facilitates translation into clinical practice with higher precision and uniformity than conventional pathology diagnosis.

The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee.

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.

Identification and Targeting of the Developmental Blockade in Extranodal Natural Killer/T-cell Lymphoma.

Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive, rare lymphoma of natural killer (NK) cell origin with poor clinical outcomes. Here we used phenotypic and molecular profiling, including epigenetic analyses, to investigate how ENKTL ontogeny relates to normal NK-cell development. We demonstrate that neoplastic NK cells are stably, but reversibly, arrested at earlier stages of NK-cell maturation. Genes downregulated in the most epigenetic immature tumors were associated with polycomb silencing along with genomic gain and overexpression of EZH2. ENKTL cells exhibited genome-wide DNA hypermethylation. Tumor-specific DNA methylation gains were associated with polycomb-marked regions, involving extensive gene silencing and loss of transcription factor binding. To investigate therapeutic targeting, we treated novel patient-derived xenograft (PDX) models of ENKTL with the DNA hypomethylating agent, 5-azacytidine. Treatment led to reexpression of NK-cell developmental genes, phenotypic NK-cell differentiation, and prolongation of survival. These studies lay the foundation for epigenetic-directed therapy in ENKTL. SIGNIFICANCE: Through epigenetic and transcriptomic analyses of ENKTL, a rare, aggressive malignancy, along with normal NK-cell developmental intermediates, we identified that extreme DNA hypermethylation targets genes required for NK-cell development. Disrupting this epigenetic blockade in novel PDX models led to ENKTL differentiation and improved survival. This article is highlighted in the In This Issue feature, p. 85.

Estudio clínico citológico de pacientes con ascitis en un hospital nacional general del Perú

Objetivo. Evaluar la sensibilidad, especifcidad y valores predictivos del estudio clínico citológico de pacientes con ascitis en un hospital nacional general del Perú. Métodos. Se incluyeron pacientes que presentaron manifestaciones clínicas de ascitis, estudios bioquímicos, citológicos e histológicos. Resultados. Se estudiaron 15 pacientes con ascitis. La media de la edad fue 62 años, siendo 80 % mujeres y 20 % varones. Los diagnósticos finales revelaron diversas neoplasias malignas (93,3 %) y tuberculosis peritoneal (6,7 %). La manifestación clínica más frecuente fue dolor abdominal de grado leve a severo (80 %). Los componentes celulares fueron: hematíes (73,3 %), histiocitos (26,7 %), linfocitos (73,3 %), polimorfonucleares (40 %), células mesoteliales (86,7 %) y grupos de células epitelioides con diverso grado de atipia (80 %). Dos casos mostraron células linfoides atípicas. La sensibilidad y el valor predictivo positivo fueron del 87 % y 80 %, respectivamente. Conclusiones. De acuerdo con una prueba dicotómica, el presente estudio demuestra la alta sensibilidad y alto valor predictivo positivo del estudio clínico citológico en pacientes con ascitis.

Gestión integrada para la prevención y control del dengue y otras arbovirosis en la Municipalidad de Ambato / Integrated management for the prevention and control of dengue and other arboviruses in the Municipality of Ambato

Las arbovirosis por Dengue (VD), Zika (VZIK) y Chikungunya (VCHIK), transmitidas por vectores del género Aedes, tienen alta prevalencia en países tropicales, especialmente en Ecuador donde se les considera problemas de salud pública. Se realizó un estudio descriptivo para identificar el nivel de cumplimiento de la estrategia de gestión integrada (EGI) para prevención y control de VD y otros arbovirus en Ambato, Tungurahua - Ecuador. Se realizó perfil comunitario a partir de fuentes oficiales y secundarias, se evaluó componentes del ambiente mediante lista de verificación y se evaluó cumplimiento de EGI mediante encuesta al personal del sector salud. Datos consultados señalan que en la provincia existe 36% y 10% de pobreza y pobreza extrema, respectivamente; además adecuado servicio de agua potable, recepción de agua por tubería, gestión de residuos sólidos y servicio de electricidad en ambas zonas, urbana y rural. Se constató que más del 50% de la población rural presenta condiciones óptimas de salud ambiental: aire limpio (90,28%) y agua potable (66,94%); en la población urbana destaca higiene de alimentos (63,89%) y microambiente doméstico (69,44%), con deficiencia en recolección de residuos sólidos (33,89%). La EGI tuvo un nivel de cumplimiento de 100% en parroquias urbanas en componentes laboratorio, atención al paciente, promoción y comunicación, mientras que en parroquias rurales, salud ambiental tuvo 63% e investigación y capacitación menor nivel (47,78%); siendo necesario mejorar sistemas de desechos sólidos en la población urbana y promover el conocimiento y capacitación epidemiológica en la rural, para reducir el riesgo de transmisión por arbovirus(AU)

Dengue (DV), Zika (ZIKV) and Chikungunya (CHIKV) arboviruses, transmitted by vectors of the Aedes genus, have a high prevalence in tropical countries, especially in Ecuador where they are considered public health problems. A descriptive study was carried out to identify the level of compliance with the integrated management strategy (EGI) for prevention and control of DV and other arboviruses in Ambato, Tungurahua - Ecuador. A community profile was made from official and secondary sources, components of the environment were evaluated by means of a checklist and compliance with EGI was evaluated by means of a survey of health sector personnel. Consulted data indicate that in the province there is 36% and 10% of poverty and extreme poverty, respectively; In addition, adequate drinking water service, receiving water through pipes, solid waste management and electricity service in both urban and rural areas. It was found that more than 50% of the rural population presents optimal environmental health conditions: clean air (90.28%) and drinking water (66.94%); In the urban population, food hygiene (63.89%) and domestic microenvironment (69.44%) stand out, with a deficiency in solid waste collection (33.89%). The EGI had a compliance level of 100% in urban parishes in laboratory, patient care, promotion and communication components, while in rural parishes, environmental health had 63% and research and training lower level (47.78%); being necessary to improve solid waste systems in the urban population and promote epidemiological knowledge and training in rural areas, to reduce the risk of transmission by arbovirus(AU)

Manejo de neoplasias oncohematológicas en el contexto de la pandemia de COVID-19: recomendación de expertos / Management of oncohematological neoplasms in the COVID-19 pandemic: experts recommendation

RESUMEN La pandemia por COVID-19 originado por el Coronavirus 2 causante de síndrome respiratorio agudo severo (SARS-CoV-2) es causante de una crisis de salud pública a nivel global. Muchos reportes indican resultados desalentadores en pacientes con cáncer respecto a la población general. Por ello, los expertos en el manejo de neoplasias oncohematológicas del Instituto Nacional de Enfermedades Neoplásicas, hospitales nacionales y una clínica privada de Lima Metropolitana han desarrollado recomendaciones obtenidas por consenso para continuar con el manejo de pacientes con neoplasias oncohematológicas en forma segura ante la coyuntura de pandemia.

ABSTRACT The ongoing COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global public health crisis. Many reports indicate disappointing results in cancer patients compared to the general population. Therefore, experts in the management of oncohematological malignancies from the National Institute of Neoplastic Diseases, national hospitals and a private clinic in Metropolitan Lima have developed recommendations obtained by consensus to continue with the management of patients with oncohematological neoplasms safely in the face of the pandemic.

Epidemiology of thymic epithelial tumors: 22-years experience from a single-institution.

BACKGROUND: To assess the correlation of WHO histological classification and Masaoka-Koga staging system of thymic epithelial tumors (TETs) with prognosis. METHODS: We retrospectively analyzed 83 patients with TETs in the Instituto Nacional de Enfermedades Neoplasicas between 1996 to 2018. We analyzed the clinical stages, histological types and treatment modalities and attempted to determine the impact on overall survival. The data was retrieved from clinical files and reviewed by a pathologist who reclassificated according to the 2004 WHO classification system. The staging was performed with the Masaoka-Koga staging system. Survival curves were constructed with Kaplan-Meir method. RESULTS: There was a total of 83 patients with a median age of 55 years old included in the study. The histological type corresponded to thymoma (T) in 63.8% (n = 53) and to thymic carcinoma (TC) in 36.1%. T were type A, AB, B1, B2 and B3 in 14.4%, 18%, 12%, 3.6%, 7.4% of cases, respectively. The proportion of advanced disease (Masaoka stage III-IV) was high (65%). With a median follow-up of 88.4 months, median overall survival (OS) was 81.6 months for T and 12.3 months for TC (P = 0.01). Univariate analysis showed that sex, histological type, clinical stage and surgery (P = 0.01) were significant independent prognostic factors. On multivariate analysis, histology type and Masaoka-Koga staging had an effect on survival. CONCLUSIONS: The results indicates a clear association between the WHO histological classification and Masaoka-Koga staging system with survival. We found a higher proportion of TETs with advanced disease at diagnosis. Further research are required and collaboration is important to foster knowledge focused on classification and treatment. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: The WHO histological classification, the Masaoka-Koga system and surgery treatment were associated with overall survival. WHAT THIS STUDY ADDS: To determine prognosis factors in TETs.

Lymphotropic Viruses EBV, KSHV and HTLV in Latin America: Epidemiology and Associated Malignancies. A Literature-Based Study by the RIAL-CYTED.

The Epstein-Barr virus (EBV), Kaposi sarcoma herpesvirus (KSHV) and human T-lymphotropic virus (HTLV-1) are lymphomagenic viruses with region-specific induced morbidity. The RIAL-CYTED aims to increase the knowledge of lymphoma in Latin America (LA), and, as such, we systematically analyzed the literature to better understand our risk for virus-induced lymphoma. We observed that high endemicity regions for certain lymphomas, e.g., Mexico and Peru, have a high incidence of EBV-positive lymphomas of T/NK cell origin. Peru also carries the highest frequency of EBV-positive classical Hodgkin lymphoma (HL) and EBV-positive diffuse large B cell lymphoma, not otherwise specified (NOS), than any other LA country. Adult T cell lymphoma is endemic to the North of Brazil and Chile. While only few cases of KSHV-positive lymphomas were found, in spite of the close correlation of Kaposi sarcoma and the prevalence of pathogenic types of KSHV. Both EBV-associated HL and Burkitt lymphoma mainly affect young children, unlike in developed countries, in which adolescents and young adults are the most affected, correlating with an early EBV seroconversion for LA population despite of lack of infectious mononucleosis symptoms. High endemicity of KSHV and HTLV infection was observed among Amerindian populations, with differences between Amazonian and Andean populations.

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.

Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy.

AIM: To determine influence of neoadjuvant-chemotherapy (NAC) over tumor-infiltrating-lymphocytes (TIL) in triple-negative-breast-cancer (TNBC). METHODS: TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays (TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS: Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response (pCR) (P = 0.0251) and outcome (P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections (ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. Post-NAC lesions with pCR had similar TIL levels than those without pCR (P = 0.6331). NAC produced a TIL decrease in full-face sections (P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival (DFS). Higher counts of CD3 in pre-NAC samples had longer overall-survival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR. CONCLUSION: TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.

Extranodal NK/T Cell Lymphoma, Nasal Type (ENKTL-NT): An Update on Epidemiology, Clinical Presentation, and Natural History in North American and European Cases.

PURPOSE OF REVIEW: Extranodal NK/T cell lymphoma, nasal type (ENKTL-NT) is an aggressive extranodal non-Hodgkin lymphoma most commonly occurring in East Asia and Latin America but with increasing incidence in the United States. Data on epidemiology, disease presentation, and outcome for European and North American ("Western") cases are very limited. We review published landmark clinical studies on ENKTL-NT in the West and report in detail recent data, including our institutional experience. RECENT FINDINGS: We highlight key observations in its epidemiology, natural history, and trends in clinical management. In the USA, ENKTL-NT is more common among Asian Pacific Islanders (API) and Hispanics compared to non-Hispanic whites. Published studies indicate less heterogeneity in clinical presentation in Western ENKTL-NT compared to Asian patients. While there is variation in age at diagnosis, presence of antecedent lymphoproliferative disorders, and outcomes among racial/ethnic groups, the universal association of ENKTL-NT with EBV and the poor response of this neoplasm to anthracycline-based therapy is consistent across all geographic areas. Data on epidemiology, disease presentation, and clinical outcomes in mature T cell and NK cell (T/NK cell) neoplasms, including ENKTL-NT, in Europe and North America are very limited. As the classification and diagnostic characterization of the currently recognized T/NK cell lymphoma disease entities continue to evolve, gaps and inconsistencies in data reporting across different studies are being recognized. Despite these limitations, several studies from the USA suggest that the incidence of ENKTL-NT is higher in Asian Pacific Islanders (API) and non-white Hispanics and that outcomes may be worse in non-whites. However, the universal association of ENKTL-NT with Epstein-Barr virus (EBV) across all ethnic groups suggests a common pathogenesis. Given the overlap between the entities included in the category of T/NK cell neoplasms, there is a need to further define biological and clinical differences that may affect diagnosis, treatment, and outcome.

[Eccrine Porocarcinoma: clinical-pathological study of 19 cases in the Instituto Nacional de Enfermedades Neoplásicas, Lima - Peru]. / Porocarcinoma ecrino: estudio clínico-patológico de 19 casos en el Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú

In order to describe the clinical-pathological characteristics of the cases of Eccrine Porocarcinoma (EP) found in the Instituto Nacional de Enfermedades Neoplásicas (INEN), a cross-sectional study was carried out, including all EP cases recorded between 1998 and 2009. A revision of the clinical-pathological records indentified and a new reading of the pathology slides of the cases found were performed. 19 EP cases were found, the median age of which was 64 years (range: 37-98). EP was primarily found on male patients (57.9%) and was most commonly located on the foot (21.1%), followed by the head, thorax and thigh (15.8%, respectively). In one case, EP was located on the gluteal region, and showed an unusually invasive behavior and rectal involvement. We conclude that EP is a rather uncommon entity in Peru. Its most common location is on the foot and it affects mostly male patients for the most part.

Porocarcinoma ecrino: estudio clínico-patológico de 19 casos en el instituto nacional de enfermedades neoplásicas, Lima - Perú / Eccrine porocarcinoma: clinical-pathological study of 19 cases in the instituto nacional de enfermedades neoplásicas, Lima - Peru

Con el objetivo de describir las características clínico-patológicas de los casos de porocarcinoma ecrino (PE) registrados en el Instituto Nacional de Enfermedades Neoplásicas (INEN), se realizó un estudio trasversal que incluyó todos los casos entre 1998-2009. Para ello se realizó una revisión de fichas clínico-patológicas y una nueva lectura de las láminas de patología de los casos encontrados. Se hallaron 19 casos de PE; la mediana de edad fue de 64 años (rango: 37-98); con mayor frecuencia en el sexo masculino (57,9%); la localización más frecuente fue en el pie (21,1%), seguida de cabeza, tórax y muslo (15,8%, en todos los casos). Se describe un caso de localización glútea que cursó con una conducta inusualmente invasiva y con compromiso rectal. Se concluye que el PE es una entidad poco frecuente en el Perú, su localización más común es en el pie, y afecta predominantemente al sexo masculino.

In order to describe the clinical-pathological characteristics of the cases of Eccrine Porocarcinoma (EP) found in the Instituto Nacional de Enfermedades Neoplásicas (INEN), a cross-sectional study was carried out, including all EP cases recorded between 1998 and 2009. A revision of the clinical-pathological records indentified and a new reading of the pathology slides of the cases found were performed. 19 EP cases were found, the median age of which was 64 years (range: 37-98). EP was primarily found on male patients (57.9%) and was most commonly located on the foot (21.1%), followed by the head, thorax and thigh (15.8%, respectively). In one case, EP was located on the gluteal region, and showed an unusually invasive behavior and rectal involvement. We conclude that EP is a rather uncommon entity in Peru. Its most common location is on the foot and it affects mostly male patients for the most part.

Oligodendroglioma anaplásico primario de la médula espinal / Primary anaplastic oligodendroglioma of the spinal cord

El oligodendroglioma de la médula espinal es una neoplasia extremadamente rara y solo se han reportado 52 casos en la literatura. Se reporta el caso de un paciente varón de 52 años, con paraplejia y un tumor en la medula espinal a nivel de C7 a T4. El diagnóstico final fue oligodendroglioma anaplásico con deleción del cromosoma 1p.

Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been reported at this time. We report the case of a 52 year-old man with paraplegia and an intramedullary tumor of the spinal cord at levels C7 to T4. The final diagnosis was anaplastic oligodendroglioma with an isolated chromosome 1p deletion.

Sarcoma granulocítico de primario de útero / granulocytic sarcoma Primary of the uterus

El sarcoma granulicítico primario ginecológico es una rara neoplasia maligna de difícil diagnóstico. En este reporte describimos el caso de una mujer de 27 años con sarcoma granulosítico en ausencia de enfermedad hematológica demostrable. Asimismo, se presenta una revisión de la literatura concerniente al diagnóstico de esta enfermedad.

Primary gynecologic granulocytic sarcoma is a rare malignancy with a complex diagnosis. In this report we describe the case of a 27- year –old woman with granulocytic sarcoma in the absence of demonstrable hematologic disease. A review of the literature is also presented, regarding the diagnosis of this diseases.