Experience with the BIOMED-2 standardized polymerase chain reaction protocol for immunoglobulin and T- cell receptor clonality analysis in the Instituto Nacional de Cancerología, Colombia / Experiencia en el uso de protocolos Biomed-2 para el estudio de reordenamientos de TCR e inmunoglobulinas en proliferaciones linfoides en el Instituto Nacional de Cancerología, Colombia

Introduction: The European BIOMED-2 consortium was created to evaluate clonality in lymphoproliferations that are difficult to diagnose. In Colombia, the implementation of these tests began in 2015 at the Instituto Nacional de Cancerología E.S.E., Bogotá. Objectives: To determine the behavior of the rearrangement tests for lymphoid clonality and the difficulties of its implementation in our field through a series of retrospective and consecutive cases of lymphoid proliferation subjected to the BIOMED-2 protocols. Materials and methods: Clinical and histological data and the results of the rearrangement analysis of all cases of lymphoid proliferation subjected to the BIOMED-2 protocols between February 2015 and May 2019 were collected from clinical histories. Results: We recovered 132 samples from which 47 corresponded to reactive lymphoid hyperplasias, 62 to T lymphomas, 19 to B lymphomas, and three to lymphoid neoplasms of unestablished lineage. Only in one case did DNA extraction fail. According to these results, the greatest diagnostic difficulty for the pathologist was the analysis of T lymphoid infiltrates, most of which (44) were skin lesions. Conclusions: Clonality tests can be used in tissues of different quality to help in the diagnosis of lymphoid proliferations that are difficult to classify. It is important to implement and interpret them in an interdisciplinary way considering each case separately.

Introducción. El consorcio europeo BIOMED-2 se creó para determinar si una población linfoide de difícil clasificación patológica es clonal. En Colombia, la implementación de estas pruebas comenzó en el 2015 en el Instituto Nacional de Cancerología E.S.E. (Bogotá). Objetivos. Determinar el comportamiento de las pruebas de reordenamiento clonal o clonalidad linfoide. y determinar las dificultades de su uso en nuestro medio verificando su adaptación local y los resultados en una serie retrospectiva de casos y consecutiva de proliferaciones linfoides sometidas a los protocolos BIOMED-2. Materiales y métodos. A partir de las historias clínicas, se recolectaron los datos clínicos e histológicos y los resultados de los análisis de los reordenamientos en todos los casos de proliferaciones linfoides sometidas a los protocolos BIOMED-2, entre febrero de 2015 y mayo de 2019. Resultados. Se hallaron 132 casos, de los cuales 47 se clasificaron mediante los protocolos de Biomed-2 como hiperplasias linfoides reactivas, 62 como linfomas T, 19 como linfomas B y 3 como neoplasias linfoides de linaje no establecido. Solo en un caso falló la extracción de ADN. Según estos resultados, la mayor dificultad diagnóstica para el patólogo fue el análisis de los infiltrados linfoides T, la mayoría (44) de los cuales correspondía a lesiones cutáneas. Conclusiones. Las pruebas de clonalidad pueden usarse en tejidos de diversa calidad en nuestro medio como ayuda en el diagnóstico de proliferaciones linfoides de difícil clasificación. Es importante hacerlas e interpretarlas de manera multidisciplinaria y considerar cada caso por separado.

Angiosarcoma óseo en el humero de un paciente pediátrico, un reto diagnóstico: reporte de caso / Bone angiosarcoma in the humerus of a pediatric patient, a whole diagnostic challenge: Case report

Resumen El angiosarcoma óseo es una neoplasia maligna rara, agresiva y de mal pronóstico, que es inusual en niños. Esta entidad afecta preferentemente a los huesos tubulares y se puede presentar como lesión solitaria o multicéntrica. Presentamos el caso de una niña de 7 años, sin antecedentes médico quirúrgicos, quien consultó al Instituto Nacional de Cancerología - Colombia, por presentar una lesión tumoral que comprometía la totalidad del húmero, destruyéndolo y deformando el brazo. Para orientar el diagnóstico de la lesión, se realizó un estudio histopatológico minucioso y marcadores de inmunohistoquímica, estos sugirieren una neoplasia vascular maligna. Por el extenso compromiso tumoral, la única opción terapéutica, fue la desarticulación escapulotorácica de la extremidad, seguida de manejo adyuvante con protocolo de quimioterapia. Durante los ciclos de quimioterapia, la paciente presentó lesiones metastásicas en pulmón, que fueron resecadas. En el momento, se encuentra sin lesiones tumorales y en seguimiento estricto.

Summary Angiosarcoma of the bone is a rare, aggressive and poor-prognosis malignancy, that is unusual in children. This entity preferentially affects the tubular bones, and can present as a solitary or multicentric lesion. We present the case of a 7-year-old girl, without medical surgical history, who consulted to the National Cancer Institute - Colombia, for presenting a tumor lesion that compromised the entire humerus, destroying it and deforming the arm. To guide the diagnosis of the lesion, a detailed histopathological study and immunohistochemical markers were performed, which suggested a malignant vascular neoplasm. Due to the extensive tumor involvement, the only therapeutic option was scapulothoracic disarticulation of the limb, followed by adjuvant management with a chemotherapy protocol. During the chemotherapy cycles, the patient presented metastatic lesions in the lung, which were resected. At the moment, she is without tumor lesions and under close follow-up.

Experiencia en el uso de los protocolos Biomed-2 para el estudio de reordenamientos de TCR e inmunoglobulinas en proliferaciones linfoides en el Instituto Nacional de Cancerología, Colombia / Experience with the BIOMED-2 standardized polymerase chain reaction protocol for immunoglobulin and T- cell receptor clonality analysis in the Instituto Nacional de Cancerología, Colombia

Introducción. El consorcio europeo BIOMED-2 se creó para determinar si una población linfoide de difícil clasificación patológica es clonal. En Colombia, la implementación de estas pruebas comenzó en el 2015 en el Instituto Nacional de Cancerología E.S.E. (Bogotá). Objetivos. Determinar el comportamiento de las pruebas de reordenamiento clonal o clonalidad linfoide. y determinar las dificultades de su uso en nuestro medio verificando su adaptación local y los resultados en una serie retrospectiva de casos y consecutiva de proliferaciones linfoides sometidas a los protocolos BIOMED-2. Materiales y métodos. A partir de las historias clínicas, se recolectaron los datos clínicos e histológicos y los resultados de los análisis de los reordenamientos en todos los casos de proliferaciones linfoides sometidas a los protocolos BIOMED-2, entre febrero de 2015 y mayo de 2019. Resultados. Se hallaron 132 casos, de los cuales 47 se clasificaron mediante los protocolos de Biomed-2 como hiperplasias linfoides reactivas, 62 como linfomas T, 19 como linfomas B y 3 como neoplasias linfoides de linaje no establecido. Solo en un caso falló la extracción de ADN. Según estos resultados, la mayor dificultad diagnóstica para el patólogo fue el análisis de los infiltrados linfoides T, la mayoría (44) de los cuales correspondía a lesiones cutáneas. Conclusiones. Las pruebas de clonalidad pueden usarse en tejidos de diversa calidad en nuestro medio como ayuda en el diagnóstico de proliferaciones linfoides de difícil clasificación. Es importante hacerlas e interpretarlas de manera multidisciplinaria y considerar cada caso por separado.

Introduction: The European BIOMED-2 consortium was created to evaluate clonality in lymphoproliferations that are difficult to diagnose. In Colombia, the implementation of these tests began in 2015 at the Instituto Nacional de Cancerología E.S.E., Bogotá. Objectives: To determine the behavior of the rearrangement tests for lymphoid clonality and the difficulties of its implementation in our field through a series of retrospective and consecutive cases of lymphoid proliferation subjected to the BIOMED-2 protocols. Materials and methods: Clinical and histological data and the results of the rearrangement analysis of all cases of lymphoid proliferation subjected to the BIOMED-2 protocols between February 2015 and May 2019 were collected from clinical histories. Results: We recovered 132 samples from which 47 corresponded to reactive lymphoid hyperplasias, 62 to T lymphomas, 19 to B lymphomas, and three to lymphoid neoplasms of unestablished lineage. Only in one case did DNA extraction fail. According to these results, the greatest diagnostic difficulty for the pathologist was the analysis of T lymphoid infiltrates, most of which (44) were skin lesions. Conclusions: Clonality tests can be used in tissues of different quality to help in the diagnosis of lymphoid proliferations that are difficult to classify. It is important to implement and interpret them in an interdisciplinary way considering each case separately.

[Identification of epithelial-mesenchymal transition markers (EMT) by immunohistochemistry in pediatric osteosarcoma and association with clinical outcomes]. / Identificación de marcadores de transición epitelio-mesénquima (TEM) por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos.

The epithelial-mesenchymal transition (EMT) is the ability of epithelial and mesenchymal cells to exchange phenotypes transiently. Its identification in carcinomatous cells has been associated with aggressive clinical phenotypes. In sarcomas, this ability is under study. OBJECTIVE: to evaluate the expression of two transcription factors involved in EMT by immunohistochemistry in pediatric osteosarcoma and its association with clinical outcomes. PATIENTS AND METHOD: A retrospective cohort study in children under 18 years of age with osteosarcoma diagnosis. Immunohistochemistry was performed for Snail and Twist-1 expressions from samples collected at the time of diagnosis. Correlations between immunohistochemistry and the clinical outcomes and overall survival were performed. RESULTS: 53 patients were included. There were 26 positive cytoplasmic cases (49.1%) in Snail expression and were correlated with the presence of multiple metastases (p = 0.02) and distant bone metastases (p = 0.01). On the other hand, 45 cases (84.9%) were positive in Twist-1 expression in the nuclear location, showing no association with the analyzed clinical variables. CONCLUSIONS: Snail and Twist-1 were frequently expressed in pediatric cases of osteosarcoma. Cytoplasmic Snail was correlated with the presence of multiple metastatic disease and distant bone metastases. The positivity of both markers suggests the activation of these proteins as regulators of EMT events in this tumor, suggesting a role in the phenomena related to the clinical presentation of the disease.

Hematopoyesis Clonal de Potencial Indeterminado (HCPI): más allá de un modelo de campo de cancerización / Clonal hematopoiesis of indeterminate potential (CHIP): Beyond a model of field cancerization

Resumen La Hematopoyesis Clonal de Potencial Indeterminado (HCPI), más conocida como CHIP por sus siglas en inglés, se define como la expansión clonal de Células Madre Hematopoyéticas (CMHs) que albergan una o más mutaciones somáticas (en la mayoría de los casos una sola mutación) sin un cáncer hematológico subyacente ni evidencia morfológica definitiva de displasia, con una frecuencia alélica mayor al 2%. Los individuos con HCPI progresan a malignidad a una tasa de cerca del 0.5% a 1% por año, convirtiéndose así en un modelo de campo de cancerización. Sin embargo, sus implicaciones van más allá debido a que se ha encontrado asociación con enfermedades inflamatorias crónicas, como enfermedad cardiovascular ateroesclerótica, diabetes y enfermedades autoinmunes. Además, es considerado un factor predictivo en pacientes con cáncer hematolológico y no hematológico que reciben quimioterapia y radioterapia.

Abstract Clonal hematopoiesis of indeterminate potential (CHIP) is the expansion of hematopoietic stem cells harboring one or more somatic mutations. These patients do not have underlying hematologic neoplasia, myelodysplasia, or dysplasia, but can progress to a malignant state at a rate of 0.5 to 1% per year. CHIP could be used as a model of field cancerization, since it has been associated with chronic inflammatory diseases, arteriosclerosis, diabetes, and autoimmune conditions. CHIP is also considered a predictive factor in hematological and non-hematological cancer patients receiving chemotherapy and radiotherapy.

Clinical characteristics, surgical approach, BRAFV600E mutation and sodium iodine symporter expression in pediatric patients with thyroid carcinoma.

Objectives Thyroid cancer is the most common endocrine neoplasm in childhood. There are few studies characterizing pediatric population in Colombia. We intend to detail the clinical, histological characteristics, BRAFV600E mutational status and NIS (sodium-iodine symporter) expression of children with papillary thyroid carcinoma (PTC) managed at Hospital de La Misericordia. Methods Medical records of the Department of Pediatric Surgery and Pathology from 2009 to 2018 were scrutinized in search of cases of differentiated thyroid carcinoma. A descriptive analysis was made. Paraffin embedded tumoral tissue was recovered to assess BRAF V600E mutational status by PCR and NIS expression by immunohistochemistry. Results Sixteen patients were selected, 81.2% were girls. Average age of presentation was 11.8 years. Only one patient had previous radiation exposure. Most frequent symptom was cervical adenopathy with a mean time of 29.2 weeks before diagnosis. 93.7% underwent total thyroidectomy and lymphadenectomy. 62.5% were PTC combining both classic and follicular pattern. 6.25% cases had BRAFV600E mutation and 25% showed NIS focal reactivity. Conclusions We found greater female predominance, lower percentage of risk factors described and a high percentage of patients requiring aggressive surgical treatment. We consider important to contemplate thyroid cancer as a differential diagnosis of cervical lymph node enlargement in children. Diagnosis can be challenging in benign and indeterminate categories of the FNA cytology and biomolecular profiles such as BRAF and NIS could be determinant in guiding treatment. More studies with larger sample size, complete genetic analysis, evaluation to iodine response and long term follow up are required.

Gliomas tipo astrocytoma pilocítico "atípico recurrente" y gen B-RAF: presentación de caso clínico, discusión / Glioma type pilocytic astrocytoma "atypical recurrent" and gen BRAF: Clinical case presentation, discussion

RESUMEN El astrocitoma pilocítico (AP) es una neoplasia bien diferenciada, grado I OMS,que predomina en la infancia y es raro en la población adulta. Se reportan casos atípicos con una biología tumoral agresiva que continúan preservando la histología benigna o se transforman hacia gliomas de alto grado. Algunos estudios genéticos en esté subtipo de tumor referencian la activación de la vía MAPK/ERK a través de cambios en el gen BRAF. El objetivo del grupo es presentar un caso clínico representativo de un AP con evolución "atípica" y realizar una revisión actualizada desde la biología, genética, las posibilidades terapéuticas emergentes y exponer las controversias del tratamiento desde lo quirúrgico y las terapias complementarias.

SUMMARY The pilocytic astrocytoma (PA), formerly referred to as juvenile pilocytic astrocytomas, are WHO grade I tumors, that commonly occur during childhood and rarely in the adult population. Genetic studies of this tumor report an activation of the MAPK / ERK pathway through changes in the BRAF gene. The aim of this article is to report a series of atypical PA cases with an aggressive tumor biology that continue preserving the benign histology or transformed into high-grade gliomas, and review the biology, genetics, and emerging therapeutic possibilities for these cases. And finally expose controversies from the surgical treatment and complementary therapies.

Proliferación linfoide indolente cutánea CD8 positiva a propósito de tres casos con compromiso facial / Indolent CD8-positive t-cell lymphoid proliferation: on purpose three cases of facial commitment

Resumen La proliferación linfoide indolente cutánea CD8 positiva es una variante recientemente descrita de linfoma T cutáneo que se caracteriza por un nódulo, pápula o placa eritematosa de crecimiento lento que puede afectar la región facial o extrafacial. En el estudio de patología se caracteriza por un infiltrado monomorfo de linfocitosTalo largo de la dermis con presencia de zona de Grenz y ausencia de epidermotropismo. El infiltrado es característicamente CD8+ así como CD3+, TIA-1+, CD4-, CD56- CD30-, PD-1-, Granzima B- y EBER negativo. El índice de proliferación Ki-67 es inferior al 10% y se observan reordenamientos clonales de los genes del receptor de antígeno de la célula T, TCR. El seguimiento clínico es favorable y no se ha observado compromiso sistémico. Se presentan tres casos con compromiso facial (dos casos en pabellón auricular y un caso con compromiso nasal), con presentación clínica y hallaz gos histopatológicos típicos (curiosamente un caso con cambio de célula clara), y además se realizaron estudios de clonalidad.

Abstract Primary cutaneous indolent CD8-positive lymphoid proliferation is a recent variant of cutaneous T lymphoma that is characterized by nodule, papule or plaque erythematous with slow growth that can affect the facial or extrafacial region. In the histopathology study it is characterized by an infiltration of monomorphic T lymphocytes throughout the dermis with presence of Grenz zone and absence of epidermotropism. The infiltrate is characteristically CD 8+ and CD3+ TIA-1+ CD4-, CD56- CD30, PD-1, Granzyme B- and negative EBER. Ki-67 Proliferación linfoide indolente cutánea CD8 positiva a propósito de tres casos proliferation index is less than 10% and clonal T-cell receptor gene rearrangements. Clinical follow-up is favorable and has not been observed systemic involvement. We present three cases with facial involvement (two cases in ear and one case with nasal commitment) with typical clinical presentation, histopathological findings (curiously a case with clear cell change) and clonality studies.

Histological variants and prognostic factors of papillary thyroid carcinoma at the Colombian Instituto Nacional de Cancerología, 2006-2012 / Variantes histológicas y factores pronósticos del carcinoma papilar de tiroides en el Instituto Nacional de Cancerología de Colombia, 2006-2012

Introduction: Thyroid cancer is the most common endocrine neoplasia and the papillary subtype is the most frequent; there are histological and clinical factors associated with a higher risk of recurrence and metastasis. Objective: The aim of this study was to examine the histological, prognostic and clinical characteristics of papillary thyroid carcinomas diagnosed at the National Cancer Institute of Colombia. Materials and methods: A retrospective cohort study was carried out on 619 patients with papillary thyroid carcinoma between 2006 and 2012; we analyzed the sociodemographic, histological, prognostic and clinical characteristics. Results: 87.7% of cases were women. The presence of two or more variants in the same case was considered a particular variant, which we called combined pattern. Combined pattern was then the most frequent (50.9%), followed by the follicular variant (23.4%) including subtypes encapsulated and unencapsulated, and the classic variant (22.1%). Mean tumor size was 20.8 mm. More than half of the cases had capsular invasion, extrathyroidal invasion and lymph node involvement. When compared with the other variants, the combined pattern carcinomas had a higher risk of invasion of the thyroid capsule, extraganglionar invasion and metastasis. Conclusions: Our results are in many aspects similar to those already reported. However, the presence of the combined pattern implied a higher risk for capsular invasion, nodal involvement, extranodal involvement and metastasis in comparison with those which had just one variant. Further studies are necessary to confirm these results.

Introducción. El cáncer de tiroides es la neoplasia más común y el subtipo papilar es el más frecuente; hay factores histológicos y clínicos asociados con un mayor riesgo de recidiva y metástasis. Objetivo. Examinar las características histológicas, clínicas y de pronóstico de los carcinomas papilares de tiroides diagnosticados en el Instituto Nacional de Cancerología de Colombia. Materiales y métodos. Se llevó a cabo un estudio de cohorte retrospectiva que incluyó a 619 pacientes con carcinoma papilar de tiroides entre 2006 y 2012; se analizaron las características sociodemográficas, histológicas, de pronóstico y clínicas. Resultados. El 87,7% de casos correspondió a mujeres. La presencia de dos o más variantes histológicas en un mismo caso se consideró como una variante a la cual se denominó patrón combinado; esta fue la más frecuente (50,9 %), seguida de la variante folicular (23,4 %), incluidos los subtipos encapsulados o no encapsulado y la variante clásica (22,1 %). El promedio del tamaño tumoral fue de 20,8 mm. En más de la mitad de los casos se evidenció invasión capsular, invasión extratiroidea y metástasis en ganglios linfáticos. Comparados con otras variantes histológicas, los carcinomas con patrón combinado presentaron mayor riesgo de invasión de la cápsula tiroidea, de invasión extraganglionar y de metástasis. Conclusión. En muchos aspectos los resultados fueron similares a los reportados previamente; sin embargo, se encontró que la presencia del patrón combinado aumentaba el riesgo de invasión capsular, metástasis en nódulos linfoides y extensión extratiroidea en comparación con los que tenían una sola variante. Sería necesario hacer estudios acerca del mecanismo biológico de la diferenciación en células cancerosas con el fin de ahondar sobre este fenómeno.

Determinación de la clonalidad en tejidos humanos / Clonality evaluation in human tissues / Determinação da clonagem em tecidos humanos

Las proliferaciones malignas suelen ser clonales. La mayoría de las veces el potencial de una lesión se establece por medio del análisis clínico y el estudio anatomopatológico, pero algunos casos son de difícil diagnóstico. Por otra parte, existen situaciones en las que se producen clonas dominantes cuyo análisis es importante, tal como ocurre en enfermedades autoinmunes e inmunodeficiencias. Este artículo presenta de manera comprensible las técnicas principales para el estudio de la clonalidad, a saber: la evaluación de los reordenamientos génicos del receptor de antígeno y la evaluación del gen del receptor de antígeno humano.

Malignant proliferations are usually clonal. While most times the biological potential can be established through routine pathologic and clinical examinations, some cases are difficult to classify. Moreover, in some situations there are dominant clones whose analysis is important, such as in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality, namely: evaluation of gene rearrangements of antigen receptor, and evaluation of human antigen receptor gene.

As proliferações malignas costumam ser clonadas. A maioria das vezes o potencial biológico de uma lesão se estabelece por meio da análise clínica e o estudo anatomopatológico, mas alguns casos são de difícil diagnóstico. Por outra parte, existem situações nas que se produzem clones dominantes cujo análise é importante, tal como ocorre em doenças autoimunes e imunodeficiências. Este artigo apresenta de maneira compreensível as técnicas principais para o estudo da clonagem, a saber: a avaliação dos reordenamentos genéticos do receptor de antígeno e a avaliação do gene do receptor de antígeno humano.

[Clonality lymphoid study through rearrangement analysis of antigen receptor]. / Estudio de la clonalidad linfoide por medio del análisis de reordenamientos del receptor de antígeno.

As a rule, malignant lymphoid proliferations are clonal. While most of the time the biological potential can be established through routine pathologic examination and auxiliary techniques, some cases are difficult to classify. Moreover, there are situations in which there are dominant clones whose analysis are important, such as occur in autoimmune diseases and immunodeficiency. This paper presents in an understandable way the main techniques for the study of clonality in lymphoid lesions, i.e. the analysis of rearrangements of antigen receptor genes by multiplex polymerase chain reaction (PCR) based tests.

Las proliferaciones linfoides malignas suelen ser clonales. La mayoría de las veces el potencial biológico de una lesión se establece por medio del análisis clínico y el estudio anatomopatológico, pero algunos casos son de difícil diagnóstico. Por otra parte, existen situaciones en las cuales se producen clones dominantes cuyo análisis es importante, tal como ocurre en enfermedades autoinmunes e inmunodeficiencias. Este artículo presenta de manera comprensible las técnicas principales para el estudio de la clonalidad en lesiones linfoides, es decir, el análisis de reordenamientos de genes del receptor de antígeno por medio de pruebas basadas en reacción en cadena de la polimerasa (PCR) multiplex.

Histological variants and prognostic factors of papillary thyroid carcinoma at the Colombian Instituto Nacional de Cancerología, 2006-2012.

INTRODUCTION: Thyroid cancer is the most common endocrine neoplasia and the papillary subtype is the most frequent; there are histological and clinical factors associated with a higher risk of recurrence and metastasis. OBJECTIVE: The aim of this study was to examine the histological, prognostic and clinical characteristics of papillary thyroid carcinomas diagnosed at the National Cancer Institute of Colombia. MATERIALS AND METHODS: A retrospective cohort study was carried out on 619 patients with papillary thyroid carcinoma between 2006 and 2012; we analyzed the sociodemographic, histological, prognostic and clinical characteristics. RESULTS: 87.7% of cases were women. The presence of two or more variants in the same case was considered a particular variant, which we called combined pattern. Combined pattern was then the most frequent (50.9%), followed by the follicular variant (23.4%) including subtypes encapsulated and unencapsulated, and the classic variant (22.1%). Mean tumor size was 20.8 mm. More than half of the cases had capsular invasion, extrathyroidal invasion and lymph node involvement. When compared with the other variants, the combined pattern carcinomas had a higher risk of invasion of the thyroid capsule, extraganglionar invasion and metastasis. CONCLUSIONS: Our results are in many aspects similar to those already reported. However, the presence of the combined pattern implied a higher risk for capsular invasion, nodal involvement, extranodal involvement and metastasis in comparison with those which had just one variant. Further studies are necessary to confirm these results.

Desenlaces del manejo no quirúrgico posterior a neoadyuvancia del cáncer localmente avanzado de recto / Outcomes of the nonsurgical management of locally advanced rectal cancer after neoadjuvant treatment / Outcomesofthenon-surgicalmanagementoflocallyadvancedrectalcancerafterneoadjuvanttreatment

Objetivos: Describir características clínicas, histopatológicas y desenlaces de pacientes con cáncer localmente avanzado de recto y respuesta clínica completa posterior a la neoadyuvancia, sin manejo quirúrgico. Métodos: Estudio de cohorte retrospectiva de pacientes con cáncer de recto estadios II y III, llevados a quimiorradiación, en seguimiento clínico. Se evaluó supervivencia libre de enfermedad, global y tasa de recaída. Se describen características biológicas (Kras, Ki67, p53) y morfológicas del tumor (grado, invasión linfovascular y perineural). Resultados: Entre enero de 2003 y junio de 2013, 19 pacientes con cáncer localmente avanzado de recto y respuesta clínica completa postneoadyuvancia, no aceptaron el tratamiento quirúrgico radical. Con mediana de seguimiento de 21 meses (4-92 meses), se presentaron recaídas del: 21% en el primer año, 36% a los 3 años y 42% a los 5 años (total: 8 pacientes). Se presentó recaída local en 50% de casos, regional en 50% y no hubo recaída sistémica. La tasa estimada de recaída local fue 2,3 recaídas por 100 pacientes/mes (IC 95%:1,21-4,5) y de recaída regional 1,3 recaídas por 100 pacientes/mes (IC 95%:0,5-3,1). No se estableció relación, entre la expresión de factores biológicos del tumor primario y los desenlaces. Conclusiones: Se ratifica la indicación del tratamiento quirúrgico radical, posterior a la neoadyuvancia, en todos los pacientes con cáncer localmente avanzado de recto. Las bajas tasas de recaída local y regional de nuestra serie, sugieren la posibilidad de resección local u observación, en casos seleccionados. La individualización y deseo del paciente, debe orientar la toma de decisiones.

Objectives: To describe the clinical and histopathological characteristics and outcomes of patient with non-surgically managed locally advanced rectal cancer and a complete clinical response to neoadjuvant treatment. Methods: A retrospective study was conducted on a cohort of patients with stages II and III rectal cancer, on clinical follow up after subjected to chemoradiotherapy. The overall disease free survival and recurrence rates were evaluated. The biological (Kras, Ki67, p53) and morphological (grade, lymphovascular and perineural invasion) characteristics of the tumor were recorded. Results: Between January 2003 and June 2013, a total of 19 patients with locally advanced rectal cancer and a complete clinical response after neoadjuvant treatment, did not accept radical surgical treatment. With a median follow-up of 21 months (range 4-92 months), the recurrences were: 21% in the first year, 36% at 3 years, and 42% at 5 years (total: 8 patients). There was local recurrence in 50% of the cases, regional in 50%, and there were no systemic recurrences. The estimated local recurrence rate was 2.3 recurrences per 100 patients/month (95% CI; 1.21 - 4.5), and a regional recurrence of 1.3 recurrences per 100 patients/month (95% CI: 0.5 - 3.1). No relationship was found between the expression of biological factors of the primary tumor and the outcomes. Conclusions: The indication for radical surgical treatment after neoadjuvant treatment is demonstrated in all patients with locally advanced rectal cancer. The low local and regional recurrence rates of this series suggest the possibility of local resection or observation in selected cases. Individualization and the wishes of the patient must be taken into account when making decisions.

Location and Density of Immune Cells in Precursor Lesions and Cervical Cancer.

Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm(2)) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR = 4.20, 95% CI 1.2-15), CIN2 (OR = 7.86, 95% CI 1.7-36.4) and CIN1 (OR = 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.

Increased CD4+/CD8+ double-positive T cells in chronic Chagasic patients.

BACKGROUND: CD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out. METHODOLOGY/PRINCIPAL FINDINGS: Seventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1% ± 0.9) compared with healthy (1.1% ± 0.5) and non-chagasic cardiomyopathy (1.2% ± 0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor. CONCLUSIONS: Chagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.

El diagnóstico prenatal no invasor: análisis de células y ADN fetal circulantes en la sangre materna / Non invasive prenatal diagnosis: analysis of circulating fetal DNA and cells in maternal blood

El diagnóstico prenatal temprano y no invasor por medio del análisis de células o ADN fetalescirculantes en la sangre materna es un área prometedora de la obstetricia moderna. Entre lasenfermedades que se pueden diagnosticar o cuyo comportamiento es posible predecir por estosmétodos se encuentran la preeclampsia, la restricción del crecimiento intrauterino y el partopretérmino. Algunas condiciones fetales que podrían detectarse son el sexo, ciertas anomalíascromosómicas y los defectos de un solo gen. Sin embargo, estas técnicas tienen limitaciones y hastael momento no se practican de manera rutinaria. Con esta revisión pretendemos darles a loslectores información actualizada sobre las principales técnicas para el estudio de las células y elADN fetales circulantes en la sangre materna y sus aplicaciones. Para tal fin se hizo una búsqueda enrevistas indexadas hasta 2008 en las bases Pubmed, Scielo y Latindex y se escogieron, a juicio de lasautoras, artículos especialmente relevantes.

Non invasive prenatal diagnosis: analysis of circulating fetal DNA and cells in maternal bloodPrenatal non invasive diagnosis by means of analyses of foetal DNA or cells circulating in maternalblood is one of the most promising areas of obstetrics. Among maternal diseases that could bediagnosed by these methods, or whose behaviour could be predicted, are preeclampsia, growthrestriction and preterm labour. Some foetal conditions that could be detected are sex, chromosomalanomalies and single-gene defects. However, these are complex and expensive techniques that arenot regularly performed in health care institutions. With this review we intend to provide the readerswith up to date information on the main techniques available for the study of circulating foetal cellsand DNA, and on their possible clinical applications. The review was based on a search for journalsindexed up to 2008 in Pubmed, Scielo and Latindex. Especially relevant articles were chosen by theauthors.

Embarazo ectópico esplénico: reporte de caso y revisión de la literatura / Splenic ectopic pregnancy: a case report and literature review

El embarazo esplénico primario es considerado la forma más rara de embarazo extrauterino, con sólo pocos casos bien documentados reportados. En el presente reporte se informa un caso de embarazo esplénico en una mujer de 32 años con historia de aborto recurrente, que se presentó con cuadro de abdomen agudo y hemoperitoneo. El embarazo esplénico requiere esplenectomía de urgencia y debe ser considerado en el diagnóstico diferencial en mujeres en edad reproductiva con aborto recurrente y abdomen agudo.

Primary splenic pregnancy is considered to be the rarest form of extrauterine pregnancy, only a few well-documented cases having been reported. We report a case of splenic pregnancy in a 32-year-old woman having poor obstetric history, presenting acute abdomen and haemoperitoneum. Splenic pregnancy requires an emergency splenectomy and should be considered in the differential diagnosis of acute abdomen in reproductive-aged women, particularly if they have had recurrent abortions.

Neuroblastoma congénito metastásico. Reporte de caso / Metastasic congenital neuroblastoma. A case report

El neuroblastoma congénito es raro, pero es el tumor maligno más común en fetos y neonatos. Produce metástasis entre el 25 y el 50 por ciento de los casos. Aunque el pronóstico del neuroblastoma fetal suele ser favorable, incluso en el estadio IV, puede ocurrir muerte fetal o neonatal por hidropesía no inmune. Reportamos un caso de un feto con un neuroblastoma congénito con múltiples metástasis que murió en el útero.