ZEB1 hypermethylation is associated with better prognosis in patients with colon cancer.

BACKGROUND: Colon cancer (CC) is a heterogeneous disease that is categorized into four Consensus Molecular Subtypes (CMS) according to gene expression. Patients with loco-regional CC (stages II/III) lack prognostic factors, making it essential to analyze new molecular markers that can delineate more aggressive tumors. Aberrant methylation of genes that are essential in crucial mechanisms such as epithelial mesenchymal transition (EMT) contributes to tumor progression in CC. We evaluate the presence of hyper- and hypomethylation in subrogate IHC markers used for CMS classification (CDX2, FRMD6, HTR2B, ZEB1) of 144 stage II/III patients and CC cell lines by pyrosequencing. ZEB1 expression was also studied in control and shRNA-silenced CC cell lines and in paired normal tissue/tumors by quantitative PCR. The pattern of ZEB1 staining was also analyzed in methylated/unmethylated tumors by immunohistochemistry. RESULTS: We describe for the first time the hypermethylation of ZEB1 gene and the hypomethylation of the FRMD6 gene in 32.6% and 50.9% of tumors, respectively. Additionally, we confirm the ZEB1 re-expression by epigenetic drugs in methylated cell lines. ZEB1 hypermethylation was more frequent in CMS1 patients and, more importantly, was a good prognostic factor related to disease-free survival (p = 0.015) and overall survival (p = 0.006) in our patient series, independently of other significant clinical parameters such as patient age, stage, lymph node involvement, and blood vessel and perineural invasion. CONCLUSIONS: Aberrant methylation is present in the subrogate genes used for CMS classification. Our results are the first evidence that ZEB1 is hypermethylated in CC and that this alteration is an independent factor of good prognosis.

Cardiac Metastasis From Solid Cancers: A 35-Year Single-Center Autopsy Study.

CONTEXT.­: Cardiac metastases are more prevalent than primary cardiac tumors, and although rare, the incidence is anticipated to increase with the extended survival of oncology patients. OBJECTIVE.­: To estimate the current incidence of cardiac metastasis from solid tumors in adult autopsies. DESIGN.­: Adult autopsy cases from 1984 through 2019 from patients diagnosed with any type of solid cancer were retrieved. The medical charts and pathologic autopsy data were reviewed in detail. RESULTS.­: A total of 1294 adult autopsies performed on patients diagnosed with any type of cancer within the past 35 years were reviewed. We found 124 secondary cardiac tumors. Eighty-five were due to cardiac involvement by solid tumors. Of these, 61 were true cardiac metastases of solid cancers. We focused on these 61 cases. The age range was 32 to 85 years. Forty-four patients were men and 17 were women. The lung was the most common primary site, with 21 cases (34.43%). The most frequent histologic type was carcinoma, with 54 cases (88.52%). The predominant layer of the heart involved was the pericardium, with 35 cases (57.38%). Twenty-one cases (34.43%) had pericardial effusion, with 4 being hemorrhagic. All cases had multiple extracardiac metastases, with 56 cases (91.8%) having distant metastases in 4 or more different organs. CONCLUSIONS.­: Cardiac metastasis is a rare occurrence, with an incidence of 4.71% (61 of 1294 cases) in our series. Lung cancer accounted for most of the cardiac metastases seen, and carcinomas were the most frequent histologic type. The pericardium was the most frequent location. Cardiac metastases occurred most frequently in cases of massive metastatic dissemination.

Adenoma hipofisario ectópico asociado a silla turca vacía / Ectopic pituitary adenoma associated with empty sella turcica

El adenoma hipofisario ectópico es una entidad poco frecuente que se localiza más frecuentemente en el seno esfenoidal. Presentamos el caso de un paciente con adenoma hipofisario ectópico sin expresión funcional asociado a silla turca vacía, lo cual plantea un amplio diagnóstico diferencial. Es un tumor de naturaleza benigna a pesar de que se describe la presencia de necrosis en un porcentaje de casos. La resonancia es el método diagnóstico que permite estudiar los trastornos endocrinos relacionados con el eje hipotálamo-hipofisario y la biopsia endoscópica, su confirmación histológica. Es importante incluir marcadores hipofisarios en el panel de técnicas inmunohistoquímicas

Ectopic pituitary adenoma is a rare entity that is most commonly located in the sphenoid sinus. We report a case of a patient with ectopic pituitary adenoma with no functional expression associated with empty sella turcica, which gives rise to a broad differential diagnosis. Although it is a benign neoplasm, necrosis is encountered in a proportion of cases. Magnetic resonance imaging is the diagnostic method of choice for hypothalamic-pituitary-related endocrine diseases with endoscopic biopsy for histological confirmation. It is important to include pituitary markers in the immunohistochemical diagnostic panel

[Ectopic pituitary adenoma associated with empty sella turcica]. / Adenoma hipofisario ectópico asociado a silla turca vacía.

Ectopic pituitary adenoma is a rare entity that is most commonly located in the sphenoid sinus. We report a case of a patient with ectopic pituitary adenoma with no functional expression associated with empty sella turcica, which gives rise to a broad differential diagnosis. Although it is a benign neoplasm, necrosis is encountered in a proportion of cases. Magnetic resonance imaging is the diagnostic method of choice for hypothalamic-pituitary-related endocrine diseases with endoscopic biopsy for histological confirmation. It is important to include pituitary markers in the immunohistochemical diagnostic panel.

Nuestra experiencia en el tratamiento del PEComa hepático / Our experience in the surgical treatment of liver PEComa

No disponible

Pólipos serrados y su asociación con neoplasia avanzada de colon / Serrated polyps and their association with synchronous advanced colorectal neoplasia

INTRODUCCIÓN: Los pólipos serrados (PS) grandes, PS proximales, PS con displasia y la presencia de múltiples adenomas sésiles serrados (P/ASS), que englobamos bajo el término PS con riesgo aumentado de lesiones metacrónicas (PSRALM), se asocian a un mayor riesgo de presentar dichas lesiones, pero desconocemos si también se asocian a un mayor riesgo de neoplasia avanzada de colon (NA) sincrónica. OBJETIVO: Estimar la prevalencia de PSRALM y evaluar la asociación con NA sincrónica. MÉTODOS: Se trata de un estudio transversal de base poblacional que incluyó a todos los pacientes (1.538) con diagnostico histológico de PS de muestras procedentes de colonoscopias, rectosigmoidoscopias e intervenciones quirúrgicas de los hospitales públicos del Servicio Navarro de Salud durante el año 2011. Se analizaron parámetros demográficos y presencia de lesiones sincrónicas de colon (adenomas, adenomas avanzados [AA] y NA) RESULTADOS: La cuarta parte de los pacientes (384) presentaron PSRALM, con una edad media más avanzada, un ligero predominio en mujeres y sin diferencias en cuanto al IMC respecto a los pacientes sin PSRALM. En el análisis multivariante el grupo PSRALM presentó un mayor riesgo de AA y NA sincrónicos (OR: 2,38 [1,77-3,21] y OR: 2,29 [1,72-3,05] respectivamente) y en el caso de NA, este riesgo fue estadísticamente significativo en ambas localizaciones (proximal y distal), con OR superior para la proximal. Los distintos subtipos de PSRALM presentaron un mayor riesgo de AA y NA sincrónicos. CONCLUSIÓN: Los PSRALM fueron frecuentes entre los pacientes con PS y se asociaron a un mayor riesgo de presentar NA sincrónica

INTRODUCTION: Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). AIM: The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. METHODS: A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. RESULTS: One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. CONCLUSION: SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous CAN

[Serrated polyps and their association with synchronous advanced colorectal neoplasia]. / Pólipos serrados y su asociación con neoplasia avanzada de colon.

INTRODUCTION: Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). AIM: The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. METHODS: A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. RESULTS: One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. CONCLUSION: SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN.

Recomendaciones para el estudio patológico de las metástasis hepáticas de cáncer colorrectal tras neoadyuvancia. Consenso Nacional de la Sociedad Española de Anatomía Patológica / Recommendations for the study of liver metastases of colorectal cancer after neoadjuvant therapy. National Consensus of the Spanish Society of Pathology (SEAP)

Las resecciones hepáticas por metástasis de cáncer colorrectal (CCR) son una pieza quirúrgica frecuente en muchos servicios de anatomía patológica. Si al aumento de la incidencia de CCR añadimos otros factores como la frecuencia de metástasis hepáticas sincrónicas o metacrónicas, la ampliación en los criterios quirúrgicos de resecabilidad y el tratamiento neoadyuvante que facilita la resecabilidad, nos encontramos con una patología en aumento. El estudio anatomopatológico de estas piezas quirúrgicas se ha modificado y ha aumentado su complejidad debido a que se deben valorar nuevos datos histológicos como son los cambios potenciales producidos por el tratamiento neoadyuvante quimioterápico en el hígado no tumoral, y en el tumor el grado de regresión tumoral patológico, por su valor pronóstico. Teniendo en cuenta estos antecedentes, un grupo de patólogos se propuso revisar su papel en el diagnóstico y pronóstico de los pacientes con metástasis hepáticas de CCR con el objetivo de elaborar unas recomendaciones prácticas de procedimiento. De esta revisión se han obtenido unas directrices que podrían ser adaptadas por los distintos departamentos de patología con el fin de unificar procedimientos y obtener diagnósticos comparables. En este trabajo se exponen los resultados de este consenso (AU)

Liver resections for colorectal cancer (CRC) metastasis are common in most pathology departments. In addition, the frequency of liver resections for CRC specimens has increased due to an increased incidence of CRC the frequency of synchronous or metachronous liver metastases, the use of neoadjuvant therapy, and the increased surgical criteria of resectability. The pathological study of the specimens should include new histological data, i.e.: changes caused by therapy, both in the tumour and in the liver parenchyma, such as the pathological tumour regression grade, and the histologic degree of liver damage by the therapy, because of its prognostic value. On this setting, a group of pathologists has elaborated a guideline proposal, in order to obtain a more uniform procedure and diagnosis of CRC liver metastasis specimens. The aim was to give useful recommendations in order to obtain homogeneous and comparable pathologic reports among different pathology departments. The results of this consensus are presented in this paper (AU)

[Bilharziasis. Case report]. / Bilharziasis: presentación de un caso clínico.

OBJECTIVE: To report one case of bilharziasis treated at our centre and to briefly comment the literature in the current context of increase of parasitical diseases in Europe, imported from the Third World by immigrants and tourists. METHODS: We report the case of a male patient from a Central African country referred to our department due to penile pain with painful voiding and ejaculation for several months, without other clinical symptoms. We performed a bibliographic search in the PubMed and Up-to-date databases with the following search terms: schistosomiasis, bilharziasis, hematuria, bladder infection, parasitosis, combined by boolean operators. RESULTS: After cystoscopy and pathologic study of the biological material the final diagnosis was chronic bilharziasis. The patient remains asymptomatic 14 months after treatment with praziquantel. CONCLUSIONS: Bilharziasis or schistosomiasis is a rare parasite disease, potentially severe which can severely compromise the urinary tract. In developed countries the cases are mainly imported from sub-saharian countries and other areas of North Africa, South Africa, Asia and Middle East. The cause is a parasite, Schistosoma haematobium, from the family of trematodes, genus helmints. In the active phasee the diagnosis is facilitated by the presence of Schistosomal eggs in urine. In latent or non active phase it is necessary the performance of cystoscopy and analysis of the biological material to reach the diagnosis.

Bilharziasis: presentación de un caso clínico / Bilharziasis. Case report

OBJETIVO: Presentar un caso clínico atendido en nuestro centro y comentar brevemente la literatura en el contexto actual del incremento de las enfermedades parasitarias en Europa, importadas del tercer mundo con la inmigración y el turismo. MÉTODO: Estudio de un paciente varón procedente de un país centroafricano que fue remitido a nuestro servicio debido a dolor en pene acompañado de micciones y eyaculaciones dolorosas de varios meses de evolución sin otra clínica acompañante. Como estrategia de búsqueda bibliográfica se utilizó la bases Pubmed y Uptodate con los siguientes descriptores: Schistosomiasis, Bilharziasis, Haematuria, Vesical Infection, Parasitosis, combinados con operadores boleanos. RESULTADO: Tras cistoscopia y estudio anatomopatológico del material biológico se llegó al diagnóstico de Bilharziasis en estadio crónico. El paciente permanece asintomático 14 meses tras tratamiento con Praziquantel. CONCLUSIONES: La bilharziasis o esquistosomiasis es una enfermedad parasitaria poco frecuente pero potencialmente grave que puede comprometer seriamente el aparato urinario. En los países desarrollados los casos son importados principalmente del África subsahariana y también de otras zonas como África del Norte, Sudáfrica, zonas de Asia y de Oriente Medio. Su causante es el parásito Schistosoma haematobium del género platelminto, familia de los tremátodos. En fase activa el diagnóstico es facilitado por la presencia de los huevos del schistosoma en la orina. En fase latente o inactiva es necesario la realización de uretrocistoscopia y el análisis de materiales biológicos para llegar al diagnóstico

OBJECTIVE: To report one case of bilharziasis treated at our centre and to briefly comment the literature in the current context of increase of parasitical diseases in Europe, imported from the Third World by immigrants and tourists. METHODS: We report the case of a male patient from a Central African country referred to our department due to penile pain with painful voiding and ejaculation for several months, without other clinical symptoms. We performed a bibliographic search in the PubMed and Up-to-date databases with the following search terms: schistosomiasis, bilharziasis, hematuria, bladder infection, parasitosis, combined by boolean operators. RESULTS: After cystoscopy and pathologic study of the biological material the final diagnosis was chronic bilharziasis. The patient remains asymptomatic 14 months after treatment with praziquantel. CONCLUSIONS: Bilharziasis or schistosomiasis is a rare parasite disease, potentially severe which can severely compromise the urinary tract. In developed countries the cases are mainly imported from sub-saharian countries and other areas of North Africa, South Africa, Asia and Middle East. The cause is a parasite, Schistosoma haematobium, from the family of trematodes, genus helmints. In the active phasee the diagnosis is facilitated by the presence of Schistosomal eggs in urine. In latent or non active phase it is necessary the performance of cystoscopy and analysis of the biological material to reach the diagnosis

Condrometaplasia sinovial en bursa secundaria a osteocondroma costal / Synovial chondriometaplasia in bursa secondary to rib osteochondroma

Presentamos el caso de un varón de 39 años diagnosticado de un osteocondroma en la sexta costilla izquierda. Tres años después, en un control radiológico; se objetivó una tumoración de gran tamaño en relación con la misma costilla. Ante una posible malignización se realizó la extirpación qui-rúrgica de la lesión.Histológicamente se confirmó la naturaleza cartilaginosa benigna del tumor costal y la exis-tencia de un saco compartimental revestido fundamentalmente por epitelio sinovial con áreas papilares de metaplasia condroide. (AU)

Tumor neuroectodérmico primitivo renal (PNET): 26 casos. Estado actual de su diagnóstico y tratamiento

OBJETIVOS: Aportamos un caso de tumor neuroectodérmico primitivo de riñón (PNET) y revisamos la literatura sobre este tumor, describiendo los únicos 25 casos que a nuestro entender han sido publicados anteriormente como PNET.MÉTODOS: Presentamos un paciente de 39 años en estudio por cólicos nefríticos, con hallazgo ecográfíco de masa renal izquierda. Describimos la iconografía, estrategia terapéutica y diagnósticos diferenciales con otros tumores de célula pequeña. Destacamos el valor de la inmunohistoquímica (positividad de membrana en las células tumorales frente a los anticuerpos O13 o 12E7) y citogenética (detección de una translocación específica t(11;22)(q24;q12) o una variante t(21;22)(q22;q12), mediante técnicas de hibridación in situ (FISH) o reacción en cadena de la polimerasa-transcriptasa inversa -PCR-RT-).RESULTADOS: Nuestro paciente logró una supervivencia de 20 meses. La serie revisada ofrece 3 casos de mayor supervivencia, 60, 48 y 24 meses (tabla I) con una supervivencia media de 10 meses (gráfico 1). El 95,24 por ciento de los casos presentó positividad para NSE. Solamente en 16 pacientes se llevo a cabo la tinción frente a CD99, siendo en todos ellos positiva. Hemos encontrado 11 casos en los que se realizó estudio citogenético y/o molecular, describiéndose dos casos en los que la PCR-RT resultó negativa, circunstancia que incluye nuestro caso (Tabla II).CONCLUSIONES: Los PNET renales se caracterizan por su agresividad, tendencia a la recurrencia y capacidad de metastatizar. Aunque los resultados son pobres con el tratamiento estándar que combina cirugía, quimioterapia y radioterapia, investigaciones en terapia génica basadas en la creación de secuencias de oligonucleótidos complementarias al transcripto de fusión anómalo EWS/ FLI 1, pueden cambiar los resultados actuales (AU)