Paired Primary and Recurrent Rhabdoid Meningiomas: Cytogenetic Alterations, BAP1 Gene Expression Profile and Patient Outcome.

Rhabdoid meningiomas (RM) are a rare meningioma subtype with a heterogeneous clinical course which is more frequently associated with recurrence, even among tumors undergoing-complete surgical removal. Here, we retrospectively analyzed the clinical-histopathological and cytogenetic features of 29 tumors, from patients with recurrent (seven primary and 14 recurrent tumors) vs. non-recurrent RM (n = 8). Recurrent RM showed one (29%), two (29%) or three (42%) recurrences. BAP1 loss of expression was found in one third of all RM at diagnosis and increased to 100% in subsequent tumor recurrences. Despite both recurrent and non-recurrent RM shared chromosome 22 losses, non-recurrent tumors more frequently displayed extensive losses of chromosome 19p (62%) and/or 19q (50%), together with gains of chromosomes 20 and 21 (38%, respectively), whereas recurrent RM (at diagnosis) displayed more complex genotypic profiles with extensive losses of chromosomes 1p, 14q, 18p, 18q (67% each) and 21p (50%), together with focal gains at chromosome 17q22 (67%). Compared to paired primary tumors, recurrent RM samples revealed additional losses at chromosomes 16q and 19p (50% each), together with gains at chromosomes 1q and 17q in most recurrent tumors (67%, each). All deceased recurrent RM patients corresponded to women with chromosome 17q gains, although no statistical significant differences were found vs. the other RM patients.

Serum DNA methylome of the colorectal cancer serrated pathway enables non-invasive detection.

The clinical relevance of the colorectal cancer serrated pathway is evident, but the screening of serrated lesions remains challenging. We aimed to characterize the serum methylome of the serrated pathway and to evaluate circulating cell-free DNA (cfDNA) methylomes as a potential source of biomarkers for the non-invasive detection of serrated lesions. We collected serum samples from individuals with serrated adenocarcinoma (SAC), traditional serrated adenomas, sessile serrated lesions, hyperplastic polyps and individuals with no colorectal findings. First, we quantified cfDNA methylation with the MethylationEPIC array. Then, we compared the methylation profiles with tissue and serum datasets. Finally, we evaluated the utility of serum cfDNA methylation biomarkers. We identified a differential methylation profile able to distinguish high-risk serrated lesions from no serrated neoplasia, showing concordance with tissue methylation from SAC and sessile serrated lesions. Serum methylation profiles are pathway-specific, clearly separating serrated lesions from conventional adenomas. The combination of ninjurin 2 (NINJ2) and glutamate-rich 1 (ERICH1) methylation discriminated high-risk serrated lesions and SAC with 91.4% sensitivity (64.4% specificity), while zinc finger protein 718 (ZNF718) methylation reported 100% sensitivity for the detection of SAC (96% specificity). This is the first study exploring the serum methylome of serrated lesions. Differential methylation of cfDNA can be used for the non-invasive detection of colorectal serrated lesions.

Clinical, Histopathologic and Genetic Features of Rhabdoid Meningiomas.

Rhabdoid meningiomas (RM) shows heterogeneous histological findings, and a wide variety of chromosomal copy number alterations (CNA) are associated with an unpredictable course of the disease. In this study, we analyzed a series of 305 RM samples from patients previously reported in the literature and 33 samples from 23 patients studied in our laboratory. Monosomy 22-involving the minimal but most common recurrent region loss of the 22q11.23 chromosomal region was the most observed chromosomal alteration, followed by losses of chromosomes 14, 1, 6, and 19, polysomies of chromosomes 17, 1q, and 20, and gains of 13q14.2, 10p13, and 21q21.2 chromosomal regions. Based on their CNA profile, RM could be classified into two genetic subgroups with distinct clinicopathologic features characterized by the presence of (1) chromosomal losses only and (2) combined losses and gains of several chromosomes. The latter displays a higher frequency of WHO grade 3 tumors and poorer clinical outcomes.

Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature.

OBJECTIVES: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma. MATERIAL AND METHODS: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens. RESULTS: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period. CONCLUSIONS: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia.

Intraductal Carcinoma of the Prostate without High-Grade Invasive Adenocarcinoma: Report of Two Cases and Review of the Literature

Objectives: Intraductal carcinoma of the prostate (IDC-P) is usually associated with high grade, aggresive acinar adenocarcinomas. IDC-P is supposed to result from the spread of the adenocarcinoma along the prostatic ducts. IDC-P rarely occurs without invasive carcinoma or with a coexistent low grade adenocarcinoma. Material and Methods: We report two patients, 66 and 75 year-old, who presented IDC-P and low-grade acinar adenocarcinoma foci in their radical prostatectomy surgical specimens. Results: Acinar adenocarcinomas were grade group 1, PTEN+, pT2. In the first case, the invasive adenocarcinoma was adjacent but nor intermingled with the IDC-P, and a discordance in the immunophenotype between them was outstanding (positivity for ERG in the acinar carcinoma being negative in the IDC-P). In the second case, the foci of adenocarcinoma were distant from the IDC-P. The first patient had not biochemical recurrence after a 34 month follow-up period. Conclusions: This kind of cases supports the existence of an infrequent subtype of IDC-P that could be considered as an in situ neoplasia (AU)

Objetivos: El carcinoma intraductal de la próstata(CIDP) aparece generalmente asociado a adenocarcinomasacinares agresivos, de alto grado. En general se cree que elCIDP representa una forma de diseminación deladenocarcinoma a los ductos prostáticos. En ocasiones elCIDP aparece, sin embargo, sin tumor infiltrante o conadenocarcinomas de bajo grado.Material y Métodos: Presentamos dos pacientes de66 y 75 años, que en las piezas de prostatectomía radicalpresentaron CIDP y focos de adenocarcinoma acinar degrupo de grado bajo.Resultados: Los adenocarcinomas acinares eran degrupo de grado 1, PTEN+, pT2. En el primer caso, eladenocarcinoma se localizaba adyacente, pero noentremezclado, con el CIDP, y destacaba la discordanciaen el inmunofenotipo entre el adenocarcinoma, ERG+, y elCIDP, que era ERG-. En el segundo, los focos de adenocarcinoma se localizaban a distancia del CIDP. Elprimer paciente no ha presentado recidiva bioquímica tras34 meses de seguimiento.Conclusiones: Las características de los casos quepresentamos apoyan la existencia de un subtipoinfrecuente de CIDP que se podría considerar como unaneoplasia in situ. (AU)

Resultados preliminares de un programa de cribado del cáncer anal y sus precursores en hombres VIH que tienen sexo con hombres en Vigo-España / Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain

Antecedentes y objetivos: los hombres VIH que tienen sexo con hombres (VIH-HSH) presentan la mayor incidencia de cáncer anal (CA). El estudio tiene como objetivo conocer la prevalencia de la infección anal por virus del papiloma humano de alto riesgo (VPH-AR) y de los hallazgos citológicos e histológicos, así como la implementación de un programa de cribado en el contexto de una ciudad media española, Vigo (España). Método: análisis prospectivo de una cohorte de 264 hombres (VIH-HSH). A los pacientes se les realizó una citología anal y genotipado de VPH-AR para el estudio de la prevalencia de alteraciones citológicas y de la infección VPH-AR. A 209 se les realizó una anoscopia de alta resolución (AAR). Los resultados se relacionaron con variables epidemiológicas, clínicas y analíticas. Resultados: de los 209 pacientes seleccionados, la prevalencia de VPH-AR, alteraciones citológicas e histológicas anales fue de 85,6%, 47,5% y 39,3% respectivamente. La sensibilidad y especificidad para la citología ≥ ASCUS (atipia de células escamosas de significado indeterminado) respecto a las alteraciones histológicas fue de 61% y 85% (OR: 8,7; IC95%: 4,4-17,2), respectivamente. La concordancia observada entre la citología HSIL (lesión escamosa intraepitelial de alto grado) e histología HSIL (AIN-2/3, neoplasia intraepitelial tipo 2 y 3) fue del 64%,(OR: 11,4; IC95%: 3,5-36,7). Un paciente con citología HSIL presentó cáncer escamoso anal prevalente. Conclusiones: la AAR resultó factible y con resultados similares a los de grupos relevantes. Gran prevalencia de la infección anal por VPH-AR y de alteraciones citológicas e histológicas (AU)

Background: Men who have sex with men (MSM) infected with human immunodeficiency virus (HIV) have the highest risk of developing anal cancer (AC). The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV) anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain). Method: Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV)-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA) was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. Results: Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance) cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2), respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL) cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3) histology was 64% (OR: 11.4; IC 95%: 3.6-36.7). One patient with HSIL cytology presented a prevalent anal squamous carcinoma. Conclusions: HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations (AU)

Preliminary results of a screening program for anal cancer and its precursors for HIV-infected men who have sex with men in Vigo-Spain.

BACKGROUND: Men who have sex with men (MSM) infected with human immunodeficiency virus (HIV) have the highest risk of developing anal cancer (AC). The objective of this study was to describe our screening implementation program in this population, and report the prevalence of human papillomavirus (HPV) anal infection, and cytological and histological findings in a Spanish medium-size community (Vigo, Spain). METHOD: Prospective cohort analysis of 240 HIV-infected MSM. Cellular anal sample and high risk HPV (HR-HPV)-tests were performed to study cytological changes and HPV genotyping. High resolution anoscopy (HRA) was performed in 209 patients. Results were analyzed with respect to epidemiological, clinical and analytical factors. RESULTS: Of 209 patients selected for HRA, the prevalence of HR-HPV anal infection, cytological and histological alterations was 85.6%, 47.5%, and 39.8%, respectively. Sensitivity and specificity for ≥ ASCUS (atypia of squamous cells of undetermined significance) cytology in relation to histological alterations were 61% and 85%, (OR: 8.7; IC 95%: 4.4-17.2), respectively. Observed concordance between high-grade squamous intraepithelial lesion (HSIL) cytology and HSIL anal intraepithelial neoplasia types 2 and 3 (AIN-2/3) histology was 64% (OR: 11.4; IC 95%: 3.6-36.7). One patient with HSIL cytology presented a prevalent anal squamous carcinoma. CONCLUSIONS: HRA was feasible with similar results to relevant groups. There was a high prevalence of anal HR-HPV infection, and cytological and histological alterations.

Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana / Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus

El cáncer de ano, una enfermedad infrecuente en la población general, presenta una incidencia elevada y progresiva en ciertos grupos de riesgo, fundamentalmente en hombres que tienen sexo con hombres, y particularmente en aquellos con infección por el virus de la inmunodeficiencia humana. La anoscopia de alta resolución se considera actualmente la técnica estándar en el diagnóstico de la neoplasia intraepitelial anal, pero su uso protocolizado aún está por consensuar en los sistemas sanitarios. Aunque no está exenta de dificultades, es una técnica asequible que puede llegar a ser fundamental en el cribado del cáncer de ano y sus lesiones precursoras. Actualmente estamos estudiando la estrategia más efectiva para el manejo de las lesiones premalignas anales, y con esta publicación intentamos animar a otros grupos interesados en la reducción de una neoplasia epidemiológicamente en progresión

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia

[Practical considerations for high resolution anoscopy in patients infected with human immunodeficiency virus]. / Consideraciones prácticas de la anoscopia de alta resolución en pacientes infectados por el virus de la inmunodeficiencia humana.

Anal cancer is uncommon in the general population, however its incidence is increasing significantly in certain risk groups, mainly in men who have sex with men, and particularly those infected with human immunodeficiency virus. High resolution anoscopy technique is currently considered the standard in the diagnosis of anal intraepithelial neoplasia, but at present there is no agreed standard method between health areas. High resolution anoscopy is an affordable technique that can be critical in the screening of anal carcinoma and its precursor lesions, but is not without difficulties. We are currently studying the most effective strategy for managing premalignant anal lesions, and with this article we attempt to encourage other groups interested in reducing the incidence of an increasing neoplasia.

Tumor estromal gástrico de riesgo intermedio: diagnóstico mediante ecografía hidrogástrica / Intermediate-risk gastrointestinal stromal tumor: diagnosis through hydrogastric ultrasonography

La endoscopia convencional valora de forma deficitaria las lesiones submucosas del tracto digestivo por la imposibilidad de su observación directa, ya que no permite determinar su tamaño adecuadamente, establecer un diagnóstico etiológico en la mayoría de los casos ni valorar la capa de origen del tumor. Sin embargo, la ultrasonografía endoscópica permite, en la mayoría de las ocasiones, solucionar estos problemas: logra diferenciar con cierta seguridad las lesiones malignas de las benignas, puede medir su tamaño y establecer su capa de origen. Es la técnica de elección para establecer la presencia y las características de un tumor submucoso y si éste es subsidiario de tratamiento; además, permite seleccionar los casos que pueden ser extirpados endoscópicamente sin excesivos riesgos. La ecografía hidrogástrica puede ser una buena alternativa a la ecoendoscopia para el estudio de las lesiones submucosas y la estadificación de tumores situados en el antro gástrico en los pacientes en que no se pueda disponer de esta técnica o no se pueda realizar. Es una técnica muy fiable, poco costosa, y muy bien tolerada por los pacientes. Presentamos a continuación el caso de una paciente que presentaba un tumor estromal gastrointestinal que pudo estudiarse mediante ecografía hidrogástrica, estableciéndose con precisión el tamaño, la capa de origen y la naturaleza maligna de la lesión

Evaluation of submucosal lesions of the digestive tract with conventional endoscopy is unsatisfactory since this technique does not allow direct observation or correct evaluation of the size and layer of origin of the tumor; therefore, in most patients an etiological diagnosis cannot be established with this procedure. However, in most patients, endoscopic ultrasonography can resolve these problems: to a fair degree of certainty, this technique can differentiate malignant from benign lesions, measure their size, and establish their layer of origin. Endoscopic ultrasonography is the technique of choice to establish the presence and characteristics of submucosal tumors and their suitability for treatment. Moreover, this procedure can identify tumors that can be removed endoscopically without excessive risk. Hydrogastric ultrasonography can be an effective substitute for echoendoscopy when evaluating submucosal lesions and for staging tumors of the gastric antrum when echoendoscopy is not available or in patients in whom it cannot be performed. Hydrogastric ultrasonography is safe, inexpensive and very well tolerated by patients. We present the case of a female patient with a gastric GIST that was evaluated using hydrogastric ultrasonography. The size, layer of origin, and malignancy of the tumor were accurately established

[Intermediate-risk gastrointestinal stromal tumor: diagnosis through hydrogastric ultrasonography]. / Tumor estromal gástrico de riesgo intermedio: diagnóstico mediante ecografía hidrogástrica.

Evaluation of submucosal lesions of the digestive tract with conventional endoscopy is unsatisfactory since this technique does not allow direct observation or correct evaluation of the size and layer of origin of the tumor; therefore, in most patients an etiological diagnosis cannot be established with this procedure. However, in most patients, endoscopic ultrasonography can resolve these problems: to a fair degree of certainty, this technique can differentiate malignant from benign lesions, measure their size, and establish their layer of origin. Endoscopic ultrasonography is the technique of choice to establish the presence and characteristics of submucosal tumors and their suitability for treatment. Moreover, this procedure can identify tumors that can be removed endoscopically without excessive risk. Hydrogastric ultrasonography can be an effective substitute for echoendoscopy when evaluating submucosal lesions and for staging tumors of the gastric antrum when echoendoscopy is not available or in patients in whom it cannot be performed. Hydrogastric ultrasonography is safe, inexpensive and very well tolerated by patients. We present the case of a female patient with a gastric GIST that was evaluated using hydrogastric ultrasonography. The size, layer of origin, and malignancy of the tumor were accurately established.