Innovación continuada en cirugía radioguiada de precisión / Continuous innovation in precision radio-guided surgery

Desde sus inicios, la medicina nuclear se ha enfrentado a cambios tecnológicos que la han obligado a modificar sus modos operativos y a adecuar sus protocolos. En el campo de la cirugía radioguiada (CRG), la incorporación de la imagen gammagráfica preoperatoria y la detección intraoperatoria con la sonda gamma proporcionó un impulso definitivo a la biopsia del ganglio centinela (GC) para convertirse en el procedimiento estándar de aplicación en el melanoma y el cáncer de mama. Las diversas innovaciones tecnológicas y la adaptación consiguiente de protocolos confluyen en lo disruptivo y lo gradual. Como ejemplos evidentes tenemos la introducción de la tomografía por emisión de fotón único/tomografía computarizada (SPECT/TC) en el campo preoperatorio y las sondas Drop-in (Lightpoint Medical Ltd; Crystal photonics, Eurorad) en el intraoperatorio. Otros aspectos innovadores con posible aplicación en la CRG se basan en la utilización de la inteligencia artificial (IA), navegación y teleasistencia (AU)

Since its origins, nuclear medicine has faced technological changes that led to modifying operating modes and adapting protocols. In the field of radioguided surgery, the incorporation of preoperative scintigraphic imaging and intraoperative detection with the gamma probe provided a definitive boost to sentinel lymph node biopsy to become a standard procedure for melanoma and breast cancer. The various technological innovations and consequent adaptation of protocols come together in the coexistence of the disruptive and the gradual. As obvious examples we have the introduction of SPECT/CT in the preoperative field and Drop-in probes in the intraoperative field. Other innovative aspects with possible application in radio-guided surgery are based on the application of artificial intelligence, navigation and telecare (AU)

Synovial sarcoma with ossification and calcification with SS18 immunochemical expression and rearrangement by fluorescent in situ hybridization / Sarcoma sinovial con osificación y calcificación, con expresión de SS18 por inmunohistoquímica y reordenamiento de SS18 por hibridación in situ fluroescente

Synovial sarcoma is a soft tissue tumor of uncertain origin. Generally, it is a monophasic spindle cell neoplasm that can have glandular-like structures. Ossification and presence of calcification is a rare phenomenon with only a few reported cases. We present the case of a young male with a synovial sarcoma of the right foot. Histology revealed prominent deposits of tumoral osteoid and coarse calcifications. The diagnosis was confirmed by the expression of SS18 by immunohistochemistry and the demonstration of the rearrangement of the SS18 gene by fluorescent in situ hybridization. We reviewed the literature for synovial sarcoma with prominent ossification or calcification, and to the best of our knowledge, this is the first case with expression of SS18 by immunohistochemistry. The main differential diagnoses are osteosarcoma (both primary of bone and extraosseous) and sclerosing epithelioid fibrosarcoma.(AU)

El sarcoma sinovial (SS) es un tumor de partes blandas de origen incierto. Generalmente es una neoplasia monofásica de células fusiformes que puede tener estructuras de tipo glandular. La osificación y la presencia de calcificaciones es un fenómeno raro, con pocos casos reportados. A continuación presentamos el caso de un hombre joven con un sarcoma sinovial del pie derecho que en la histología mostró depósitos de osteoide tumoral y calcificaciones gruesas. El diagnóstico fue confirmado por la expresión de SS18 por inmunohistoquímica y la demostración del reordenamiento del gen SS18 por hibridación in situ fluorescente. Revisamos la literatura referente a sarcoma sinovial con osificación o calcificación prominente, y este es el primer caso con expresión de SS18 por inmunohistoquímica. Los principales diagnósticos diferenciales son con osteosarcoma (tanto primario de hueso como extraóseo) y fibrosarcoma epitelioide esclerosante (sclerosing epithelioid fibrosarcoma [SEF]).(AU)

LncRNA HOTAIR enhances RCC2 to accelerate cervical cancer progression by sponging miR-331-3p

Purpose Long noncoding RNAs (lncRNAs) have been gradually regarded as influential indicators of various cancers. The present study aimed to identify the effects of lncRNA HOTAIR on cervical cancer progression. Methods RNA and protein expressions were quantified by RT-qPCR and western blot assays. Fluorescence in situ hybridization (FISH) assay was carried out to examine the intracellular location of HOTAIR. Cancer cell viability and mobility were detected by CCK-8, colony formation, transwell and wound healing assays. Binding relationships between miR-331-3p and HOTAIR/RCC2 were validated by luciferase reporter assay. Results RT-qPCR assays showed that HOTAIR levels were notably upregulated in cervical cancer tissues and cell lines. Furthermore, a fluorescence in situ hybridization (FISH) assay suggested that HOTAIR was mostly located in the cytoplasm of cancer cells, indicating a sponging function. CCK-8, colony formation, Transwell and wound-healing assays indicated that knockdown of HOTAIR in HeLa and SiHa cells significantly reduced cell growth, migration and invasion. Subsequently, miR-331-3p was proven to be the target molecule of HOTAIR. In addition, results from Pearson's correlation analysis indicated negative correlation between HOTAIR and miR-331-3p in cervical cancer tissues. HOTAIR negatively modulated miR-331-3p expression. Ultimately, the target gene of miR-331-3p was verified to be RCC2, and miR-331-3p negatively modulated RCC2 expression. In addition, analysis on clinical cervical cancer tissues confirmed the negative correlation between miR-331-3p and RCC2. HOTAIR and RCC2 showed oncogenic functions in HeLa and SiHa cells, while miR-331-3p exerted the reverse effect. Conclusions HOTAIR plays a carcinogenic role in cervical cancer by targeting the miR-331-3p/RCC2 axis (AU)

Discordant results for ALK based on immunohistochemistry versus fluorescence in situ hybridization in a cohort of patients diagnosed with lung adenocarcinoma / Discordancia de los resultados para ALK basados en inmunohistoquímica e hibridación fluorescente in situ en una cohorte de pacientes diagnosticados con adenocarcinoma de pulmón

Introduction: Anaplastic lymphoma kinase (ALK) rearrangement located on the short arm of chromosome 2, region 2 and band 3 is frequent in lung cancer patients who respond to targeted therapies with ALK inhibitors Therefore, their identification has become a standard diagnostic test in patients with advanced NSCLS, as such chromosomal alterations may lead to the activation of important signalling pathways involved in cell survival and proliferation. Methods: To investigate the ALK gene status, we performed FISH and IHC assays in 18 lung adenocarcinoma patients, 12 women and 6 men, aged between 29 and 85 years. Paraffin-embedded samples were analyzed in the Pathology Department of the Hospital Universitario San Ignacio. Results: Results between the two techniques in 5 patients showed discordant patterns, being positive for FISH and negative for IHC. The borderline to define ALK positivity was set at 15%, These results present experimental evidence that the techniques differ in specific situations. Conclusions: Our findings show that it is advisable to investigate the ALK gene status in patients with suspected lung cancer using both FISH and IHC in combination.(AU)

Introducción: La reorganización de la (anaplastic lymphoma kinase) ALK ubicada en el brazo corto del cromosoma 2, región 2 y banda 3 es frecuente en los pacientes con cáncer de pulmón que responden a terapias dirigidas con inhibidores de la ALK. Por ello, su identificación se ha establecido como una prueba diagnóstica estándar en pacientes con CPCNP, ya que dichas alteraciones cromosómicas puedan determinar la activación de importantes vías de señalización implicadas en la supervivencia y proliferación celulares. Métodos: Para determinar el estatus de gen ALK se realizaron pruebas FISH e IHC en 18 pacientes con adenocarcinoma pulmonar, 12 mujeres y 6 varones, con edades comprendidas entre 29 y 85 años. Las muestras fueron analizadas en el Departamento de Anatomía Patológica del Hospital Universitario San Ignacio. Resultados: Los resultados entre ambas técnicas mostraron patrones discordantes en 5 pacientes, con positividad de FISH y negatividad con IHC. El límite para definir la positividad de ALK se estableció en el 15%. Estos resultados muestran evidencia experimental que dichas técnicas difieren en situaciones específicas. Conclusiones: Este estudio recomienda la investigación del estatus del gen ALK en los pacientes con sospecha de cáncer de pulmón, mediante la combinación de FISH e IHC.(AU)

Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia

Purpose Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse. Methods In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Results Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively. Conclusions MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed (AU)

Liposarcoma desdiferenciado paratesticular simulando un tumor miofibroblástico inflamatorio. Estudio histológico, inmunohistoquímico y molecular / Histological, immunohistochemical and molecular study of a paratesticular dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features

Se presenta un estudio histológico, inmunohistoquímico (IHQ) y molecular de un liposarcoma desdiferenciado paratesticular remitido a nuestro centro, con hallazgos histológicos similares a un tumor miofibroblástico inflamatorio. Las células tumorales fueron positivas para actina músculo liso (AML) y focalmente positivas para CD56, CD99, Bcl2 y EMA. La expresión de WT1, calretinina, miogenina, CK(AE1/AE3), desmina, H-caldesmona, CD34, ALK, CKIT, DOG1, MUC4 y STAT6 fue negativa. MDM2 mostró positividad nuclear intensa y difusa por IHQ y alto nivel de amplificación génica mediante hibridación fluorescente in situ (FISH). La FISH no reveló reordenamiento del gen SYT. En el estudio histológico del corte remitido no encontramos evidencias de componente liposarcomatoso bien diferenciado, aunque el aspecto macroscópico de la pieza lo sugería. El liposarcoma desdiferenciado puede presentar hallazgos histológicos que recuerdan a un tumor miofibroblástico inflamatorio y que expanden el espectro histológico de esta variante de liposarcoma. El conocimiento de la existencia de esta variante de liposarcoma es de crucial importancia para no confundirla con otras neoplasias que, aunque histológicamente similares, difieren en la evolución clínica y/o tratamiento.(AU)

We report the histological, immunohistochemical, and molecular findings of a dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features occurring in the paratesticular region. Histologically, the dedifferentiated component closely resembled an inflammatory myofibroblastic tumor. The neoplastic cells were positive for smooth muscle actin with focal CD56, CD99, Bcl2 and EMA expression. WT1, calretinin, myogenin, CK(AE1/AE3), desmin, H-caldesmon, CD34, ALK, CKIT, DOG1, MUC4 and STAT6 were negative. MDM2 showed diffuse and strong nuclear positivity in neoplastic cells and fluorescence in situ hybridization (FISH) revealed amplified MDM2 (high level) but no SYT rearrangement. Although a lipomatous component was evident macroscopically, well-differentiated liposarcomatous components were not evident in the section examined. Dedifferentiated liposarcoma can have prominent inflammatory myofibroblastic tumor-like features. Pathologists should be aware of this histological variant in order to avoid misdiagnosing dedifferentiated liposarcoma as inflammatory myofibroblastic tumor or other spindle cell tumors which have different behavioral patterns and treatment requirements.(AU)

Papel de la activación adicional del gen RA en el desarrollo del fenotipo resistente a la castración en el cáncer de próstata / Additional activation of the AR gene may be involved in the development of the castration resistance phenotype in prostate cancer

Introducción Diversos estudios han demostrado que los cambios en el gen RA pueden estar asociados a un fenotipo de enfermedad más agresivo e incluso al cáncer de próstata resistente a la castración. Por este motivo, hemos investigado las alteraciones citogénicas y moleculares asociadas al RA.Materiales y métodos Para evaluar la metilación del RA, realizamos un análisis citogenético-molecular mediante hibridación fluorescente in situ que utiliza sondas específicas para el gen del RA (Xq11.12) y el centrómero del cromosoma X. Respecto a la actividad del RA, realizamos un análisis cualitativo de la actividad del receptor de andrógenos humano. Para analizar la expresión del RA en las líneas celulares PC3 y LNCaP, utilizamos ensayos de qPCR.ResultadosEn el ensayo qPCR, encontramos una regulación a la baja del RA en la línea celular PC3 en comparación con la LNCaP. Hallamos la presencia de polisomía del cromosoma X en las líneas celulares PC-3 y LNCaP mediante el ensayo FISH. En el ensayo HUMARA-Q encontramos la presencia de dos cromosomas X/célula y actividad en ambos RA de la línea celular PC-3. En las células LNCaP hallamos la presencia de dos cromosomas X/célula y la metilación de solo un RA.Conclusión El fenotipo del cáncer de próstata resistente a la castración representa un gran desafio en el tratamiento urológico. Estos cromosomas X y las alteraciones ligadas al RA pueden contribuir a una mejor comprensión de la enfermedad; sin embargo, deben realizarse más estudios para arrojar más luz sobre el papel del RA en el fenotipo del cáncer de próstata resistente a la castración (AU)

Introduction Several studies have already shown that changes in the AR gene may be associated with a more aggressive disease phenotype and even castration-resistant prostate cancer. Thus, we investigated cytogenetic and molecular alterations linked to AR.Materials and methods To evaluate AR methylation, we performed a cytogenetic-molecular analysis using fluorescence in situ hybridization that uses specific probes for the AR gene (Xq11.12) and the X chromosome centromere. For AR activity, we performed a qualitative analysis of human androgen receptor activity. To analyze the expression of AR in PC3 and LNCaP cell lines, we used qPCR assays.ResultsIn the qPCR assay, we found downregulation of AR in the PC3 cell line compared with the LNCaP. We found the presence of X chromosome polysomy in PC-3 and LNCaP cell lines by FISH assay. In the HUMARA-Q assay, we found two X chromosomes/cell and the activity of both AR in the PC-3 cell line. In LNCaP cells, we found two X chromosomes/cell and methylation of only one AR.Conclusion Castration-resistant prostate cancer phenotype represents a significant challenge in the setting of urological management. The X chromosomes and AR-linked alterations may contribute to a better understanding of the disease. However, further studies should be performed in an attempt to elucidate as much as possible the role of AR in the castration-resistant prostate cancer phenotype (AU)

Multidisciplinary consensus on optimising the detection of NTRK gene alterations in tumours

The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionised the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children; and they are either rare tumours with common NTRK fusions that may be diagnostic, or more prevalent tumours with rare NTRK fusions. To assess currently available evidence on this matter, three key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathological Anatomy (SEAP), and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical, and therapeutic aspects of NTRK-fusion tumours. This document also discusses the challenges related to the routine detection of these genetic alterations in a mostly public Health Care System (AU)

Distinctive expression pattern of Peg10 in the mouse brain

Peg10 (paternally expressed 10) is a retrotransposon-derived gene that is highly conserved across mammalian species. Peg10 is involved in cell proliferation and differentiation, and is essential for placenta formation in mice. Although a number of studies have examined Peg10 expression in the placenta, its cellular localization in the brain is still unclear. The function of Peg10 in the brain is also unknown. Here, we examined Peg10 distribution in the mouse brain. In situ hybridization revealed intense expression of the gene in the core region of the accumbens nucleus, lateral division of the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, premammillary nucleus, central amygdaloid nucleus and lateral parabrachial nucleus. Moderate to intense expression of Peg10 was also observed in monoaminergic nuclei such as the substantia nigra, dorsal raphe nucleus and locus coeruleus. These results suggest that Peg10 may play a role in motivational processes, emotional regulation, and autonomic functions in the brain. The findings also suggest that Peg10 may have contributed to the evolution of mammals, not only by participating in placenta formation, but also by regulating parental behavior and hormonal secretions necessary for maternal responsiveness

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Calcificaciones cerebrales en el diagnóstico precoz del síndrome de DiGeorge sin cardiopatía / Brain calcifications in the early diagnosis of DiGeorge's syndrome without heart disease

Introducción: Las calcificaciones cerebrales son un hallazgo frecuente y no siempre tienen un significado patológico. El diagnóstico diferencial incluye diversas entidades en la población pediátrica, como tumores cerebrales, infecciones connatales y perinatales, síndromes neurocutáneos, enfermedades autoinmunes (p. ej., celiaquía) y, con mayor frecuencia, trastornos del metabolismo del calcio, entre los que se incluye el hipoparatiroidismo. Caso clínico: Varón de 12 años de edad que ingresa en la unidad de pediatría tras haber presentado 2 crisis tónico-clónicas generalizadas, sin relajación de esfínteres. Estuvo afebril en todo momento. Durante el ingreso presentó un estatus convulsivo con características similares a las crisis previas, acompañado de espasmos carpopedales. En las pruebas complementarias realizadas durante el ingreso destacaba la presencia de una calcemia de 5,3 mg/dL, un calcio iónico de 0,84 mmol/L y un fósforo de 6,9 mg/dL. El paciente se encontraba en fase de seguimiento debido a un retraso psicomotor, y 2 años antes, a raíz de otro episodio comicial, se habían detectado calcificaciones cerebrales bilaterales en la resonancia magnética realizada. Conclusiones: En el amplio abordaje de las calcificaciones cerebrales, es obligado realizar un estudio del metabolismo del calcio, aun en el caso de que éstas sean asintomáticas y se consideren un hallazgo casual

Introduction: Cerebral calcifications are a frequent finding and do not always have a pathological significance. The differential diagnosis in the pediatric population is large and includes entities such as brain tumors, connatal and perinatal infections, neurocutaneous syndromes, autoimmune diseases, such as celiac disease, and more frequently calcium metabolism disorders, including hypoparathyroidism. Case report: We present a 12-year-old male admitted to the pediatric unit after having presented two generalized tonic-clonic seizures without sphincter relaxation. No fever at all times. During admission, he presented convulsive status with characteristics similar to previous crises and accompanied by carpopedal spasms. In the complementary tests performed during admission, the presence of a 5.3 mg/dL calcemia, an ionic calcium of 0.84 mmO/L, and a phosphorus of 6.9 mg/dL was noteworthy. The patient was in follow-up due to psychomotor retardation and two years earlier, following another seizure episode, bilateral cerebral calcifications had been detected in magnetic resonance. Conclusions: In the large approach of cerebral calcifications, the study of calcium metabolism is mandatory, even if they are asymptomatic and are considered a casual finding

Histopatología y perfil molecular de un caso de sarcoma de Ewing prostático / Histopathology and molecular profile of a case of prostatic Ewing sarcoma

Reportamos un caso de sarcoma de Ewing prostático en un paciente de 33 años sin afectación ósea ni de partes blandas con evidencia de translocación en los genes EWS y FLI1 detectada por técnicas de hibridación fluorescente in situ (FISH). En la literatura actual se han reportado casos aislados, aunque no todos cuentan con estudios de biología molecular, consideradas en la actualidad indispensable para la realización del diagnóstico

We report a case of Ewing sarcoma localized in the prostate gland of a 33-year-old patient without bone or soft tissue involvement. Evidence of EWS and FLI1 gene translocation was detected by fluorescence in situ hybridization (FISH). This is an unusual case with an interesting clinical presentation; indeed, only a few cases have been reported to date and not all have the supporting biological studies now considered essential for the diagnosis

Radioterapia más temozolomida o PCV en pacientes con oligodendroglioma anaplásico con codeleción 1p19q / Radiotherapy plus temozolomide or PCV in patients with anaplastic oligodendroglioma 1p19q codeleted

Introducción. La hipotonía constituye un signo habitual de enfermedad en el neonato. Ahora bien, se trata de un signo inespecífico: puede ser la manifestación inicial de una enfermedad neurológica o multisistémica. Objetivos. Estudiar las principales causas de la hipotonía neonatal y evaluar la exactitud diagnóstica de la anamnesis y la exploración física en el neonato hipotónico. Pacientes y métodos. Estudio retrospectivo de 22 años con recién nacidos afectados por hipotonía e ingresados en la unidad de cuidados intensivos neonatales. A partir de la anamnesis y de los datos recabados durante la exploración física, se hizo una clasificación inicial en condiciones de enmascaramiento del tipo de hipotonía: central, periférica o indeterminada. Resultados. El número de pacientes estudiados ascendió a 91. De ellos, 42 (46,2%) presentaban antecedentes de alteraciones prenatales: polihidramnios (28,6%), retraso del crecimiento intrauterino (21,4%) y presentación de nalgas (19%). Cincuenta y tres (58,2%) habían precisado reanimación al nacer. Los principales síntomas asociados consistieron en disnea (65,9%), dificultades de alimentación (36,5%) y escasez de movimientos espontáneos (22,4%). El diagnóstico definitivo se obtuvo en 64 neonatos (70,3%): el 81,3% mostraba hipotonía central, y el 18,7%, hipotonía periférica. El valor predictivo positivo de la clasificación inicial alcanzó el 97,9% en la hipotonía central y el 66,7% en la hipotonía periférica. La tasa de mortalidad fue del 8,8%, y resultó superior en el grupo de hipotonía periférica (58,3% frente a 1,3%). Conclusiones. La hipotonía neonatal aparece vinculada con una larga lista de trastornos. Una anamnesis minuciosa y una valoración neurológica cuidadosa brindan un alto valor predictivo diagnóstico que debe orientar el estudio etiológico

Introduction. Radiotherapy with procarbazine, lomustine, and vincristine (PCV) improves overall survival in patients with anaplastic oligodendroglioma 1p19q codeleted. Patients and methods. This retrospective analysis investigated outcomes in patients with anaplastic oligodendroglioma 1p19q codeleted compared two different protocols (radiotherapy plus temozolomide or PCV). The primary end points were overall survival and progression-free survival. Secondary endpoint was the radiological response. Results. A total of 48 patients were included. Mean age was 43 years (range: 19-66 years), 26 were male (54.1%). Twenty-one patients received PCV and 27 temozolomide. The baseline characteristics were not difference between the groups. The progression-free survival and overall survival in the PCV group were 7.2 and 10.6 years respectively and temozolomide were 6.1 and 9.2 years, both statistically significant. The radiological response was present in 80.9% in PCV arm and 70.2% in temozolomide arm there was not statistical differences. The multivariate Cox model showed only the significant parameters the use of PCV protocol. The toxicity grade 3 or 4 was present in 42.8% in PCV arm and 11.1% in temozolomide arm. Conclusions. The most common strategy in the Latin America community is the substitution of the PCV or temozolomide. This retrospective study showed superior efficacy of PCV than temozolomide. The Latin American community effort must be made to be able to have the drugs to available for using as a first line of treatment

Virus del papiloma humano y riesgo de desarrollo de carcinoma escamocelular en la hidradenitis supurativa / Human Papilloma Virus and the Risk of Squamous Cell Carcinoma Arising in Hidradenitis Suppurativa

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A novel capillary nano-immunoassay for assessing androgen receptor splice variant 7 in plasma. Correlation with CD133 antigen expression in circulating tumor cells. A pilot study in prostate cancer patients

Purpose. Androgen receptor (AR) splice variant 7 (AR-V7) has been related with both a higher risk of prostate cancer (PC) progression and differential responsiveness to hormonal agents versus chemotherapy. The objective of this study was to investigate the feasibility of a novel capillary nano-immunoassay in assessing AR-V7 in plasma from PC patients. Methods. Patients with either localized or advanced PC were included in the study. Assessment of AR-V7 in plasma was performed through a capillary nano-immunoassay platform. Correlation with clinical data, stem cell biomarkers (such as CD133+), AR amplification and PTEN status was identified. Results. The study included 72 PC patients. AR-V7 signal was detected in 21 (29%) patients: 17 (81%) had a Gleason score ≥7, 15 (71%) castration-resistant prostate cancer (CRPC), 18 (86%) metastatic disease and PSA (median) high than AR-V7 negative (p < 0.05). CD133 was expressed in 69 (96%) patients. The median CD133+ expression in circulating tumor cells CTCs was higher among the 21 AR-V7 positive cases versus AR-V7 negative (7 vs. 3). Androgen Receptor and PTEN fluorescence in situ hybridization (FISH) on CD133+ captured cells were performed: 37 cases showed ≥four CD133+ CTCs, of which 81% showed an increased AR copy number. This percentage was similar in both AR-V7-positive and AR-V7-negative patients. A total of 68% of the cases showed deletion of PTEN: 70% were ARV-7 positive vs. 67%, which were AR-V7 negative. Conclusions. Assessing the presence of AR-V7 in plasma from PC patients is feasible by a novel capillary nano-immunoassay. AR-V7 was observed in 29% of the tumors and is more frequent in aggressive tumors (AU)

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Update on the diagnosis of invasive fungal infection / Actualización en el diagnóstico de la infección fúngica invasora

The number of patients at risk of suffering invasive fungal infection (IFI) is increasing. Because of its high mortality, new rapid and accurate diagnostic tools are needed. Last advances in invasive candidiasis diagnosis comprise Peptide Nucleic Acid Fluorescent In-Situ Hybridization (PNA-FISH), direct MALDI-TOF or multiplex acid nucleic testing. While all of them rely in positive blood cultures, T2Candida(R) uses PCR coupled with T2Magnetic resonance detection directly in whole blood, allowing detection of 1-3 UFC/mL of Candida in about four hours. Beyond galactomannan (GM), novelties in IFI caused by molds include the international standardization of PCR techniques, with several commercial kits available. A combination of GM and PCR appears to be a good diagnostic strategy for invasive aspergillosis. PCR coupled to electrospray ionization/mass spectrometry and detection of volatile organic compounds in exhaled air by gas chromatography/mass spectrometry are other promising approaches to IFI diagnostic that still need to be validated (AU)

El número de pacientes en riesgo de padecer infección fúngica invasora (IFI) está en aumento. Debido a su elevada mortalidad, es necesario disponer de nuevas herramientas diagnósticas más rápidas, sensibles y específicas que las que disponemos en la actualidad. Los últimos avances en el diagnóstico de la candidiasis invasora incluyen Hibridación In Situ de Ácidos Péptidonucleicos (PNA-FISH), MALDI-TOF directo o PCR múltiple. Mientras que todas estas técnicas se realizan sobre frascos de hemocultivo positivos, T2Candida(R) se basa en una PCR con detección por resonancia magnética T2 directamente en sangre total, y permite la detección de entre 1-3 UFC/mL de Candida en aproximadamente 4 horas. Más allá del galactomanano (GM), una de las últimas novedades en el diagnóstico de IFI causada por hongos filamentosos es la estandarización internacional de las técnicas moleculares, con la aparición de varios kits comerciales. Una buena estrategia para el diagnóstico de aspergilosis invasora es la combinación de GM y PCR. La PCR asociada a ionización por electrospray/espectrometría de masas y la detección de compuestos orgánicos volátiles en aire exhalado mediante cromatografía de gases asociada a espectrometría de masas son otras aproximaciones prometedoras al diagnóstico de IFI que aún deben ser validadas (AU)

Lesiones lipomatosas uterinas: presentación de un caso y revisión de la literatura / Uterine fatty lesions: case report and a review of the literature

Las lesiones lipomatosas uterinas son una variante poco frecuente de los tumores mesenquimales benignos. Se dividen en lipomas puros y lesiones lipomatosas (difusas o focales) en el seno de un leiomioma. Presentamos el caso de una mujer de 70 años con histerectomía simple tras el diagnóstico ecográfico de «mioma gigante». Macroscópicamente la lesión correspondía a una formación lipomatosa de 13,8cm de eje máximo e histológicamente estaba constituida por células adiposas maduras, sin septos, y con cambios atróficos y traumáticos, positivas para S100 y vimentina y negativas para MDM2 y CDK4 por inmunohistoquímica e hibridación fluorescente in situ. Focalmente se identificaban áreas de degeneración mixoide y no se observaba necrosis ni hemorragia. El estudio ultraestructural fue congruente con una proliferación celular con diferenciación adiposa (AU)

Uterine fatty lesions are a rare variant of benign mesenchymal tumours. They are divided into pure and lipomatous lesions (diffuse or focal) within a leiomyoma. We report the case of a 70 year old woman who underwent a simple hysterectomy after an ultrasound diagnosis of «giant leyomioma». Macroscopically the lesion corresponded to a lipomatous formation of 13.8cm maximum diametre. Histologically the lesion consisted of mature adipose cells without septa and traumatic and atrophic changes. There was focal myxoid degeneration, but necrosis and hemorrhage were not observed. The cells were S100 and vimentin positive on immunochemistry. MDM2 and CDK4 were negative by immunochemistry and fluorescence in situ hybridization. The ultrastructural study was consistent with a cell proliferation with adipose differentiation (AU)

Use of New Techniques in Addition to IHC Applied to the Diagnosis of Melanocytic Lesions, With Emphasis on CGH, FISH, and Mass Spectrometry / Empleo de nuevas técnicas complementarias a la IHQ para diagnóstico de lesiones melanocíticas, con énfasis en HGC, FISH y espectrometría de masas

Melanoma remains one of the most aggressive forms of cutaneous malignancies. While its diagnosis based on histologic parameters is usually straight forward in most cases, distinguishing a melanoma from a melanocytic nevus can be challenging in some instances, especially when there are overlapping clinical and histopathologic features. Occasionally, melanomas can histologically mimic other tumors and even demonstration of melanocytic origin can be challenging. Thus, several ancillary tests may be employed to arrive at the correct diagnosis. The objective of this review is to summarize these tests, including the well-established and commonly used ones such as immunohistochemistry, with specific emphasis on emerging techniques such as comparative genomic hybridization, fluorescence in situ hybridization and imaging mass spectrometry

Los melanomas continúan siendo unas de las neoplasias cutáneas más agresivas. Si bien su diagnóstico por medio de parámetros histológicos suele ser sencillo en la mayoría de los casos, la distinción entre un melanoma y un nevo melanocítico puede suponer un reto en ocasiones, sobre todo cuando las características histopatológicas y clínicas se solapan. A veces los melanomas pueden imitar histológicamente a otros tumores, e incluso demostrar el origen. melanocítico resulta complicado. Por tanto, se deben realizar varias pruebas complementarias para alcanzar el diagnóstico correcto. El objetivo de la presente revisión es resumir dichas pruebas, entre las que se incluyen algunas de uso habitual como la inmunohistoquímica, enfatizando de manera específica en las técnicas emergentes como la hibridación genómica comparativa, la hibridación in situ con fluorescencia y la espectrometría de masas

Ausencia de translocaciones cromosómicas y de expresión proteica de ALK en los adenocarcinomas nasosinusales / Absence of chromosomal translocations and protein expression of ALK in sinonasal adenocarcinomas

Introducción. Las translocaciones de la región cromosómica 2p23 causan la sobreexpresión del gen de la quinasa del linfoma anaplásico (ALK), un receptor tirosinquinasa involucrado en rutas de señalización celular que regulan la proliferación. Dicha alteración se identifica en el 5% de los adenocarcinomas de pulmón, representando una diana terapéutica en dicho subgrupo de tumores. Debido a que los adenocarcinomas nasosinusales (ACNS) tienen una histología similar a los adenocarcinomas de pulmón, el objetivo de este estudio fue evaluar si existen alteraciones en el gen ALK en los ACNS. Método. La presencia de translocaciones del gen ALK se analizó en 96 muestras de ACNS mediante fluorescence in situ hybridization usando unas sondas «break apart». Además se estudió la expresión proteica de ALK por inmunohistoquímica. Resultados. En ninguno de los casos se observó la presencia de translocaciones de ALK. Además, no se detectó expresión proteica en ninguno de los casos. Conclusiones. Los resultados obtenidos sugieren que ALK no desempeña un papel relevante en la oncogénesis de los ACNS (AU)

Introduction. Chromosomal translocations at 2p23 cause overexpression of anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase involved in signalling pathways that regulate cell proliferation. This translocation occurs in 5% of lung adenocarcinoma and has been demonstrated to be useful as a therapeutic target for crizotinib. sinonasal adenocarcinomas (SNAC) are histologically similar to lung adenocarcinomas; the aim of this study was to evaluate the presence of ALK alterations in SNAC. Method. Break-apart fluorescent in-situ hybridization was used to analyse the presence of ALK translocations in 96 tumour samples. In addition, ALK protein expression was studied by immunohistochemistry. Results. The samples of SNAC did not show ALK translocation. Moreover, ALK protein expression was absent in all cases. Conclusions. These results suggest that ALK is not involved in SNAC (AU)

Classical Hodgkin's lymphoma of the thyroid / Linfoma de Hodgkin clásico del tiroides

Hodgkin's lymphoma is characterized by the presence of Reed–Sternberg cells. The majority of cases originate at nodal sites and only rarely does it occur in extranodal locations. Here we report a case of a woman with a classical Hodgkin's lymphoma of the thyroid developed from a Hashimoto thyroiditis. She presented with a mass in her thyroid which was surgically removed. Biopsy showed a nodular sclerosis classical Hodgkin's lymphoma. Our results were similar to previously reported cases. It would appear that the lesions grew over a MALT tissue created by the lymphoid proliferation of the thyroiditis. Differential diagnosis was made between the different types of lymphomas considering those most commonly occurring in extranodal lymphoid tissues. A final diagnosis was reached after consideration of the histopathology, immunophenotyping and molecular biology (AU)

El linfoma de Hodgkin se caracteriza por la presencia de células de Reed–Sternberg. La mayor parte de los casos se originan en ganglios linfáticos y raramente en localizaciones extranodales. Comunicamos un caso de una paciente con un linfoma de Hodgkin clásico desarrollado sobre una tiroiditis de Hashimoto. Se presentó como una masa tiroidea que fue extirpada. Histológicamente mostró un linfoma de Hodgkin clásico de tipo esclerosis nodular. Nuestros resultados concuerdan con casos publicados anteriormente. La lesión posiblemente se originó sobre un tejido MALT creado por la proliferación linfoide relacionada con la tiroiditis. Realizamos diagnósticos diferenciales entre diferentes tipos de linfoma que tienen lugar en tejido linfoide extranodal. El diagnóstico final fue realizado tras considerar su histopatología, inmunofenotipo y genética molecular (AU)

Staging and evaluation of neoadjuvant chemotherapy response with 18F-FDG PET/CT in NUT-midline carcinoma in a child: A case report and review of the literature / Estadificación y evaluación de la respuesta a quimioterapia neoadyuvante con 18F-FDG PET/TAC en carcinoma de línea media - NUT en un niño: presentación de un caso y revisión de la bibliografía

NUT midline carcinoma (NMC) is a newly defined and lethal cancer with aggressive course. It mostly affects children and young adults. Diagnosis is confirmed with the evidence of BRD4-NUT mutation on the chromosome 15q14 by fluorescence in situ hybridization. Use of 18F-FDG PET/CT in NMC patients is very limited in the literature. In this report, we describe a 7-year-old boy with the diagnosis of NMC who was scanned with 18F-FDG PET/CT for staging and treatment response evaluation after the chemotherapy. It was disseminated and had moderate FDG avidity in the initial scan and showed progression after 4 cycles of chemotherapy. We also reviewed the literature related to 18F-FDG PET/CT in staging and assessment of chemotherapy response of NMC (AU)

El Carcinoma de línea media - NUT (NMC), es un cáncer letal recientemente definido con un curso agresivo. Afecta sobre todo a niños y jóvenes adultos. El diagnóstico se confirma con la evidencia de la mutación de BRD4-NUT en el cromosoma 15q14 mediante hibridación fluorescente in situ. El uso de 18F-FDG PET/TAC en pacientes con NMC está muy limitado en la bibliografía. En este informe describimos un niño de 7 años con un diagnóstico de NMC que ha sido explorado con 18F-FDG PET/TAC para la preparación y evaluación de la respuesta a la quimioterapia. El NMC estaba diseminado y mostraba una moderada captación de FDG en una exploración inicial y presentando una progresión después de 4 ciclos de quimioterapia. También analizamos la bibliografía relacionada con 18F-FDG PET/TAC en la estadificación y evaluación de la repuesta a la quimioterapia del NMC (AU)