High-Risk Clinicopathological and Genetic Features and Outcomes in Patients Receiving Neoadjuvant Radiochemotherapy for Locally Advanced Rectal Cancer.

Administering preoperative radiochemotherapy (RCT) in stage II-III tumors to locally advanced rectal carcinoma patients has proved to be effective in a high percentage of cases. Despite this, 20-30% of patients show no response or even disease progression. At present, preoperative response is assessed by a combination of imaging and tumor regression on histopathology, but recent studies suggest that various genetic abnormalities may be associated with the sensitivity or resistance of rectal cancer tumor cells to neoadjuvant therapy. In the present study we investigated the relationship between genetic lesions detected by high-density single-nucleotide polymorphisms (SNP) arrays 6.0 and response to neoadjuvant RCT, evaluated according to Dworak criteria in 39 rectal cancer tumors before treatment. The highest frequency of copy-number (CN) losses detected corresponded to chromosomes 18q (n = 27; 69%), 1p (n = 22; 56%), 15q (n = 19; 49%), 8p (n = 18; 48%), 4q (n = 17; 46%), and 22q (n = 17; 46%); in turn, CN gains more frequently involved chromosomes 20p (n = 22; 56%), 8p (n = 20; 51%), and 15q (n = 16; 41%). There was a significant association between alterations in the 1p, 3q, 7q, 12p, 17q, 20p, and 22q chromosomal regions and the degree of response to therapy prior to surgery. However, 4q, 15q11.1, and 15q14 chromosomal region alterations were identified as important by five prediction algorithms, i.e., those with the greatest influence on predicting the tumor response to treatment with preoperative RCT. Multivariate analysis of prognostic factors showed that gains on 15q11.1 and carcinoembryonic antigen (CEA) levels serum at diagnosis were the only independent variables predicting disease-free survival (DFS). Lymph node involvement also showed a prognostic impact on overall survival (OS) in the multivariate analysis. A deep-learning-based algorithm showed a 100% success rate in predicting both DFS and OS at 60 months after diagnosis of the disease. In summary, our results indicate the existence of an association between tumor genetic abnormalities at diagnosis, response to neoadjuvant therapy, and survival of patients with locally advanced rectal cancer. In addition to the clinical and biological characteristics of locally advanced rectal cancer patients, these could be used in the future as therapeutic and prognostic biomarkers, to identify patients sensitive or resistant to preoperative treatment, helping guide therapeutic decision-making. Additional prospective studies in larger series of patients are required to confirm the clinical utility of the newly identified biomarkers.

[Detection of herpes virus and human enterovirus in pathology samples using low-density arrays]. / Detección de virus herpes y enterovirus humanos mediante arrays de baja densidad en muestras de anatomía patológica.

Despite the frequency of infections with herpesviridae family, only eight subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and 8). Amongst enteroviruses infections, the most important are Poliovirus, Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early diagnosis is of upmost importance. Nowadays, low-density arrays can detect different types of viruses in a single assay using DNA extracted from biological samples. We analyzed 70 samples of formalin-fixed and paraffin-embedded tissue, searching for viruses (HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7 y HHV-8, Poliovirus, Echovirus and Coxsackievirus) using the kit CLART® ENTHERPEX. Out of the total of 70 samples, 29 were positive for viral infection (41.43%), and only 4 of them showed cytopathic effect (100% correlation between histology and the test). 47.6% of GVHD samples were positive for virus; 68.75% of IBD analyzed showed positivity for viral infection; in colitis with ulcers (neither GVHD nor IBD), the test was positive in 50% of the samples and was also positive in 50% of ischemic lesions. The high sensitivity of the technique makes it a useful tool for the pathologist in addition to conventional histology-based diagnosis, as a viral infection may affect treatment.

Detección de virus herpes y enterovirus humanos mediante arrays de baja densidad en muestras de anatomía patológica / Detection of herpes virus and human enterovirus in pathology samples using low-density arrays

A pesar de que las infecciones por virus de la familia Herpesviridae son muy frecuentes, tan solo 8 subtipos afectan al hombre (virus herpes simplex tipos 1 y 2, virus varicela-zoster, virus Epstein-Barr, citomegalovirus y virus herpes humano tipos 6, 7 y 8). Entre las infecciones causadas por enterovirus destacan el Poliovirus, el Coxsackievirus y el Echovirus. La clínica de estas infecciones puede variar desde un cuadro leve a una afectación sistémica grave, siendo importante el diagnóstico precoz. En la actualidad, la técnica de arrays de baja densidad es capaz de detectar diferentes virus en un mismo análisis a partir de ADN extraído de muestras biológicas. En nuestro estudio empleamos el kit CLART® ENTHERPEX, con el que analizamos 70 muestras de tejido fijado en formol y parafinado, investigando la presencia de virus (VHS-1, VHS-2, VVZ, CMV, VEB, VHH-6, VHH-7 y VHH-8, Poliovirus, Echovirus y Coxsackievirus). De las 70 muestras analizadas, en 29 (41,43%) se detectó infección vírica; solo 4 de las muestras positivas presentaban lesión citopática (correlación del 100% entre el análisis histológico y el test). Las muestras de EICH mostraron un 47,6% de positividad, en EII se detectaron un 68,75% de positivos, en colitis no EII con úlceras se detectó un 50% de positividad, y un 50% de positividad en las lesiones isquémicas. La técnica empleada tiene una alta sensibilidad, por lo que sería útil realizar la determinación como ayuda al diagnóstico basado en la histología, ya que en ocasiones la presencia de infección vírica puede modificar el manejo terapéutico (AU)

Despite the frequency of infections with herpesviridae family, only eight subtypes affect humans (Herpex Simplex Virus types 1 and 2, Varicella Zoster Virus, Epstein-Barr Virus, Citomegalovirus and Human Herpes Virus types 6, 7 and 8). Amongst enteroviruses infections, the most important are Poliovirus, Coxackievirus and Echovirus. Symptoms can vary from mild to severe and early diagnosis is of upmost importance. Nowadays, low-density arrays can detect different types of viruses in a single assay using DNA extracted from biological samples. We analyzed 70 samples of formalin-fixed and paraffin-embedded tissue, searching for viruses (HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, HHV-7 y HHV-8, Poliovirus, Echovirus and Coxsackievirus) using the kit CLART® ENTHERPEX. Out of the total of 70 samples, 29 were positive for viral infection (41.43%), and only 4 of them showed cytopathic effect (100% correlation between histology and the test). 47.6% of GVHD samples were positive for virus; 68.75% of IBD analyzed showed positivity for viral infection; in colitis with ulcers (neither GVHD nor IBD), the test was positive in 50% of the samples and was also positive in 50% of ischemic lesions. The high sensitivity of the technique makes it a useful tool for the pathologist in addition to conventional histology-based diagnosis, as a viral infection may affect treatment (AU)

Tumor de células epitelioides perivasculares de íleon. Descripción de un caso / Perivascular epithelioid cell tumor of the ileum. A case report

Los tumores de células epiteliodes perivasculares son tumores de células epiteliales vasculares con características inmunohistoquímicas de músculo liso y células melanocíticas. Los gastrointestinales son infrecuentes. El tratamiento es quirúrgico aunque existen datos que indican buena respuesta a la rapamicina (AU)

Perivascular epithelioid cell tumors (PEComa) are tumors of perivascular epithelioid cells with immunohistochemical features of smooth muscle and melanocytic tumors. The PEComa of the gastrointestinal tract is rare. The treatment is surgical, although there are data that suggest a good response to rapamycin (AU)

Tumor glioneuronal formador de rosetas. Ejemplo poco frecuente de neoplasia del IV ventrículo / Rosette-forming glioneuronal tumor. A rare neoplasm of the fourth ventricle

Presentamos un caso de tumor glioneuronal formador de rosetas del iv ventrículo observado en un adolescente de 14 años, sin antecedentes clínicos de interés. El paciente presentó un cuadro de hidrocefalia obstructiva y se le detectó radiológicamente una lesión ocupante de espacio que afectaba al vermis cerebeloso y que obstruía el iv ventrículo. Los hallazgos histopatológicos mostraron un tumor de apariencia benigna, constituido por estructuras rosetoides centradas por un material fibrilar acidófilo. Dicho tumor fue positivo tanto para marcadores neuronales (sinaptofisina y enolasa) como gliales (PGFA). Tras la descripción, se comentan brevemente las principales características de esta rara entidad (AU)

We present a case of a rosette-forming glioneuronal tumour of the fourth ventricle in a 14-year-old with no relevant previous clinical history. The patient presented with hypertensive hydrocephalus and radiology revealed a space-occupying lesion affecting the cerebellar vermis and obstructing the fourth ventricle. The tumour was removed and was seen to have a benign appearance and to be formed of rosette-like structures composed of acidophilic fibrillary material. It was positive for neuronal markers (synaptophysin and enolase) and glial markers (GRAP). The main features of this rare entity are discussed (AU)

Perivascular epithelioid cell tumor of the ileum. A case report.

Perivascular epithelioid cell tumors (PEComa) are tumors of perivascular epithelioid cells with immunohistochemical features of smooth muscle and melanocytic tumors. The PEComa of the gastrointestinal tract is rare. The treatment is surgical, although there are data that suggest a good response to rapamycin.