Level of tumor-infiltrating lymphocytes and density of infiltrating immune cells in different malignancies.

Aim: To correlate levels of tumor-infiltrating lymphocytes (TIL) evaluated using the International Immuno-Oncology Biomarker Working Group methodology, and both density of tumor-infiltrating immune cell and clinicopathological features in different malignancies. Methods: 209 pathological samples from gastric cancer, cervical cancer (CC), non-small-lung cancer, cutaneous melanoma (CM) and glioblastoma were tested for TIL in hematoxylin eosin, and density of CD3+, CD4+, CD8+, CD20+, CD68+ and CD163+ cells by digital analysis. Results: TIL levels were higher in invasive margin compartments (IMC). TIL in IMC, intratumoral and stromal compartments predicted survival. CC and gastric cancer had higher TIL in intratumoral; CC and CM had higher TIL in stromal compartment and IMC. CM had the highest density of lymphocyte and macrophage populations. CD20 density was associated with survival in the whole series. Conclusion: Standardized evaluation of TIL levels may provide valuable prognostic information in a spectrum of different malignancies.

MGMT promoter methylation in Peruvian patients with glioblastoma.

PURPOSE: O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation predicts the outcome and response to alkylating chemotherapy in glioblastoma. The aim of this study is to evaluate the prevalence of MGMT methylation in Peruvian glioblastoma cases. PATIENTS AND METHODS: We evaluated retrospectively 50 cases of resected glioblastoma during the period 2008-2013 at Instituto Nacional de Enfermedades Neoplasicas in Peru. Samples consisted of paraffin embedded and frozen tumour tissue. MGMT-promoter methylation status and the expression level of MGMT gene were evaluated by methylation-specific PCR and real-time PCR, respectively. RESULTS: Unmethylated, methylated and partially methylated statuses were found in 54%, 20% and 26% of paraffin-embedded samples, respectively. Methylation status was confirmed in the Virgen de la Salud Hospital and frozen samples. There was an association between the status of MGMT-promoter methylation and the level of gene expression (p = 0.001). Methylation was associated with increased progression-free survival (p = 0.002) and overall survival (OS) (p < 0.001). CONCLUSION: MGMT-promoter methylation frequency in Peruvian glioblastoma is similar to that reported in other populations and the detection test has been standardised.

Impact of pathological features of brain metastases in prognosis.

AIM: To evaluate the prognostic value of tumor-infiltrating lymphocytes (TILs) and Ki67 in brain metastasis lesions, and the effect of adding them to variables of graded prognostic assessment score. PATIENTS & METHODS: Clinicopathological information from 111 medical charts of brain metastasis patients was obtained, and TIL distribution (n = 84), Ki67 index (n = 79) and CD3 TIL (n = 64) were prospectively evaluated. RESULTS: Most frequent TIL pattern was perivascular (67.8%), and median Ki67 and CD3 TIL percents were 30 and 4.8%, respectively. Ki67 ≥15 was associated with shorter survival (p = 0.018) but CD3 TIL was not (p = 0.870). The highest graded prognostic assessment score was not associated with survival (p = 0.648), however, those with low Ki67 and high score was associated with better outcome (p = 0.007). CONCLUSION: High Ki67 index in brain metastasis carries a worse prognosis.

Distribution of tumor-infiltrating immune cells in glioblastoma.

AIM: Evaluation of features related to infiltrating immune cell level in glioblastoma. METHODS: Tumor-infiltrating lymphocytes (TILs) through H&E staining, and TILs (CD3, CD4, CD8 and CD20) and macrophage (CD68 and CD163) levels through immunohistochemistry were evaluated through digital analysis. RESULTS: CD68 (9.1%), CD163 (2.2%), CD3 (1.6%) and CD8 (1.6%) had the highest density. Higher CD4+ was associated with unmethylated MGMT (p = 0.016). Higher CD8+ was associated with larger tumoral size (p = 0.027). Higher CD163+ was associated with higher age (p = 0.044) and recursive partitioning analysis = 4. Women (p < 0.05), total resection (p < 0.05), MGMT-methylation (p < 0.001), radiotherapy (p < 0.001), chemotherapy (p < 0.001) and lower CD4+ (p < 0.05) were associated with longer overall survival. CONCLUSION: Macrophages are more frequent than TILs. Some subsets are associated with clinical features.

Glioblastoma of pineal region: report of four cases and literature review.

We report four cases of glioblastoma in the pineal region. The patients presented a severe headache and vomiting. Brain imaging showed a heterogeneously enhanced tumor in the pineal region with obstructive hydrocephalus. Case 3 developed a subependymal dissemination. The patient went to ventricular-peritoneal shunt and subtotal or total resection and radiotherapy with/without chemotherapy. Cases 1 and 2 received radiation and died 8 and 11 later months. Cases 3 and 4 completed radiotherapy and chemotherapy, and survived 28 and 31 months after the initial diagnosis. Glioblastoma in the pineal region carry a poor prognosis and require neurooncology teams.

[Microsurgical resection of glioblastoma guided with intraoperative fluorescein: a Retrospective evaluation]. / Resección microquirúrgica de glioblastoma guiada con fluoresceína intraoperatoria: evaluación retrospectiva.

OBJECTIVES: To evaluate the influence of the use of sodium fluorescein (FLS-Na) in surgery of glioblastoma (GB) on the degree of tumor resection and survival in patients treated at the National Institute of Neoplastic Diseases. MATERIALS AND METHODS: A total of 238 cases of GB treated between 2008 and 2013 were reviewed and 150 cases of GB who underwent surgical resection with clinicopathological information and adequate follow-up were selected. RESULTS: The mean age was 51 years, 58.7% of the cases presented a Karnofsky score of at least 90. FLS-Na was administered in 80 cases (53.3%) and a subtotal and total resection was obtained in 69 (46%) and 81 (54%) cases, respectively. The group that received FLS-Na obtained higher rates of total resection than the group operated with white light alone (77.5 vs 27.1%, p<0.001). The median overall survival (OS) was higher in the group subject to total compared to subtotal resection (17 vs 7 months, p<0.001). The median OS in those who received FLS-Na was higher than in those who did not (15.0 vs 8 months, p=0.003). Other factors affecting OS were age (p=0.002), the Karnofsky score (p=0.052) and radiation therapy (p=0.016) and chemotherapy (p=0.011). CONCLUSIONS: The microsurgical technique with administration of FLS-Na was associated with an increase in the rate of total resection and survival.

[Glioblastoma: Molecular analysis and its clinical implications]. / Glioblastoma: Análisis molecular y sus implicancias clínicas.

Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic information indicate that its incidence is lower in Hispanic race. Surgery is the only curative strategy and has recently introduced new strategies that increase resection rates. The use of concurrent chemotherapy with radiotherapy improves survival of patients but is associated with toxicity. Improved understanding of molecular biology of GB allows the identification of predictive biomarkers of response and prognosis as well as therapeutic targets for the development of new therapeutic strategies. Among biomarkers are currently available 1p /19q codeletion, IDH mutation and O6-methylguanine DNAmethyltransferase promoter methylation. The identification therapeutic targets enables the development of new drugs and their evaluation in clinical trials, but none has been prospectively validated in phase III clinical trials.

Glioblastoma: análisis molecular y sus implicancias clínicas / Glioblastoma: molecular analysis and its clinical implications

El glioblastoma multiforme (GB) es el tumor cerebral primario del sistema nervioso central (SNC) más frecuente y más letal en la edad adulta. La evidencia epidemiológica indica que su incidencia es menor en la raza hispana. El tratamiento quirúrgico es la opción terapéutica preferente. Recientemente se han introducido nuevas estrategias que incrementan el volumen de resección. El uso de quimioterapia y radioterapia concurrentes mejora la supervivencia de los pacientes, aunque se asocia a toxicidad. La mejora en la comprensión de la biología molecular del GB ha permitido la identificación de biomarcadores predictivos de respuesta terapéutica y pronóstico, así como la identificación de dianas terapéuticas que han permitido el desarrollo de nuevas estrategias en el tratamiento de estos tumores. Entre los biomarcadores actualmente disponibles se encuentran la codelección 1p/19q, la mutación de IDH y la metilación del promotor O6- metilguanina DNA-metiltransferasa. La identificación de dianas terapéuticas permite el desarrollo de nuevas drogas y su evaluación posterior en ensayos clínicos, aunque ninguna de ellas ha sido validada prospectivamente en ensayos clínicos de fase III.

Glioblastoma (GB) is the most common and most lethal primary brain tumor. Epidemiologic information indicate that its incidence is lower in Hispanic race. Surgery is the only curative strategy and has recently introduced new strategies that increase resection rates. The use of concurrent chemotherapy with radiotherapy improves survival of patients but is associated with toxicity. Improved understanding of molecular biology of GB allows the identification of predictive biomarkers of response and prognosis as well as therapeutic targets for the development of new therapeutic strategies. Among biomarkers are currently available 1p /19q codeletion, IDH mutation and O6-methylguanine DNAmethyltransferase promoter methylation. The identification therapeutic targets enables the development of new drugs and their evaluation in clinical trials, but none has been prospectively validated in phase III clinical trials.

Resección microquirúrgica de glioblastoma guiada con fluoresceína intraoperatoria: evaluación retrospectiva / Microsurgical resection of glioblastoma guided with intraoperative fluorescein: a retrospective evaluation

Evaluar la influencia del uso de fluoresceína sódica (FLS-Na) en la cirugía del glioblastoma (GB) sobre el grado de resección tumoral y la supervivencia en pacientes atendidos en el Instituto Nacional de Enfermedades Neoplásicas. Materiales y métodos. Se revisó un total de 238 casos de GB atendidos entre los años 2008 y 2013 y se seleccionó 150 casos de GB sometidos a resección quirúrgica, con información clínico-patológica y seguimiento adecuado. Resultados. La media de edad fue 51 años, el 58,7% de casos presento Karnofsky de al menos 90. Se administró FLS-Na en 80 casos (53,3%) y se obtuvo una resección subtotal y total en 69 (46%) y 81 (54%) de los casos, respectivamente. El grupo que recibió FLS-Na obtuvo mayores tasas de resección total que el grupo operado solo con luz blanca (77,5 vs 27,1%, p<0,001). La mediana de sobrevida global (SG) fue mayor en el grupo sometido a resección total que a subtotal (17 vs 7 meses, p<0,001). La mediana de SG en los que recibieron FLS-Na fue mayor que en los que no la recibieron (15,0 vs 8 meses, p=0,003). Otros factores que afectaron la SG fueron la edad (p=0,002), el Karnofsky (p=0,052) y la administración de radioterapia (p=0,016) y quimioterapia (p=0,011). Conclusiones. La técnica microquirúrgica con administración de FLS-Na se asoció con un aumento en la tasa de resecciones totales y de supervivencia...

To evaluate the influence of the use of sodium fluorescein (FLS-Na) in surgery of glioblastoma (GB) on the degree of tumor resection and survival in patients treated at the National Institute of Neoplastic Diseases. Materials and methods. A total of 238 cases of GB treated between 2008 and 2013 were reviewed and 150 cases of GB who underwent surgical resection with clinicopathological information and adequate follow-up were selected. Results. The mean age was 51 years, 58.7% of the cases presented a Karnofsky score of at least 90. FLS-Na was administered in 80 cases (53.3%) and a subtotal and total resection was obtained in 69 (46%) and 81 (54%) cases, respectively. The group that received FLS-Na obtained higher rates of total resection than the group operated with white light alone (77.5 vs 27.1%, p<0.001). The median overall survival (OS) was higher in the group subject to total compared to subtotal resection (17 vs 7 months, p<0.001). The median OS in those who received FLS-Na was higher than in those who did not (15.0 vs 8 months, p=0.003). Other factors affecting OS were age (p=0.002), the Karnofsky score (p=0.052) and radiation therapy (p=0.016) and chemotherapy (p=0.011). Conclusions. The microsurgical technique with administration of FLS-Na was associated with an increase in the rate of total resection and survival...

Glioblastoma multiforme metastásico a ganglio linfático cervical: reporte de un caso y revisión de la literatura / Glioblastoma multiforme metastatic cervical lymph node: a case report and literature review

El Glioblastoma Multiforme (GBM) es el tumor cerebral primario más común en los adultos, la metástasis extra-craneal de GBM detectada clínicamente es bastante rara, debido a la ausencia de linfáticos en el cerebro y a la dificultad de los tumores en penetrar los vasos sanguíneos. Se producen entre el 0,2 a 2% según 10 reportado en la literatura disponible. Se reporta un caso de rara presentación de una paciente de 53 añ os con diagnóstico de Glioblastoma multiforme localizado en región interparietal derecha y otra lesion en region fronto-parietal derecha (multifocal). Se le realiza biopsia estereotáxica para diagnóstico y recibio tratamiento con radioterapia conformada en 3D al primario. Posteriormente a los 2 meses presenta metástasis linfática en ganglio cervical derecho, diagnosticado por citología y biopsia incisional. Así mismo se realiza revisión de la literatura. Se discuten el impacto de la cirugía en la diseminación tumoral y las posibles vías de diseminación.

Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in adults. The presence of extra-cranial GBM metastasis is very rare, because the absence of brain lympha- tics and the difficulty of tumors cells to penetrate into blood vessels, occurring only between 0.2 to 2% of the cases reported in the available literature. A case of extreme rarity is presented: A female 53 year old patient, with diagnosis ofGliobastoma multiforme localized in the right interparietal region and another lesion in the rightfrontal-parietal region (multifocal). She underwent diagnostic stereotactic biopsy and was treated with 3D conformal radiotherapy in the primary. Two months later the patient presents lymphatic metastasis in the right cervical lymph node, diagnosed by cytology and incisional biopsy. A review of the literature is presented. The impacts of surgery in tumor dissemination and possible tumor dissemination schemes are discussed.

Oligodendroglioma anaplásico primario de la médula espinal / Primary anaplastic oligodendroglioma of the spinal cord

El oligodendroglioma de la médula espinal es una neoplasia extremadamente rara y solo se han reportado 52 casos en la literatura. Se reporta el caso de un paciente varón de 52 años, con paraplejia y un tumor en la medula espinal a nivel de C7 a T4. El diagnóstico final fue oligodendroglioma anaplásico con deleción del cromosoma 1p.

Spinal cord oligodendroglioma is an extremely unusual glial neoplasm and only 52 cases have been reported at this time. We report the case of a 52 year-old man with paraplegia and an intramedullary tumor of the spinal cord at levels C7 to T4. The final diagnosis was anaplastic oligodendroglioma with an isolated chromosome 1p deletion.