Actualización sobre la biología molecular de los gliomas: hacia una clasificación patomolecular de los gliomas

To review the current state of the classification and oncogenesis of gliomas, emphasizing those biologic parameters with special clinical significance. DEVELOPMENT: In the current classification, both histologic grade and phenotype are considered the pathological features with more relevant clinical impact. These factors are an obligatory reference for both all molecular studies and a new classification. The relationship between the oligodendroglial phenotype and the loss of chromosomes 1p and 19q is a useful data in the histopathologic differential diagnosis. The new pathologic-molecular classification should take into account the current state of knowledge about the malignization pathways of gliomas, which have prognostic significance. The neoplastic biological potential should be determined in each case according with the tumoral heterogeneity. Then, this evaluation can be based on tumoral microdissection. Although no well established prognostic molecular profiles are available, several molecular alterations are relevant such as chromosome 10 deletion, especially of the 10q23 region, mutation of PTEN and TP53 genes and amplification or mutation of EGFR. For treatment purposes, the combined deletion 1p/19q identifies the anaplastic type of oligodendrogliomas that are more responsive to chemotherapy. CONCLUSIONS: The new pathomolecular classification of gliomas should improve the old one, especially being concerned about the oncogenesis and heterogeneity of these tumors. It is desirable that this classification has clinical applicability and can integrate new molecular findings with some known histological features with prognostic value

Cutaneous polyarteritis nodosa

Classic polyarteritis nodosa (PAN) is a segmentary leucocytoclastic vasculitis that affects small- and medium-sized arteries. In 1931, Lindberg (Acta Med Scand 1931; 76: 183-225) described the existence of a cutaneous variant of PAN, without visceral involvement and with a more favourable prognosis. We present four patients diagnosed with cutaneous PAN in our hospital between 1987 and 1998. The study group was composed of three women and one child, whose ages ranged from 11 to 70 years old. The follow-up period was between 2 and 13 years. Each patient was submitted for an initial clinical, histological and laboratory evaluation and subsequent follow-up. The presence of nodules was the most frequent cutaneous lesion, preferentially located in the lower limbs. The erythrocyte sedimentation rate was the only parameter that was altered in all patients. Cutaneous biopsies from all patients showed a segmentary leucocytoclastic vasculitis in the arteries of the deep dermis and/or hypodermis. Direct immunofluorescence was positive in just one patient. No visceral involvement was found in any patient. There is confusion about the correct definition of cutaneous PAN. Some clinical findings, such as nodules or livedo reticularis, typical of cutaneous PAN suggest a good prognosis; however, we consider that it is necessary to evaluate these patients for systemic involvement for the possibility of arteritis in other organs as the term polyarteritis suggests

Disseminated epidermolytic acanthoma probably related to trauma

Epidermolytic acanthoma is a rare benign tumour, which may occur in both isolated and disseminated forms. Only seven cases of disseminated epidermolytic acanthoma (DEA) have been described. This entity should be distinguished from other hereditary or acquired conditions which involve epidermolytic hyperkeratosis and other benign acanthomas. On the basis of the clinical history and the histological findings, we diagnosed a case of DEA which was probably secondary to repeated trauma

Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p=0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p=0.25), 16.6% versus 0% in luminal B (p=0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p<0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p<0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome. Trial registration: ClinicalTrials.gov number: NCT01431196. EudraCT 2009-017402-36

A new animal model of atrophy–hypertrophy complex and liver damage following Yttrium-90 lobar selective internal radiation therapy in rabbits

Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy–hypertrophy complex after SIRT. Three groups of 5–8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy–hypertrophy complex and liver damage without toxicity.Instituto de Salud Carlos III (ISCIII

Síndrome de Pseudomeigs en paciente con tumor de Krukenberg

e presenta el caso de una mujer de 51 años con antecedente de Linfoma no Hodking y adenocarcinoma gástrico con células en anillo de sello. Acude a nuestro centro por llevar 20 meses con disnea por derrame pleural, linfedema en ambas piernas y ascitis. Se detectan en la TC y en la ecografía dos masas anexiales bilaterales, que se biopsian. El diagnóstico histológico es metástasis ovárica bilateral por adenocarcinoma de células en anillo de sello (tumor de Krukenberg). Esta paciente presenta un síndrome de Pseudomeigs, que comprende un tumor maligno de ovario asociado con ascitis y derrame pleural con citología maligna negativa. En pacientes oncológicos con ascitis y derra- me pleural benignos se debería considerar en el diagnóstico diferencial el síndrome de PseudoMeigs. INGLÉS: We report the case of a fiftyone-year-old woman with a past medical history of Linfoma no Hodking and a gastric adenocarcinoma with signet ring cells. She came to our institution with a twenty month history of dysnea secondary to pleural effussion, bilateral lower extremity edema and probably had ascitis. On CT and US two bilateral pelvic masses were found and biopsied. The anatomopathological analysis showed bilateral ovarian implants from signet ring cell adenocarcinoma (Krukenberg tumor). This patient developed a PseudoMeigs syndrome consisting on malignant ovarian tumor asociated with ascitis and pleural effusion without malignant cells. Oncological patients who present with ascitis and benign pleural effusion, the diagnosis of PseudoMeigs syndrome should be considered

Final results regarding the addition of dendritic cell vaccines to neoadjuvant chemotherapy in early HER2-negative breast cancer patients: clinical and translational analysis

Background: Primary breast cancer (BC) has shown a higher immune infiltration than the metastatic disease, justifying the optimal scenario for immunotherapy. Recently, neoadjuvant chemotherapy (NAC) combined with immune checkpoint inhibitors has demonstrated a gain in pathological complete responses (tpCR) in patients with BC. The aim of our study is to evaluate the safety, feasibility, and efficacy of the addition of dendritic cell vaccines (DCV) to NAC in HER2-negative BC patients. Methods: Thirty-nine patients with early BC received DCV together with NAC conforming the vaccinated group (VG) and compared with 44 patients as the control group (CG). All patients received anthracyclines and taxanes-based NAC (ddECx4→Dx4) followed by surgery ± radiotherapy ± hormonotherapy. Results: The tpCR rate was 28.9% in the VG and 9.09% in the CG (p = 0.03). Pathological CR in the triple negative (TN) BC were 50.0% versus 30.7% (p = 0.25), 16.6% versus 0% in luminal B (p = 0.15), and none among luminal A patients in VG versus CG, respectively. Impact of DCV was significantly higher in the programmed cell death ligand 1 (PD-L1) negative population (p < 0.001). PD-L1 expression was increased in patients with residual disease in the VG as compared with the CG (p < 0.01). No grade ⩾3 vaccine-related adverse events occurred. With a median follow-up of 8 years, no changes were seen in event-free survival or overall survival. Phenotypic changes post DCV in peripheral blood were observed in myeloid-derived suppressor cells (MDSC), NK, and T cells. Increase in blood cell proliferation and interferon (IFN)-γ production was detected in 69% and 74% in the VG, respectively. Humoral response was also found. Clonality changes in TCR-β repertoire were detected in 67% of the patients with a drop in diversity index after treatment. Conclusion: The combination of DCV plus NAC is safe and increases tpCR, with a significant benefit among PD-L1-negative tumors. DCV modify tumor milieu and perform cellular and humoral responses in peripheral blood with no impact in outcome