Manejo clínico, tratamiento y control local del tumor phyllodes mamario / Clinical management, treatment and local control of phyllodes tumors

Objetivo. Describir nuestra casuística de los últimos 13 años de acuerdo con un manejo clínico-quirúrgico y control local del tumor phyllodes según el grado tumoral. Material y método. Estudio descriptivo retrospectivo de todos los casos diagnosticados de tumor phyllodes mamario (N = 34) procedentes del Servicio de Anatomía Patológica del Hospital Clínico San Carlos de Madrid entre 1997-2010. Se realizó un análisis de los factores clínico-patológicos que pueden influir en la recidiva y en el intervalo libre de enfermedad. Resultados. La media de edad de las pacientes al diagnóstico fue de 41 años (± 13,3). Se realizó una primera cirugía conservadora en todas las pacientes (N = 34), y en 17 casos, segundas cirugías (50,0%). En 7 casos fueron mastectomías: 5 mastectomías simples y 2 mastectomías con linfadenectomía axilar. Tres casos de mastectomía se realizaron en tumor phyllodes benigno y tamaño tumoral voluminoso (12%) para lograr un buen resultado estético y en 2 pacientes con tumores phyllodes maligno (33,3%). En los otros 2 casos, además de la mastectomía se realizó una linfadenectomía axilar, en un caso por tumor phyllodes maligno con histología agresiva y en otro por recidiva voluminosa de tumor phyllodes benigno, sin evidencia de enfermedad en ambos vaciamientos axilares. En el análisis univariante hubo diferencias significativas en la necrosis histológica encontrada en los tumores phyllodes malignos. Las recidivas locales aparecieron en 8 pacientes (23,5%), principalmente durante los 2 primeros años de seguimiento. Conclusión. El principal objetivo fue conseguir mediante la cirugía (conservadora o mastectomía) márgenes de seguridad mayores de 1 cm, motivo por el que se sometió a algunas pacientes a reintervenciones posteriores. La histología agresiva en los tumores phyllodes malignos determinó en algunos casos la necesidad de realizar una mastectomía y la aplicación de radioterapia adyuvante posterior con el fin de lograr un mejor control local de la enfermedad(AU)

Aim. To describe the clinical and surgical management of phyllodes tumors in our center in the last 13 years, as well as local tumor control, according to tumoral grade. Material and method. We performed a retrospective study of all patients with a diagnosis of phyllodes tumor (N = 34) in the Pathology Department of Hospital Clínico San Carlos in Madrid between 1997 and 2010. The clinical and pathological factors that could influence recurrence and disease-free survival were analyzed. Results. The mean age of the patients at diagnosis was 41 years (± 13.3). Conservative surgery was initially performed in all patients (N = 34) and reoperation in 17 (50.0%). Mastectomies were performed in 7 patients: 5 simple mastectomies and 2 mastectomies with axillary lymphadenectomy. Three mastectomies were performed for benign phyllodes tumor and large tumor size (12%), with good cosmetic outcome, and 2 mastectomies were performed for malignant phyllodes tumors (33.3%). In the remaining 2 patients, mastectomy plus axillary lymphadenectomy was performed for a malignant phyllodes tumor with aggressive histology in one patient and for a recurrent, bulky, benign phyllodes tumor in the other. There was no evidence of disease in either of the 2 axillary dissections. In the univariate analysis, significant differences in histological necrosis were found in malignant phyllodes tumors. Local recurrences occurred in 8 patients (23.5%) mainly during the first 2 years of follow up. Conclusion. Our main objective was to achieve larger safety margins (of at least 1 cm) through surgery (mastectomy or conservative surgery), leading to reoperation in some patients. In histologically-aggressive malignant phyllodes tumors, mastectomy and adjuvant radiotherapy were required to achieve better disease control(AU)

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer.

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.

Parkin deletion causes cerebral and systemic amyloidosis in human mutated tau over-expressing mice.

Deposition of proteins leading to amyloid takes place in some neurodegenerative diseases such as Alzheimer's disease and Huntington's disease. Mutations of tau and parkin proteins produce neurofibrillary abnormalities without deposition of amyloid. Here we report that mature, parkin null, over-expressing human mutated tau (PK(-/-)/Tau(VLW)) mice have altered behaviour and dopamine neurotransmission, tau pathology in brain and amyloid deposition in brain and peripheral organs. PK(-/-)/Tau(VLW) mice have abnormal behaviour and severe drop out of dopamine neurons in the ventral midbrain, up to 70%, at 12 months and abundant phosphorylated tau positive neuritic plaques, neuro-fibrillary tangles, astrogliosis, microgliosis and plaques of murine beta-amyloid in the hippocampus. PK(-/-)/Tau(VLW) mice have organomegaly of the liver, spleen and kidneys. The electron microscopy of the liver confirmed the presence of a fibrillary protein deposits with amyloid characteristics. There is also accumulation of mouse tau in hepatocytes. These mice have lower levels of CHIP-HSP70, involved in the proteosomal degradation of tau, increased oxidative stress, measured as depletion of glutathione which, added to lack of parkin, could trigger tau accumulation and amyloidogenesis. This model is the first that demonstrates beta-amyloid deposits caused by over-expression of tau and without modification of the amyloid precursor protein, presenilins or secretases. PK(-/-)/Tau(VLW) mice provide a link between the two proteins more important for the pathogenesis of Alzheimer disease.

Carcinoma invasor de la mama: estadificación molecular del ganglio centinela / Breast invasive carcinoma: the molecular stratification of sentinel node

Demostrar que existe un grupo de pacientes estadios patológicos N0 que presentan metástasis en el estudio del ganglio centinela no diagnosticados por métodos de rutina. El estudio del análisis molecular nos informa o no sobre el pronóstico, y podría considerarse como factor independiente. Se observó una relación agrupando los casos de mayor riesgo conocido, detectándose una población de bajo riesgo en la que se obviaría la quimioterapia. Observamos, que si agrupamos las pacientes con Ki-67 mayor de 5 por ciento, la mayoría de los casos en las que se observaron micro metástasis estaban en este grupo; aceptamos una relación entre los dos factores pronóstico. Algo similar sucede con pacientes grado II y III; la relación con la existencia de micrometástasis es evidente, pudiendo aceptarse que existe un grupo de carcinomas de mama de menor agresividad; se plantea que estas pacientes no reciban tratamiento adyuvante, y no planificar tratamientos quirúrgicos agresivos.

Demonstrated that exist a group of patients with pathological stage No who present metastases in the study of sentinel nodule no diagnostic for routine method. The study of molecular analysis inform or not about the prognosis and be considered a prognosis independent factor. We observed a relation between the mayor risk known cases and detected a low risk population in which obviated the chemotherapy. We observed that grouped patients with Ki-67 raised of 5 % the majority of the cases in which observed micro metastases were in these group; we accepted a relationship between this two prognosis factors. Some similar occur with patient’s grade II and grade III; the relation with the existence of micro metastases is evident, and we accepted that exist a group of breast carcinoma of less aggressive; for these reason we planted that these patient does not receive adjuvant treatment, and no planned surgical aggressive treatment.

Diagnóstico por imagen del carcinoma de mama. Nuevos signos con mamografía digital / Diagnostic imaging in breast carcinoma. New digital mammographic signs

Diagnosticar lo más precozmente el carcinoma de mama es la misión fundamental del radiólogo en la época del “screening” de mama. Para ello deben utilizarse los mamógrafos que proporción en imágenes con la mejor resolución posible, para nosotros la mamografía digital de campo completo. Aportamos en este capítulo nuestra experiencia en las microcalcificaciones del carcinoma ductal in situ y en los nódulos no palpables malignos, exponiendo nuevos signos radiológicos que ayudan en el diagnóstico mamográfico del cáncer (AU)

An early diagnosis of breast carcinoma is the fundamental goal of radiologist at breast screening. Senographes that could bring the best image resolution should be used, and the best method is considered to be the full field digital mammography. In this chapter we provide our experience of microcalcifications in ductal carcinoma in situ and not palpable malignant nodules exposing new radiographic signs that help in the diagnosis of breast cancer (AU)

The CHEK2 1100delC allele is not relevant for risk assessment in HNPCC and HBCC Spanish families.

The frame-shift mutation 1100delC in the cell-cycle-checkpoint kinase 2 gene (CHEK2) has been reported to be a low penetrance breast cancer gene in Northern European populations. However, the variant may be relevant for breast cancer risk in other populations, due to its low prevalence. Recent studies have proposed a role for the mutation in colorectal cancer, finding a strong association between the CHEK21100delC mutation and hereditary breast and colorectal cancer (HBCC). A previous study suggested that the CHEK21100delC variant was not of clinical relevance in Spanish breast/ovarian cancer families. Here, we demonstrate that this genetic variant is not of clinical relevance for HNPCC and HBCC Spanish families.

Ultrasonographic autopsy (echopsy): a new autopsy technique.

Autopsy has been one of the most important techniques for the development of modern medicine, mainly during the nineteenth century and the first half of last century. However, in the last few years, the number of autopsies performed in hospitals has dramatically decreased all over the world. This loss of interest can be attributed both to important advances in other diagnostic and therapeutic techniques and to the fear of malpractice suits. Several groups have tried to overcome this problem, developing different autopsy techniques, one of which is needle autopsy. Most authors using this technique have acknowledged that it is difficult to obtain material from certain organs and lesions, which makes its diagnostic reliability worse than that of conventional autopsy. To overcome this drawback, our team has recently developed a modification of needle autopsy, called ultrasonographic autopsy or echopsy, in which samples are obtained under ultrasonographic control. We report the results of the first 100 cases of echopsy performed in our hospital, comparing this technique with conventional autopsy performed on all the corpses. The concordance rate for the cause of death and the main pathological diagnosis between echopsy and classical autopsy was 83% in our series, which makes echopsy a feasible and reliable alternative to conventional autopsy in cases in which families refuse to give their consent for classical autopsy or in cases of infectious diseases.