ABSTRACT
BACKGROUND: Hereditary breast cancer comprises 5-10% of all breast cancers. Mutations in two high-risk susceptibility genes, BRCA1 and BRCA2, along with rare intermediate-risk genes and common low-penetrance alleles identified, altogether explain no more than 45% of the high-risk breast cancer families, although the majority of cases are unaccounted for and are designated as BRCAX tumours. Micro RNAs have called great attention for classification of different cancer types and have been implicated in a range of important biological processes and are deregulated in cancer pathogenesis. METHODS: Here we have performed an exploratory hypothesis-generating study of miRNA expression profiles in a large series of 66 primary hereditary breast tumours by microarray analysis. RESULTS: Unsupervised clustering analysis of miRNA molecular profiles revealed distinct subgroups of BRCAX tumours, 'normal-like' BRCAX-A, 'proliferative' BRCAX-B, 'BRCA1/2-like' BRCAX-C and 'undefined' BRCAX-D subgroup. These findings introduce a new insight in the biology of hereditary breast cancer, defining specific BRCAX subgroups, which could help in the search for novel susceptibility pathways in hereditary breast cancer. CONCLUSION: Our data demonstrate that BRCAX hereditary breast tumours can be sub-classified into four previously unknown homogenous groups characterised by specific miRNA expression signatures and histopathological features.
Subject(s)
Breast Neoplasms/congenital , MicroRNAs/genetics , Transcriptome , Adult , Aged , Aged, 80 and over , Algorithms , Breast Neoplasms/classification , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Cluster Analysis , Female , Gene Expression Regulation, Neoplastic , Genes, BRCA1 , Genes, BRCA2 , Humans , Microarray Analysis , Middle AgedABSTRACT
El hemangioendotelioma epitelioide pulmonar es un raro tumor de estirpe vascular endotelial, de bajo-intermedio grado de malignidad y con comportamiento clínico impredecible. Afecta principalmente a mujeres en edad media de la vida, con escasos síntomas en el momento del diagnóstico que suele ser incidental al realizar una exploración radiológica por otro motivo. Suele cursar con nódulos pulmonares múltiples bilaterales, sin afectación ganglionar mediastínica ni pleural, que obliga al diagnóstico diferencial principalmente con enfermedad metastásica e inflamatoria granulomatosa. Aunque la tomografía por emisión de positrones (PET) puede ayudar a discernir el carácter tumoral de las lesiones, es necesario el estudio histológico tras toracotomía, en el que las técnicas de inmunohistoquímica definen el carácter vascular. El pronóstico es incierto y el tratamiento no está estandarizado. Se contempla la exéresis quirúrgica en las formas limitadas principalmente, con escasos resultados en las formas diseminadas al tratamiento quimioterápico y experiencias escasas con antiangiogénicos (AU)
Pulmonary epithelioid hemangioendothelioma is a rare vascular tumor of endothelial lineage, low-intermediate grade malignancy and unpredictable clinical behavior. It mainly affects middle-aged women of life, with few symptoms at the time of diagnosis is usually incidental when making a radiological for another reason. Usually present with multiple bilateral pulmonary nodules without mediastinal lymph node or pleural, forcing the differential diagnosis with metastatic disease primarily granulomatous inflammatory. Although positron emission tomography (PET) may help to discern the nature of the injuries tumor, histologic examination is necessary after thoracotomy, in which immunohistochemistry vascular define the character. The prognosis is uncertain and treatment is not standardized. Surgical excision is contemplated in the limited ways mainly to poor results in disseminated forms to chemotherapy and antiangiogenic drug scarce experiences (AU)
Subject(s)
Humans , Female , Middle Aged , Hemangioendothelioma, Epithelioid/diagnosis , Multiple Pulmonary Nodules/diagnosis , Diagnosis, Differential , Lung Neoplasms/diagnosis , Angiogenesis Inhibitors/therapeutic useABSTRACT
Breast tumors in adolescents are very rare and mostly benign. Fibroadenomas are the most frequent, but within the extensive differential diagnosis, the phyllodes tumor must be mentioned, which accounts for about 1% of breast tumors and the diagnosis of which is very rare in patients younger than 20 years. There are no specific symptoms or radiological images to distinguish phyllodes tumor from fibroadenoma; therefore, histological examination is mandatory for diagnosis. Histology also allows the classification of phyllodes tumor into benign, borderline, or malignant types for appropriate surgical treatment: freemargin excision in benign tumors and mastectomy in the other two types. Fortunately, the majority of these tumors are benign, and treatment maximizes breast conservation with free infiltration margins surgery, given that this fact is the most important factor to prevent local recurrence. In this article, we describe a rare case of borderline cystosarcoma phyllodes in a 12-year-old girl (AU)
Subject(s)
Humans , Female , Child , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Mastectomy/methods , Mastectomy , Phyllodes Tumor/surgeryABSTRACT
The aim of the present study was to evaluate the expression of blood group antigens in squamous bronchial metaplasia in order to determine whether this factor could identify patients at risk of lung cancer. In total, 100 bronchial biopsies were included in the present study. The cases were classified according to the World Health Organization grading system. Immunohistochemical stains for histo-blood groups A and B, and reactivity tests to p53 and the cellular proliferation index were performed. A total of 56 (56%) patients belonged to blood group A. Among them, six (10.7%) patients who did not express antigen in squamous metaplasia, showed carcinoma at the moment of the biopsy (n = 3) or developed synchronous lung carcinoma (n = 3). A total of nine (9%) patients belonged to blood group B. Loss of antigenic expression was observed in five cases. All of them developed synchronous lung carcinoma. The patients with low- and high-grade dysplasia developed lung cancer in 71 and 100% of the cases, respectively. In conclusion, the findings of the present study suggest that the loss of histo-blood antigens expression is an event in the carcinogenesis of bronchial mucosa and it is usually associated with high-grade lesions and hyperproliferative activity.
Subject(s)
ABO Blood-Group System/analysis , Bronchi/chemistry , Bronchial Neoplasms/diagnosis , Carcinoma, Squamous Cell/diagnosis , Adult , Aged , Aged, 80 and over , Bronchi/pathology , Bronchial Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Female , Humans , Male , Metaplasia/pathology , Middle Aged , Prognosis , Tumor Suppressor Protein p53/analysisABSTRACT
UNLABELLED: Bronchial mucoepidermoid tumors are uncommon neoplasms, morphologically similar to their salivary gland counterpart. The histogenesis is controversial. The aim of this study is to identify myoepithelial cells and speculate on their role in the origin of these tumors. METHODS AND RESULTS: Sixteen bronchial mucoepidermoid tumor surgical specimens were formalin-fixed, paraffin-embedded and studied using a panel of nine antibodies in order to identify a myoepithelial differentiation. Additional antigens against several cytokeratins were performed in four cases and five of the biopies were studied using the electron microscopy. The different types of cells of the primary bronchial mucoepidermoid tumor (mucous luminal, intermediate and squamous) reacted strongly against AE1, CK7, 34bE12 and weakly with AE3, CK18 and CK8/18/19. S-100, alpha-smooth muscle actin, muscle actin HHF35 and alpha-actinin were consistently negative in all cell types. CD10 was positive in very few cells in just one case. CONCLUSION: The immunohistochemical and the ultrastructural study of bronchial mucoepidermiod tumors support a ductal unit origin, without a myoepithelial participation.
Subject(s)
Bronchi/pathology , Bronchi/ultrastructure , Bronchial Neoplasms/pathology , Bronchial Neoplasms/ultrastructure , Gene Expression Regulation, Neoplastic , Mucoepidermoid Tumor/pathology , Mucoepidermoid Tumor/ultrastructure , Adult , Aged , Antigens, Neoplasm/biosynthesis , Biopsy , Female , Humans , Immunohistochemistry , Male , Microscopy, Electron , Middle AgedABSTRACT
Propósito: Los tumores pulmonares con diferenciación neuroendocrina (DN) son un grupo heterogéneode neoplasias que incluyen tumores carcinoides típicos, carcinoides atípicos, carcinomas neuroendocrinosde células grandes (CNCG) y carcinoma pulmonar de células pequeñas. Los CNCGconstituyen menos del 5% de los carcinomas pulmonares no células pequeñas (CPNCP). En este trabajose describe una serie de CNCG, tratados en un solo centro a lo largo de 10 años.Material y métodos: Se analizan 11 pacientes diagnosticados de CNCG (5 con histologías mixtas).Resultados: La edad media de los pacientes fue de 66 años, 5 fueron varones, 4 tuvieron enfermedadlocalizada, 5 localmente avanzada y 2 diseminada. Siete pacientes, con tumores localizados,fueron tratados con cirugía radical, 2 de ellos recibieron quimioterapia adyuvante; 1 quimioterapia yradioterapia y los otros 3 solo quimioterapia. La mediana de supervivencia de la serie es de 24 meses,y la supervivencia global a 2 y 5 años del 45% y 27% respectivamente.Conclusión: Los datos de nuestra serie corroboran las recomendaciones de que el manejo de losCNCG debe hacerse de forma similar al del resto de los CPNCP. La cirugía radical es el tratamientofundamental en los tumores localizados. No hay datos suficientes que indiquen una peor respuesta alos tratamientos de quimioterapia o radioterapia en este tipo de tumores
Purpose: Lung carcinomas with neuroendocrine differentiation are a heterogeneous group oftumors related to typical and atypical carcinoids, neuroendocrine large-cell carcinomas (NLCC) andsmall-cell lung cancer (SCLC). NLCC comprises less than 5% of non small-cell lung cancer (NSCLC).In this report, we describe a series of NLCC treated in a single institution in the last ten years.Material and methods: Eleven patients diagnosed as having NLCC (5 of them with mixedhistology).Results: At diagnosis, the mean age of the patients was 66 years (5 males and 6 females); 4 hadlocalized disease, 5 locally advanced disease, and 2 metastatic disease. Seven patients underwent initialradical surgery (2 of them followed by adjuvant chemotherapy), 1 patient received chemotherapy andradiotherapy, and 3 patients only chemotherapy. Median overall survival for the whole series was 24months, and the overall 2-year and 5-year survival were 45% and 27% respectively.Conclusion: Our data corroborate the general recommendation of treating NLCC in a similar wayas the rest of the non small-cell lung cancer (NSCLC) are treated. Radical surgery is the maintreatment for localized tumors. There are no data indicating a worse response of these tumors toradiation therapy or chemotherapy
Subject(s)
Male , Female , Aged , Middle Aged , Humans , Carcinoma, Neuroendocrine/pathology , Lung Neoplasms/pathology , Carcinoma, Large Cell/pathologyABSTRACT
We assessed the clinicopathological features of solitary fibrous tumors of the pleura in a case series comprising 30 patients (20 women, 66.6%) with a mean age of 58.39 years. Forty-five percent of the cases were asymptomatic. In 70% of the cases the tumors arose in the visceral pleura. Twenty percent presented multiple tumors, a finding that was associated with intrapulmonary localization and malignant behavior (P<.0001) Histology revealed low cell density in 15% of the cases, moderate density in 50%, and high density in 35%; further findings showed atypia in 45% of the cases, necrosis in 25%, and hemorrhage in 15%. More than 4 mitoses per 10 high-power fields were noted in 30% of the cases. Immunohistochemistry results were positive for vimentin in all cases; cells were CD34+ in 85% of the cases, BCL2+ in 65%, and CD99+ in 40%. Findings for keratin and protein S100 were negative in all cases. Malignant biological behavior (local recurrence and metastasis) was observed in 4 cases, 2 of which were CD34-. Solitary fibrous tumors of the pleura are uncommon neoplasms with unpredictable biological behavior; follow-up should therefore be based on early detection of recurrence or metastasis.
Subject(s)
Neoplasms, Fibrous Tissue/pathology , Pleural Neoplasms/pathology , Adolescent , Adult , Aged , Female , Humans , Male , Middle AgedABSTRACT
Hemos evaluado las características clinicopatológicas del tumor fibroso solitario pleural en una serie de 30 casos. El 70% de los pacientes eran mujeres. El promedio de edad fue de 58,39 años. El 45% de los casos fueron asintomáticos. La localización más frecuente fue la pleura visceral (70%). En el 20% de los casos se observaron tumoraciones múltiples y se asociaron a localización intrapulmonar (p < 0,0001). Histológicamente mostraron densidad celular escasa en el 15% de los casos, moderada en el 50% e intensa en el 35%; atipia en el 45%; necrosis en el 25%; hemorragia en el 15%, y mitosis mayor de 4 por 10 campos en el 30%. La inmuhistoquímica mostró positividad para vimentina (100%), CD34 (85%), BCL2 (65%) y CD99 (40%), y negatividad en el 100% de los casos para queratinas y la proteína S100. Cuatro pacientes presentaron un comportamiento biológico maligno (recurrencia local y metástasis); en 2 de ellos el CD34 había sido negativo. El tumor fibroso solitario pleural es una neoplasia poco común de comportamiento biológico impredecible, por lo que el seguimiento debe centrarse en la detección precoz de la recurrencia o de metástasis
We assessed the clinicopathological features of solitary fibrous tumors of the pleura in a case series comprising 30 patients (20 women, 66.6%) with a mean age of 58.39 years. Forty-five percent of the cases were asymptomatic. In 70% of the cases the tumors arose in the visceral pleura. Twenty percent presented multiple tumors, a finding that was associated with intrapulmonary localization and malignant behavior (P<.0001) Histology revealed low cell density in 15% of the cases, moderate density in 50%, and high density in 35%; further findings showed atypia in 45% of the cases, necrosis in 25%, and hemorrhage in 15%. More than 4 mitoses per 10 high-power fields were noted in 30% of the cases. Immunohistochemistry results were positive for vimentin in all cases; cells were CD34+ in 85% of the cases, BCL2+ in 65%, and CD99+ in 40%. Findings for keratin and protein S100 were negative in all cases. Malignant biological behavior (local recurrence and metastasis) was observed in 4 cases, 2 of which were CD34. Solitary fibrous tumors of the pleura are uncommon neoplasms with unpredictable biological behavior; follow-up should therefore be based on early detection of recurrence or metastasis
