Antonio Gómez

Radiologic Evaluation of Breast Disorders Related to Pregnancy and Lactation

During pregnancy and lactation, the breast can be affected by a variety of specific and unique disorders, including benign disorders closely related to physiologic changes, inflammatory and infectious diseases, juvenile papillomatosis, and benign and malignant tumors. Patients with pregnancy-associated breast carcinoma tend to have more advanced neoplasms at diagnosis and a poorer prognosis due to delayed diagnosis and a more aggressive biologic pattern. Pregnancy-related Burkitt lymphoma characteristically manifests with bilateral and diffuse involvement of the breasts. Fibroadenoma may manifest with growth, infarction, large cysts, prominent ducts, and secretory hyperplasia during pregnancy and lactation. Galactocele is the breast lesion most commonly found during lactation and manifests as either pseudolipoma, a cystic mass with a fat-fluid level, or pseudohamartoma. Tumors and diseases affecting the breasts during pregnancy and lactation are basically the same as those observed in nonpregnant women but may have a different appearance. The sensitivity of mammography in pregnant and lactating women is decreased due to increased parenchymal density. Instead, ultrasonography is the most appropriate radiologic method for evaluating breast masses in this setting and is particularly useful in the diagnosis and treatment of abscesses. Knowledge of the unique entities that are specifically related to pregnancy and lactation and of their radiologic-pathologic appearances can help the radiologist make the correct diagnosis.

Lymphoma of the breast: clinical and radiologic features with pathologic correlation in 28 patients.

The objective of this study was to determine the clinical and radiologic findings of lymphoma involving the breast, separately evaluating primary and secondary forms. We retrospectively reviewed the medical reports of 28 patients with lymphoma of the breast: 12 patients with primary lymphoma and 16 with secondary lymphoma. In primary lymphoma, mammography revealed a solitary mass (58.3%), multiple unilateral masses (8.3%), unilateral diffuse involvement (25%), and bilateral diffuse involvement (8.3%). The margins of masses were irregular (50%), partially defined (37.5%), and well defined (12.5%). The mean diameter of the masses was 4.6 cm. In secondary lymphoma, mammography revealed multiple masses (56.2%), solitary masses (12.5%), and diffuse unilateral breast involvement (31.2%). Their margins were irregular (18.1%), partially defined (27.2%), and well‐defined (54.5%). The mean diameter of the masses was 2.8 cm. Cytologic examination (n = 13) was demonstrative of lymphomatous involvement in all cases. We observed an association between high‐grade types of malignancy and a diffuse pattern of radiologic breast involvement. Masses in primary disease tended to have less‐defined margins and greater diameters than those observed in secondary cases. Cytologic examination proved to be a useful diagnostic procedure in the evaluation of secondary disease. The involvement of the breast in extranodal lymphomas does not seem to affect the prognosis of the disease.

MAX Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1

Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplification of L-MYC, N-MYC, and C-MYC being some of the well-established gene alterations. Here, we report our discovery of tumor-specific inactivation of the MYC-associated factor X gene, MAX, in SCLC. MAX inactivation is mutually exclusive with alterations of MYC and BRG1, the latter coding for an ATPase of the switch/sucrose nonfermentable (SWI/SNF) complex. We demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to upregulate MYC targets, such as glycolysis-related genes. Finally, inactivation of the MAX dimerization protein, MGA, was also observed in both non-small cell lung cancer and SCLC. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development.

Nuevos criterios de clasificación de artritis reumatoide

In September 2010, new criteria for the classification of rheumatoid arthritis (RA) were published, with the intention of allowing an early diagnosis of the disease. These new criteria are targeted to an earlier form of RA than allowed by the criteria that had been used up to that point. In this review we comment the methodology used for the creation of the new classification criteria, its advantages with respect to the older ones, its shortcomings and the consequences their application will have.

Validation of DNA methylation profiling in formalin-fixed paraffin-embedded samples using the Infinium HumanMethylation450 Microarray

A formalin-fixed paraffin-embedded (FFPE) sample usually yields highly degraded DNA, which limits the use of techniques requiring high-quality DNA, such as Infinium Methylation microarrays. To overcome this restriction, we have applied an FFPE restoration procedure consisting of DNA repair and ligation processes in a set of paired fresh-frozen (FF) and FFPE samples. We validated the FFPE results in comparison with matched FF samples, enabling us to use FFPE samples on the Infinium HumanMethylation450 Methylation array.

Lupus panniculitis involving the breast

Lupus panniculitis is an unusual immunological disease that characteristically affects the subcutaneous fat and occurs in 2% of patients with systemic lupus erythematosus. We report a case of lupus panniculitis involving the breast, which represents a very uncommon location. Mammographically, it presented as a suspicious irregular mass involving the subcutaneous fat pad with skin thickening. High echogenicity constituted the most relevant sonographic finding. To the best of our knowledge, the magnetic resonance (MR) features have not been previously described. High signal intensity was found on both T1- and T2-weighted precontrast MR images. A dynamic contrast-enhanced study revealed a suspicious focal mass with irregular margins and rim enhancement, with a type 3 time-signal intensity curve. Differential diagnosis with carcinoma and fat necrosis and the value of core biopsy are discussed.

Déficit de vitamina D en la fractura osteoporótica de cadera y factores asociados

Fundamento Y Objetivo La hipovitaminosis D es frecuente entre los ancianos y especialmente prevalente en los pacientes con fractura de cadera. La prevalencia y los factores asociados a este deficit vitaminico son poco conocidos en nuestro medio. El objetivo del presente trabajo ha sido determinar la prevalencia de hipovitaminosis D en los pacientes con fractura osteoporotica de cadera y analizar los posibles factores que favorecen dicho deficit. Pacientes Y Metodo Se ha realizado un estudio transversal, en el que se incluyo de forma consecutiva a todos los pacientes mayores de 65 anos ingresados con fractura osteoporotica de cadera durante el periodo comprendido entre marzo de 2002 y febrero de 2003. Se investigo la prevalencia de hipovitaminosis D y de hiperparatiroidismo secundario. Se recogieron el grado de exposicion solar, la capacidad funcional, el estado nutricional y la presencia de comorbilidad. Resultados Se incluyo a 324 pacientes con una edad media (desviacion estandar) de 83 (7) anos; un 80% eran mujeres. Se observo hipovitaminosis D en 217 casos (67%; intervalo de confianza [IC] del 95%, 62-72%), de los que el 57% presentaba hiperparatiroidismo secundario. El mal estado nutricional –valores de albumina Conclusiones La prevalencia de hipovitaminosis D es alta en los pacientes con una fractura osteoporotica de cadera y en mas de la mitad de ellos condiciona la presencia de hiperparatiroidismo secundario. Este deficit es especialmente prevalente entre los individuos con poca exposicion solar, mal estado nutricional y baja capacidad funcional.

A dynamic model of the proteins that form the initial iron-sulfur cluster biogenesis machinery in yeast mitochondria.

The assembly of iron-sulfur clusters (ISCs) in eukaryotes involves the protein Frataxin. Deficits in this protein have been associated with iron inside the mitochondria and impair ISC biogenesis as it is postulated to act as the iron donor for ISCs assembly in this organelle. A pronounced lack of Frataxin causes Friedreich’s Ataxia, which is a human neurodegenerative and hereditary disease mainly affecting the equilibrium, coordination, muscles and heart. Moreover, it is the most common autosomal recessive ataxia. High similarities between the human and yeast molecular mechanisms that involve Frataxin have been suggested making yeast a good model to study that process. In yeast, the protein complex that forms the central assembly platform for the initial step of ISC biogenesis is composed by yeast frataxin homolog, Nfs1–Isd11 and Isu. In general, it is commonly accepted that protein function involves interaction with other protein partners, but in this case not enough is known about the structure of the protein complex and, therefore, how it exactly functions. The objective of this work is to model the protein complex in order to gain insight into structural details that end up with its biological function. To achieve this goal several bioinformatics tools, modeling techniques and protein docking programs have been used. As a result, the structure of the protein complex and the dynamic behavior of its components, along with that of the iron and sulfur atoms required for the ISC assembly, have been modeled. This hypothesis will help to better understand the function and molecular properties of Frataxin as well as those of its ISC assembly protein partners.

Microglandular adenosis of the breast in a BRCA1 mutation carrier: radiological features

Abstract. Microglandular adenosis is a very uncommon benign proliferative disorder of the breast that may mimic tubular carcinoma radiologically and pathologically. We describe the radiological features of this rare condition in a patient with BRCA 1 mutation. To our knowledge, this is the first case of microglandular adenosis reported in the radiology literature. The relationship between microglandular adenosis and malignancy and the association between BRCA 1 and proliferative benign disorders are also discussed.

GENOMIC PROFILING OF PATIENT-DERIVED XENOGRAFTS FOR LUNG CANCER IDENTIFIES B2M INACTIVATION IMPAIRING IMMUNORECOGNITION

Purpose: We aimed to maximize the performance of detecting genetic alterations in lung cancer using high-throughput sequencing for patient-derived xenografts (PDXs). Experimental Design: We undertook an integrated RNA and whole-exome sequencing of 14 PDXs. We focused on the genetic and functional analysis of β2-microglobulin (B2M), a component of the HLA class-I complex. Results: We identified alterations in genes involved in various functions, such as B2M involved in immunosurveillance. We extended the mutational analysis of B2M to about 230 lung cancers. Five percent of the lung cancers carried somatic mutations, most of which impaired the correct formation of the HLA-I complex. We also report that genes such as CALR, PDIA3, and TAP1, which are involved in the maturation of the HLA-I complex, are altered in lung cancer. By gene expression microarrays, we observed that restitution of B2M in lung cancer cells upregulated targets of IFNα/IFNγ. Furthermore, one third of the lung cancers lacked the HLA-I complex, which was associated with lower cytotoxic CD8+ lymphocyte infiltration. The levels of B2M and HLA-I proteins correlated with those of PD-L1. Finally, a deficiency in HLA-I complex and CD8+ infiltration tended to correlate with reduced survival of patients with lung cancer treated with anti-PD-1/anti-PD-L1. Conclusions: Here, we report recurrent inactivation of B2M in lung cancer. These observations, coupled with the mutations found at CALR, PDIA3, and TAP1, and the downregulation of the HLA-I complex, indicate that an abnormal immunosurveillance axis contributes to lung cancer development. Finally, our observations suggest that an impaired HLA-I complex affects the response to anti-PD-1/anti-PD-L1 therapies. Clin Cancer Res; 23(12); 3203–13. ©2016 AACR.