Valor del protocolo abreviado de resonancia magnética mamaria en el cribado de pacientes de alto riesgo / Value of an abbreviated protocol of breast magnetic resonance imaging for screening high-risk patients

OBJETIVO: Valorar la utilidad de los protocolos abreviados de resonancia magnética (RM) mamaria en el cribado de cáncer de mama en pacientes de alto riesgo, en comparación con el protocolo completo, y determinar la precisión diagnóstica en la caracterización de las lesiones mamarias de ambos protocolos. MATERIAL Y MÉTODOS: Se revisaron retrospectivamente 157 estudios de RM mamaria de 82 pacientes de alto riesgo realizadas en nuestro centro, desde enero de 2011 hasta enero de 2017. Se analizaron parámetros clínicos, radiológicos y anatomopatológicos. Se realizó la lectura de los diferentes protocolos: MIP, abreviado y completo por un radiólogo experto. Posteriormente se hizo un análisis estadístico. RESULTADOS: Se identificaron un total de 12 lesiones clasificadas en categoría BI-RADS 4 y 5 que fueron biopsiadas, de las cuales 11 resultaron ser malignas (91,67%) y 1 benigna (8,33%). Las lesiones malignas fueron: 4 carcinomas ductales in situ (33,33%) y 7 carcinomas ductales infiltrantes (58,33%). Todas las lesiones fueron detectadas con los tres protocolos y no se encontraron diferencias significativas entre sus respectivas áreas bajo la curva (p = 0,0650). CONCLUSIONES: En nuestro estudio no existen diferencias significativas entre los distintos protocolos (MIP, abreviado y completo). El protocolo abreviado se perfila como una herramienta prometedora en el cribado de cáncer de mama en pacientes de alto riesgo

OBJECTIVE: Value the utility of breast MRI abbreviated protocols for the screening of breast cancer in high-risk patients compared to the full protocol. METHODS: We performed a retrospective review of 157 breast MRI of 82 high-risk patients practiced in our hospital between January 2011 and January 2017. Clinical, radiological and anatomopathological parameters were analyzed. Reading of the different protocols (MIP, abbreviated and full) was made by an expert radiologist. Subsequent statistical analysis was done. RESULTS: A total amount of 12 findings classified as BI-RADS 4 and 5 were identified and performed a biopsy, resulting 11 of them to be malignant (91.67%) and 1 benign (8.33%). The malignant wounds included 4 intraductal carcinoma (33.33%) and 7 infiltrating ductal carcinoma (58.33%). All injuries were detected with the three protocols and no significant differences were found between their respective area under the ROC curve (p = 0.0650). CONCLUSIONS: In our study there are no significant differences between the different protocols (MIP, abbreviated and full), which places the abbreviated protocol as a promising tool for breast cancer screening in high-risk patients

Value of an abbreviated protocol of breast magnetic resonance imaging for screening high-risk patients. / Valor del protocolo abreviado de resonancia magnética mamaria en el cribado de pacientes de alto riesgo.

OBJECTIVE: Value the utility of breast MRI abbreviated protocols for the screening of breast cancer in high-risk patients compared to the full protocol. METHODS: We performed a retrospective review of 157 breast MRI of 82 high-risk patients practiced in our hospital between January 2011 and January 2017. Clinical, radiological and anatomopathological parameters were analyzed. Reading of the different protocols (MIP, abbreviated and full) was made by an expert radiologist. Subsequent statistical analysis was done. RESULTS: A total amount of 12 findings classified as BI-RADS 4 and 5 were identified and performed a biopsy, resulting 11 of them to be malignant (91.67%) and 1 benign (8.33%). The malignant wounds included 4 intraductal carcinoma (33.33%) and 7 infiltrating ductal carcinoma (58.33%). All injuries were detected with the three protocols and no significant differences were found between their respective area under the ROC curve (p=0.0650). CONCLUSIONS: In our study there are no significant differences between the different protocols (MIP, abbreviated and full), which places the abbreviated protocol as a promising tool for breast cancer screening in high-risk patients.

Novel clinical and molecular findings in Spanish patients with naevoid basal cell carcinoma syndrome.

BACKGROUND: Naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental alterations and multiple basal cell carcinomas. Mutations in PTCH1, which encodes a membrane receptor for Sonic Hedgehog, are associated with the development of the disease. Most of them produce a truncated protein, which is unable to suppress Smoothened protein and continuously activates the downstream pathway. OBJECTIVES: We aimed to characterize 22 unrelated Spanish patients with NBCCS, the largest cohort with Gorlin syndrome reported to date in Spain. METHODS: Genomic analysis of PTCH1 was performed in patients with NBCCS and controls, and mutations were analysed using bioinformatics tools. RESULTS: We report for the first time two young patients, one each with uterus didelphys and ganglioneuroma, within the context of NBCCS. One patient showing a severe phenotype of the disease had developed basal cell carcinomas since childhood. Sanger sequencing of PTCH1 in this cohort identified 17 novel truncating mutations (11 frameshift, five nonsense and one mutation affecting an exon-intron splice site) and two novel missense mutations that were predicted to be pathogenic. The patients showed great clinical variability and inconsistent genotype-phenotype correlation, as seen in relatives carrying similar mutations. CONCLUSIONS: This study contributes to increase the pool of clinical manifestations of NBCCS, as well as increasing the number of pathogenic mutations identified in PTCH1 predisposing to the condition. The inconsistencies found between phenotype and genotype suggest the involvement of other modifying factors, genetic, epigenetic or environmental.

Valoración de los factores pronósticos radiopatológicos del cáncer de mama triple negativo y análisis del carcinoma in situ como factor pronóstico / Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor

Objetivos. Analizar qué factores valorados en resonancia magnética (RM) y anatomopatológicos de los tumores triple negativo (TN) se relacionan con la recidiva tumoral y con una menor supervivencia libre de enfermedad. Valorar la supervivencia y las recidivas en función de la presencia de componente in situ (CIS). Material y métodos. Estudio retrospectivo de las RM realizadas desde 2007 a 2014, con inclusión de 122 mujeres con cáncer de mama TN y RM de estadificación. En RM se valoraron las características morfológicas (tamaño, márgenes, morfología y señal interna en secuencia T2) y dinámicas (perfusión y difusión). Se estudiaron también los factores anatomopatológicos (Ki67, p53, CK5/6, grado nuclear y Scarff-Bloom) y se analizó la presencia de CIS y el grado tumoral (alto o no alto grado). Se compararon las distintas variables con la presencia de recidiva y se realizó estudio de supervivencia. Resultados. El realce no nodular presentó mayor porcentaje en el grupo de recidivas, y la diferencia fue estadísticamente significativa (p=0,038) y se relacionó con una menor supervivencia libre de enfermedad (p=0,023). La restricción a la difusión (p=0,079) y el ki67 (p=0,052) no asociaron un peor pronóstico. Se detectó CIS en el 44% de los TN, con mayor proporción en el grupo de recidiva, sin relación con una menor supervivencia (p = 0,185). Conclusión. El realce no nodular demostró ser un factor de peor pronóstico. La restricción a la difusión, el ki67 y la presencia de CIS no se asociaron a una menor supervivencia libre de enfermedad (AU)

Objectives. To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. Material and methods. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Results. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Conclusion. Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival (AU)

Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor. / Valoración de los factores pronósticos radiopatológicos del cáncer de mama triple negativo y análisis del carcinoma in situ como factor pronóstico.

OBJECTIVES: To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. MATERIAL AND METHODS: This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. RESULTS: Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). CONCLUSION: Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival.

Resonancia magnética en el cáncer de mama tratado con neoadyuvancia: correlación radiopatológica de la respuesta y supervivencia libre de enfermedad en función del subtipo molecular / Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: Radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype

Objetivos. Valorar la respuesta radiológica, patológica y su correlación en los subtipos moleculares del cáncer de mama y analizar su implicación en la supervivencia libre de enfermedad. Material y métodos. Se incluyeron 205 pacientes con cáncer de mama tratadas con quimioterapia neoadyuvante. Se valoró la respuesta radiológica con RM pre y posquimioterapia. La respuesta patológica se clasificó según la escala de Miller y Payne. Se valoró la respuesta radiológica y patológica en cada subtipo (HER2+, TN, luminal A, luminal B HER2- y luminal B HER2+), la correlación radiopatológica y la supervivencia libre de enfermedad mediante las pruebas χ2, t de Student, ANOVA y Tau-b de Kendall. Resultados. Los subtipos HER2+ (62,1%) y TN (45,2%) mostraron mayor tasa de respuesta radiológica completa. La respuesta patológica fue del 65,5% en el HER2+, 38,1% en el TN, 2,6% en los luminales A, 8,2% en los luminales B HER2- y 31% en los luminales B HER2+. El índice de correlación radiopatológico fue significativo en todos los subtipos, mayor en los TN y HER2 (coeficientes Tau-b 0,805 y 0,717 respectivamente). La supervivencia libre de enfermedad fue mayor para HER2+ (91,9 ± 3,3 meses) y menor en el TN (69,5 ± 6,3 meses), con diferencias significativas entre los casos de mala y buena respuesta radiológica (p = 0,040). La supervivencia fue superior en los casos de buena respuesta radiológica a excepción del subtipo luminal A. Conclusión. La RM puede ser una herramienta que aporta información de la evolución del CM tratado con neoadyuvancia, variable según el subtipo inmunohistoquímico (AU)

Objectives. To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. Material and methods. We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ2 test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. Results. The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9 ± 3.3 months) and lower in TN (69.5 ± 6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. Conclusion. MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype (AU)

Magnetic resonance imaging in breast cancer treated with neoadjuvant chemotherapy: radiologic-pathologic correlation of the response and disease-free survival depending on molecular subtype.

OBJECTIVES: To evaluate the radiologic and pathologic responses to neoadjuvant chemotherapy and their correlation in the molecular subtypes of breast cancer and to analyze their impact in disease-free survival. MATERIAL AND METHODS: We included 205 patients with breast cancer treated with neoadjuvant chemotherapy. We evaluated the radiologic response by comparing MRI images acquired before and after chemotherapy. The pathologic response was classified on the Miller and Payne scale. For each subtype (HER2+, TN, luminal A, luminal B HER2-, and luminal B HER2+), we used the χ(2) test, Student's t-test, ANOVA, and Kendall's Tau-b to evaluate the radiologic response and the pathologic response, the radiologic-pathologic correlation, and the disease-free survival. RESULTS: The subtypes HER2+ (62.1%) and TN (45.2%) had higher rates of complete radiologic response. The pathologic response was 65.5% in the HER2+ subtype, 38.1% in the TN subtype, 2.6% in the luminal A subtype, 8.2% in the luminal B HER2- subtype, and 31% in the luminal B HER2+ subtype. The rate of radiologic-pathologic correlation was significant in all subtypes, higher in TN and HER2 (Tau-b coefficients 0.805 and 0.717, respectively). Disease-free survival was higher in HER2+ (91.9±3.3 months) and lower in TN (69.5±6.3 months), with significant differences between the cases with poor and good radiologic responses (P=.040). Survival was greater in cases with good radiologic response, except in cases with luminal A subtype. CONCLUSION: MRI can be a useful tool that provides information about the evolution of breast cancer treated with neoadjuvant chemotherapy, which varies with the immunohistochemical subtype.

Ectodermal dysplasia-skin fragility syndrome: a novel mutation in the PKP1 gene.

Ectodermal dysplasia-skin fragility syndrome (EDSFS) is an autosomal recessive genodermatosis characterized by skin fragility, palmoplantar hyperkeratosis, onichodystrophy, perioral fissuring and noncicatricial alopecia. It is caused by plakophilin-1 (PKP1) deficiency, which results in desmosomal abnormality and poor intercellular cohesion between the epidermal cells. We report a case with a novel PKP1 mutation in intron 6.

Tratamiento híbrido de un aneurisma sintomático de un divertículo de Kommerell / Hybrid treatment of a symptomatic aneurysm of a Kommerell's diverticulum

El arco aórtico izquierdo con arteria subclavia derecha aberrante constituye la anomalía vascular congénita más común del arco aórtico. En el 60% de casos se origina de un segmento dilatado, denominado divertículo de Kommerell. El aneurisma de la arteria subclavia derecha aberrante es raro, puede ser clínicamente silente o cursar con síntomas inespecíficos y su rotura se asocia a una elevada mortalidad. No hay criterios precisos para el tratamiento, pero se recomienda su reparación cuando se producen síntomas por compresión o cuando alcanza 30-50mm. La radiografía puede hacer sospechar la malformación, pero la resonancia magnética (RM) o la tomografía computarizada (TC) son las pruebas de elección para realizar el diagnóstico y planificar el tratamiento. Presentamos un caso de una arteria subclavia derecha aberrante con un pequeño aneurisma calcificado en un divertículo de Kommerell que provocó dolor torácico y disfagia y fue tratado mediante un procedimiento combinado endovascular y quirúrgico (AU)

Left aortic arch with aberrant right subclavian artery is the most common congenital vascular anomaly involving the aortic arch. In 60% of cases, the aberrant right subclavian artery arises from a dilated segment of the aortic arch called Kommerell's diverticulum. Aneurysm of the aberrant right subclavian artery is rare; this condition could remain clinically silent or it could originate nonspecific symptoms. Rupture of an aneurysm of the aberrant right subclavian artery is associated with high mortality. Although there are no exact criteria to indicate the treatment of this condition, repair of the aneurysm is recommended when symptoms occur or when it reaches a size of 30mm to 50mm. The malformation can be suspected at plain-film X-ray examination, but magnetic resonance imaging (MRI) or computed tomography (CT) are the imaging tests of choice for the diagnosis and for planning treatment. We present the case of a patient with an aberrant right subclavian artery with a small calcified aneurysm in a Kommerell's diverticulum that caused chest pain and dysphagia; the patient underwent a procedure combining endovascular and surgical treatment (AU)

[Hybrid treatment of a symptomatic aneurysm of a Kommerell's diverticulum]. / Tratamiento híbrido de un aneurisma sintomático de un divertículo de Kommerell.

Left aortic arch with aberrant right subclavian artery is the most common congenital vascular anomaly involving the aortic arch. In 60% of cases, the aberrant right subclavian artery arises from a dilated segment of the aortic arch called Kommerell's diverticulum. Aneurysm of the aberrant right subclavian artery is rare; this condition could remain clinically silent or it could originate nonspecific symptoms. Rupture of an aneurysm of the aberrant right subclavian artery is associated with high mortality. Although there are no exact criteria to indicate the treatment of this condition, repair of the aneurysm is recommended when symptoms occur or when it reaches a size of 30 mm to 50mm. The malformation can be suspected at plain-film X-ray examination, but magnetic resonance imaging (MRI) or computed tomography (CT) are the imaging tests of choice for the diagnosis and for planning treatment. We present the case of a patient with an aberrant right subclavian artery with a small calcified aneurysm in a Kommerell's diverticulum that caused chest pain and dysphagia; the patient underwent a procedure combining endovascular and surgical treatment.

Clinical, molecular and biochemical characterization of nine Spanish families with Conradi-Hünermann-Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature.

BACKGROUND: Conradi-Hünermann-Happle syndrome (CDPX2, OMIM 302960) is an inherited X-linked dominant variant of chondrodysplasia punctata which primarily affects the skin, bones and eyes. CDPX2 results from mutations in EBP (emopamil binding protein), and presents with increased levels of sterol precursors 8(9)-cholesterol and 8-dehydrocholesterol. OBJECTIVES: To expand the understanding of CDPX2, clinically, biochemically and genetically. METHODS: We present one of the largest series reported to date, including 13 female patients belonging to nine Spanish families. Patients were studied biochemically using gas chromatography-mass spectrometry, genetically using polymerase chain reaction and in their methylation status using the HUMARA assay. RESULTS: In our cases, there was a clear relationship between abnormal sterol profile and the EBP gene mutation. We describe three novel mutations in the EBP gene. EBP mutations were inherited in three out of nine families and were sporadic in the remaining cases. CONCLUSIONS: No clear genotype-phenotype correlation was found. Patients' biochemical profiles did not reveal a relationship between sterol profiles and severity of disease. A skewed X-chromosome inactivation may explain the clinical phenotype in CDPX2 in some familial cases.

Una nueva mutación en el gen EDA en una familia española con displasia ectodérmica hipohidrótica ligada al cromosoma X / A novel EDA gene mutation in a Spanish family with X-linked hypohidrotic ectodermal dysplasia

La displasia ectodérmica hipohidrótica ligada al cromosoma X (XLHED) se caracteriza por un desarrollo anormal del pelo, los dientes y las glándulas sudoríparas. Está producida por mutaciones en el gen EDA, que se localiza en el cromosoma X y codifica para la proteína Ecdodisplasina A, miembro de la familia de ligandos relacionados con el factor de necrosis tumoral. Los varones afectados normalmente exhiben todas las características de la enfermedad, pero los portadores heterocigotos pueden mostrar manifestaciones de leves a moderadas. Aquí se describe una familia española en la que hemos identificado una mutación c.733_734insGA, previamente no descrita, en el gen EDA. Se localizaba en el exón 5 y producía un cambio en la fase de lectura en el codón 245 de la proteína, lo que daba lugar a un codón de parada prematuro tras 35 residuos. El análisis genético en familias con XLHED es fundamental para la identificación de las portadoras, para el diagnóstico prenatal y en general para proporcionar un asesoramiento genético correcto (AU)

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormal development of the hair, teeth, and sweat glands. It is caused by mutations in the EDA gene, which maps to the X chromosome and encodes a protein called ectodysplasin-A, a member of the tumor necrosis factor-related ligand family. Affected males typically exhibit all the typical features of HED, but heterozygous carriers may show mild to moderate clinical manifestations. We describe the case of a Spanish family in which a novel heterozygous c.733_734insGA mutation at the EDA gene was identified. It was located in exon 5 and consisted of a frame-shift mutation at codon 245, which gave rise to an abnormal protein with a premature stop codon after 35 residues. Genetic analyses in families with XLHED are useful for checking carrier status, but they also provide information for genetic counseling and prenatal diagnosis (AU)

A novel EDA gene mutation in a Spanish family with X-linked hypohidrotic ectodermal dysplasia.

X-linked hypohidrotic ectodermal dysplasia (XLHED) is characterized by abnormal development of the hair, teeth, and sweat glands. It is caused by mutations in the EDA gene, which maps to the X chromosome and encodes a protein called ectodysplasin-A, a member of the tumor necrosis factor-related ligand family. Affected males typically exhibit all the typical features of HED, but heterozygous carriers may show mild to moderate clinical manifestations. We describe the case of a Spanish family in which a novel heterozygous c.733_734insGA mutation at the EDA gene was identified. It was located in exon 5 and consisted of a frame-shift mutation at codon 245, which gave rise to an abnormal protein with a premature stop codon after 35 residues. Genetic analyses in families with XLHED are useful for checking carrier status, but they also provide information for genetic counseling and prenatal diagnosis.

Analysis of the STS gene in 40 patients with recessive X-linked ichthyosis: a high frequency of partial deletions in a Spanish population.

BACKGROUND: Recessive X-linked ichthyosis (RXLI) (OMIM 308100) is a genodermatosis characterized by polygonal, dark, adherent and mild-to-moderate scales that normally improve during summer. RXLI is caused by a deficiency in steroid sulphatase (STS), whose gene has been located on the X chromosome (locus Xp22.3). Up to 90% of the mutations described in this gene are complete deletions. OBJECTIVES: Previous reports of partial deletion of STS gene in cases of RXLI prompted us to determine the incidence of these abnormalities in a Spanish population. METHODS: We have studied exons 1, 5 and 10 of the STS gene by polymerase chain reaction in 40 patients with clinical features of RXLI. RESULTS: Our results revealed that 30 patients presented complete deletions (75%) while 10 patients had partial deletions (25%) a rate higher than that reported in the previous studies. CONCLUSIONS: Amplification of exons 1, 5 and 10 is reliable in screening RXLI in the population studied here. No correlation was found between phenotype and the extent of the deletions.