In vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.

Successful treatment of recalcitrant discoid lupus erythematosus with ustekinumab.

We report a 52-year old woman with a 28-year historyof disfiguring facial discoid lupus erythematosus(DLE), persistent despite both classical therapiesand rituximab. Ustekinumab 45 mg was started incombination with methotrexate and intralesionalcorticosteroids. Methotrexate and intralesionalcorticosteroids were withdrawn 30 months later andustekinumab maintained as monotherapy. Fortyeight months later stable improvement was achievedwithout side effects. Only nine patients with cutaneouslupus erythematosus (CLE) treated with ustekinumabhave been reported to date. Ustekinumab could be apromising alternative in severe and recalcitrant casesof CLE. Possibly, the Th17-inflammation pathway isplaying a role in these patients.

Angioma serpiginosum: report of an unusual acral case and review of the literature.

We report the case of a 35-year-old woman with deep-red asymptomatic macules on the plantar and dorsal skin of the right great toe. Histopathologic findings were compatible with Angioma serpiginosum. Immunohistochemical stains for estrogens and progesterone receptors were negative. Dermoscopy showed an erythematous parallel ridge pattern with double rows of irregular dots and globules. We report an unusual case of angioma serpiginosum with acral volar skin involvement. The dermoscopic features described may aid in the diagnosis of AS in this specific skin area. Acral volar skin involvement must be included in the clinical spectrum of Angioma serpiginosum and in the differential diagnosis of acral vascular lesions.

Angioma serpiginosum: report of an unusual acral case and review of the literature

We report the case of a 35-year-old woman with deep-red asymptomatic macules on the plantar and dorsal skin of the right great toe. Histopathologic fi ndings were compatible with Angioma serpiginosum. Immunohistochemical stains for estrogens and progesterone receptors were negative. Dermoscopy showed an erythematous parallel ridge pattern with double rows of irregular dots and globules. We report an unusual case of angioma serpiginosum with acral volar skin involvement. The dermoscopic features described may aid in the diagnosis of AS in this specifi c skin area. Acral volar skin involvement must be included in the clinical spectrum of Angioma serpiginosum and in the differential diagnosis of acral vascular lesions.

Relación del estudio dinámico de la resonancia magnética de mama con características biológicas e histopatológicas de los carcinomas mamarios / Relation between dynamic magnetic resonance imaging with biological and histopathological prognostic factors of invasive breast cancer

Objetivo. Evaluar la posible relación entre parámetros cinéticos de captación del contraste paramagnético del estudio dinámico de la RM de mama y características histopatológicas y moleculares de los carcinomas mamarios. Material y métodos. Estudio observacional longitudinal retrospectivo analítico de una serie de casos. Se revisaron un total de 309 pacientes diagnosticadas de carcinoma de mama invasivo en el Hospital de Fuenlabrada entre abril de 2004 y enero de 2009. Resultados. Cuanto más elevada es la captación de contraste en el «primer minuto» y más bajo es el tiempo en alcanzar el pico de máxima captación en las curvas de intensidad de señal-tiempo, mayor será el grado histológico y el Ki-67 de los carcinomas invasivos mamarios. Conclusiones. Se encontraron asociaciones estadísticamente significativas entre las variables del estudio cinético de la RM de mama y el grado histológico y la determinación de Ki-67(AU)

Objective. To evaluate the relationship between kinetic parameters in dynamic contrast-enhanced magnetic resonance with biological and histopathological prognostic factors of invasive breast cancer. Materials and methods. Observational, longitudinal, analytical and retrospective study. Three hundred and nine patients with invasive breast cancer diagnosis were evaluated at Fuenlabrada Hospital between april 2004 and january 2009. Results. We found that the higher the saturation in the first minute, and the lower the time to peak in the time-intensity curves, the higher was the histological grade and Ki-67 labelling index of the invasive breast cancers. Conclusion. Significant correlations were found between variables of the kinetic MRI study with histological grade and Ki-67(AU)

Cutaneous leishmaniasis with histopathologic pattern of non-necrotizing granulomatous dermatitis in patients treated with adalimumab.

Human leishmaniasis produced by Leishmania infantum is endemic in Mediterranean countries. In the context of a leishmaniasis outbreak in the town of Fuenlabrada, Madrid, Spain, we had two patients with cutaneous leishmaniasis that developed non-necrotizing cutaneous granulomas. They had both been receiving anti-TNF treatment with adalimumab for rheumatic diseases. Neither of them developed visceral disease and did not require anti-TNF treatment withdrawal to control the cutaneous disease. It is well known that anti-TNF therapy is associated with opportunistic diseases, especially with those in which granuloma formation is an important part of the host defence, as in tuberculosis. We think that granuloma formation through activation of Toll-like receptor-9 and via induction of a Th17 response may be precipitated by the parasites in the dermis.

Hemangioma elastótico adquirido ¿Una entidad infradiagnosticada? / Acquired elastotic hemangioma: an underrecognized entity?

Planteamiento: Describimos una variante clínicopatológica de hemangioma adquirido que aparece en el adulto y que probablemente sea una entidad infradiagnosticada. Material y métodos: Este artículo informa sobre los hallazgos clínicos, histológicos e inmunohistoquímicos de una variante de hemangioma cutáneo llamada hemangioma elastótico adquirido. Resultados: El hemangioma elastótico adquirido se presenta en la piel con daño actínico como placas eritematosas con una apariencia angiomatosa. Histológicamente muestra una proliferación en dermis superficial de capilares que se disponen paralelos a la epidermis. Conclusiones: El hemangioma elastótico adquirido es una variante clínicopatológica de hemangioma diferente de otras proliferaciones vasculares cutáneas (AU)