RESUMEN
Germline mutations leading to aneuploidy are rare, and their tumor-promoting properties are mostly unknown at the molecular level. We report here novel germline biallelic mutations in MAD1L1, encoding the spindle assembly checkpoint (SAC) protein MAD1, in a 36-year-old female with a dozen of neoplasias. Functional studies demonstrated lack of full-length protein and deficient SAC response, resulting in ~30 to 40% of aneuploid blood cells. Single-cell RNA analysis identified mitochondrial stress accompanied by systemic inflammation with enhanced interferon and NFκB signaling both in aneuploid and euploid cells, suggesting a non-cell autonomous response. MAD1L1 mutations resulted in specific clonal expansions of γδ T cells with chromosome 18 gains and enhanced cytotoxic profile as well as intermediate B cells with chromosome 12 gains and transcriptomic signatures characteristic of leukemia cells. These data point to MAD1L1 mutations as the cause of a new variant of mosaic variegated aneuploidy with systemic inflammation and unprecedented tumor susceptibility.
RESUMEN
BACKGROUND: There is limited literature on efficacy in 5-aminolaevulinic acid (BF-200 ALA) and methyl-5-aminolaevulinate (MAL) for superficial basal cell carcinoma (sBCC). AIMS: To investigate the efficacy and safety of PDT in sBCC. METHODS: Analytical observational study between January 2014 and January 2017. Follow-up at 12, 24 and 52 weeks. Lesions were treated with one BF-200 ALA-PDT or MAL-PDT cycle of two sessions in one week. A second treatment cycle, with the same photosensitizer precursor, was performed in cases of clinical persistence at 12 weeks. RESULTS: A total of 22 patients (30 lesions) were enrolled in the study. By sex, 13 men and 9 women. Average age of 72,14 years. In the 12-month follow-up 15/16 lesions were resolved (93,75%) after one or two BF-200 ALA-PDT cycle and 7/14 lesions (50%) after one or two MAL-PDT cycles. In most patients, tolerance to the therapy was good or regular, with no differences between the two groups. No long-term adverse effects were reported. LIMITATIONS: The observational nature and the low number of patients. CONCLUSION: PDT is a safe and non-invasive treatment option in sBCC. Our results suggest a better response with BF-200 ALA-PDT over MAL-PDT, at 12 months of follow-up.
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Ácido Aminolevulínico/uso terapéutico , Carcinoma Basocelular/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Anciano , Ácido Aminolevulínico/análogos & derivados , Femenino , Humanos , MasculinoAsunto(s)
Foliculitis , Dermatosis del Cuero Cabelludo , Adulto , Edad de Inicio , Antibacterianos/uso terapéutico , Bacterias/aislamiento & purificación , Biopsia , Enfermedad Crónica , Fármacos Dermatológicos/uso terapéutico , Estudios de Seguimiento , Folículo Piloso/microbiología , Folículo Piloso/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
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.
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Fármacos Dermatológicos/uso terapéutico , Dermatosis Facial/tratamiento farmacológico , Lupus Eritematoso Discoide/tratamiento farmacológico , Ustekinumab/uso terapéutico , Corticoesteroides/uso terapéutico , Dermatosis Facial/patología , Femenino , Humanos , Factores Inmunológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Inyecciones Intralesiones , Lupus Eritematoso Discoide/patología , Metotrexato/uso terapéutico , Persona de Mediana Edad , Rituximab/uso terapéutico , Insuficiencia del TratamientoAsunto(s)
Deformidades Congénitas del Pie/patología , Lipomatosis/patología , Dedos del Pie/anomalías , Fosfatidilinositol 3-Quinasa Clase I , Deformidades Congénitas del Pie/diagnóstico por imagen , Deformidades Congénitas del Pie/genética , Humanos , Recién Nacido , Lipomatosis/diagnóstico por imagen , Lipomatosis/genética , Masculino , Fosfatidilinositol 3-Quinasas/genética , Radiografía , Dedos del Pie/diagnóstico por imagenRESUMEN
OBJECTIVE: To validate dermoscopy as a real-time noninvasive diagnostic imaging technique for actinic keratosis (AK). DESIGN: Prospective study to validate a diagnostic test. SETTING: Dermatology department of a tertiary university hospital in Fuenlabrada, Madrid, Spain. PATIENTS: A total of 178 patients with a clinical diagnosis of AK participated in the study. MAIN OUTCOME MEASURES: An independent blinded comparison was performed between dermoscopy results and histopathological findings, the gold standard for the diagnosis of AK. All the patients underwent both diagnostic tests. RESULTS: One hundred seventy-eight lesions were evaluated. The concordance between dermoscopy results and histopathological findings was 0.917. The sensitivity of dermoscopy for the diagnosis of AK was 98.7%, with a specificity of 95.0%, a positive likelihood ratio of 19.74, and a negative likelihood ratio of 0.01. A diagnostic algorithm that combined follicular openings and erythematous pseudonetwork demonstrated a sensitivity of 95.6% and a specificity of 95.0% for the diagnosis of AK. CONCLUSIONS: The sensitivity and specificity of dermoscopy for the diagnosis of AK were high, as was the concordance between dermoscopy results and histopathological findings. As a real-time noninvasive diagnostic imaging technique for AK, dermoscopy may be incorporated in the management of patients with these lesions.
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Dermoscopía , Queratosis Actínica/patología , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Distribución de Chi-Cuadrado , Método Doble Ciego , Femenino , Humanos , Queratosis Actínica/diagnóstico , Funciones de Verosimilitud , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Dermatomyofibroma represents a rare benign fibroblastic/ myofibroblastic cutaneous tumor that mostly occurs in young adult women. It has been seldom reported in pediatric patients. In this analysis, the clinical, histopathological and immunohistochemical findings of 12 dermatomyofibromas occurring in patients up to 16 years of age are compared with those reported in adults. Six patients were male and six were female. Nine lesions were located on the neck, two on the back and one involved the chest. The usual presentation was as an asymptomatic plaque composed of bland spindled cells arranged in dermal fascicles that were oriented parallel to the epidermis. Immunohistochemically, the lesional cells expressed calponin in 11 cases, smooth muscle actin in six and muscle-specific actin in three. In contrast to prior reports from adults, dermatomyofibromas in pediatric patients do not show a female predilection. In addition, they are mostly located on the neck (56%), while in adults the most frequent location is the shoulder (35%). Dermatomyofibromas seem to stabilize after an initial period of enlargement. Punch biopsy and clinical follow up could be an alternative approach to the surgical excision in some cases of dermatomyofibroma, particularly in instances in which surgery might inflict cosmetic defects.
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Neoplasias de Cabeza y Cuello/patología , Histiocitoma Fibroso Benigno/patología , Miofibroma/patología , Neoplasias Cutáneas/patología , Actinas/biosíntesis , Adolescente , Adulto , Proteínas de Unión al Calcio/biosíntesis , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/cirugía , Histiocitoma Fibroso Benigno/metabolismo , Histiocitoma Fibroso Benigno/cirugía , Humanos , Inmunohistoquímica/métodos , Masculino , Proteínas de Microfilamentos/biosíntesis , Miofibroma/metabolismo , Miofibroma/cirugía , Proteínas de Neoplasias/biosíntesis , Estudios Retrospectivos , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/cirugía , CalponinasAsunto(s)
Cabello/patología , Nevo Sebáceo de Jadassohn/patología , Cuero Cabelludo/patología , Biopsia , Femenino , Humanos , Recién NacidoRESUMEN
Erythrodermic psoriasis is a chronic condition that is difficult to treat. Biological agents offer a new alternative, but there are no controlled trials to support their use; there are a few reports of patients treated with these agents, but often only with short term results. We report a 68-year-old man with erythrodermic psoriasis and ankylosing spondylitis, treated with infliximab for 48 weeks and then low-dose etanercept monotherapy for 34 additional months. Excellent results were obtained for both conditions without significant side effects. We think etanercept can be a good therapeutic option for long-term control of erythrodermic psoriasis.
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Dermatitis Exfoliativa/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Inmunoglobulina G/uso terapéutico , Psoriasis/tratamiento farmacológico , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Espondilitis Anquilosante/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Anciano , Anticuerpos Monoclonales/uso terapéutico , Etanercept , Humanos , Infliximab , Masculino , Resultado del TratamientoAsunto(s)
Dermatitis por Contacto/etiología , Erupciones por Medicamentos/etiología , Hemorroides/tratamiento farmacológico , Espirostanos/efectos adversos , Vasoconstrictores/efectos adversos , Administración Cutánea , Adulto , Dermatitis por Contacto/diagnóstico , Erupciones por Medicamentos/diagnóstico , Humanos , Masculino , Pruebas del Parche , Espirostanos/administración & dosificación , Vasoconstrictores/administración & dosificaciónRESUMEN
A distinctive clinical entity of acute genital ulcers occurring in adolescents, with nonvenereal infectious etiology was described by Lipschütz in 1913. We describe four puberal virgin girls who developed fever and painful genital ulcers. The main causes infectious and noninfectious of ulceration were rejected. Although the etiology is unknown, recent cases related with Epstein-Barr virus acute infection have been reported.
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Úlcera/patología , Vulva/patología , Enfermedades de la Vulva/patología , Adolescente , Anticuerpos Antivirales/análisis , Bacillus/aislamiento & purificación , Niño , Edema/etiología , Infecciones por Virus de Epstein-Barr/complicaciones , Femenino , Fiebre/etiología , Herpesvirus Humano 4/aislamiento & purificación , Humanos , Staphylococcus epidermidis/aislamiento & purificación , Úlcera/microbiología , Enfermedades de la Vulva/microbiologíaRESUMEN
The association between leukocytoclastic vasculitis and solid tumors like renal carcinoma has been infrequently described. We present the case of a 76-year-old woman who began with skin lesions on the legs that were clinically and histologically diagnosed as leukocytoclastic vasculitis. During analysis of the symptoms, she was diagnosed with renal carcinoma. After the tumor was excised, the vasculitis lesions disappeared, with no recurrence during the follow-up period.
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Carcinoma de Células Renales/complicaciones , Neoplasias Renales/complicaciones , Vasculitis Leucocitoclástica Cutánea/etiología , Anciano , Carcinoma de Células Renales/diagnóstico por imagen , Femenino , Humanos , Neoplasias Renales/diagnóstico por imagen , Neoplasias Renales/cirugía , Nefrectomía , Radiografía , Inducción de Remisión , Vasculitis Leucocitoclástica Cutánea/cirugíaRESUMEN
La asociación entre vasculitis leucocitoclástica y tumores sólidos como el carcinoma renal se ha descrito con poca frecuencia. Presentamos el caso de una mujer de 76 años que empezó con lesiones cutáneas en piernas clínica e histológicamente diagnosticadas de vasculitis leucocitoclástica y a la que, en el transcurso del estudio del cuadro, se le diagnosticó un carcinoma renal. Tras la extirpación del tumor renal, las lesiones de vasculitis desaparecieron sin recidiva en el seguimiento
The association between leukocytoclastic vasculitis and solid tumors like renal carcinoma has been infrequently described. We present the case of a 76-year-old woman who began with skin lesions on the legs that were clinically and histologically diagnosed as leukocytoclastic vasculitis. During analysis of the symptoms, she was diagnosed with renal carcinoma. After the tumor was excised, the vasculitis lesions disappeared, with no recurrence during the follow-up period
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Femenino , Persona de Mediana Edad , Humanos , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/diagnóstico , Vasculitis Leucocitoclástica Cutánea/complicaciones , Vasculitis Leucocitoclástica Cutánea/patología , Biopsia/métodos , Prednisona/administración & dosificación , Prednisona/uso terapéutico , Enfermedades Cutáneas Vesiculoampollosas/complicaciones , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Radiografía Torácica/métodosAsunto(s)
Dermatosis de la Mano/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Mycobacterium marinum/aislamiento & purificación , Adulto , Animales , Animales Domésticos , Reservorios de Enfermedades/microbiología , Eritema/etiología , Peces/microbiología , Dermatosis de la Mano/microbiología , Humanos , Masculino , Infecciones por Mycobacterium no Tuberculosas/microbiología , Infecciones por Mycobacterium no Tuberculosas/transmisión , Mycobacterium chelonae/aislamiento & purificación , Tuberculoma/etiología , Microbiología del AguaRESUMEN
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