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Infecciones por Helicobacter , Helicobacter pylori , Leucemia-Linfoma de Células T del Adulto , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/complicaciones , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Antibacterianos/uso terapéutico , Masculino , Progresión de la Enfermedad , Persona de Mediana Edad , FemeninoRESUMEN
The standard therapies for primary cutaneous anaplastic large cell lymphoma (pcALCL) in an advanced stage remain undefined. A 71-year-old man presented with multiple erythema and nodules. He was diagnosed with lymphomatoid papulosis (LyP) through a skin biopsy from the left postauricular area. All skin lesions achieved complete response by electron beam irradiation. However, nodular lesions appeared in both inner canthi 5 months later. Histopathological evaluation of the lesional biopsy revealed dominant infiltration of CD30-positive large cells. Positron emission tomography/computed tomography revealed fluorodeoxyglucose-positive cervical and inguinal lymph node swelling and right tonsillitis, followed by the diagnosis of pcALCL and TNM classification T3bN3M0. Since the patient had severe chronic obstructive pulmonary disease and recurrent pneumonia, he received low-dose methotrexate (MTX) (15 mg/week) therapy. Low-dose MTX effectively debulked the lymphadenopathies over time without particular adverse effects. Although the standard therapies for pcALCL are not established, low-dose MTX was effective and considered safe for patients with frailty and compromised respiratory function. Further study is warranted on the pathophysiology of pcALCL after the development of LyP and mechanisms of action of low-dose MTX against LyP and pcALCL.
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Linfoma Anaplásico de Células Grandes , Linfoma Anaplásico Cutáneo Primario de Células Grandes , Papulosis Linfomatoide , Neoplasias Cutáneas , Anciano , Humanos , Inmunoterapia , Linfoma Anaplásico Cutáneo Primario de Células Grandes/tratamiento farmacológico , Papulosis Linfomatoide/diagnóstico , Papulosis Linfomatoide/tratamiento farmacológico , Papulosis Linfomatoide/patología , Masculino , Metotrexato/uso terapéutico , Neoplasias Cutáneas/patologíaRESUMEN
Band-shaped presentation of cutaneous angiosarcoma has not been reported. Cutaneous angiosarcoma should be included in the differential diagnosis when a persistent erythematous lesion is observed in the head and neck region of an elderly patient without a clear explanation, but skin biopsy is required for an accurate diagnosis.
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Artritis , Melanoma , Protocolos de Quimioterapia Combinada Antineoplásica , Bencimidazoles , Carbamatos/uso terapéutico , Humanos , Melanoma/tratamiento farmacológico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas B-raf/genética , SulfonamidasRESUMEN
Cowden syndrome (CS) is an autosomal dominant inherited disorder characterized by macrocephaly and multiple hamartomas. The responsible gene is PTEN (phosphate and tensin homolog detected on chromosome 10), which negatively regulates cell proliferation and survival. We herein present a 46-year-old woman with the typical clinical features of CS. A DNA sequencing analysis of the coding regions and flanking introns of the PTEN gene revealed a novel heterozygous mutation (c.403Aâ >â G, p.Ile135Val) in exon 5 that had not been previously reported in CS. J. Med. Invest. 67 : 200-201, February, 2020.
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Síndrome de Hamartoma Múltiple/genética , Mutación , Fosfohidrolasa PTEN/genética , Femenino , Humanos , Persona de Mediana EdadAsunto(s)
Quinasa I-kappa B/genética , Incontinencia Pigmentaria/genética , Análisis Mutacional de ADN , Humanos , Incontinencia Pigmentaria/diagnóstico , Incontinencia Pigmentaria/patología , Recién Nacido , Cariotipificación , Mutación con Pérdida de Función , Masculino , Índice de Severidad de la Enfermedad , Piel/patologíaAsunto(s)
Angioqueratoma/complicaciones , Queratosis/etiología , Mancha Vino de Oporto/radioterapia , Radiodermatitis/complicaciones , Neoplasias Cutáneas/complicaciones , Anciano , Angioqueratoma/diagnóstico , Mejilla , Femenino , Humanos , Queratosis/diagnóstico , Piel/patología , Piel/efectos de la radiación , Neoplasias Cutáneas/diagnóstico , Factores de TiempoAsunto(s)
Amalgama Dental/efectos adversos , Granulomatosis Orofacial/inducido químicamente , Hipersensibilidad Tardía/etiología , Indio/efectos adversos , Enfermedades de los Labios/inducido químicamente , Granulomatosis Orofacial/patología , Humanos , Hipersensibilidad Tardía/patología , Enfermedades de los Labios/patología , Pruebas del ParcheAsunto(s)
Ictiosis Ligada al Cromosoma X/complicaciones , Queratodermia Palmoplantar/complicaciones , Niño , Análisis Mutacional de ADN , Humanos , Ictiosis Ligada al Cromosoma X/diagnóstico , Ictiosis Ligada al Cromosoma X/genética , Queratodermia Palmoplantar/diagnóstico , Queratodermia Palmoplantar/genética , Masculino , Análisis por Micromatrices , Linaje , Eliminación de Secuencia , Serpinas/genética , Esteril-Sulfatasa/genéticaRESUMEN
PURPOSE: Nivolumab, an anti-programmed death 1 antibody, produces antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs). The aim of this study was to analyze the association between antitumor effect and irAEs induced by nivolumab in patients with melanoma. METHODS: Fifteen patients with melanoma who had received nivolumab at Tokushima University Hospital or Ehime University Hospital between January 2015 and December 2016 were enrolled in this study. Patients who had and did not have irAEs during nivolumab treatment were classified into an irAEs-positive group (n = 8) and an irAEs-negative group (n = 7), respectively. We compared the disease control rate (DCR) and overall survival (OS) between the 2 groups. Data on blood cell counts were also analyzed. FINDINGS: After a median of 4 cycles of nivolumab treatment, irAEs occurred. The DCRs were 75% and 14% in the irAEs-positive and irAEs-negative groups, respectively (p < 0.05). OS in the irAEs-positive group was higher than that in the irAEs-negative group (p < 0.05). Multivariable Cox proportional hazards regression analysis revealed that irAE occurrence affected OS with nivolumab treatment. Moreover, the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment (p < 0.05). IMPLICATIONS: Our study indicated that clinical response with nivolumab treatment improves with irAE occurrence in patients with melanoma. Moreover, the early increase in peripheral lymphocyte count may act as a biomarker for predicting the occurrence of irAEs induced by nivolumab.
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Melanoma/tratamiento farmacológico , Nivolumab/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nivolumab/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. OBJECTIVE: To improve the method for the molecular diagnosis of NBCCS. METHODS: We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). RESULTS: Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. CONCLUSION: TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases.
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Síndrome del Nevo Basocelular/genética , Biomarcadores de Tumor/genética , Cromosomas Humanos , Secuenciación de Nucleótidos de Alto Rendimiento , Técnicas de Diagnóstico Molecular , Análisis de Secuencia por Matrices de Oligonucleótidos , Adolescente , Adulto , Síndrome del Nevo Basocelular/diagnóstico , Biología Computacional , Variaciones en el Número de Copia de ADN , Análisis Mutacional de ADN , Exoma , Femenino , Dosificación de Gen , Predisposición Genética a la Enfermedad , Humanos , Mutación INDEL , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Nucleótido Simple , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Adulto JovenAsunto(s)
Eosinofilia/complicaciones , Eosinofilia/patología , Foliculitis/complicaciones , Foliculitis/patología , Complicaciones del Embarazo/patología , Enfermedades Cutáneas Vesiculoampollosas/complicaciones , Enfermedades Cutáneas Vesiculoampollosas/patología , Adulto , Eosinofilia/inmunología , Femenino , Foliculitis/inmunología , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo/inmunología , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Células Th2/inmunologíaRESUMEN
Skin tumors are supposed to develop through accumulations of genetic and/or epigenetic events in normal cells of the skin. Among them, we focus on common skin tumors, including benign, seborrheic keratosis, and malignant, squamous cell carcinoma and melanoma. Many important molecules have been detected on the molecular tumorigenesis of each of them to date, and some drugs targeted for their molecules have been already developed. We review updates on the molecular tumorigenesis of these tumors with our current works.