RESUMEN
Inflammatory processes affecting the vulva may present a unique challenge due to location specific changes. Different factors are behind the intricacy in the presentation of vulvar dermatoses. First, the vulva is lined by different epithelia (hair-bearing keratinized epithelium, modified mucosa, and mucosa). Furthermore, among other factors, this organ is exposed to friction, occlusion, and trauma. Lastly, as there is a tendency to look for health care advice at an advanced stage of the disease, the lesion may be modified by secondary changes due to self-treatment. This article describes the clinical presentation and pathologic features of vulvar dermatoses with a lichenoid pattern and highlights practical points for their diagnoses.
Asunto(s)
Dermatitis/patología , Diagnóstico Diferencial , Vulva/patología , Enfermedades de la Vulva/patología , Dermatitis/diagnóstico , Femenino , Humanos , Patólogos , Enfermedades de la Vulva/diagnósticoRESUMEN
We report the case of a 66-year-old man with adult-onset seizures and multiple cerebral cavernous malformations who developed numerous eruptive cutaneous angiokeratomas on the legs, scrotum, abdomen, and back as well as lobular and cavernous hemangiomas on the arms. Genetic analysis demonstrated a mutation in the KRIT1, ankyrin repeat containing gene (also known as CCM1).
Asunto(s)
Angioqueratoma/diagnóstico , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico , Hemangioma/diagnóstico , Neoplasias Cutáneas/diagnóstico , Anciano , Angioqueratoma/genética , Angioqueratoma/patología , Hemangioma/genética , Hemangioma/patología , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Humanos , Proteína KRIT1 , Masculino , Proteínas Asociadas a Microtúbulos/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaAsunto(s)
Porfiria Cutánea Tardía/diagnóstico , Esclerodermia Localizada/diagnóstico , Enfermedades de la Piel/diagnóstico , Biopsia , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Porfiria Cutánea Tardía/patología , Esclerodermia Localizada/patología , Enfermedades de la Piel/patologíaRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common human cancer with over 250,000 new cases annually in the US and is second in incidence only to basal cell carcinoma. cSCC typically manifests as a spectrum of progressively advanced malignancies, ranging from a precursor actinic keratosis (AK) to squamous cell carcinoma (SCC) in situ (SCCIS), invasive cSCC, and finally metastatic SCC. In this Review we discuss clinical and molecular parameters used to define this range of cutaneous neoplasia and integrate these with the multiple experimental approaches used to study this disease. Insights gained from modeling cSCCs have suggested innovative therapeutic targets for treating these lesions.
Asunto(s)
Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/fisiopatología , Queratinocitos/fisiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatología , Animales , Carcinoma de Células Escamosas/etiología , Progresión de la Enfermedad , Matriz Extracelular/metabolismo , Humanos , Queratinocitos/citología , Queratosis Actínica/patología , Mutación , Lesiones Precancerosas/patología , Transducción de Señal/fisiología , Neoplasias Cutáneas/etiología , Luz Solar/efectos adversos , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
Foscarnet-induced genital erosions have been reported in patients treated for HIV-related herpesvirus infections in adults. We report the case of a boy with penile erosions associated with foscarnet therapy in the setting of umbilical cord blood transplantation (CBT).
Asunto(s)
Antivirales/efectos adversos , Infecciones por Citomegalovirus/tratamiento farmacológico , Foscarnet/efectos adversos , Enfermedades del Pene/inducido químicamente , Enfermedades del Pene/diagnóstico , Aciclovir/uso terapéutico , Antivirales/uso terapéutico , Preescolar , Foscarnet/uso terapéutico , Humanos , Masculino , Enfermedades del Pene/patología , Resultado del TratamientoRESUMEN
Src family tyrosine kinases (SFK) regulate cell proliferation, and increased SFK activity is common in human carcinomas, including cutaneous squamous cell carcinomas (SCC) and its precursors. The elevated SFK activity in cutaneous SCCs was modeled using K14-Fyn Y528F transgenic mice, which spontaneously form punctate keratotic lesions, scaly plaques, and large tumors resembling actinic keratoses, SCC in situ, and SCCs, respectively. Lesional tissue showed increased levels of activated SFKs, PDK1, STAT3, and ERK1/2, whereas Notch1/NICD protein and transcript levels were decreased. p53 levels also were decreased in SCC in situ and SCCs. Increasing Srcasm levels using a K14-Fyn Y528F/K14-Srcasm double transgenic model markedly inhibited cutaneous neoplasia. In contrast, increased expression of a nonphosphorylatable Srcasm mutant maintained the neoplastic phenotype. Increasing Srcasm levels decreased levels of Fyn, activated SFKs, ERK1/2, PDK1, and phospho-STAT3, and increased Notch1/NICD and p53 levels. Analysis of human specimens revealed that levels of Fyn and activated SFKs were elevated in SCCs compared with adjacent nonlesional epidermis. In addition, Notch1 and Srcasm protein and transcript levels were decreased in human SCCs compared with nonlesional epidermis. Therefore, the SCCs produced by the Fyn Y528F mice resemble their human counterparts at the molecular level. K14-Fyn Y528F mice represent a robust model of cutaneous carcinogenesis that manifests precancerous lesions and SCCs resembling human disease. The Fyn/Srcasm signaling nexus modulates activity of STAT3, PDK1, ERK1/2, Notch1, and p53. Further study of Fyn and Srcasm should provide insights into the mechanisms regulating keratinocyte proliferation and skin carcinogenesis.
Asunto(s)
Proteínas Proto-Oncogénicas c-fyn/metabolismo , Receptor Notch1/metabolismo , Neoplasias Cutáneas/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Familia-src Quinasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Animales , Carcinoma de Células Escamosas/metabolismo , Femenino , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos CBA , Ratones Transgénicos , Fosforilación , Lesiones Precancerosas/metabolismo , Proteínas Proto-Oncogénicas c-fyn/antagonistas & inhibidores , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptor Notch1/genética , Factor de Transcripción STAT3/metabolismo , Piel/patología , Familia-src Quinasas/biosíntesis , Familia-src Quinasas/genéticaRESUMEN
The thymus is a lymphoid organ that selects T cells for release to the peripheral immune system. Unfortunately, thymopoiesis is highly susceptible to damage by physiologic stressors and can contribute to immune deficiencies that occur in a variety of clinical settings. No treatment is currently available to protect the thymus from stress-induced involution. Leptin-deficient (ob/ob) mice have severe thymic atrophy and this finding suggests that this hormone is required for normal thymopoiesis. In this study, the ability of leptin to promote thymopoiesis in wild-type C57BL/6 and BALB/c mice, as well as in leptin-deficient (ob/ob) and endotoxin-stressed (Escherichia coli LPS) mice, was determined. Leptin administration induced weight loss and stimulated thymopoiesis in ob/ob mice, but did not stimulate thymopoiesis in wild-type C57BL/6 nor BALB/c mice. In endotoxin-stressed mice, however, leptin prevented LPS-induced thymus weight loss and stimulated TCRalpha gene rearrangement. Coadministration of leptin with LPS blunted endotoxin-induced systemic corticosterone response and production of proinflammatory cytokines. Thus, leptin has a selective thymostimulatory role in settings of leptin deficiency and endotoxin administration, and may be useful for protecting the thymus from damage and augmenting T cell reconstitution in these clinical states.