RESUMEN
Lymphomatoid papulosis (LyP) is a self-limiting cutaneous T-cell lymphoproliferative disorder that may progress into malignant lymphoma. Most of the previously reported associated lymphomas are primary cutaneous anaplastic large-cell lymphoma and mycosis fungoides with a low mortality rate. We report a case of primary cutaneous peripheral T-cell lymphoma, not otherwise specified (pcPTCL-NOS), associated with LyP after long-term follow up. The patient was a 79-year old Japanese man followed up for 9 years. He suddenly developed a 3-cm ulcerated lesion on his forehead, which was diagnosed as an exacerbation of LyP. The lesion regressed after conservative treatment, but the patient soon developed multifocal pcPTCL-NOS. Thereafter, the patient developed pneumonia and cerebral infarction and died within a few months of the onset of malignant lymphoma. Aggressive cutaneous lymphoma may develop in LyP patients. The present case re-emphasizes the need for careful follow up of patients with persistent LyP.
Asunto(s)
Linfoma Cutáneo de Células T/diagnóstico , Linfoma de Células T Periférico/diagnóstico , Papulosis Linfomatoide/diagnóstico , Neoplasias Cutáneas/diagnóstico , Administración Cutánea , Anciano , Anciano de 80 o más Años , Biopsia , Quimioradioterapia/métodos , Progresión de la Enfermedad , Resultado Fatal , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Humanos , Linfoma Cutáneo de Células T/etiología , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Linfoma de Células T Periférico/etiología , Linfoma de Células T Periférico/patología , Linfoma de Células T Periférico/terapia , Papulosis Linfomatoide/complicaciones , Papulosis Linfomatoide/tratamiento farmacológico , Papulosis Linfomatoide/patología , Masculino , Piel/patología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapiaRESUMEN
Malignant blue nevus is rare, and a common blue nevus rarely needs a differential diagnosis from malignant melanoma. Although a melanocytic nevus with a satellite lesion is usually suggestive of a peripherally disseminating malignant melanoma, very few cases of blue nevus with satellite lesions have been reported thus far. To our knowledge, this is the seventh case of a blue nevus with satellitosis. Periappendageal and perivascular concentrations of the nevus cells were observed in the main papule as well as in the satellite lesions. These findings suggest that blue nevus cells could infiltrate along the perivascular area in the dermis and form multiple satellite lesions. Blue nevus should be considered as a differential diagnosis when a locally disseminating malignant melanoma is suspected.
RESUMEN
Transient receptor potential vanilloid 1 (TRPV1) is a highly polymodal TRP channel activated by various stimuli, including capsaicin, heat and acids. TRPV1 expression can be detected widely but is highest in sensory neurons and its activation alerts the body to noxious signals via neurogenic pain. Although TRPV1 is reportedly localized in the epidermis, it remains unclear how TRPV1 is involved in the chemical peeling processes with cytotoxic acids. Therefore, in this study, the role of TRPV1 on the effects of trichloroacetic acid (TCA) peeling was assessed using TRPV1-deficient mice. Following the confirmation of TRPV1 expression in murine keratinocytes with reverse transcription-polymerase chain reaction and immunohistochemistry, the effects of TCA on TRPV1-deficient mouse skin were compared with those on wild-type mouse skin. Our results indicated that TRPV1 expression was not required for TCA-induced DNA damage, as shown by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling, but was indispensable for the TCA-induced production of distinct growth factors and cytokines by keratinocytes. Ulceration after TCA peeling was actually more severe in the absence of TRPV1, suggesting that the TRPV1-mediated epidermal production of growth factors and cytokines affected the damaging and healing processes of TCA-peeled skin to induce rejuvenation.
Asunto(s)
Quimioexfoliación , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Queratinocitos/metabolismo , Úlcera Cutánea/metabolismo , Piel/metabolismo , Canales Catiónicos TRPV/metabolismo , Animales , Cáusticos/farmacología , Daño del ADN , Factor 1 de Crecimiento de Fibroblastos/genética , Factor 1 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1alfa/genética , Interleucina-1alfa/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Queratinocitos/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-sis/genética , Proteínas Proto-Oncogénicas c-sis/metabolismo , ARN Mensajero/metabolismo , Rejuvenecimiento/fisiología , Piel/efectos de los fármacos , Úlcera Cutánea/inducido químicamente , Úlcera Cutánea/genética , Canales Catiónicos TRPV/genética , Factores de Tiempo , Factor de Crecimiento Transformador alfa/genética , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Ácido Tricloroacético/farmacología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Cicatrización de Heridas/genéticaRESUMEN
Solar lentigines are common acquired pigmented lesions on sun-exposed skin. Their histopathological features have been reported as large numbers of melanocytes at the base of clubbed and budding rete ridges. In this study, biopsies were taken from facial solar lentigines in 40 Japanese women, and the sections were stained using hematoxylin-eosin, Fontana-Masson, and immunostained for melanocytes and Langerhans cells in order to verify the histological patterns of Japanese patients. We characterized the histopathological features of solar lentigines on the face and identified two patterns: one pattern (20/40 cases) demonstrated a flattened epidermis with basal melanosis, and the other pattern (20/40 cases) showed epidermal hyperplasia with elongated rete ridges composed of deeply pigmented basaloid cells. We termed the former pattern the "flattened epidermis" group, and the latter the "budding" group, respectively. The flattened epidermis group showed a significantly thinner epidermis, more severe solar elastosis and fewer Langerhans cells in the epidermis as compared with the budding group. We concluded that more severely sun-damaged solar lentigines might show the changes observed in the flattened epidermis group. Langerhans cells in the epidermis of solar lentigines might play a role in the remission of postinflammatory pigmentation due to aesthetic treatment.
Asunto(s)
Lentigo/patología , Envejecimiento de la Piel/patología , Adulto , Anciano , Pueblo Asiatico , Biopsia , Cara , Femenino , Humanos , Células de Langerhans/patología , Melanocitos/patología , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
Skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC)-derived peptides, such as adrenocorticotropic hormone (ACTH), a-melanocyte-stimulating hormone (MSH) and b-endorphin that are locally generated in response to locally provided stressors or proinflammatory cytokines. This system would restrict tissue damage and restore local homoeostasis. Trichloroacetic acid (TCA) is one of the most widely used peeling agents and applied for cosmetic treatment of photodamaged skin. However, the biological mechanism responsible for TCA peeling has yet to be fully determined. While our investigation focused on the inflammation and wound healing pathways, in the recent study, we have examined involvement of the SSRS as the third pathway. Mostly depending on our findings that TCA peeling activates the SSRS by inducing the POMC expression of keratinocytes in the CRH-independent manner, together with the results reported by other researchers, we can say that the biological effect of POMC seems to be responsible for the TCA-induced epidermal SSRS activation.
Asunto(s)
Quimioexfoliación/efectos adversos , Piel/patología , Hormona Adrenocorticotrópica/metabolismo , Animales , Quimioexfoliación/métodos , Hormona Liberadora de Corticotropina/metabolismo , Endorfinas/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Queratinocitos/citología , Péptidos/metabolismo , Sistema Hipófiso-Suprarrenal/fisiología , Proopiomelanocortina/metabolismo , ARN Mensajero/metabolismo , Piel/efectos de los fármacos , Fenómenos Fisiológicos de la Piel , alfa-MSH/metabolismoRESUMEN
Although trichloroacetic acid (TCA) peeling is widely applied for cosmetic treatment of photodamaged skin, the entire biological mechanisms have yet to be determined. The skin stress response system (SSRS) involves corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) products that are locally-generated in response to locally-provided stressors or pro-inflammatory cytokines. This system would restrict tissue damage and restore local homeostasis. To determine the influence of TCA peeling on the SSRS in vitro and in vivo, expressions of POMC, melanocortin receptor 1 (MC1R), CRH and CRH receptor 1 (CRHR1) mRNA were examined by reverse transcription polymerase chain reaction in Pam212 murine keratinocytes, murine plantar and healthy human abdominal skin specimens after TCA treatment. In addition, their protein expressions as well as those of POMC-derived peptides were examined immunohistochemically. After TCA treatment, transient upregulation of POMC and MC1R mRNA expressions was observed in both murine and human skin, as well as in Pam212. Enhanced POMC protein, recovery of once-impaired MC1R protein, and no enhancement of POMC-derived peptide productions were revealed immunohistochemically in both murine and human epidermis. In contrast, neither expression levels of CRH and CRHR1 mRNA nor epidermal protein were enhanced after TCA application in murine and human skin, except for induction of human CRH mRNA expression. These results suggest that TCA activates the SSRS by inducing POMC and MC1R productions of keratinocytes in the CRH-independent manner, and that the biological effects of POMC itself are responsible for the TCA-induced epidermal SSRS activation.
Asunto(s)
Queratolíticos/toxicidad , Piel/efectos de los fármacos , Ácido Tricloroacético/toxicidad , Animales , Células Clonales , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Femenino , Humanos , Queratolíticos/administración & dosificación , Ratones , Ratones de la Cepa 129 , Persona de Mediana Edad , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptor de Melanocortina Tipo 1/genética , Receptor de Melanocortina Tipo 1/metabolismo , Receptores de Hormona Liberadora de Corticotropina/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Piel/metabolismo , Estrés Fisiológico/efectos de los fármacos , Ácido Tricloroacético/administración & dosificaciónRESUMEN
Skin ulcers in systemic lupus erythematosus (SLE) patients are non-healing or intractable, because various factors or complications, including vasculitis and immunosuppressants, impair wound healing. In the present study, we applied cultured dermal substitutes (CDSs) to 3 cases of SLE skin ulcers because various systemic or topical therapies were ineffective. CDSs are prepared by culturing human fibroblasts on two-layered spongy matrices of hyaluronic acid and atelo-collagen, and they effectively promote the healing of severe skin defects. After using CDSs in the 3 cases, healthy granulation tissues formed within 6 weeks, and skin grafts were successfully performed. These results indicate that allogeneic CDSs provide new therapeutic alternatives as topical therapies for intractable skin ulcers in SLE.
Asunto(s)
Pierna , Lupus Eritematoso Sistémico/cirugía , Trasplante de Piel , Úlcera Cutánea/cirugía , Ingeniería de Tejidos/métodos , Adulto , Anciano , Femenino , Fibroblastos/citología , Humanos , Pierna/patología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Índice de Severidad de la Enfermedad , Úlcera Cutánea/etiología , Úlcera Cutánea/patología , Trasplante Homólogo , Cicatrización de HeridasRESUMEN
BACKGROUND: Cutaneous angiosarcoma (AS) is an aggressive endothelial sarcoma that arises in elderly people. Effective treatment options are limited. Phenol application has been reported to be effective and economical. AIMS: To evaluate the efficacy of phenol application for the treatment of AS, and to examine the histologic changes in three cases of cutaneous AS with phenol application. METHODS: After phenol application, biopsy specimens were collected from three patients with cutaneous AS. Paraffin-embedded sections of the skin specimens were then stained with hematoxylin and eosin. The detection of apoptosis was performed using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick end labeling (TUNEL) method, and the depth of TUNEL-positive cell staining was examined. RESULTS: Phenol treatment induced a strong degeneration of tumor cells and endothelial cells in the dermis, when compared with nontreated areas. Positive staining of tumor cells and/or endothelial cells by the TUNEL method was found in phenol-treated lesions, but not in nontreated lesions. The injurious effects on these tumor cells persisted for as long as 6 h after phenol application. CONCLUSION: From a comparison of noninvasive therapy with standard surgical therapy, it is obvious that phenol peeling has several advantages with regard to the ease of the procedure, time efficiency, no need for special equipment, low therapeutic costs, good pain control, and post-treatment follow-up. This study suggests that phenol application can be a supportive treatment for AS.
Asunto(s)
Hemangiosarcoma/tratamiento farmacológico , Hemangiosarcoma/patología , Fenol/uso terapéutico , Soluciones Esclerosantes/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Anciano , Anciano de 80 o más Años , Apoptosis/efectos de los fármacos , Biopsia , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Piel/patologíaRESUMEN
BACKGROUND: Although chemical peels may be used for precancerous lesions, no histologic or immunohistochemical studies have been performed to validate clinical impressions and/or outcome. OBJECTIVE: Our purpose was to investigate the efficacy and prognostic relevance of phenol peels in Japanese patients with actinic keratosis and Bowen disease using clinical and histologic criteria. METHODS: A total of 46 patients were treated with phenol peels, and followed up for at least 1 year after treatment. Biopsy specimens were taken before and after treatment. Cases of complete response were classified by the number of treatment sessions. We evaluated parameters for epidermal thickness, proliferation, dysplasia, and apoptosis, and clinical characteristics to correlate phenol peels with assessments of efficacy, patient-selection criteria, and risk for transformation to cutaneous squamous cell carcinoma. RESULTS: There were 39 (84.8%) patients with a complete response after one to 8 treatment sessions. Statistically, differences in clinical improvement with peels and the number of treatment sessions correlated with histology, personal history of skin cancer, tumor thickness, and cyclin A expression. LIMITATIONS: This study was a prospective pilot trial. Blinded, placebo-controlled, randomized studies would be ideal. CONCLUSION: We conclude that phenol peels are very effective for treating precancerous lesions of actinic keratosis and Bowen disease. In addition, our study clearly demonstrates that tumor thickness and cyclin A could be specific and useful markers as adjunctive diagnostic tools to predict the efficacy of phenol treatment of these lesions.
Asunto(s)
Enfermedad de Bowen/tratamiento farmacológico , Queratolíticos/uso terapéutico , Queratosis Actínica/tratamiento farmacológico , Fenoles/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Estudios ProspectivosRESUMEN
Trichloroacetic acid (TCA) is one of the most widely used peeling agents, and induces full necrosis of the whole epidermis, followed by reconstitution of the epidermis and the matrix of the papillary dermis. The cytotoxic effects of TCA, such as suppressing proliferation of keratinocytes and fibroblasts and protein synthesis by fibroblasts, have already been reported. However, the entire biological mechanism responsible for TCA peeling has yet to be determined. Hypothetical activation effects of TCA treatment on epidermal cells to induce production of growth factors and cytokines are examined, and are compared with its cytotoxic effects in terms of time course and applied TCA concentrations. After various periods of incubation with TCA, viability of Pam212 murine keratinocytes was investigated with MTT assay and dye exclusion assay, and production of growth factors and cytokines with reverse transcription-polymerase chain reaction (RT-PCR). Changes in platelet-derived growth factor (PDGF)-B mRNA expression and protein production in the human skin specimens after TCA application were then examined by RT-PCR and immunohistochemistry, respectively. Incubation with TCA showed cytotoxicity and induced death of Pam212 cells, depending on the incubation period and the TCA concentration. In addition, expressions of PDGF-B, tumor growth factor (TGF)-alpha, TGF- beta1 and vascular endothelial growth factor, which are the growth factors reportedly secreted from keratinocytes during wound healing, were all detected in Pam212 cells after short-term treatment with TCA. Expressions of inflammatory cytokines such as interleukin (IL)-1 and IL-10 were also induced. In TCA-treated NIH-3T3 fibroblasts, in contrast, observed was upregulation of only keratinocyte growth factor, which is reportedly secreted from fibroblasts, as well as the similar cytotoxic effect. In human skin, PDGF-B mRNA expression became significantly upregulated after TCA application, and then immediately downregulated. Immunoreactive PDGF-B in the cytoplasm of keratinocytes became detectable throughout the epidermis after TCA application, reached maximum after the peak of mRNA expression, and then declined significantly over 24 h when the epidermis became completely necrotic. The TCA-treated epidermis acts as a major source of growth factors, including PDGF-B, before undergoing full necrosis. This effect might contribute to a promotion of re-epithelialization and dermal regeneration without wound contraction and scarring.
Asunto(s)
Cáusticos/farmacología , Epidermis/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Proteínas Proto-Oncogénicas c-sis/metabolismo , Ácido Tricloroacético/farmacología , Administración Cutánea , Adulto , Animales , Cáusticos/administración & dosificación , Cáusticos/toxicidad , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Epidermis/metabolismo , Epidermis/patología , Femenino , Factor 7 de Crecimiento de Fibroblastos/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Inmunohistoquímica , Interferón gamma/metabolismo , Interleucinas/metabolismo , Queratinocitos/metabolismo , Queratinocitos/patología , Ratones , Células 3T3 NIH , Necrosis , Proteínas Proto-Oncogénicas c-sis/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Factor de Crecimiento Transformador alfa/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Ácido Tricloroacético/administración & dosificación , Ácido Tricloroacético/toxicidad , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
This study was designed to investigate whether trichloroacetic acid (TCA) peeling induces cellular proliferation in human skin using an immunohistochemical method. A 40% TCA peel resulted in a greater number of proliferating cell nuclear antigen (PCNA)-immunopositive cells in the whole epidermis as compared with 60% TCA or phenol peels. This finding suggests that long-term and frequent TCA peelings of low concentration would require special attention for unexpected cutaneous lesions such as skin tumors.
Asunto(s)
Quimioexfoliación , Antígeno Nuclear de Célula en Proliferación/análisis , Piel/inmunología , Ácido Tricloroacético , Proliferación Celular , Quimioexfoliación/efectos adversos , Humanos , Fenol , Piel/citología , Ácido Tricloroacético/efectos adversosRESUMEN
Dystrophic epidermolysis bullosa (DEB) is caused by mutations in the COL7A1 gene encoding collagen, the major component of anchoring fibrils. Premature termination codon (PTC) mutations in both alleles usually lead to the Hallopeau-Siemens variant that shows the most severe phenotype. We experienced a case of the non-Hallopeau-Siemens variant (nHS-RDEB), which had a mild clinical severity although it has PTC mutations in both alleles. Our patient was a compound heterozygote for a nonsense mutation (R669X) in exon 15 and a nonsense mutation (E2857X) in exon 116. But we confirmed the existence of some anchoring fibrils on electron micrograph. This suggested that a PTC close to the 3' end of COL7A1 does not completely abolish the collagen VII mRNA. We hypothesized that the truncated procollagen VII from the mutant allele with a nonsense mutation (E2857X) in exon 116 included two out of eight cysteines needed for disulfide bond formation, and hence a few functional anchoring fibrils could be formed.
Asunto(s)
Codón de Terminación , Colágeno/genética , Epidermólisis Ampollosa Distrófica/diagnóstico , Epidermólisis Ampollosa Distrófica/genética , Predisposición Genética a la Enfermedad , Adulto , Alelos , Diagnóstico Diferencial , Epidermólisis Ampollosa Distrófica/patología , Femenino , Genes Recesivos , HumanosRESUMEN
Alpha-hydroxy acid (AHA) agents, such as glycolic acid and lactic acid, have been used as therapeutic agents for more than a quarter of a century. Recently, they have been used as agents to rejuvenate photo-aged skin. It is believed that these AHA agents induce the epidermis to remodel and accelerate desquamation, thus exerting their therapeutic effects. In this study, we investigated the histological differences in skin treated with glycolic, lactic, citric and acetic acids once daily for 6 weeks. The melanin pigments in the basal layer were less prominent in the glycolic and lactic acid-treated skin than in the citric and acetic acid-treated skin. The melanin deposits in the horny layers were equal for all AHA. However, the melanin deposits in the squamous layers were less prominent in the glycolic and lactic acid-treated skins than in the citric and acetic acid-treated skins; this was analogous to observations of the basal layers. Collagen I and procollagen I were increased after treatment with glycolic, lactic and citric acid in the upper dermis, but were not increased with acetic acid treatment. However, the staining of the epidermis and dermis for matrix metalloproteinase-1 (MMP-1) after treatment was not significantly different among the agents. Our data suggest that longer treatment intervals with glycolic and lactic acid can cause improvements in both the epidermal and dermal components and support the usefulness of AHA for rejuvenating photo-damaged skin.