Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma.

BACKGROUND: Promoter methylation of tumour suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over 100 genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. OBJECTIVES: This is a retrospective observational study that aims to analyse the prevalence of CpG island methylation in a series of primary melanomas, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival. MATERIALS AND METHODS: DNA methylation was analysed using methylation-specific multiplex ligation-dependent probe amplification in a series of 170 melanoma formalin-fixed paraffin-embedded tumour samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method. RESULTS: In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6% and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow thickness, presence of mitosis and ulceration, fast-growing melanomas, advancing stage and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and OS. CONCLUSIONS: Aberrant methylation of TSGs is a frequent event in melanoma. It is associated with aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.

Aproximación a la enfermedad injerto contra huésped cutánea / Review of Cutaneous Graft-vs-Host Disease

La enfermedad injerto contra huésped (EICH) es una enfermedad multisistémica que aparece como complicación de un trasplante de progenitores hematopoyéticos alogénico. Se basa en el reconocimiento de tejidos del receptor por parte de la inmunidad heredada del donante. La piel y las mucosas son los órganos más frecuentemente afectados. Se clasifica en aguda y crónica, en función de su fisiopatología y presentación clínica. La forma aguda se manifiesta típicamente con la tríada de exantema, diarrea e hiperbilirrubinemia, y el tratamiento se basa en el uso de corticoides e inmunosupresores sistémicos. Las manifestaciones cutáneas de la forma crónica se dividen en esclerodermiformes y no esclerodermiformes. Puede afectar también a mucosas y faneras. El diagnóstico es fundamentalmente clínico, aunque en casos dudosos la biopsia cutánea puede ayudar a confirmarlo. El tratamiento puede ser tópico, sistémico o físico, en función de la extensión, localización, profundidad de las lesiones y afectación de otros órganos

Graft-vs-host disease (GVHD) is a multisystem disease that arises as a complication of allogeneic hematopoietic stem cell transplant. It is due to recognition of the recipient's tissues by immune cells from the donor. The skin and mucous membranes are the organs most commonly affected. GVHD is classified as acute or chronic depending on the pathophysiology and clinical presentation. Acute GVHD typically presents with the triad of rash, diarrhea, and hyperbilirubinemia, and treatment is based on systemic corticosteroid and immunosuppressant therapy. The cutaneous manifestations of chronic GVHD are divided into sclerodermiform and nonsclerodermiform, and the mucous membranes and skin appendages may also be affected. The diagnosis is mainly clinical, but skin biopsy can help in doubtful cases. Treatment can be topical, systemic, or physical, depending on the size, site, and depth of the lesions and the involvement of other organs

Pembrolizumab, un nuevo fármaco capaz de inducir un brote psoriasis / Pembrolizumab: a new Drug That Can Induce Exacerbations of Psoriasis

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Review of Cutaneous Graft-vs-Host Disease.

Graft-vs-host disease (GVHD) is a multisystem disease that arises as a complication of allogeneic hematopoietic stem cell transplant. It is due to recognition of the recipient's tissues by immune cells from the donor. The skin and mucous membranes are the organs most commonly affected. GVHD is classified as acute or chronic depending on the pathophysiology and clinical presentation. Acute GVHD typically presents with the triad of rash, diarrhea, and hyperbilirubinemia, and treatment is based on systemic corticosteroid and immunosuppressant therapy. The cutaneous manifestations of chronic GVHD are divided into sclerodermiform and nonsclerodermiform, and the mucous membranes and skin appendages may also be affected. The diagnosis is mainly clinical, but skin biopsy can help in doubtful cases. Treatment can be topical, systemic, or physical, depending on the size, site, and depth of the lesions and the involvement of other organs.

Análisis retrospectivo del papel de la fototerapia en la enfermedad injerto contra huésped crónica cutánea. Revisión de la literatura / The Role of Phototherapy in Cutaneous Chronic Graft-vs-Host Disease: A Retrospective Study and Review of the Literature

INTRODUCCIÓN Y OBJETIVOS: La enfermedad injerto contra huésped (EICH) crónica cutánea es una complicación frecuente tras un trasplante de progenitores hematopoyéticos. La fototerapia es una modalidad terapéutica para pacientes con afectación cutánea o para aquellos que precisan altas dosis de corticoesteroides (CE). El objetivo de este estudio es revisar los casos tratados en nuestro servicio y hacer una revisión de la literatura. MATERIAL Y MÉTODOS: Recogida de datos de manera retrospectiva de todos los casos tratados desde marzo de 2011 a octubre de 2014 en el Servicio de Dermatología del Hospital Universitario y Politécnico la Fe de Valencia. RESULTADOS: Recogimos un total de 16 pacientes, 10 tratados con PUVA y 6 con UVB-BE. Nueve pacientes obtuvieron una respuesta completa y 7 una respuesta parcial, aunque 2 recidivaron tras el tratamiento. Diez pacientes pudieron disminuir la dosis de CE durante el tratamiento y 3 pudieron disminuir el número de otros inmunosupresores. No se presentaron efectos adversos graves. CONCLUSIONES: La fototerapia es una buena opción terapéutica para pacientes con EICH crónica con gran afectación cutánea, para aquellos que no responden al tratamiento tópico o para pacientes corticodependientes. Su mayor beneficio es el de ser un tratamiento dirigido a la piel que permite ahorrar CE y que presenta un buen perfil de seguridad. La pauta de tratamiento se realiza de manera individualizada y, según nuestra experiencia, con dosis iniciales y dosis máximas por sesión menores que para otras enfermedades

INTRODUCTION AND OBJECTIVES: Cutaneous chronic graft-vs-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Phototherapy is a therapeutic option for patients with skin involvement and for those who require high doses of corticosteroids. We analyze the cases treated in our department and review the literature. MATERIAL AND METHODS: All patients with GVHD treated with phototherapy in the dermatology department of Hospital Universitario y Politécnico la Fe in Valencia, Spain between March 2011 and October 2014 were identified. Data were gathered retrospectively. RESULTS: There were 16 patients: 10 treated with psoralen-UV-A and 6 with narrowband-UV-B. Complete response was achieved in 9 patients and partial response in 7; 2 patients with partial responses relapsed after treatment. Ten patients were able to decrease their dose of corticosteroids during treatment, and a further 3 decreased the number of other immunosuppressant drugs. No serious adverse effects occurred. CONCLUSIONS: Phototherapy is a good therapeutic option for patients with chronic GVHD with extensive cutaneous involvement, as well as for those who fail to respond to topical treatment or who have become steroid-dependent. The main benefits are that, as the treatment targets the skin, it reduces corticosteroid requirements and has a good safety profile. Treatment must be individualized and, in our experience, both the initial dose and the maximum dose per session can be lower than for other diseases

The role of phototherapy in cutaneous chronic graft-vs-host disease: a retrospective study and review of the literature.

INTRODUCTION AND OBJECTIVES: Cutaneous chronic graft-vs-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Phototherapy is a therapeutic option for patients with skin involvement and for those who require high doses of corticosteroids. We analyze the cases treated in our department and review the literature. MATERIAL AND METHODS: All patients with GVHD treated with phototherapy in the dermatology department of Hospital Universitario y Politécnico la Fe in Valencia, Spain between March 2011 and October 2014 were identified. Data were gathered retrospectively. RESULTS: There were 16 patients: 10 treated with psoralen-UV-A and 6 with narrowband-UV-B. Complete response was achieved in 9 patients and partial response in 7; 2 patients with partial responses relapsed after treatment. Ten patients were able to decrease their dose of corticosteroids during treatment, and a further 3 decreased the number of other immunosuppressant drugs. No serious adverse effects occurred. CONCLUSIONS: Phototherapy is a good therapeutic option for patients with chronic GVHD with extensive cutaneous involvement, as well as for those who fail to respond to topical treatment or who have become steroid-dependent. The main benefits are that, as the treatment targets the skin, it reduces corticosteroid requirements and has a good safety profile. Treatment must be individualized and, in our experience, both the initial dose and the maximum dose per session can be lower than for other diseases.

Actualización en melanoma mucoso / Mucosal Melanoma: An Update

El melanoma mucoso es un subtipo infrecuente de melanoma que difiere del melanoma cutáneo en su biología, clínica y manejo. El diagnóstico suele realizarse de forma tardía debido a su localización en zonas de difícil acceso a la exploración física y a la falta de signos específicos y tempranos. La cirugía es el tratamiento de elección en caso de enfermedad localizada. El papel de la biopsia selectiva de ganglio centinela y de la linfadenectomía permanece todavía incierta. La radioterapia se puede emplear como tratamiento adyuvante con el fin de controlar localmente la enfermedad. Existe un mayor porcentaje de mutaciones en c-KIT que en otros tipos de melanoma, lo que ha llevado a avances significativos en el tratamiento de la enfermedad metastásica con imatinib

Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma

Mucosal melanoma: an update.

Mucosal melanoma is a rare melanoma subtype that differs from the cutaneous form of the tumor in its biology, clinical manifestations, and management. Diagnosis is usually late due to a lack of early or specific signs and the location of lesions in areas that are difficult to access on physical examination. Surgical excision is the treatment of choice for localized disease. The value of sentinel lymph node biopsy and lymphadenectomy is still unclear. Radiotherapy can be used as adjuvant therapy for the control of local disease. c-KIT mutations are more common than in other types of melanoma and this has led to significant advances in the use of imatinib for the treatment of metastatic mucosal melanoma.

Epstein-Barr virus-positive diffuse large B-cell lymphoma in an elderly patient.

Epstein-Barr virus-positive (EBV) diffuse large B-cell lymphoma (DLCBL) of the elderly is a newly described lymphoproliferative disorder that arises in elderly patients without a predisposing immunodeficiency. Clinical features at presentation may include lymphadenopathy, B-symptoms and extranodal involvement. The main sites of extranodal involvement are the skin, lung, tonsil and stomach. Histopathological findings include atypical large lymphoid cells with variable amounts of reactive cells, such as small lymphocytes, plasma cells and histiocytes. The neoplastic cells are positive for CD20, and in situ hybridization for EBV-encoded RNA is positive in the majority of neoplastic cells. We present a new case of EBV-positive DLBCL in an 85-year-old man, who presented to our clinic with a 2-month history of asymptomatic cutaneous lesions involving his face and scalp.

Placa en la nariz / Plaque on the Nose

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