A customized pigmentation SNP array identifies a novel SNP associated with melanoma predisposition in the SLC45A2 gene.

As the incidence of Malignant Melanoma (MM) reflects an interaction between skin colour and UV exposure, variations in genes implicated in pigmentation and tanning response to UV may be associated with susceptibility to MM. In this study, 363 SNPs in 65 gene regions belonging to the pigmentation pathway have been successfully genotyped using a SNP array. Five hundred and ninety MM cases and 507 controls were analyzed in a discovery phase I. Ten candidate SNPs based on a p-value threshold of 0.01 were identified. Two of them, rs35414 (SLC45A2) and rs2069398 (SILV/CKD2), were statistically significant after conservative Bonferroni correction. The best six SNPs were further tested in an independent Spanish series (624 MM cases and 789 controls). A novel SNP located on the SLC45A2 gene (rs35414) was found to be significantly associated with melanoma in both phase I and phase II (P<0.0001). None of the other five SNPs were replicated in this second phase of the study. However, three SNPs in TYR, SILV/CDK2 and ADAMTS20 genes (rs17793678, rs2069398 and rs1510521 respectively) had an overall p-value<0.05 when considering the whole DNA collection (1214 MM cases and 1296 controls). Both the SLC45A2 and the SILV/CDK2 variants behave as protective alleles, while the TYR and ADAMTS20 variants seem to function as risk alleles. Cumulative effects were detected when these four variants were considered together. Furthermore, individuals carrying two or more mutations in MC1R, a well-known low penetrance melanoma-predisposing gene, had a decreased MM risk if concurrently bearing the SLC45A2 protective variant. To our knowledge, this is the largest study on Spanish sporadic MM cases to date.

Cutaneous polyarteritis nodosa.

The term polyarteritis nodosa (PAN) presently includes classic systemic PAN, cutaneous PAN, and microscopic PAN (microscopic polyangeiitis). Cutaneous PAN involves the deep dermis and the panniculus, with anatomopathological findings diagnostic for arteritis. The most frequent clinical manifestation of cutaneous PAN is the presence of nodules on the lower legs, which frequently are found at different stages of development. At times, they may not leave residual changes, but generally a violaceous livedoid color or pigmentation with retiform appearance persists for months and even years. Ulceration also is a frequent complication of cutaneous PAN. Pain, arthralgias, malaise, and moderate fever are frequently associated symptoms. Histopathologically, cutaneous PAN shows a single artery involved with diagnostic inflammatory changes. The involved artery is always located in the deep dermis or in the panniculus. Inflammatory active skin nodules show a necrotizing arteritis with variable amounts of fibrinoid necrosis and leukocytoclasia, edema and inflammatory cells. The presence of focal panniculitis surrounding the involved artery is characteristic, in contrast with the more diffuse panniculitis usually found in other nodular diseases. Cutaneous PAN has a variable course, with repeated exacerbations. Salicilates relieve the pain in most instances and may be the only treatment required to improve the symptoms in patients with moderate flare-ups. A short course of corticosteroids therapy at a moderate dose is the most effective treatment to relieve the symptoms and to reduce the inflammation. Patients with an increased ASO titer should always be treated with penicillin.

[Necrobiosis lipoidica over appendectomy scar in a patient with morphea of the breast]. / Necrobiosis lipoídica sobre cicatriz de apendicectomía en una paciente con morfea de mama.

Morphea is a sclerosing skin disease that may be clinically confused with a carcinoma when it involves the breast. It has been described in association with earlier radiotherapy and with silicone breast implants. We describe the case of a woman with morphea of the breast who developed necrobiosis lipoidica over the scar of an appendectomy performed 38 years earlier. Necrobiosis lipoidica over surgical scars is infrequently found in the literature. We review the published cases and discuss the association of necrobiosis lipoidica with morphea.

Necrobiosis lipoídica sobre cicatriz de apendicectomía en una paciente con morfea de mama / Necrobiosis lipoidica over appendectomy scar in a patient with morphea of the breast

La morfea es una enfermedad esclerosante de la piel que cuando afecta a la mama puede confundirse clínicamente con un carcinoma. Se ha descrito asociada con radioterapia previa y con implantes mamarios de silicona. Se describe el caso de una mujer con morfea de mama que desarrolló una necrobiosis lipoídica sobre una cicatriz de apendicectomía realizada 38 años antes. La necrobiosis lipoídica sobre cicatrices quirúrgicas es un hallazgo poco frecuente en la literatura médica. En este artículo se revisan los casos publicados y se discute la asociación de la necrobiosis lipoídica con la morfea

Morphea is a sclerosing skin disease that may be clinically confused with a carcinoma when it involves the breast. It has been described in association with earlier radiotherapy and with silicone breast implants. We describe the case of a woman with morphea of the breast who developed necrobiosis lipoidica over the scar of an appendectomy performed 38 years earlier. Necrobiosis lipoidica over surgical scars is infrequently found in the literature. We review the published cases and discuss the association of necrobiosis lipoidica with morphea

Tratamiento de linfomas cutáneos de células T con bexaroteno / Treatment of cutaneous T-cell lymphomas with bexarotene

Introducción. La elección del tratamiento en los linfomas cutáneos de células T (LCCT) depende del estadio clínico de la enfermedad y del estado general del paciente. Hasta hoy no existe ningún tratamiento curativo para esta enfermedad y el objetivo es controlar los síntomas y prevenir la progresión de la enfermedad. El bexaroteno es un retinoide agonista específico de los receptores X de los retinoides con actividad antitumoral. Su uso fue aprobado por la Food and Drug Administration (FDA) como tratamiento de LCCT refractarios a al menos una terapia sistémica previa. Pacientes y métodos. Realizamos un estudio descriptivo de 9 pacientes que han sido tratados con bexaroteno en la Unidad de Linfomas de nuestro servicio. Analizamos las características clínicas de los pacientes y eficacia del tratamiento y recogemos los efectos secundarios presentados. Resultados. La respuesta global al tratamiento fue del 44,4 % (4/9). Un total de 2 pacientes presentaron una remisión completa y los otros dos, una remisión parcial. La tolencia al tratamiento fue buena y los efectos secundarios más frecuentes fueron la hipertrigliceridemia, la hipercolesterolemia y el hipotiroidismo central. Conclusiones. Aunque se trata de una serie de únicamente 9 pacientes los resultados que obtuvimos son similares a los descritos previamente. El bexaroteno es una opción terapéutica eficaz en este grupo heterogéneo de enfermedades

Introduction. The choice of treatment in cutaneous T-cell lymphomas (CTCLs) depends on the clinical stage of the disease and the patient's general condition. To date, there is no curative treatment for this disease, and the objective is to control the symptoms and prevent the disease from progressing. Bexarotene is an X receptor-specific retinoid with anti-tumor activity. Its use as treatment for CTCLs refractory to at least one prior systemic therapy has been approved by the FDA. Patients and methods. We carried out a descriptive study of 9 patients treated with bexarotene in the Lymphoma Unit of our department. We analyzed the clinical characteristics of the patients and the efficacy of the treatment, and we collected data on the side effects that appeared. Results. The overall response to the treatment was 44.4 % (4/9). 2 patients had full remission and 2 had partial remission. Tolerance to the treatment was good, and the most frequent side effects were hypertriglyceridemia, hypercholesterolemia and central hypothyroidism. Conclusions. Even though this is a series of only 9 patients, the results that we obtained are similar to ones previously described. Bexarotene is an effective therapeutic option in this heterogeneous group of diseases

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

UNLABELLED: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. AIM: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. METHODS: Extensive review of the literature cited in Medline and own data of the authors. RESULTS: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. CONCLUSION: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior.

Erupción acneiforme por inhibidores del receptor de crecimiento epidérmico / Acneiform eruption from epidermal growth factor receptor inhibitors

Uno de los objetivos fundamentales de la investigación oncológica es la búsqueda de moléculas con mayor eficacia antitumoral y menor toxicidad que los agentes quimioterápicos habituales. Los inhibidores del receptor de crecimiento epidérmico son un nuevo grupo de fármacos que, por su efecto más específico frente a las células neoplásicas, parecen cumplir estas características. Entre los efectos adversos asociados a su uso, destacan por su frecuencia las erupciones cutáneas, secundarias a un efecto inhibitorio directo del fármaco sobre la homeostasis de la epidermis y del folículo pilosebáceo 1,2. Recientemente se han publicado varios casos de toxicidad cutánea en pacientes tratados con inhibidores del receptor de crecimiento epidérmico. Presentamos 3 casos de erupciones acneiformes atribuibles a diferentes fármacos de esta familia (cetuximab, gefitinib y erlotinib)

One of the fundamental aims of oncological research is the search for molecules with greater efficacy against tumors and less toxicity than the usual chemotherapeutic agents. Epidermal growth factor receptor inhibitors are a new group of drugs which, because of their more specific effect against neoplastic cells, seem to meet these characteristics. Skin eruptions are one of the most frequent adverse effects associated with their use, secondary to the drug's direct inhibitory effect on homeostasis of the epidermis and of the pilosebaceous follicle. Several cases of cutaneous toxicity in patients treated with epidermal growth factor receptor inhibitors have recently been published. We present three cases of acneiform eruptions attributable to different drugs in this family (cetuximab, gefitinib and erlotinib)

Xantogranuloma múltiple del adulto / Multiple adult xanthogranuloma

El xantogranuloma juvenil es una histiocitosis decélulas no Langerhans (HCNL) poco frecuente, de carácter benigno y que afecta predominantemente a niños pequeños. Clínicamente se caracteriza por la aparición de una o varias lesiones papulonodulares amarillo-parduzcas localizadas en zona superior del cuerpo, sobre todo en cabeza y cuello. Los xantogranulomas en adultos son menos frecuentes y generalmente se presentan como lesiones solitarias. El diagnóstico de xantogranulomas múltiples en adultos es excepcional. Se describe el caso de una paciente diagnosticada de esta rara enfermedad

Juvenile xanthogranuloma is an infrequent, benign,normolipemic, non-Langerhans cell histiocytosis, which primarily affects young children. Clinically, it is characterized by the appearance of one or several brownish-yellow papulonodular lesions on the upper body, especially on the head andn eck. Xanthogranulomas are less frequent in adults, and generally present as solitary lesions. The diagnosis of multiple xanthogranulomasin adults is exceptional. We describe the case of a female patient diagnosed with this rare disease

Placas amarillentas en tronco y flexuras axilares / Yellowish plaques on the trunk and the axillary folds

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WHO-EORTC classification for cutaneous lymphomas.

Primary cutaneous lymphomas are currently classified by the European Organization for Research and Treatment of Cancer (EORTC) classification or the World Health Organization (WHO) classification, but both systems have shortcomings. In particular, differences in the classification of cutaneous T-cell lymphomas other than mycosis fungoides, Sezary syndrome, and the group of primary cutaneous CD30+ lymphoproliferative disorders and the classification and terminology of different types of cutaneous B-cell lymphomas have resulted in considerable debate and confusion. During recent consensus meetings representatives of both systems reached agreement on a new classification, which is now called the WHO-EORTC classification. In this paper we describe the characteristic features of the different primary cutaneous lymphomas and other hematologic neoplasms frequently presenting in the skin, and discuss differences with the previous classification schemes. In addition, the relative frequency and survival data of 1905 patients with primary cutaneous lymphomas derived from Dutch and Austrian registries for primary cutaneous lymphomas are presented to illustrate the clinical significance of this new classification.

Urticaria solar. Estudio de 20 casos / Solar urticaria. Study of 20 cases

Introducción. La urticaria solar es una enfermedad poco frecuente, pero probablemente infradiagnosticada. Se caracteriza por la aparición de forma súbita de habones en zonas habitualmente no fotoexpuestas tras irradiación solar o con otras fuentes artificiales de luz visible o ultravioleta. Los casos publicados en la literatura médica son pocos, por lo que la información que tenemos acerca de la enfermedad y su evolución natural es limitada. Material y métodos. Se han recopilado los datos de los 20 pacientes que han sido diagnosticados de urticaria solar en nuestro servicio en los últimos 12 años (1990-2002), para intentar obtener información acerca de las características de esta enfermedad. Resultados. Como características más relevantes de nuestra serie cabe destacar que el 60 % de los pacientes eran mujeres; la duración media de la enfermedad antes de acudir a un dermatólogo era de alrededor de 3 años. En el 55 % de los pacientes se respetaban zonas habitualmente fotoexpuestas como cara y manos (fenómeno de habituación o hardening). Los espectros responsables de la urticaria solar eran luz visible, UVA y UVB, por ese orden. Respecto a los tratamientos, con antihistamínicos y fotoprotectores se obtuvo una respuesta parcial y buenos resultados mediante desensibilizaciones progresivas con UVA/sol. Conclusión. La urticaria solar es probablemente una enfermedad infradiagnosticada en nuestro medio. Hay pocas series publicadas que nos permitan conocer las características más importantes de la enfermedad. Se han recopilado los datos más interesantes de nuestros pacientes y se han comparado con el resto de las series publicadas en el intento de conocer mejor esta fotodermatosis

Introduction. Solar urticaria is an infrequent disorder, but is probably underdiagnosed. It is characterized by the sudden appearance of weals in areas that are not usually photoexposed after exposure to the sun or to artificial sources of visible or ultraviolet light. Few cases have been published in literature, so the information available about this disorder and its natural evolution is limited. Material and methods. We have compiled data from 20 patients diagnosed with solar urticaria in our department in the last 12 years (1990-2002) in order to try to obtain information about the characteristics of this condition. Results. As the most relevant characteristics of our series, we can mention the fact that 60 % of the patients were women, and the average duration of the condition before consulting a dermatologist was 3 years. In 55 % of the patients, areas that are usually photoexposed, such as the face and hands, were less severely affected (due to acclimatization or hardening). The spectra responsible for the SU were visible light, UVA and UVB, in that order. With regard to treatment, we obtained a partial response with antihistamines and photoprotectors, and good results using progressive desensitization with UVA/sunlight. Conclusion. Solar urticaria is probably an underdiagnosed condition in our milieu. There are few series in literature that provide any information about the most significant characteristics of this disorder. We have compiled the most relevant data from our patients and we have compared it with the other published series in an attempt to learn more about this photodermatosis

[Acneiform eruption from epidermal growth factor receptor inhibitors]. / Erupción acneiforme por inhibidores del receptor de crecimiento epidérmico.

One of the fundamental aims of oncological research is the search for molecules with greater efficacy against tumors and less toxicity than the usual chemotherapeutic agents. Epidermal growth factor receptor inhibitors are a new group of drugs which, because of their more specific effect against neoplastic cells, seem to meet these characteristics. Skin eruptions are one of the most frequent adverse effects associated with their use, secondary to the drug's direct inhibitory effect on homeostasis of the epidermis and of the pilosebaceous follicle. Several cases of cutaneous toxicity in patients treated with epidermal growth factor receptor inhibitors have recently been published. We present three cases of acneiform eruptions attributable to different drugs in this family (cetuximab, gefitinib and erlotinib).

[Treatment of cutaneous T-cell lymphomas with bexarotene]. / Tratamiento de linfomas cutáneos de células T con bexaroteno.

INTRODUCTION: The choice of treatment in cutaneous T-cell lymphomas (CTCLs) depends on the clinical stage of the disease and the patient's general condition. To date, there is no curative treatment for this disease, and the objective is to control the symptoms and prevent the disease from progressing. Bexarotene is an X receptor-specific retinoid with anti-tumor activity. Its use as treatment for CTCLs refractory to at least one prior systemic therapy has been approved by the FDA. PATIENTS AND METHODS: We carried out a descriptive study of 9 patients treated with bexarotene in the Lymphoma Unit of our department. We analyzed the clinical characteristics of the patients and the efficacy of the treatment, and we collected data on the side effects that appeared. RESULTS: The overall response to the treatment was 44.4% (4/9). 2 patients had full remission and 2 had partial remission. Tolerance to the treatment was good, and the most frequent side effects were hypertriglyceridemia, hypercholesterolemia and central hypothyroidism. CONCLUSIONS: Even though this is a series of only 9 patients, the results that we obtained are similar to ones previously described. Bexarotene is an effective therapeutic option in this heterogeneous group of diseases.

[Solar urticaria. Study of 20 cases]. / Urticaria solar. Estudio de 20 casos.

INTRODUCTION: Solar urticaria is an infrequent disorder, but is probably underdiagnosed. It is characterized by the sudden appearance of weals in areas that are not usually photoexposed after exposure to the sun or to artificial sources of visible or ultraviolet light. Few cases have been published in literature, so the information available about this disorder and its natural evolution is limited. MATERIAL AND METHODS: We have compiled data from 20 patients diagnosed with solar urticaria in our department in the last 12 years (1990-2002) in order to try to obtain information about the characteristics of this condition. RESULTS: As the most relevant characteristics of our series, we can mention the fact that 60 % of the patients were women, and the average duration of the condition before consulting a dermatologist was 3 years. In 55 % of the patients, areas that are usually photoexposed, such as the face and hands, were less severely affected (due to acclimatization or hardening). The spectra responsible for the SU were visible light, UVA and UVB, in that order. With regard to treatment, we obtained a partial response with antihistamines and photoprotectors, and good results using progressive desensitization with UVA/sunlight. CONCLUSION: Solar urticaria is probably an underdiagnosed condition in our milieu. There are few series in literature that provide any information about the most significant characteristics of this disorder. We have compiled the most relevant data from our patients and we have compared it with the other published series in an attempt to learn more about this photodermatosis.

[Multiple adult xanthogranuloma]. / Xantogranuloma múltiple del adulto.

Juvenile xanthogranuloma is an infrequent, benign, normolipemic, non-Langerhans cell histiocytosis, which primarily affects young children. Clinically, it is characterized by the appearance of one or several brownish-yellow papulonodular lesions on the upper body, especially on the head and neck. Xanthogranulomas are less frequent in adults, and generally present as solitary lesions. The diagnosis of multiple xanthogranulomas in adults is exceptional. We describe the case of a female patient diagnosed with this rare disease.

Cytotoxic/natural killer cell cutaneous lymphomas. Report of EORTC Cutaneous Lymphoma Task Force Workshop.

BACKGROUND: Cutaneous lymphomas expressing a cytotoxic or natural killer (NK) cell phenotype represent a group of lymphoproliferative disorders for which there is currently much confusion and little consensus regarding the best nomenclature and classification. METHODS: This study analyzes 48 cases of primary cutaneous lymphoma expressing cytotoxic proteins and/or the NK cell marker, CD56. These cases were collected for a workshop of the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Task Force, to better clarify the clinical, morphologic, and phenotypic features of these uncommon tumors. RESULTS: Several categories with different clinical and pathologic features were delineated: 1) aggressive, CD8+, epidermotropic, cytotoxic T-cell lymphoma; 2) mycosis fungoides, cytotoxic immunophenotype variant; 3) subcutaneous panniculitis-like T-cell lymphoma; 4) NK/T-cell lymphoma, nasal type; 5) CD4+, NK cell lymphoma; 6) blastoid NK cell lymphoma; (7) intravascular NK-like lymphoma; and 8) cytotoxic, peripheral T-cell lymphoma. CONCLUSIONS: Our data show that primary cutaneous cytotoxic/NK cell lymphomas include distinct groups of diseases, clinically, histologically, and biologically. Because the finding of a cytotoxic phenotype often has prognostic significance, the routine use of cytotoxic markers in the diagnosis and classification of cutaneous lymphomas should be expanded.