La linfangiogénesis. Sus implicaciones en el diagnóstico, tratamiento y pronóstico del melanoma / Lymphangiogenesis: Implications for Diagnosis, Treatment, and Prognosis in Patients With Melanoma

En pacientes con melanoma los factores pronósticos utilizados en muchas ocasiones no permiten una predicción precisa de la evolución de la enfermedad, lo que hace evidente la necesidad de búsqueda de nuevos factores pronósticos. Existe una evidencia científica cada vez más sólida de que los vasos linfáticos tumorales desempeñan un papel importante en la producción de metástasis linfáticas y también hematógenas en pacientes con melanoma. En este trabajo expondremos el estado actual del conocimiento y las implicaciones del proceso de linfangiogénesis en el diagnóstico, tratamiento y pronóstico de los pacientes con melanoma (AU)

Disease course in melanoma often cannot be accurately predicted by means of the prognostic factors usually considered in patients with melanoma; therefore, new factors are clearly needed. Increasingly robust scientific evidence shows that tumor lymph vessels play a key role in melanoma that metastasizes by lymphatic and hematogenous pathways. We review current knowledge and examine the implications of lymphangiogenesis in the diagnosis, treatment, and prognosis of patients with melanoma (AU)

Lymphangiogenesis: implications for diagnosis, treatment, and prognosis in patients with melanoma.

Disease course in melanoma often cannot be accurately predicted by means of the prognostic factors usually considered in patients with melanoma; therefore, new factors are clearly needed. Increasingly robust scientific evidence shows that tumor lymph vessels play a key role in melanoma that metastasizes by lymphatic and hematogenous pathways. We review current knowledge and examine the implications of lymphangiogenesis in the diagnosis, treatment, and prognosis of patients with melanoma.

Mechanisms of tumour vascularization in cutaneous malignant melanoma: clinical implications.

Malignant melanoma represents < 10% of all skin cancers but is responsible for the majority of skin-cancer-related deaths. Metastatic melanoma has historically been considered as one of the most therapeutically challenging malignancies. Fortunately, for the first time after decades of basic research and clinical investigation, new drugs have produced major clinical responses. Angiogenesis has been considered an important target for cancer treatment. Initial efforts have focused primarily on targeting endothelial and tumour-related vascular endothelial growth factor signalling. Here, we review different mechanisms of tumour vascularization described in melanoma and discuss the potential clinical implications.

Blood microvessel density, lymphatic microvessel density and lymphatic invasion in predicting melanoma metastases: systematic review and meta-analysis.

In malignant melanoma (MM) there is an urgent need to identify new markers with predictive value superior to the traditional clinical and histological parameters. Angiogenesis and lymphangiogenesis have been recognized as critical processes in tumour growth and metastasis development, and numerous studies have evaluated the significance of these parameters in predicting the prognosis in solid tumours, including MM. We set out to determine whether angiogenesis, lymphangiogenesis and lymphatic invasion (LI) are valuable prognostic markers in MM. We systematically reviewed the available literature and subsequently performed a meta-analysis on the compiled data. To be eligible for the systematic review, a study had to provide the microvessel density (MVD), the lymphatic vessel density (LVD) or information about LI, assessed by immunohistochemistry on the primary site in patients with MM. To be evaluable for the meta-analysis, a study also had to provide information on clinical outcome. We approached selected studies with the Reporting recommendations for tumour marker (REMARK) criteria, verifying whether they had followed the recommendations. In total, nine angiogenesis, seven lymphangiogenesis and 10 LI studies were included in our meta-analysis, representing 419, 474 and 802 patients, respectively. Using meta-analysis, we showed that peritumoral LVD and the presence of LI have prognostic value for patients with MM. In contrast, MVD and intratumoral LVD did not have prognostic value in these patients. LVD and LI seem to have prognostic value for patients with MM.

[Solar elastosis in cutaneous squamous cell carcinoma]. / Elastosis solar en carcinomas espinocelulares cutáneos.

INTRODUCTION: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. MATERIAL AND METHODS: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. RESULTS: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. CONCLUSIONS: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both.

Elastosis solar en carcinomas espinocelulares cutáneos / Solar Elastosis in Cutaneous Squamous Cell Carcinoma

Introducción: El hallazgo de elastosis solar (degeneración basófila del colágeno) se podría considerar como un signo histológico del daño solar crónico. Material y método: Se ha realizado un estudio retrospectivo sobre 222 carcinomas espinocelulares (CE). Se ha valorado si existía elastosis solar y si esta se extendía hasta la dermis reticular superficial, media o profunda. También se han analizado otras variables clínicas como la localización, la ubuicación en áreas fotoexpuestas, así como la edad, el sexo y la inmunodepresión de los pacientes a los que se extirparon estos CE. Resultados: En la mayoría de CE (182CE, un 82%) se observa una intensa elastosis solar: 87CE presentaban elastosis solar hasta la dermis reticular media y 95CE hasta la dermis reticular profunda. Sólo hubo 6CE (2,7%) que no presentaban elastosis solar. En algunos CE la elastosis solar era tan intensa que se extendía hasta el tejido celular subcutáneo o afectaba a la pared de venas y/o arteriolas. Existía una relación significativa entre la observación de elastosis solar a más profundidad y una edad mayor, así como con el sexo femenino. Conclusiones: En la mayoría de CE se observa elastosis solar, lo que podría traducir un intenso daño solar crónico. La radiación ultravioleta sería el principal factor etiopatogénico en la mayoría de CE, aunque también podrían estar implicados otros factores etiopatogénicos, sobre todo en aquellos CE sin una elastosis solar intensa. Casi todos estos CE estudiados se asociarían a inmunodepresión (sistémica o localizada), basándonos en los importantes efectos inmunosupresores que producen las radiaciones solares, la edad avanzada o ambas (AU)

Introduction: Solar elastosis, or basophilic degeneration of collagen, may be a histologic sign of chronic sun damage. Material and methods: We reviewed 222 cases of squamous cell carcinoma (SCC) to identify the presence of solar elastosis and its possible invasion of the upper, middle, or deep reticular dermis. We also analyzed clinical variables such as SCC location, location in exposed areas of the skin, age, sex, and immunosuppression. Patients included had undergone surgical excision of an SCC. Results: Severe solar elastosis was found in most cases (182 patients, 82%): 87 extended to the middle reticular dermis and 95 had reached the deep reticular dermis. Only 6 (2.7%) patients had no solar elastosis. In some cases elastosis was so severe that it had affected the subcutaneous cellular tissue or venous or arteriolar walls. Deeper solar elastosis was significantly associated with older age and female sex. Conclusions: Solar elastosis was found in most patients with SCC and seems to indicate chronic severe solar damage. Exposure to ultraviolet radiation would be the main cause of SCC, although other factors might also be implicated, particularly in patients who did not have severe solar elastosis. Systemic or localized immunosuppression was associated with nearly all the SCC cases studied, consistent with the marked immunosuppressant effects of sun exposure, the aging process, or both (AU)

Sarcoidosis aguda. Síndrome de Löfgre / Acute Sarcoidosis. Löfgren síndrome

El Síndrome de Löfgren es una variante de presentación aguda de la sarcoidosis, de carácter benigno, caracterizada por la presencia de eritema nodoso, adenopatías hiliares bilaterales y poliartralgias o poliartritis. Presentamos un caso de Síndrome de Löfgren cuyo interés reside en el diagnóstico de una enfermedad sistémica como es la sarcoidosis a través de las lesiones cutáneas (AU)

Löfgren syndrome is an acute form sarcoidosis that is caracterized by erythema nodosum, bilateral hilar lymphadenopathy, and polyarthralgia or polyarthitis. We report a case of Löfgren syndrome whose interest lies in the diagnosis of a systemic disease like sarcoidosis throught cutaneous manifestation (AU)

Estudio epidemiológico sobre la demandahistopatológica en Dermatología, en unÁrea de Salud de la provincia de Zaragoza (1997-2001) / Epidemiologic study about the histopathologic requirements in Dermatology in a Sanitary Area of Zaragoza

En el presente estudio hemos recogido, de forma retrospectiva y descriptiva, los datos referentes a los diagnósticos histopatológicos de todos lospacientes que requirieron estudio histopatológico, bien por motivo diagnóstico (biopsia cutánea) o terapéutico (cirugía), en el Departamento de Dermatologíadel Hospital Clínico, durante el periodo comprendido entre el 1 de Enero de 1997 y el 31 de Diciembre de 2001 (periodo total de 5 años).Con ello, se obtiene y describe un perfil de aquellas patologías que más frecuentemente requieren biopsia cutánea, así como su distribución por gruposde edad y sexo. Durante el periodo estudiado, se han contabilizado un total de 11.647 registros histopatológicos con una media de 2.329 biopsiaspor año y de 6,4 biopsia por día. El 59,3% (N: 6.911) de los registros corresponde a pacientes del sexo femenino, mientras que el 40,7% (N: 4.736)corresponde a pacientes varones, con una proporción varón:mujer de 1:1,46.De forma global, el grupo de diagnóstico más frecuentemente biopsiado es el de Tumores Pigmentarios, el cual supone un 40,4% (N: 4.706) del totalde las biopsias. Los siguientes grupos en frecuencia son el de los Tumores Cutáneos Benignos (de origen no pigmentario), el cual reúne un 28% (N:3.256) de los registros, y el de los Carcinomas Cutáneos, con un 16% (N: 1.859) del total.Con mucho menor porcentaje, aparecen los grupos de Lesiones Premalignas (3,7%; N: 432), Patología no concluyente o ausencia de ésta (2,5%: N:291), y Lesiones de Origen Traumático (2,4%; N: 275). De un total de 250 diagnósticos histopatológicos registrados diferentes, los de mayor frecuenciason el de Nevus Intradérmico con un 24,1% (N: 2.812) y el Nevus Melanocítico Compuesto con un 12,1% (N: 1.406) (AU)

All the patients requiring histopathologic study in our Dermatology Department of HCU Lozano Blesa in Zaragoza, from January 1997 to december2001, were registered.So, we have obtained and described a feature about the more frequent histopathological diagnoses, and its distribution by sex and groups of age. Atotal among of 11647 patients were studied during this survey (2329 biopsies per year, and 6.4 per day); including 4736 male (40.7%) and 6911female (59.3%). The ratio male/female was 1:1.46.The five groups more frequently biopsed in a decreased order was: Pigmentary Tumours (40.1%, N: 4706), Benign Tumours (28%, N: 3256), CutaneousCarcinomas (16%, N: 1859), Cutaneous Premalign Lesions (3.7%, N: 432), and Dermatosis with Traumatic origen (2.4%, N: 275).The most frequent histopathologic diagnose was Intradermal Nevus (24.1%, N: 2812), and the second was Compound Melanocytic Nevus (12.1%,N:1406) (AU)

[Clear cells in cutaneous squamous cell carcinoma]. / Las células claras en el carcinoma espinocelular cutáneo.

INTRODUCTION: Although few cases of squamous cell carcinoma (SCC) with clear cells have been published, we believe that these cells are often present in SCC. MATERIAL AND METHODS: We studied 249 SCCs, analyzing a number of clinical and histological variables. Various immunohistochemical techniques (immunoperoxidase method) were used to determine whether adnexal differentiation was present. RESULTS: There were 96 SCCs with a proportion of clear cells of over 25 %. Advanced or established SCCs and SCCs associated with Bowen disease contained a larger proportion of clear cells. We defined 2 histological patterns: a) clear cells around the keratin pearls of SCCs arising from pre-existing actinic keratosis and with indirect signs of human papilloma virus infection in hair follicles; and b) clear cells that simulate adnexal differentiation in lesions arising on pre-existing Bowen disease lesions. There were also 19 carcinomas with true adnexal differentiation. DISCUSSION: Clear cells are frequently observed in SCC, though large numbers of clear cells are present only in certain SCCs. The appearance of clear cells in SCCs is progressive and they are only present in more advanced SCC. The presence of clear cells is suggestive of adnexal differentiation; however, in the majority of cases, their presence is due to infiltration of normal adnexal structures by the cells of pagetoid Bowen disease. True adnexal differentiation exists only in a small percentage of cases (7.6 % in our study). The histological pattern described as clear cells around keratin pearls practically rules out this differentiation.

Histiocitoma fibroso maligno pleomórficocutáneo de rápido crecimiento / Cutaneous pleomorphic malignant fibrous histiocytoma with a rapidly growing

El histiocitoma fibroso maligno es un sarcoma de partes blandas, de presentación preferente entre la cuarta y quinta década de la vida, localizándoseprincipalmente en la zona proximal de extremidades inferiores. Histológicamente existen varios tipos según la morfología celular del tumor: la formapleomórfica, estoriforme (predominando los fibroblastos o los histiocitos como células dominantes), mixoide, de células gigantes e inflamatorio.La forma clínica más frecuente de presentación es como lesión tumoral profunda, localizada en el músculo esquelético, que puede protuir la piel que larecubre.Comentamos el caso de un varón de 81 años que consultó por una tumoración cutánea asintomática, de gran tamaño y rápido crecimiento (siete meses),localizado en pared torácica izquierda. Histológicamente el tumor mostraba un patrón típicamente estoriforme, formado por histiocitos y fibroblastos atípicos.Las células fueron positivas para vimentina, lisozima y CD68, hallazgos compatibles, con un histiocitoma fibroso maligno pleomórfico.Se revisan las características clínico patológicas y citogenéticas de este tumor, así como las distintas opciones terapéuticas (AU)

Malignant fibrous histiocytoma,(MFH) is the most common soft-part sarcoma arising between the fourth an fifth decades of life, that usually involvesthe proximal lower extremities. Its histology has shown a wide variety of cell morphology, including storiform-pleomophic (fibroblastic or histiocyticcells dominant), myxoid, giant cell and inflammatory types. The most usual presentation is a tumoral lesion located within skeletal muscle that mayspread to the skin as a painless nodule.We report a 82-years-old man who was seen with 7-month history of a rapidly growing and asynthomatic tumour of the left flank. Histologically thetumor showed a typical storiform pattern consisting of atypical histiocytic and fibroblastic cells. The cells were positive for vimentina, lisozima andCD68. These findings were compatible with a pleomorphic malignant fibrous histiocytoma.We review the clinical manifestations, histological findings and histogenesis of this tumour, and the different therapeutical options (AU)

'Bowenoid wart': wart with bowenoid histological changes? Report of 9 cases.

INTRODUCTION: Cases of lesions that simulate Bowen's disease have been previously described in the literature. CASE REPORT: Nine exophytic verruca-like lesions with histological findings of Bowen's disease (BD) are described. All cases had a rapid growth, and were located on the face and neck of elderly patients with chronic solar skin damage. We carried out p16 immunohistochemical staining using the immunoperoxidase technique, which was negative in all cases. DISCUSSION: We think that these 9 lesions are only histologically mimicking BD, and could be a subtype of verruca ('bowenoid wart'). These lesions could be provoked by nononcogenic human papillomavirus (HPV), as in other cases previously described. The p16 staining was negative in all cases, in contrast with most BD cases. It would be interesting to study whether positive p16 staining is related to oncogenic HPV, whereas negative p16 staining could be associated with low or nononcogenic HPV; thus, more studies are needed.

[Epidermodysplasia verruciformis-like cells as histologic markers of immunosuppression: review of 229 squamous cell carcinomas]. / Las células tipo epidermodisplasia verruciforme como marcador histológico de inmunodepresión: revisión de 229 carcinomas espinocelulares.

INTRODUCTION: Epidermodysplasia verruciformis (EV) is associated with greater susceptibility to infection by certain oncogenic subtypes of human papillomavirus (HPV). Among other histologic findings, large, clear, oval or rounded cells (EV cells) are observed in the granular layer in EV, and some authors consider these cells to be markers of immunosuppression. MATERIAL AND METHODS: We analyzed 229 squamous cell carcinomas (SCC) to determine whether EV cells were present and to assess whether their presence was associated either with localized or cutaneous immunosuppression (tumors with signs of severe chronic actinic damage or severe stasis dermatitis) or with systemic immunosuppression (immunocompromised or elderly patients). RESULTS: We observed EV cells in 33 SCC. No statistically significant relationship was observed between the presence of EV cells and immunosuppression. We performed polymerase chain reaction in 8 lesions, but the results were not informative as the DNA was denatured. CONCLUSIONS: We found no relationship between the presence of EV cells and localized or systemic immunosuppression, possibly because the sample was inadequate (almost all SCC studied were associated with signs of immunosuppression, irrespective of the presence or absence of EV cells). Further studies will be required to compare lesions associated with immunosuppression with those in which immunosuppression is absent. The presence of EV cells may be the result of cytopathic effects of certain HPV subtypes, such as HPV 5 or 8, but this will need to be demonstrated using techniques such as polymerase chain reaction.

Histiocitosis eruptiva generalizada en un varón de 53 años de edad / Generalized eruptive histiocytosis in a 53-years old male

La histiocitosis eruptiva generalizada es un cuadro clínico muy poco frecuente, incluída dentro de las histiocitosis de células distintas de las de Langerhans.Presentamos un caso recientemente visto en nuestro Servicio, planteando el diagnóstico diferencial con otras formas de histiocitosis, aunque losúltimos estudios sugieren que pueden tratarse de distintas entidades formando parte de un único espectro clínico (AU)

Generalized eruptive histiocytosis is a rare benign disorder, categorized into non-LCH histiocytosis. We present a case of this disease and provide thedifferential diagnosis with other forms of histiocytosis. Recent literature has suggested that generalized eruptive histiocytosis may be a part of a continuousspectrum of non-LCH histiocytic disorders (AU)