Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors.

Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.

Albinism: epidemiology, genetics, cutaneous characterization, psychosocial factors

Abstract Oculocutaneous albinism is an autosomal recessive disease caused by the complete absence or decrease of melanin biosynthesis in melanocytes. Due to the reduction or absence of melanin, albinos are highly susceptible to the harmful effects of ultraviolet radiation and are at increased risk of actinic damage and skin cancer. In Brazil, as in other parts of the world, albinism remains a little known disorder, both in relation to epidemiological data and to phenotypic and genotypic variation. In several regions of the country, individuals with albinism have no access to resources or specialized medical care, and are often neglected and deprived of social inclusion. Brazil is a tropical country, with a high incidence of solar radiation during the year nationwide. Consequently, actinic damage and skin cancer occur early and have a high incidence in this population, often leading to premature death. Skin monitoring of these patients and immediate therapeutic interventions have a positive impact in reducing the morbidity and mortality associated with this condition. Health education is important to inform albinos and their families, the general population, educators, medical professionals, and public agencies about the particularities of this genetic condition. The aim of this article is to present a review of the epidemiological, clinical, genetic, and psychosocial characteristics of albinism, with a focus in skin changes caused by this rare pigmentation disorder.

Parotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System.

OBJECTIVE: Facial nerve injury, affecting mainly the marginal mandibular branch, is the most frequent neurologic complication from parotidectomy. To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch. METHODS: We reviewed the medical records of 73 post-parotidectomy patients (40 female, 18-84 years old, mean age 53.2 years) with facial nerve sparing, referred to the Department of Physical Therapy. All patients had parotid neoplasms or advanced skin cancer, and were followed by the principal author between 2006 and 2014. RESULTS: The muscles innervated by the marginal mandibular branch were the most frequently affected (72.6%), particularly in patients undergoing neck dissection (p = 0.023). The voluntary movement scores obtained with the modified system were significantly lower compared with the original version (p < 0.001). The best and worst scores were observed in patients with benign parotid tumors and skin cancer, respectively. Patients requiring neck dissection (p = 0.031) and resection of other structures (p = 0.021) had the lowest scores, evidenced only with the modified version. Patients with malignant tumors had significantly worse ratings, regardless of the Sunnybrook system version. The post-physiotherapy analysis involved 50 patients. The worst facial rehabilitation outcomes were related to the marginal mandibular branch function. CONCLUSION: The modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.

Parotidectomy-related facial nerve lesions: proposal for a modified Sunnybrook Facial Grading System / Lesões do nervo facial relacionadas à parotidectomia: proposta de um sistema Sunnybrook de graduação facial modificado

ABSTRACT Facial nerve injury, affecting mainly the marginal mandibular branch, is the most frequent neurologic complication from parotidectomy. Objective To test a modified Sunnybrook Facial Grading System as a new tool to assess the facial nerve function following parotidectomy, emphasizing the marginal mandibular branch. Methods We reviewed the medical records of 73 post-parotidectomy patients (40 female, 18-84 years old, mean age 53.2 years) with facial nerve sparing, referred to the Department of Physical Therapy. All patients had parotid neoplasms or advanced skin cancer, and were followed by the principal author between 2006 and 2014. Results The muscles innervated by the marginal mandibular branch were the most frequently affected (72.6%), particularly in patients undergoing neck dissection (p = 0.023). The voluntary movement scores obtained with the modified system were significantly lower compared with the original version (p < 0.001). The best and worst scores were observed in patients with benign parotid tumors and skin cancer, respectively. Patients requiring neck dissection (p = 0.031) and resection of other structures (p = 0.021) had the lowest scores, evidenced only with the modified version. Patients with malignant tumors had significantly worse ratings, regardless of the Sunnybrook system version. The post-physiotherapy analysis involved 50 patients. The worst facial rehabilitation outcomes were related to the marginal mandibular branch function. Conclusion The modified Sunnybrook Facial Grading System improved the marginal mandibular branch assessment, preserving the evaluation of other facial nerve branches.

RESUMO A lesão do nervo facial é a principal complicação neurológica relacionada às parotidectomias e, em geral, o ramo marginal mandibular é o mais frequentemente acometido. Objetivo Testar um Sistema Sunnybrook de Graduação Facial modificado (mS-FGS) como uma nova ferramenta para avaliar a função do nervo facial após a parotidectomia, enfatizando o ramo marginal mandibular. Métodos Estudo retrospectivo, baseado em prontuários de 73 casos (40 do sexo feminino, 18-84 anos, idade média = 53,2), submetidos à parotidectomia, com preservação do nervo facial. Todos os pacientes apresentavam neoplasias parotídeas ou câncer de pele avançado, e foram tratados pela autora principal entre 2006 e 2014. Resultados Neste estudo, os músculos inervados pelo ramo marginal mandibular foram os mais acometidos (72,6% dos casos), principalmente nos pacientes que realizaram esvaziamento cervical (p = 0,023). Os Escores de Movimento Voluntário obtidos pelo sistema modificado foram inferiores aos obtidos pelo original (p < 0,001). As melhores pontuações foram observadas em pacientes com tumores benignos parotídeos e os piores resultados, naqueles com câncer de pele. Pacientes que necessitaram de esvaziamento cervical e ressecção de outras estruturas, além da parótida, apresentaram escores menores (p = 0,031 e p = 0,021), evidenciados apenas pelo sistema modificado. Os tumores malignos geraram escores significativamente menores, independentemente do instrumento empregado. A análise pós fisioterapia envolveu 50 casos. Os piores resultados, após a intervenção fisioterapêutica, também foram observados nos músculos inervados pelo ramo marginal mandibular. Conclusão A avaliação da disfunção facial pós-parotidectomia, através do Sistema Sunnybrook com a modificação proposta permitiu uma apreciação mais detalhada do ramo marginal mandibular, sem prejuízo à avaliação dos demais ramos.

Infantile hemangioma: pathogenesis and mechanisms of action of propranolol.

Infantile hemangioma (IH) is the most common benign tumor of childhood, with a prevalence of 4 % to 10 %. It is characterized by a proliferative rapid growth phase, which starts after a few weeks of life, followed by a slow regression phase. In IH cases that are potentially disfiguring or life-threatening (10 % to 15 % of all cases), systemic therapy should be promptly initiated. Data source The present study reviews published scientific articles available in reliable electronic databases. Selected were all studies that evaluated the pathogenesis of IH and the mechanisms of action of propranolol. Conclusions The pathogenesis of IH has not been fully elucidated. Studies show that, in the proliferative phase of IH, there is an imbalance of angiogenic factors and an increase in the levels of vascular endothelial growth factor and matrix metalloproteinases 2 and 9. In the regression phase, the levels of these factors decrease, whereas those of antiangiogenic factors, including tissue inhibitors of matrix metalloproteinases, increase. Since 2008, propranolol has become the drug of choice in the treatment of IH, targeting vascular tone, angiogenesis, and apoptosis. Current insights into the pathogenesis of IH allow for the development of new therapeutic strategies.

[Kaposi's Sarcoma in patients with late HIV diagnosis. Case report and review of literature.] / Sarcoma de Kaposi en paciente con diagnóstico tardío de VIH. Presentación de un caso y revisión.

Kaposi's sarcoma is a limphoangioproliferous tumor described for the first time in the year 1872 by Moritz Kaposi. There are four clinical variants, the classical form, the endemic, the iatrogenic associated to transplantation or immunosuppression and the epidemic associated with AIDS, which will be referred in this publication. In this research,(case, paperwork, investigation) a 31 year old male patient, who was diagnosed AIDS and Kaposi's sarcoma at the same time while in hospital, is described.

El sarcoma de Kaposi es un tumor linfoangioproliferativo descripto por primera vez en el año 1872 por Moritz Kaposi. Hay cuatro variantes clínicas, la forma clásica, la endémica, la iatrogénica asociada a trasplante o inmunosupresión y la epidémica asociada a SIDA, de la cual se hará referencia en esta publicación. Se describe un paciente varón de 31 años, al cual durante la misma internación se hace el diagnóstico de SIDA y de sarcoma de Kaposi.

Rare Presentation of a Marjolin's Ulcer Secondary to a Post-Traumatic Injury.

Marjolin's ulcer is a rare and aggressive cutaneous malignancy arising from previously traumatized skin, most commonly at the site of previous burns. We present a unique case of Marjolin's ulceration secondary to an orthopedic injury and a nonburn history of trauma. The patient had been involved in a motorcycle accident >20 years earlier. For 17 months, the patient had refused to acknowledge the severity of his disease state. He had refused the standard of care and opted for local wound care only until a minor fall caused a pathologic fracture, leading to an above the knee amputation. Road traffic incidents remain an uncommon cause of subsequent Marjolin's transformation in developed countries. As such, we present the case of a patient with a unique combination of a continued lack of compliance after diagnosis and the unusual cause of his initial trauma.

Papular Epidermal Nevus with Skyline Basal Cell Layer (PENS): Three New Cases and Review of the Literature.

BACKGROUND/OBJECTIVE: Papular epidermal nevus with skyline basal cell layer (PENS) is a recently described type of epidermal nevus with characteristic histopathologic findings, mainly regular, rectangular acanthosis and a well-demarcated basal cell layer with clear palisading and separation between basal cell nuclei and the first row of Malpighian cell nuclei. Although the first reports described randomly distributed lesions appearing sporadically in otherwise healthy patients, cases of Blaschkoid distribution, lesions associated with extracutaneous manifestations, and familial cases have been reported. METHODS: We performed a review of the clinical charts of all patients with histologic diagnosis of PENS in our hospital. We evaluated epidemiologic, clinical, and histologic features. We then reviewed the literature with a particular emphasis on the presence or absence of extra-cutaneous associations. RESULTS: Three patients with PENS are described. One had a single lesion, one had three lesions, and one, a patient with mild developmental delay, a curved penis, and hypospadias, had multiple lesions. CONCLUSION: The probability of having extracutaneous manifestations is 6.3 times as great in individuals with more than four lesions. Therefore these patients may need closer follow-up.

Correlations between clinical and pathological features in 17 cases of mycosis fungoides before and after transformation.

BACKGROUND: Mycosis fungoides (MF) may progress to transformed MF (T-MF), a condition with aggressive behavior. OBJECTIVES: This study was designed to compare the clinical and pathological features of biopsies in 17 cases of MF before and after transformation. METHODS: During a revision of primary cutaneous T cell lymphomas, 53 cases of MF were identified, including 17 cases of T-MF. Clinical, pathological, and immunohistochemical data for the MF patients were evaluated. Cases of T-MF and intermediate transformed (IT) MF were diagnosed according to previous criteria. The histological and immunohistochemical features of T-MF biopsies were compared with those of MF/IT-MF biopsies taken before or concomitant with transformation. RESULTS: At the initial diagnosis, three patients were found to have more advanced stages of disease: two had MF and T-MF simultaneously, and another had only oral T-MF. Four patients considered to show histological transformation maintained disease stages Ia and Ib and all remain alive. Of five patients with IT-MF at first diagnosis, all progressed to complete histological transformation, three developed tumors, and two died of disease. Four patients progressed to CD30+ large cell lymphoma, and three of these died of disease. In one of these patients, the MF biopsy showed a high level of expression of CD30 in the epidermis and dermis. CONCLUSIONS: No correlation between advanced MF and expression of CD25 and CD30, or frequency of Ki-67+ cells was found. The frequency of transformation among patients with initially non-transformed MF was high. Our findings support the emphasis given by other authors to IT-MF, a pattern of MF which is generally not considered in many studies.

Papel do microambiente tumoral no desenvolvimento do melamoma / Components of the tumor microenvironment in melanoma model

Nos últimos dez anos a incidência do câncer tem sido mundialmente alarmante, constituindo um grave problema de saúde pública com expectativas de aumento para as próximas décadas. Estudos epidemiológicos no Brasil demonstraram que o câncer de maior prevalência é o de próstata, entretanto o câncer de pele tem impactado de forma significativa a população em geral. Dentre os principais tipos de câncer de pele, o melanoma é o que mais causa óbitos devido a sua alta capacidade de metástase. Vários fatores estão envolvidos no desenvolvimento do melanoma, entretanto interações entre as células neoplásicas e as células normais presentes no local onde o tumor se desenvolve é o foco de estudo da maioria dos centros de pesquisa em câncer. Assim, nesta revisão são apresentados os principais achados descritos nos últimos dez anos em relação às interações das células neoplásicas com os componentes do microambiente tumoral no modelo de melanoma.

The last ten years, the incidence of cancer has been globally alarming constituting a serious public health problem with increasing expectations for the coming decades. Epidemiological studies in Brazil showed that, the most prevalent of all cancers is prostate cancer, however skin cancer has impacted significantly the general population. Among the main types of skin cancer, melanoma causes more deaths due to its high ability to metastasize. Several factors are involved in the development of melanoma, however interactions between the neoplastic cells and the normal cells at the site where the tumor develops is the aim of many research centers in cancer. Thus, this review presents the main findings described in the last ten years in relation to the interactions between cancer cells and the components of the tumor microenvironment in melanoma model.

Papel do microambiente tumoral no desenvolvimento do melamoma / Components of the tumor microenvironment in melanoma model

Nos últimos dez anos a incidência do câncer tem sido mundialmente alarmante, constituindo um grave problema de saúde pública com expectativas de aumento para as próximas décadas. Estudos epidemiológicos no Brasil demonstraram que o câncer de maior prevalência é o de próstata, entretanto o câncer de pele tem impactado de forma significativa a população em geral. Dentre os principais tipos de câncer de pele, o melanoma é o que mais causa óbitos devido a sua alta capacidade de metástase. Vários fatores estão envolvidos no desenvolvimento do melanoma, entretanto interações entre as células neoplásicas e as células normais presentes no local onde o tumor se desenvolve é o foco de estudo da maioria dos centros de pesquisa em câncer. Assim, nesta revisão são apresentados os principais achados descritos nos últimos dez anos em relação às interações das células neoplásicas com os componentes do microambiente tumoral no modelo de melanoma.(AU)

The last ten years, the incidence of cancer has been globally alarming constituting a serious public health problem with increasing expectations for the coming decades. Epidemiological studies in Brazil showed that, the most prevalent of all cancers is prostate cancer, however skin cancer has impacted significantly the general population. Among the main types of skin cancer, melanoma causes more deaths due to its high ability to metastasize. Several factors are involved in the development of melanoma, however interactions between the neoplastic cells and the normal cells at the site where the tumor develops is the aim of many research centers in cancer. Thus, this review presents the main findings described in the last ten years in relation to the interactions between cancer cells and the components of the tumor microenvironment in melanoma model.(AU)

Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology / Micose fungoide hipocromiante: uma revisao de seus aspectos clinicos e fisiopatologicos

Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.

Ultimamente diferentes formas clínicas da micose fungoide têm sido descritas. A micose fungoide hipocromiante pode ser considerada um subtipo da micose fungoide, apresentando algumas características peculiares que contrastam com os achados da forma clássica da micose fungoide. A maioria dos pacientes com micose fungoide hipocromiante são mais jovens que aqueles acometidos pela micose fungoide clássica. Esta variante é descrita principalmente em indivíduos melanodérmicos (afroamericanos e asiáticos). O prognóstico é melhor que o observado para a forma clássica: ao diagnóstico, os pacientes apresentam somente "patches", que tendem a perdurar por longos períodos, sem evolução para estágios mais avançados. O diagnóstico é feito através da correlação clinicopatológica: biópsia da lesão cutânea frequentemente revela intenso epidermotropismo, caracterizado por linfócitos CD8+ atípicos, grandes, com halo e núcleo convoluto, contrastando com o infiltrado dérmico leve a moderado. Estas células CD8+, que participam do perfil de resposta T helper-1, impediriam a evolução da doença para o desenvolvimento de placas infiltradas e tumores, além de determinar a inibição da melanogênese nas lesões hipocrômicas. Portanto, a hipocromia poderia ser considerada um marcador de bom prognóstico na micose fungoide.

Senescent fibroblasts in melanoma initiation and progression: an integrated theoretical, experimental, and clinical approach.

We present an integrated study to understand the key role of senescent fibroblasts in driving melanoma progression. Based on the hybrid cellular automata paradigm, we developed an in silico model of normal skin. The model focuses on key cellular and microenvironmental variables that regulate interactions among keratinocytes, melanocytes, and fibroblasts, key components of the skin. The model recapitulates normal skin structure and is robust enough to withstand physical as well as biochemical perturbations. Furthermore, the model predicted the important role of the skin microenvironment in melanoma initiation and progression. Our in vitro experiments showed that dermal fibroblasts, which are an important source of growth factors in the skin, adopt a secretory phenotype that facilitates cancer cell growth and invasion when they become senescent. Our coculture experiments showed that the senescent fibroblasts promoted the growth of nontumorigenic melanoma cells and enhanced the invasion of advanced melanoma cells. Motivated by these experimental results, we incorporated senescent fibroblasts into our model and showed that senescent fibroblasts transform the skin microenvironment and subsequently change the skin architecture by enhancing the growth and invasion of normal melanocytes. The interaction between senescent fibroblasts and the early-stage melanoma cells leads to melanoma initiation and progression. Of microenvironmental factors that senescent fibroblasts produce, proteases are shown to be one of the key contributing factors that promoted melanoma development from our simulations. Although not a direct validation, we also observed increased proteolytic activity in stromal fields adjacent to melanoma lesions in human histology. This leads us to the conclusion that senescent fibroblasts may create a prooncogenic skin microenvironment that cooperates with mutant melanocytes to drive melanoma initiation and progression and should therefore be considered as a potential future therapeutic target. Interestingly, our simulations to test the effects of a stroma-targeting therapy that negates the influence of proteolytic activity showed that the treatment could be effective in delaying melanoma initiation and progression.

Unilateral livedoid vasculopathy associated with involutional phase of cutaneous infantile hemangioma: the connection to coagulation disorders.

Livedoid vasculopathy is a bilateral painful and recurrent cutaneous ulcerative disorder of the legs that leads to atrophie blanche, atrophic white-porcelain scars, and is associated with disorders of fibrinolysis and/or coagulation. We present a young boy with an association between livedoid vasculopathy in the area of a previous involuted cutaneous hemangioma. We found 4 uncommon abnormalities associated with thrombo-occlusive events: heterozygous 20210 A→G genotype of prothrombin, reduced activity of anticoagulation proteins C and S, and elevated lipoprotein (a).

Phacomatosis pigmentokeratotica--a patient with hypophosphatemic rickets.

The epidermal naevus syndrome (ENS) is a sporadic condition characterized by congenital epidermal naevi associated with anomalies in other organ systems, most commonly the central nervous system and skeleton. We report a case of ENS presenting hypophosphataemic rickets resistant to traditional therapeutic agents.

Hypopigmented mycosis fungoides: a review of its clinical features and pathophysiology.

Several distinct clinical forms of mycosis fungoides have been described. Hypopigmented mycosis fungoides should be regarded as a subtype of mycosis fungoides, insofar as it presents some peculiar characteristics that contrast with the clinical features of the classical form. Most patients with hypopigmented mycosis fungoides are younger than patients typically diagnosed with classical mycosis fungoides. In addition to typical dark-skinned individuals impairment, hypopigmented mycosis fungoides has also been described in Asian patients. The prognosis for hypopigmented mycosis fungoides is much better than for classical mycosis fungoides: hypopigmented mycosis fungoides is diagnosed when there are only patches of affected skin, and lesions usually will not progress beyond terminal stages, although they can persist for many years. Diagnosis should involve clinicopathologic correlation: skin biopsy analysis often reveals intense epidermotropism, characterized by haloed, large, and atypical CD8+ lymphocytes with convoluted nuclei, in contrast to mild to moderate dermal lymphocytic infiltrate. These CD8+ cells, which participate in T helper 1-mediated immune responses, prevent evolution to mycosis fungoides plaques and tumors and could be considered the main cause of the inhibition of melanogenesis. Therefore, hypopigmentation could be considered a marker of good prognosis for mycosis fungoides.

Malignant transformation in melanocytes is associated with increased production of procoagulant microvesicles.

Shedding of microvesicles (MVs) by cancer cells is implicated in a variety of biological effects, including the establishment of cancer-associated hypercoagulable states. However, the mechanisms underlying malignant transformation and the acquisition of procoagulant properties by tumour-derived MVs are poorly understood. Here we investigated the procoagulant and prothrombotic properties of MVs produced by a melanocyte-derived cell line (melan-a) as compared to its tumourigenic melanoma counterpart Tm1. Tumour cells exhibit a two-fold higher rate of MVs production as compared to melan-a. Melanoma MVs display greater procoagulant activity and elevated levels of the clotting initiator protein tissue factor (TF). On the other hand, tumour- and melanocyte-derived MVs expose similar levels of the procoagulant lipid phosphatidylserine, displaying identical abilities to support thrombin generation by the prothrombinase complex. By using an arterial thrombosis model, we observed that melanoma- but not melanocyte-derived MVs strongly accelerate thrombus formation in a TF-dependent manner, and accumulate at the site of vascular injury. Analysis of plasma obtained from melanoma-bearing mice showed the presence of MVs with a similar procoagulant pattern as compared to Tm1 MVs produced in vitro. Remarkably, flow-cytometric analysis demonstrated that 60% of ex vivo MVs are TF-positive and carry the melanoma-associated antigen, demonstrating its tumour origin. Altogether our data suggest that malignant transformation in melanocytes increases the production of procoagulant MVs, which may contribute for a variety of coagulation-related protumoural responses.