No / Although we have made significant progress in understanding the regulation of the UVR-exposed epidermal-melanin unit, we know relatively little about how human hair follicle pigmentation is regulated. Progress has been hampered by gaps in our knowledge of the hair growth cycle’s controls, to which hair pigmentation appears tightly coupled. However, pigment cell researchers may have overly focused on the follicular melanocytes of the nocturnal and UVR-shy mouse as a proxy for human epidermal melanocytes. Here, I emphasize the epidermis-follicular melanocyte pluralism of human skin, as research models for vitiligo, alopecia areata and melanoma, personal care/cosmetics innovation. Further motivation could be in finding answers to why hair follicle and epidermal pigmentary units remain broadly distinct? Why melanomas tend to originate from epidermal rather than follicular melanocytes? Why multiple follicular melanocyte sub-populations exist? Why follicular melanocytes are more sensitive to aging influences? In this perspective, I attempt to raise the status of the human hair follicle melanocyte and highlight some species-specific issues involved which the general reader of the pigmentation literature (with its substantial mouse-based data) may not fully appreciate.

Female ageing leads to reduced hair density and thinner fibres. The impact of the ageing dermal environment on the hair follicles (HFs) remains unclear. This study documents in situ changes in human female scalp skin of women (19-81 years (yrs)), and corresponding primary cultures of dermal fibroblast (DF) and dermal sheath (DS) cells. In situ, the papillary/reticular boundary was indistinguishable in young scalp, but delineated over 40yrs, with reduced rete ridges, changes in collagen organisation, reduced podoplanin (PDPN) and increased versican (VCAN) expression. Hyaluronic acid synthase 2 (HAS2) was highly expressed throughout the scalp. Matrix Metallopeptidase 1 (MMP1) and Metallopeptidase inhibitor 1 (TIMP1), cyclin-dependent kinase inhibitor 2A (p16INK4A), 11β-Hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1/HSD11B1 and 11β-HSD2/HSD11B2) mRNA expression increased in aged DFs. In DS cells, HAS2, Vimentin (VIM) ,PDPN, Lysosomal-associated membrane protein 1 (LAMP1), Sequestosome- 1 (P62) and Protease nexin-1 (SERPINE2) increased, while α-smooth muscle actin (aSMA) decreased. Both cell types exhibited elevated cartilage oligomeric protein (COMP) mRNA expression. Proteomics revealed elevated COMP expression in the DF secretome with age, suggesting a more fibrotic phenotype or DS migration into the dermis. DF and DS lysate protein expression suggests altered extracellular matrix (ECM) remodelling due to increased levels of MMP-2 and Protease inhibitor Plasminogen activator inhibitor-1 (Serpin E1/PAI-1). Cathepsin C/DPPI protein lysate expression decreased in DFs but increased in DS. In summary, ageing female scalp shows striking structural and biological changes in the HF environment that may impact hair growth, due to alterations in ECM, senescence and autophagy associated biomarkers.

Epigenetic mechanisms play an important role during the morphogenesis of the hair follicle and the hair cycle. Work on hair regeneration is of importance as no products are available which can provide complete reversal of hair loss. Tet2 promotes DNA demethylation by the hydroxylation of 5mC to 5hmC which in turn causes gene transcription activation. Dermal papilla (DP) cells located within the hair follicle are responsible for the regulation of development and the growth of hair follicles. Fgf20 signalling controls commitment of the mesenchymal precursor cells to the DP progenitor lineage. An immature DP cells is then formed during maturation by Shh signalling which then stimulates these to differentiate into a DP cell by BMP and Wnt signalling. Methylated DNA can be bound by the proteins recruiting transcription corepressors. DNA methyltransferases (DNMT’s) can be degraded by decitabine which reverses gene silencing. Conditional knockout of Tet2 in mouse DP cells results in a delay in anagen initiation, suggesting Tet2 is involved in the telogen-anagen transition. Additionally, by using dermal fibroblasts and RA-DPAC (Dermal Papilla activating medium supplemented with retinoic acid), it was found that decitabine can increase plasticity in dermal fibroblasts and RA-DPAC can be used to accelerate a lineage change to DP cells which is supported by the significant increase in the DP specific gene expression. Examples include AlPl, LEF1, BMP4/6/7, FGF10, BMPR1A and PDGFA. Additionally, by way of siRNA and conditional Tet2 knockout data in dermal fibroblasts, it was found Tet2 regulates signature DP genes such as Bmpr1a, ALPL, Tcf4 and SOX2.

Lack of hair due to alopecia or skin grafting procedures causes significant distress due to hair's role in social and sexual communication. Only limited pharmacological agents are currently available to stimulate hair growth; their development is hampered by inappropriate model systems. Most research involves large terminal scalp follicles rather than the clinical targets of tiny vellus or intermediate follicles. The overall aim of this thesis was to develop a novel model system based on intermediate hair follicles. Initially, intermediate follicles from female pre-auricular skin were characterised and compared to matched terminal follicles. Intermediate follicles were smaller, less pigmented, shorter and possessed a more 'tubular' bulb morphology than their more 'bulbous' terminal counterparts. Significant correlations were demonstrated between various hair follicle measurements and corresponding dermal papilla diameters. Isolated terminal follicles grew significantly more than intermediate hair follicles in organ culture for 9 days. Testosterone (10nM), the major regulator of human hair growth, increased only intermediate follicle growth; the anti-androgen, cyproterone acetate (1μM), prevented this stimulation, unlike the 5α-reductase type 2 inhibitor finasteride (40ng/ml). Immunohistochemistry demonstrated androgen receptor and 5α-reductase type 2 proteins in both follicle types, while quantitative real-time PCR and gene microarray analysis detected their increased gene expression in intermediate follicles. Thus, smaller intermediate follicles showed major morphological and gene expression differences to terminal follicles in vivo and retained significant, biologically-relevant differences in vitro in organ culture including androgen-responsiveness. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth.

Vários estudos têm relatado um aumento da incidência de câncer de pele em todo o mundo. No Brasil, o câncer de pele em geral continua sendo a neoplasia mais incidente em ambos os gêneros. Os tumores de anexos cutâneos compõem um grupo grande de neoplasias que exibem diferenciação morfológica para um dos epitélios anexiais da pele normal. Este trabalho trata dos aspectos clínicos, histológicos e imunoistoquímicos de um tumor anexial de origem folicular: o triquilemocarcinoma e sua versão benigna o triquilemoma. Os objetivos foram analisar comparativamente os dados clínicos, epidemiológicos e a expressão de citoqueratinas 15 e 16, claudinas 1,3,4,5,7 e 11, antígeno CD34, do p63 e do índice de proliferação celular pelo Ki67 entre o grupo dos Triquilemomas e Triquilemocarcinomas diagnosticados na Divisão de Dermatologia do Hospital das Clínicas da Universidade de São Paulo no período de 1991 a 2009 e definir um padrão imunofenotípico que auxilie no diagnóstico diferencial dos dois tumores. O estudo foi feito através de revisão clínico-epidemiológica de prontuário dos casos diagnosticados no período de 1991 a 2009; revisão das lâminas em HE e PAS com e sem diastase; realização das técnicas de imunoistoquímica. No período de 18 anos foram identificados 22 casos válidos de triquilemoma e 16 casos válidos de triquilemocarcinoma. Observou-se uma maior incidência de Triquilemoma entre adultos masculinos enquanto que os Triquilemocarcinomas predominaram entre os idosos femininos. A cabeça foi mais acometida entre os casos benignos que entre os malignos. A opção terapêutica predominante entre os triquilemomas foi de eletrocoagulação e de excisão cirúrgica para os demais casos. A claudina-1, claudina-4 e o CD34 apresentavam medianas mais altas nos casos benignos que nos malignos. Portanto, conclui-se que os dados epidemiológicos e clínicos dos dois grupos de tumores se distinguem em relação à idade, gênero, local de acometimento e tipo de tratamento; observou-se perda de expressão das CL1 e 4 e do CD34, marcadores de diferenciação celular, nos Triquilemocarcinomas em comparação aos Triquilemomas. Por outro lado, o índice de proliferação celular pelo Ki67 mostrou-se um marcador inútil para a distinção entre as formas benigna e maligna / Several studies have been reporting an increasing incidence in skin cancers all over the world. In Brazil, skin cancers are the most prevalent neoplasia in both genders. The skin adnexal tumors are a large group of neoplasias that differentiate into normal skin adnexal epithelium. We report here the clinical, histopathological and immunochemical aspects of the tumors of follicular origin: the trichilemmal carcinoma and its benign variation - trichilemmoma. The objectives were to analise comparatively the clinical and histological data and to compare the expression of the cytokeratins 15 and 16, claudins 1,3,4,5,7 and 11, antigen CD34, p63 and the cell proliferation index in the Ki67 between the two groups, defining a immunophenotypic pattern that could help the differential diagnosis of the two tumors. The study was made by identifying in the hospital records the cases of these tumors between 1991 and 2009. After that, a clinico-epidemiological review was made in the medical records, the histological samples were reviewed to confirm the diagnosis. The best areas were selected to compose the Tissue MicroArray that was used to immunochemical reactions. In these 18 years, there were 22 valid cases of trichilemmoma and 16 of trichilemmal carcinoma. There was a higher incidence of trichilemmoma in male adults and of trichilemmal carcinoma in female elderly. The head was more affected in the benign tumors than in the malignat ones. The treatment option was electrodissection in Trichilemmomas and surgical excision in Trichilemmal carcinomas. Claudin-1, claudin-4 and CD34 were more expressed in the first group. So, we concluded that the clinical and epidemiological data in the two groups differ in age, gender, local of the tumor and treatment option. There was loss of expression of CL1 and 4 and of CD34, cell differentiation markers, in the Trichilemmal carcinoma when compared to the Trichilemmomas. On the other hand, the Ki67 expression was of no use in differentiating the two groups of tumor

Introdução: A micose fungóide foliculotrópica (MFF) é subtipo de linfoma cutâneo de células T que atinge especialmente o folículo piloso e parece ter prognóstico mais reservado. Informações clínicas sobre a população acometida por linfomas cutâneos no Brasil são escassas. O fenômeno de imunoprivilégio (IP) diz respeito à habilidade de alguns órgãos em permanecer protegidos contra reações inflamatórias. Tem sido sugerido que o folículo piloso normal represente um local de IP. Nesse estudo aventou-se a possibilidade de haver uma quebra no equilíbrio desse fenômeno na MFF, com alteração na expressão de moléculas do complexo maior de histocompatibilidade (MHC) e na expressão de MHC não-clássicos (HLA-G), com algum papel no mecanismo do foliculotropismo. Os objetivos foram: descrever o perfil clínico-epidemiológico de paciente com MFF, descrever a histologia e imunofenótipo dos casos de MFF e investigar os mecanismos envolvidos na predileção dos linfócitos atípicos pelo folículo piloso. Metodologia: Os prontuários de pacientes com diagnóstico de MFF provenientes do ambulatório de Linfomas Cutâneos da Faculdade de Medicina da Universidade de São Paulo (FMUSP) foram revisados (n=33). O material histológico de biópsias de pele dos pacientes com MFF provenientes dos ambulatórios de Linfomas Cutâneos da FMUSP e da Northwestern University foi analisado por meio de escala semi-quantitativa (n=43). Na coloração de hematoxilina-eosina foram avaliados os seguintes parâmetros: infiltrado neoplásico epidérmico, infiltrado neoplásico dérmico, presença de acantose/espongiose, de mucinose folicular, de fibroplasia do tecido conjuntivo, de eosinófilos, de plasmócitos, o tamanho celular e o grau de dano folicular. Analisou-se a positividade do infiltrado neoplásico para os seguintes marcadores celulares: CD1a, CD56, TIA-1 e CD117. As expressões do complexo de histocompatibilidade HLA-G e do MHCII no infiltrado celular e no epitélio folicular foram investigadas no grupo de pacientes com MFF e comparadas com o grupo de pacientes com micose fungóide clássica (MFC) e pele normal. A expressão do complexo de histocompatibilidade MHCII também foi investigada na epiderme. Resultados: A mediana das idades ao diagnóstico foi de 46 anos com 61% dos pacientes classificados como portadores de estágio avançado. A proporção entre homens e mulheres foi de 1,54 e a mediana de duração de doença antes do diagnóstico foi de três anos. Ao final de três anos de acompanhamento, 67% dos casos estavam vivos com a doença. O prurido foi relatado em 82% dos casos. Histologicamente, encontrou-se associação entre a presença de eosinófilos e de plasmócitos com fibroplasia do tecido conjuntivo. Observou-se diminuição da expressão do HLA-G no epitélio folicular nos grupos MFF e MFC em relação à pele normal. Observou-se aumento da expressão do MHCII no epitélio folicular na MFF em comparação à pele normal e na epiderme na MFC quando comparada à MFF. Conclusões: Dados clínicos da população estudada assemelharam-se aos dados da literatura como estágio avançado ao diagnóstico e prognóstico reservado. Cerca de metade dos casos de MFF foi positiva para o marcador citotóxico TIA-1. Demonstrou-se haver um provável colapso do imunoprivilégio folicular nos linfomas cutâneos com expressão diminuída de moléculas HLA-G em comparação à pele normal. O aumento da expressão do MHCII poderia relaciona-se com o foliculotropismo na MFF e com o epidermotropismo na MFC / Introduction: Folliculotropic mycosis fungoides (FMF) is a subtype of cutaneous T cells lymphoma affecting mainly the hair follicle and seems to have a less favorable prognosis. Clinical information on the population affected by cutaneous lymphomas in Brazil is scarce. The immune privilege (IP) phenomenon involves the ability of some body sites remaining protected from inflammatory reactions. It has been suggested that normal hair follicle represents an IP location. We hypothesized that a collapse of this phenomenon would occur in FMF, with changes in the expression of classical major histocompatibility molecules (MHC) and in the expression of nonclassical MHC molecules (HLA-G) with a role in folliculotropism mechanism. The objectives of this study were to describe the clinical and epidemiological profile of patients with MFF, describe the histology and immunophenotype of cases of MFF and investigate the expression of MHC molecules. Methods: The medical records of patients from the outpatient Cutaneous Lymphoma Clinic of the University of Sao Paulo Medical School (FMUSP) diagnosed with MFF were reviewed (n = 33). The histological material from skin biopsies of patients with MFF from the Cutaneous Lymphomas Clinic of FMUSP and Northwestern University was stained and evaluated by semi-quantitative scale. In hematoxylin-eosin staining the following parameters were evaluated: epidermal neoplastic infiltrate, dermal neoplastic infiltrate, acanthosis/spongiosis, follicular mucinosis, connective tissue fibroplasia, presence of eosinophils and plasma cells, cell size and degree of follicular damage. We analyzed the positivity of the neoplastic infiltrate for the following cellular markers: CD1a, CD56, TIA-1, and CD117. Finally, the expression of histocompatibility complex HLA-G and MHC II in the neoplastic infiltrate and the follicular epithelium was investigated in MFF group and compared to patients with classical mycosis fungoides (CMF) and to normal skin. MHCII expression in the epidermis was also investigated. Results: The median age at diagnosis was 46 years, with 61% classified as advanced stage disease. The ratio between men and women was 1.54, the median disease duration before diagnosis was three years. After a median time of follow-up of three years, 67% of the cases were alive with disease. Pruritus was reported in 82% of the cases. Histologically, an association between the presence of eosinophils and plasma cells with fibroplasia of collagen was found. There was a decrease of HLA-G expression in the follicular epithelium in MFF and CMF groups compared to normal skin. There was an increase of MHCII expression in the follicular epithelium in FMF group compared to normal skin. There was an increased MHCII expression in the epidermis in CMF compared to FMF. Conclusions: Clinical data from the studied population were similar to the previous literature in relation to advanced stage at diagnosis and prognosis. There was a relationship between the presence of eosinophils and plasma cells in neoplastic infiltrate and the connective tissue fibrosis. Near half of the cases of FMF was positive for the cytotoxic marker TIA-1. A possible hair follicle immune privilege collapse was suggested by a decreased expression of HLA-G molecules in FMF and CMF compared to normal skin. Increased MHCII expression appears to be involved in the folliculotropism of FMF and epidermotropism of CMF

Introdução: A micose fungóide foliculotrópica (MFF) é subtipo de linfoma cutâneo de células T que atinge especialmente o folículo piloso e parece ter prognóstico mais reservado. Informações clínicas sobre a população acometida por linfomas cutâneos no Brasil são escassas. O fenômeno de imunoprivilégio (IP) diz respeito à habilidade de alguns órgãos em permanecer protegidos contra reações inflamatórias. Tem sido sugerido que o folículo piloso normal represente um local de IP. Nesse estudo aventou-se a possibilidade de haver uma quebra no equilíbrio desse fenômeno na MFF, com alteração na expressão de moléculas do complexo maior de histocompatibilidade (MHC) e na expressão de MHC não-clássicos (HLA-G), com algum papel no mecanismo do foliculotropismo. Os objetivos foram: descrever o perfil clínico-epidemiológico de paciente com MFF, descrever a histologia e imunofenótipo dos casos de MFF e investigar os mecanismos envolvidos na predileção dos linfócitos atípicos pelo folículo piloso. Metodologia: Os prontuários de pacientes com diagnóstico de MFF provenientes do ambulatório de Linfomas Cutâneos da Faculdade de Medicina da Universidade de São Paulo (FMUSP) foram revisados (n=33). O material histológico de biópsias de pele dos pacientes com MFF provenientes dos ambulatórios de Linfomas Cutâneos da FMUSP e da Northwestern University foi analisado por meio de escala semi-quantitativa (n=43). Na coloração de hematoxilina-eosina foram avaliados os seguintes parâmetros: infiltrado neoplásico epidérmico, infiltrado neoplásico dérmico, presença de acantose/espongiose, de mucinose folicular, de fibroplasia do tecido conjuntivo, de eosinófilos, de plasmócitos, o tamanho celular e o grau de dano folicular. Analisou-se a positividade do infiltrado neoplásico para os seguintes marcadores celulares: CD1a, CD56, TIA-1 e CD117. As expressões do complexo de histocompatibilidade HLA-G e do MHCII no infiltrado celular e no epitélio folicular foram investigadas no grupo de pacientes com MFF e comparadas com o grupo de pacientes com micose fungóide clássica (MFC) e pele normal. A expressão do complexo de histocompatibilidade MHCII também foi investigada na epiderme. Resultados: A mediana das idades ao diagnóstico foi de 46 anos com 61% dos pacientes classificados como portadores de estágio avançado. A proporção entre homens e mulheres foi de 1,54 e a mediana de duração de doença antes do diagnóstico foi de três anos. Ao final de três anos de acompanhamento, 67% dos casos estavam vivos com a doença. O prurido foi relatado em 82% dos casos. Histologicamente, encontrou-se associação entre a presença de eosinófilos e de plasmócitos com fibroplasia do tecido conjuntivo. Observou-se diminuição da expressão do HLA-G no epitélio folicular nos grupos MFF e MFC em relação à pele normal. Observou-se aumento da expressão do MHCII no epitélio folicular na MFF em comparação à pele normal e na epiderme na MFC quando comparada à MFF. Conclusões: Dados clínicos da população estudada assemelharam-se aos dados da literatura como estágio avançado ao diagnóstico e prognóstico reservado. Cerca de metade dos casos de MFF foi positiva para o marcador citotóxico TIA-1. Demonstrou-se haver um provável colapso do imunoprivilégio folicular nos linfomas cutâneos com expressão diminuída de moléculas HLA-G em comparação à pele normal. O aumento da expressão do MHCII poderia relaciona-se com o foliculotropismo na MFF e com o epidermotropismo na MFC / Introduction: Folliculotropic mycosis fungoides (FMF) is a subtype of cutaneous T cells lymphoma affecting mainly the hair follicle and seems to have a less favorable prognosis. Clinical information on the population affected by cutaneous lymphomas in Brazil is scarce. The immune privilege (IP) phenomenon involves the ability of some body sites remaining protected from inflammatory reactions. It has been suggested that normal hair follicle represents an IP location. We hypothesized that a collapse of this phenomenon would occur in FMF, with changes in the expression of classical major histocompatibility molecules (MHC) and in the expression of nonclassical MHC molecules (HLA-G) with a role in folliculotropism mechanism. The objectives of this study were to describe the clinical and epidemiological profile of patients with MFF, describe the histology and immunophenotype of cases of MFF and investigate the expression of MHC molecules. Methods: The medical records of patients from the outpatient Cutaneous Lymphoma Clinic of the University of Sao Paulo Medical School (FMUSP) diagnosed with MFF were reviewed (n = 33). The histological material from skin biopsies of patients with MFF from the Cutaneous Lymphomas Clinic of FMUSP and Northwestern University was stained and evaluated by semi-quantitative scale. In hematoxylin-eosin staining the following parameters were evaluated: epidermal neoplastic infiltrate, dermal neoplastic infiltrate, acanthosis/spongiosis, follicular mucinosis, connective tissue fibroplasia, presence of eosinophils and plasma cells, cell size and degree of follicular damage. We analyzed the positivity of the neoplastic infiltrate for the following cellular markers: CD1a, CD56, TIA-1, and CD117. Finally, the expression of histocompatibility complex HLA-G and MHC II in the neoplastic infiltrate and the follicular epithelium was investigated in MFF group and compared to patients with classical mycosis fungoides (CMF) and to normal skin. MHCII expression in the epidermis was also investigated. Results: The median age at diagnosis was 46 years, with 61% classified as advanced stage disease. The ratio between men and women was 1.54, the median disease duration before diagnosis was three years. After a median time of follow-up of three years, 67% of the cases were alive with disease. Pruritus was reported in 82% of the cases. Histologically, an association between the presence of eosinophils and plasma cells with fibroplasia of collagen was found. There was a decrease of HLA-G expression in the follicular epithelium in MFF and CMF groups compared to normal skin. There was an increase of MHCII expression in the follicular epithelium in FMF group compared to normal skin. There was an increased MHCII expression in the epidermis in CMF compared to FMF. Conclusions: Clinical data from the studied population were similar to the previous literature in relation to advanced stage at diagnosis and prognosis. There was a relationship between the presence of eosinophils and plasma cells in neoplastic infiltrate and the connective tissue fibrosis. Near half of the cases of FMF was positive for the cytotoxic marker TIA-1. A possible hair follicle immune privilege collapse was suggested by a decreased expression of HLA-G molecules in FMF and CMF compared to normal skin. Increased MHCII expression appears to be involved in the folliculotropism of FMF and epidermotropism of CMF

Vários estudos têm relatado um aumento da incidência de câncer de pele em todo o mundo. No Brasil, o câncer de pele em geral continua sendo a neoplasia mais incidente em ambos os gêneros. Os tumores de anexos cutâneos compõem um grupo grande de neoplasias que exibem diferenciação morfológica para um dos epitélios anexiais da pele normal. Este trabalho trata dos aspectos clínicos, histológicos e imunoistoquímicos de um tumor anexial de origem folicular: o triquilemocarcinoma e sua versão benigna o triquilemoma. Os objetivos foram analisar comparativamente os dados clínicos, epidemiológicos e a expressão de citoqueratinas 15 e 16, claudinas 1,3,4,5,7 e 11, antígeno CD34, do p63 e do índice de proliferação celular pelo Ki67 entre o grupo dos Triquilemomas e Triquilemocarcinomas diagnosticados na Divisão de Dermatologia do Hospital das Clínicas da Universidade de São Paulo no período de 1991 a 2009 e definir um padrão imunofenotípico que auxilie no diagnóstico diferencial dos dois tumores. O estudo foi feito através de revisão clínico-epidemiológica de prontuário dos casos diagnosticados no período de 1991 a 2009; revisão das lâminas em HE e PAS com e sem diastase; realização das técnicas de imunoistoquímica. No período de 18 anos foram identificados 22 casos válidos de triquilemoma e 16 casos válidos de triquilemocarcinoma. Observou-se uma maior incidência de Triquilemoma entre adultos masculinos enquanto que os Triquilemocarcinomas predominaram entre os idosos femininos. A cabeça foi mais acometida entre os casos benignos que entre os malignos. A opção terapêutica predominante entre os triquilemomas foi de eletrocoagulação e de excisão cirúrgica para os demais casos. A claudina-1, claudina-4 e o CD34 apresentavam medianas mais altas nos casos benignos que nos malignos. Portanto, conclui-se que os dados epidemiológicos e clínicos dos dois grupos de tumores se distinguem em relação à idade, gênero, local de acometimento e tipo de tratamento; observou-se perda de expressão das CL1 e 4 e do CD34, marcadores de diferenciação celular, nos Triquilemocarcinomas em comparação aos Triquilemomas. Por outro lado, o índice de proliferação celular pelo Ki67 mostrou-se um marcador inútil para a distinção entre as formas benigna e maligna / Several studies have been reporting an increasing incidence in skin cancers all over the world. In Brazil, skin cancers are the most prevalent neoplasia in both genders. The skin adnexal tumors are a large group of neoplasias that differentiate into normal skin adnexal epithelium. We report here the clinical, histopathological and immunochemical aspects of the tumors of follicular origin: the trichilemmal carcinoma and its benign variation - trichilemmoma. The objectives were to analise comparatively the clinical and histological data and to compare the expression of the cytokeratins 15 and 16, claudins 1,3,4,5,7 and 11, antigen CD34, p63 and the cell proliferation index in the Ki67 between the two groups, defining a immunophenotypic pattern that could help the differential diagnosis of the two tumors. The study was made by identifying in the hospital records the cases of these tumors between 1991 and 2009. After that, a clinico-epidemiological review was made in the medical records, the histological samples were reviewed to confirm the diagnosis. The best areas were selected to compose the Tissue MicroArray that was used to immunochemical reactions. In these 18 years, there were 22 valid cases of trichilemmoma and 16 of trichilemmal carcinoma. There was a higher incidence of trichilemmoma in male adults and of trichilemmal carcinoma in female elderly. The head was more affected in the benign tumors than in the malignat ones. The treatment option was electrodissection in Trichilemmomas and surgical excision in Trichilemmal carcinomas. Claudin-1, claudin-4 and CD34 were more expressed in the first group. So, we concluded that the clinical and epidemiological data in the two groups differ in age, gender, local of the tumor and treatment option. There was loss of expression of CL1 and 4 and of CD34, cell differentiation markers, in the Trichilemmal carcinoma when compared to the Trichilemmomas. On the other hand, the Ki67 expression was of no use in differentiating the two groups of tumor

Alopecia areata (AA) is a putative autoimmune hair loss disorder. It mainly affects the scalp hair but can also involve body hair, and can also affect the nail and the eye. While there are may be several lines of evidence to support the autoimmune basis of AA, there is still very little information on the hair follicle autoantigen(s) involved in its pathogenesis. In this project, serum antibodies (AA=10, control=10) were used to immunoprecipitate AA-relevant target antigens from normal human scalp hair follicle extracts. These immunoprecipitates were analysed by LC-MALDI-TOF/TOF mass spectrometry for target protein identification. This part of the project involved substantial methods development. Trichohyalin was immunoprecipitated by all AA sera, but by only 5 normal sera. Importantly, the mean Mascot scores of the AA group was significantly higher than the normal group (p=0.005). Keratin 16 was also identified from immunoprecipitates as another potential AA-relevant target antigen. Functional studies by ex vivo whole hair follicle organ culture using commercial antibodies to trichohyalin and keratin 16 significantly inhibited hair fibre elongation compared to controls. Indirect immunofluorescence studies revealed that AA sera contained higher immunoreactivity against normal human scalp anagen hair follicles compared to normal sera. Immunoreactivities were mainly in the outer root sheath and inner root sheath, and less so to the medulla and hair bulb matrix. Double immunofluorescence studies of AA and normal serum with anti-trichohyalin antibody (AE15) revealed co-localisation of 9 of the AA sera antibodies with trichohyalin in the inner root sheath (mostly in Henle¿s, less in Huxley¿s/inner root sheath cuticle), but only weakly in 3 normal sera. This study supports the involvement of an antibody response to anagen-specific hair follicles antigens in AA. Moreover, there may be some evidence that these antibodies may have a pathogenic role.

Background: Regenerative therapies based on autologous mesenchymal stem cells (MSC) as well as stem cells in general are still facing an unmet need for non-invasive sampling, availability, and scalability. The only known adult source of autologous MSCs permanently available with no pain, discomfort, or infection risk is the outer root sheath of the hair follicle (ORS). Methods: This study presents a non-invasively-based method for isolating and expanding MSCs from the ORS (MSCORS) by means of cell migration and expansion in air–liquid culture. Results: The method yielded 5 million cells of pure MSCORS cultured in 35 days, thereby superseding prior art methods of culturing MSCs from hair follicles. MSCORS features corresponded to the International Society for Cell Therapy characterization panel for MSCs: adherence to plastic, proliferation, colony forming, expression of MSC-markers, and adipo-, osteo-, and chondro-differentiation capacity. Additionally, MSCORS displayed facilitated random-oriented migration and high proliferation, pronounced marker expression, extended endothelial and smooth muscle differentiation capacity, as well as a paracrine immunomodulatory effect on monocytes. MSCORS matched or even exceeded control adipose-derived MSCs in most of the assessed qualities. Conclusions: MSCORS qualify for a variety of autologous regenerative treatments of chronic disorders and prophylactic cryopreservation for purposes of acute treatments in personalized medicine.