RESUMO
Pathologists often feel discomfort when confronted with scalp biopsies, especially in the case of horizontal sectioning, which is particularly useful in the event of nonscarring alopecia. Apart from a profound knowledge of follicular anatomy, one should be capable of correlating the histologic information with the clinical features of various inflammatory scalp disorders. This review addresses the basic principles of the interpretation of scalp biopsies and discusses the most common forms of scarring and nonscarring alopecia.
Assuntos
Alopecia , Couro Cabeludo , Alopecia/diagnóstico , Biópsia , Cicatriz , Humanos , Couro Cabeludo/patologiaRESUMO
Eruptive epidermoid cysts are a rare adverse event of imiquimod treatment for basal cell carcinoma. Up to date, 8 cases have been described in the literature. We present the case of a 75-year-old Caucasian woman with recurrent basal cell carcinoma on the nose. After multiple excisions and treatment with vismodegib, imiquimod 5% cream was administered 5 times per week over 6 weeks. Two months after the end of treatment, the patient presented with eruptive epidermoid cysts.
Assuntos
Antineoplásicos , Carcinoma Basocelular , Cisto Epidérmico , Imiquimode , Neoplasias Cutâneas , Idoso , Aminoquinolinas , Antineoplásicos/efeitos adversos , Carcinoma Basocelular/tratamento farmacológico , Cisto Epidérmico/induzido quimicamente , Feminino , Humanos , Imiquimode/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Resultado do TratamentoRESUMO
Dowling-Degos disease (DDD) is an autosomal-dominant genodermatosis characterized by progressive and disfiguring reticulate hyperpigmentation. We previously identified loss-of-function mutations in KRT5 but were only able to detect pathogenic mutations in fewer than half of our subjects. To identify additional causes of DDD, we performed exome sequencing in five unrelated affected individuals without mutations in KRT5. Data analysis identified three heterozygous mutations from these individuals, all within the same gene. These mutations, namely c.11G>A (p.Trp4*), c.652C>T (p.Arg218*), and c.798-2A>C, are within POGLUT1, which encodes protein O-glucosyltransferase 1. Further screening of unexplained cases for POGLUT1 identified six additional mutations, as well as two of the above described mutations. Immunohistochemistry of skin biopsies of affected individuals with POGLUT1 mutations showed significantly weaker POGLUT1 staining in comparison to healthy controls with strong localization of POGLUT1 in the upper parts of the epidermis. Immunoblot analysis revealed that translation of either wild-type (WT) POGLUT1 or of the protein carrying the p.Arg279Trp substitution led to the expected size of about 50 kDa, whereas the c.652C>T (p.Arg218*) mutation led to translation of a truncated protein of about 30 kDa. Immunofluorescence analysis identified a colocalization of the WT protein with the endoplasmic reticulum and a notable aggregating pattern for the truncated protein. Recently, mutations in POFUT1, which encodes protein O-fucosyltransferase 1, were also reported to be responsible for DDD. Interestingly, both POGLUT1 and POFUT1 are essential regulators of Notch activity. Our results furthermore emphasize the important role of the Notch pathway in pigmentation and keratinocyte morphology.
Assuntos
Glucosiltransferases/genética , Hiperpigmentação/genética , Mutação , Dermatopatias Genéticas/genética , Dermatopatias Papuloescamosas/genética , Adolescente , Adulto , Exoma , Feminino , Estudo de Associação Genômica Ampla , Heterozigoto , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Linhagem , Conformação Proteica , Análise de Sequência de DNA , Pele/patologia , Adulto JovemRESUMO
Desmoplastic malignant melanoma is a distinct melanoma entity histologically subtyped into mixed and pure forms due to significantly reduced lymph node metastases in the pure form. Recent reports investigating common actionable driver mutations have demonstrated a lack of BRAF, NRAS, and KIT mutation in pure desmoplastic melanoma. In search for alternative driver mutations next generation amplicon sequencing for hotspot mutations in 50 genes cardinal to tumorigenesis was performed and in addition the RET G691S polymorphism was investigated. Data from 21 desmoplastic melanomas (12 pure and 9 mixed) were retrieved. Pure desmoplastic melanomas were either devoid of mutations (50%) or displayed mutations in tumor suppressor genes (TP53, CDKN2A, and SMAD4) singularly or in combination with the exception of a PIK3CA double-mutation lacking established biological relevance. Mixed desmoplastic melanomas on the contrary were frequently mutated (89%), and 67% exhibited activating mutations similar to common-type cutaneous malignant melanomas (BRAF, NRAS, FGFR2, and ERBB2). Separate analysis of morphologically heterogeneous tumor areas in four mixed desmoplastic malignant melanomas displayed no difference in mutation status and RET G691 status. GNAQ and GNA11, two oncogenes in BRAF and NRAS wild-type uveal melanomas, were not mutated in our cohort. The RET G691S polymorphism was found in 25% of pure and 38% of mixed desmoplastic melanomas. Apart from RET G691S our findings demonstrate absence of activating driver mutations in pure desmoplastic melanoma beyond previously investigated oncogenes (BRAF, NRAS, and KIT). The findings underline the therapeutic dichotomy of mixed versus pure desmoplastic melanoma with regard to activating mutations primarily of the mitogen-activated protein kinase pathway.
Assuntos
Melanoma/genética , Mutação , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , GTP Fosfo-Hidrolases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Melanoma/patologia , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/genética , Receptor ErbB-2/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Neoplasias Cutâneas/patologia , Melanoma Maligno CutâneoRESUMO
Rare clinical variants of bullous pemphigoid (BP) include vesicular BP, dyshidrosiform BP, pemphigoid nodularis, seborrheic BP, pemphigoid vegetans, localized BP, erythrodermic BP, and juvenile BP. To our knowledge, this is the first report of an unusual case of purpuric BP. We present a case of 85-year-old white man who presented with a 2-week history of blisters and pruritic urticarial lesions all over his body. The diagnosis of purpuric BP was made on the basis of history, clinical presentation, histopathology report, direct and indirect immunofluorescence studies the diagnosis of purpuric BP was made. The reason for the development of palmoplantar purpuric lesions concomitant to ordinary patches and plaques of BP is unknown.
Assuntos
Penfigoide Bolhoso/diagnóstico , Púrpura/diagnóstico , Pele/patologia , Idoso de 80 Anos ou mais , Biópsia , Dapsona/administração & dosagem , Diagnóstico Diferencial , Esquema de Medicação , Quimioterapia Combinada , Imunofluorescência , Glucocorticoides/administração & dosagem , Humanos , Masculino , Penfigoide Bolhoso/tratamento farmacológico , Penfigoide Bolhoso/patologia , Valor Preditivo dos Testes , Prednisolona/administração & dosagem , Púrpura/tratamento farmacológico , Púrpura/patologia , Pele/efeitos dos fármacos , Resultado do TratamentoRESUMO
Follicular malignant melanoma (FMM) is a rare variant of melanoma arising on sun-damaged skin of elderly patients. It is characterized histopathologically by a prominent involvement of 1 or 2 adjacent hair follicles. The authors report 3 new cases of FMM (M:F = 2:1; age range, 23-67 years; median age, 50 years) located on the scalp, cheek, and upper back. Complete effacement of the hair follicle, replaced by neoplastic melanocytes, was observed in 1 case. The interfollicular epidermis and adventitial dermis were involved in all 3 cases. Our series shows that FMM is not restricted to elderly patients but may arise also in young individuals without association with chronic sun damage. FMM should be distinguished from folliculotropic metastases of melanoma and from atypical melanocytic nevi. Although the histopathological features and the term FMM may suggest a derivation from melanocytes of the hair follicle, the exact origin of neoplastic cells is yet unclear, and at least some of these cases may represent folliculotropic examples of primary epidermal malignant melanoma.
Assuntos
Folículo Piloso/patologia , Neoplasias de Cabeça e Pescoço/patologia , Melanócitos/patologia , Melanoma/patologia , Couro Cabeludo/patologia , Neoplasias Cutâneas/patologia , Idoso , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Feminino , Folículo Piloso/química , Neoplasias de Cabeça e Pescoço/química , Neoplasias de Cabeça e Pescoço/classificação , Humanos , Imuno-Histoquímica , Masculino , Melanócitos/química , Melanoma/química , Melanoma/classificação , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Couro Cabeludo/química , Neoplasias Cutâneas/química , Neoplasias Cutâneas/classificação , Adulto JovemRESUMO
Cutaneous T-cell lymphomas involving the scalp and determining scarring alopecias are difficult to be followed up during treatment because of the peculiar anatomical site of onset. In vivo reflectance confocal microscopy has already been reported to be useful for cutaneous T-cell lymphoma evaluation and for therapeutic follow-up in inflammatory skin conditions. We describe a case of a 26-year-old man affected by cutaneous T-cell lymphoma affecting the scalp in which reflectance confocal microscopy demonstrated to be useful for in vivo evaluation of the therapeutic response to topical and systemic treatment.
Assuntos
Alopecia/patologia , Linfoma Cutâneo de Células T/patologia , Microscopia Confocal/métodos , Neoplasias Cutâneas/patologia , Adulto , Alopecia/etiologia , Alopecia/terapia , Seguimentos , Humanos , Linfoma Cutâneo de Células T/complicações , Linfoma Cutâneo de Células T/terapia , Masculino , Couro Cabeludo/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/terapiaRESUMO
BACKGROUND: Alopecia areata-like hair loss may occur in the context of cutaneous T cell lymphoma (CTCL) and can very rarely evolve to alopecia universalis-like presentation. The dermoscopic findings of CTCL-related alopecia have not been described. METHODS: Two patients with alopecia areata universalis-like hair loss occurring in the context of preexisting, pathology-proven CTCL are presented. RESULTS: Clinical examination showed subtotal scalp alopecia with sparse fine hair or total scalp alopecia with loss of eyebrows, eyelashes and body hair. On dermoscopy there was follicular or diffuse scaling, reduced number of follicular openings with broken hairs, short hairs or keratotic filiform spicules. Pathology confirmed the diagnosis of CTCL-related alopecia. One patient had almost complete hair regrowth after treatment. CONCLUSION: CTCL-related alopecia universalis is a rare non-scarring form of hair loss which simulates alopecia areata universalis. We provide clues to distinguish both based on clinical, dermoscopic and pathologic findings.
Assuntos
Alopecia/etiologia , Linfoma Cutâneo de Células T/complicações , Idoso , Alopecia/diagnóstico , Dermoscopia , Diagnóstico Diferencial , Feminino , Cabelo/patologia , Humanos , Linfoma Cutâneo de Células T/diagnósticoRESUMO
Cutaneous melanomas are characterized by a range of histological appearances, and several morphological variants have been described. In this study, we report a variant of superficial spreading melanoma that is characterized by large, irregular junctional melanocytic nests. The junctional nests varied in shape and size, showed focal tendency to confluence, and were often surrounded by a cuff of epidermal keratinocytes. The melanocytes comprising the nests showed variable cytological atypia. In most of the cases, scant intraepidermal or junctional single melanocytes were seen, and other well-documented diagnostic criteria for melanoma were lacking, and as a result, histological recognition of these tumors as melanoma was difficult. Some cases were associated with an invasive dermal component or showed evidence of sun damage. To provide supporting evidence for malignancy, we analyzed these tumors for genomic aberrations. Using array comparative genomic hybridization (aCGH), we identified multiple genomic aberrations in all analyzed cases. A similar pattern of genomic aberrations was seen in a control group of bona fide superficial spreading melanomas, suggesting that these 'melanomas composed exclusively or predominantly of large nests' are indeed variants of superficial spreading melanoma. Fluorescence in-situ hybridization (FISH) was positive in 40% of the cases. However, using aCGH, the FISH-negative cases showed multiple genomic aberrations in regions that are not covered by FISH. The low sensitivity of the FISH test can be explained by the fact that FISH only evaluates four genomic loci for aberrations, whereas aCGH surveys the entire genome. In summary, we present histological and molecular genetic evidence for a morphological variant of superficial spreading melanoma. Awareness of the histological features will aid in their correct diagnosis as melanoma, and in difficult cases, judicious application of ancillary tests such as aCGH (rather than FISH) will assist accurate diagnosis.
Assuntos
Biomarcadores Tumorais/genética , Aberrações Cromossômicas , Melanócitos/patologia , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Biópsia , Hibridização Genômica Comparativa , Feminino , Predisposição Genética para Doença , Humanos , Hibridização in Situ Fluorescente , Masculino , Melanoma/classificação , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Neoplasias Cutâneas/classificaçãoRESUMO
To identify the disease-causing gene responsible for an autosomal dominantly inherited Charcot-Marie-Tooth neuropathy subtype in a family excluded for mutations in the common Charcot-Marie-Tooth genes, we used array-based sequence capture to simultaneously analyse the disease-linked protein coding exome at chromosome 14q32. A missense mutation in fibulin-5, encoding a widely expressed constituent of the extracellular matrix that has an essential role in elastic fibre assembly and has been shown to cause cutis laxa, was detected as the only novel non-synonymous sequence variant within the disease interval. Screening of 112 index probands with unclassified Charcot-Marie-Tooth neuropathies detected two further fibulin-5 missense mutations in two families with Charcot-Marie-Tooth disease and hyperextensible skin. Since fibulin-5 mutations have been described in patients with age-related macular degeneration, an additional 300 probands with exudative age-related macular degeneration were included in this study. Two further fibulin-5 missense mutations were identified in six patients. A mild to severe peripheral neuropathy was detected in the majority of patients with age-related macular degeneration carrying mutations in fibulin-5. This study identifies fibulin-5 as a gene involved in Charcot-Marie-Tooth neuropathies and reveals heterozygous fibulin-5 mutations in 2% of our patients with age-related macular degeneration. Furthermore, it adumbrates a new syndrome by linking concurrent pathologic alterations affecting peripheral nerves, eyes and skin to mutations in the fibulin-5 gene.
Assuntos
Doença de Charcot-Marie-Tooth/genética , Proteínas da Matriz Extracelular/genética , Predisposição Genética para Doença , Degeneração Macular/genética , Mutação de Sentido Incorreto/genética , Dermatopatias Genéticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Doença de Charcot-Marie-Tooth/complicações , Doença de Charcot-Marie-Tooth/patologia , Biologia Computacional , Análise Mutacional de DNA/métodos , Evolução Molecular , Saúde da Família , Feminino , Humanos , Desequilíbrio de Ligação , Degeneração Macular/complicações , Degeneração Macular/patologia , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Condução Nervosa/genética , Pele/patologia , Dermatopatias Genéticas/complicações , Dermatopatias Genéticas/patologia , Adulto JovemRESUMO
UNLABELLED: Yellow dots are the most useful dermoscopic criterion in the clinical diagnosis of alopecia areata and correspond histopathologically with dilated follicular infundibula. They are found in about 95% of alopecia areata cases and help to differentiate alopecia areata from trichotillomania, telogen effluvium and from scarring alopecias. Histopathology of alopecia areata differs with disease activity and dermatopathologist, therefore, heavily depends on other diagnostic features. Objective of the study was to determine the frequency of dilated follicular infundibula, peribulbar lymphocytic infiltrate, inflammatory infiltrates of lymphocytes and eosinophils within fibrous streamers and a shift to catagen/telogen follicles in alopecia areata. Histopathologic features of 56 specimens of 33 patients were correlated with clinical findings and alopecia areata subtype. RESULTS: 57% of all biopsies showed dilated follicular infundibula, regardless of horizontal or vertical sectioning of the slides. Dilated follicular infundibula showed a maximum occurrence of 66% in the recovery stage of alopecia areata and were seen in 33% of alopecia areata incognita. In conclusion, dilated follicular infundibula, reminiscent of a Swiss cheese in horizontally sectioned slides, is an exceedingly useful criterion in the histopathologic diagnosis of alopecia areata and are of great help in the daily routine to recognize alopecia areata.
Assuntos
Alopecia em Áreas/patologia , Humanos , Couro Cabeludo/patologiaRESUMO
Solar lentigines are benign lesions usually found on sun-damaged skin. We investigated twelve cases of solar lentigines through dermoscopy and reflectance confocal microscopy, performed before, and 30 min and 10 days after, a single treatment with a Q-switched ruby laser. At baseline, all lesions showed characteristic features of solar lentigines in reflectance confocal microscopy analysis: regular honeycomb patterns, edged dermal papillae and cord-like rete ridges at the dermoepidermal junction. Thirty minutes post-laser treatment, blurred epidermal intercellular connections, dark structureless areas of different sizes and shapes in the lower epidermal layers, and hyporeflective dermal papillae, reflecting epidermal and dermal oedema, were observed. Ten days post-treatment highly reflective round-to polygonal areas and aggregated granules, representing extracellular melanin, were detected in all epidermal layers featuring regular honeycomb patterns. Reflectance confocal microscopy can be used to visualise dynamic skin processes, allowing non-invasive in vivo follow-up of skin lesions after treatment.
Assuntos
Lasers de Estado Sólido/uso terapêutico , Lentigo/patologia , Luz Solar/efeitos adversos , Idoso , Dermoscopia , Feminino , Humanos , Terapia a Laser , Lentigo/etiologia , Lentigo/cirurgia , Microscopia Confocal/métodos , Pessoa de Meia-IdadeRESUMO
Traction alopecia denotes an often permanent hair loss resulting from prolonged physical damage to the hair shaft. We report on two adolescent Sikh brothers who wore a turban since early childhood and developed a band-like scarring alopecia at the frontal hairline. Awareness of this condition may help in preventing irreversible hair loss by early modification of the daily hair care routine.
Assuntos
Alopecia/etnologia , Alopecia/etiologia , Vestuário/efeitos adversos , Religião e Medicina , Estresse Mecânico , Adolescente , Áustria/epidemiologia , Emigrantes e Imigrantes , Folículo Piloso/lesões , Humanos , Índia/etnologia , Masculino , Adulto JovemAssuntos
Radiodermite/etiologia , Dermatoses do Couro Cabeludo/etiologia , Dermatopatias Vesiculobolhosas/etiologia , Queimadura Solar/etiologia , Luz Solar/efeitos adversos , Administração Cutânea , Adulto , Humanos , Iminas , Masculino , Piridinas/administração & dosagem , Radiodermite/classificação , Radiodermite/diagnóstico , Dermatoses do Couro Cabeludo/classificação , Dermatoses do Couro Cabeludo/diagnóstico , Dermatopatias Vesiculobolhosas/classificação , Dermatopatias Vesiculobolhosas/diagnóstico , Queimadura Solar/diagnóstico , Resultado do TratamentoRESUMO
Intralymphatic histiocytosis is a rare condition characterized by the presence of dilated lymphatic vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. The phenomenon seems to occur almost exclusively within the reticular dermis. Although its pathogenesis remains uncertain, there has been speculation about the possible relationship between intralymphatic histiocytosis and intravascular reactive angioendotheliomatosis. In addition, several examples historically have been associated with rheumatoid arthritis. We describe our experience with 16 cases of intralymphatic histiocytosis. Clinically, the lesions were located predominantly on the upper and lower limbs, and they consisted of asymptomatic and poorly demarcated erythematous plaques and livedo reticularis-like lesions. They were characterized histopathologically by dilated vascular structures involving the reticular dermis. Some of these dilated vessels had empty lumina, whereas others contained variable number of mononuclear histiocytes. An inflammatory response of variable intensity from case to case was also present in the adjacent dermis. The dilated vessels exhibited thin walls with irregular shapes, and a single discontinuous layer of flat endothelial cells lined their lumina. Immunohistochemically, the endothelial cells lining the dilated lumina expressed immunoreactivity for CD31, CD34, podoplanin, D2-40, Lyve-1, and Prox-1, which confirmed their nature as lymphatic endothelial cells. Intralymphatic mononuclear histiocytes expressed CD68 (PGM1), although some cases also had variable immunoexpression for myeloperoxidase, CD31, and podoplanin. In the 4 cases that employed double immunohistochemistry, with podoplanin + CD68 (PGM1) or with Lyve-1 + CD68 (PGM1), each marker highlighted their specific target cells unequivocally; the endothelial cells expressed podoplanin or Lyve-1 immunoreactivity, and intralymphatic histiocytes showed CD68 (PGM1) immunoexpression. Our findings expand on the previously described morphologic and immunohistochemical features of intravascular histiocytosis. We also discuss the possible relationship between intralymphatic histiocytosis and the so-called reactive intravascular angioendotheliomatosis.