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The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. The thymus is also extremely sensitive to acute insult and although capable of regeneration, this capacity declines with age for unknown reasons. We applied single-cell and spatial transcriptomics, lineage-tracing and advanced imaging to define age-related changes in nonhematopoietic stromal cells and discovered the emergence of two atypical thymic epithelial cell (TEC) states. These age-associated TECs (aaTECs) formed high-density peri-medullary epithelial clusters that were devoid of thymocytes; an accretion of nonproductive thymic tissue that worsened with age, exhibited features of epithelial-to-mesenchymal transition and was associated with downregulation of FOXN1. Interaction analysis revealed that the emergence of aaTECs drew tonic signals from other functional TEC populations at baseline acting as a sink for TEC growth factors. Following acute injury, aaTECs expanded substantially, further perturbing trophic regeneration pathways and correlating with defective repair of the involuted thymus. These findings therefore define a unique feature of thymic involution linked to immune aging and could have implications for developing immune-boosting therapies in older individuals.
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Laser cooling of a 5 cm long, 1 mm diameter ytterbium doped (6.56×1025 ions/m3) silica rod by 67 K from room temperature was achieved. For the pump source, a 100 W level ytterbium fiber amplifier was constructed along with a 1032 nm fiber Bragg grating seed laser. Experiments were done in vacuum and monitored with the non-contact differential luminescence thermometry method. Direct measurements of the absorption spectrum as a function of temperature were made, to avoid any possible ambiguities from site-selectivity and deviations from McCumber theory at low temperature. This allowed direct computation of the cooling efficiency versus temperature at the pump wavelength, permitting an estimated heat lift of 1.42 W/m as the sample cooled from ambient temperature to an absolute temperature of 229 K.
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ABSTRACT: Although the involvement of the nasal passages and nasal septum in cocaine users has been known for decades, a new presentation affecting the nostrils and upper lip with an inflamed appearance has recently been documented. The authors who identified this presentation termed it "cocaine-related plasma cell mucositis" due to the abundance of plasma cells in the infiltrate. In this article, we present a second case and emphasize the dermal involvement of the lip, leading us to consider the condition as a genuine dermatomucositis.
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Cocaína , Plasmócitos , Humanos , LábioRESUMO
We report on the optical refrigeration of ytterbium doped silica glass by >40 K starting at room temperature, which represents more than a two-fold improvement over the previous state-of-the-art. A spectroscopic investigation of the steady-state and time-dependent fluorescence was carried out over the temperature range 80 K to 400 K. The calculated minimum achievable temperature for our Yb3+ doped silica sample is ≈150 K, implying the potential for utilizing ytterbium doped silica for solid-state optical refrigeration below temperatures commonly achieved by standard Peltier devices.
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From laser design to optical refrigeration, experimentally measured fluorescence spectra are often utilized to obtain input parameters for predictive models. However, in materials that exhibit site-selectivity, the fluorescence spectra depend on the excitation wavelength employed to take the measurement. This work explores different conclusions that predictive models reach after inputting such varied spectra. Here, temperature-dependent site-selective spectroscopy is carried out on an ultra-pure Yb, Al co-doped silica rod fabricated by the modified chemical vapor deposition technique. The results are discussed in the context of characterizing ytterbium doped silica for optical refrigeration. Measurements made between 80 K and 280 K at several different excitation wavelengths yield unique values and temperature dependencies of the mean fluorescence wavelength. For the excitation wavelengths studied here, the variation in emission lineshapes ultimately lead to calculated minimum achievable temperatures (MAT) ranging between 151 K and 169 K, with theoretical optimal pumping wavelengths between 1030 nm and 1037 nm. Direct evaluation of the temperature dependence of the fluorescence spectra band area associated with radiative transitions out of the thermally populated 2F5/2 sublevel may be a better approach to identifying the MAT of a glass where site-selective behavior precludes unique conclusions.
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ABSTRACT: Understanding nail pathology is complex for general pathologists and even for those dermatopathologists who do not receive many nail samples in their laboratories. In this article, we attempt to review some of the primary entities in nail pathology with the aid of modern interpretations of nail histology and embryology. We also provide diagrams that can aid in comprehending this field of pathology.
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Técnicas Histológicas , Patologistas , HumanosRESUMO
ABSTRACT: The discovery of CD30 as a diagnostic marker was essential in the identification of not only some lymphomas but also many other solid tumors and benign reactive conditions. Many CD30+ cutaneous disorders and tumors have been categorized since the identification of the marker. With the design of targeted therapies against CD30+ tumoral cells, the interest in CD30 determination was not only diagnostic but also mainly therapeutic. In this article, we explore the historical aspects of the discovery of CD30 and examine the main CD30-related cutaneous pathology, susceptible of anti-CD30 modern treatments.
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ABSTRACT: Unna's book on dermatopathology was the one that achieved the greatest recognition in medicine and influenced the largest number of dermatopathologists in Europe at that time. However, several previous texts also gathered the requirements to be considered dermatopathological books. In this manuscript, we briefly examine some of the most relevant features of the dermatopathology books written by Simon, Leloir and Vidal, Auspitz, Bärensprung, and Jackson.
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Livros , Humanos , Europa (Continente)RESUMO
ABSTRACT: Ungual keratoacanthoma (UKA) is an infrequent tumor. Different from keratoacanthoma in other parts of the skin, UKA rarely regresses, and grows aggressively with common destruction of the subjacent phalanx. Reported cases of UKA with features of regression are exceptional, and even dermatopathologists with reputed experience in nail pathology admit to having seen very few cases. We herein report a case of a 77-year-old man who presented a painful subungual lesion on the second finger of the right hand. An x-ray showed evidence of erosion of the subjacent distal phalanx. The patient was highly concerned about the lesion and rejected conservative treatment preferring amputation of the distal phalanx. The histopathologic examination revealed a UKA with features of regression.
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Ceratoacantoma , Doenças da Unha , Masculino , Humanos , Idoso , Ceratoacantoma/cirurgia , Ceratoacantoma/diagnóstico , Doenças da Unha/diagnóstico , Dedos/patologia , Unhas/patologia , RadiografiaRESUMO
ABSTRACT: Connexins play a crucial role in the formation of gap junctions that connect cells to each other, as well as cells to the surrounding environment. In recent years, connexin 43 has been extensively studied in various human tumors. In this study, we conducted an immunohistochemical analysis to evaluate the expression of connexin in 16 dermatofibromas (DFs) and 13 dermatofibrosarcoma protuberans (DFSP). Connexin was diffusely expressed in the cytoplasm of all DFs with moderate or strong intensity, whereas all DFSPs showed negative staining. In addition to its diagnostic implications, the loss of Cx43 may elucidate the invasive capacity of DFSP and offer a potential avenue for future therapeutic interventions.
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Conexina 43 , Dermatofibrossarcoma , Regulação Neoplásica da Expressão Gênica , Histiocitoma Fibroso Benigno , Conexina 43/genética , Conexina 43/metabolismo , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/patologia , Dermatofibrossarcoma/diagnóstico , Dermatofibrossarcoma/patologia , Humanos , Biomarcadores Tumorais/metabolismo , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Imuno-Histoquímica , Citoplasma/metabolismoRESUMO
ABSTRACT: Hemosiderosis consists of an iron deposit in tissues, which does not cause organic damage to them. However, in the case of the skin, being an organ exposed to sight, siderosis can produce a brownish coloration that is aesthetically discomforting for the individual. Most cutaneous sideroses are because of venous insufficiency with hemorrhagic extravasation. There is also a group secondary to iron extravasation in the injection site of the transfusion. However, there are very few cases in which an intravenous injection of an iron preparation has produced diffuse siderosis in extensive areas of the skin. We present the case of a 31-year-old woman with hyperhidrosis, who was transfused as a result of postpartum hemorrhage and, shortly after receiving an intravenous iron infusion, developed extensive hyperpigmentation in both axillae.
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Hemossiderose , Hiperidrose , Hiperpigmentação , Siderose , Feminino , Gravidez , Humanos , Adulto , Ferro , Hemossiderose/induzido quimicamente , Siderose/complicações , Hiperpigmentação/complicações , Hiperidrose/complicaçõesRESUMO
ABSTRACT: Post-transplant lymphoproliferative disorders (PTLD) are rare complications in solid organ transplant patients. Their pathogenesis is largely unknown and closely linked to low immunity, which allows uncontrolled lymphocyte proliferation. Although transplant patients receive annual influenza vaccination as a preventive protocol, we have not found any cases where the flu vaccine triggered a PTLD. We present the case of a 49-year-old female kidney transplant recipient who developed an Epstein-Barr virus-negative PTLD, CD30 + anaplastic monomorphic type, ALK-, which presented the day after a single dose of anti-influenza vaccine. The initial clinical presentation was subcutaneous, but imaging studies revealed multiorgan involvement.
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Infecções por Vírus Epstein-Barr , Vacinas contra Influenza , Transplante de Rim , Transtornos Linfoproliferativos , Feminino , Humanos , Pessoa de Meia-Idade , Transplante de Rim/efeitos adversos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Vacinas contra Influenza/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/patologiaRESUMO
A detailed investigation into the wavelength-dependent cooling efficiencies of two ultra-pure large core diameter ytterbium-doped silica fibers is carried out by means of the laser-induced thermal modulation spectroscopy (LITMoS) method. From these measurements, an external quantum efficiency of 0.99 is obtained for both fibers. Optimal cooling is seen for pump wavelengths between 1032 and 1035 nm. The crossover wavelength from heating to cooling is identified to be between 1018 and 1021 nm. The fiber with higher Yb3+ ion density exhibits better cooling, seen by the input power normalized temperature differential.
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Goltz syndrome is an X-linked dominant, multisystem birth defect due to PORCN mutation. The skin findings follow Blaschko's lines and often show epidermal atrophy and herniation of subcutaneous fatty tissue. Regarding treatment, light sources can offer a good therapeutic option for some manifestations of this rare disease and improve the aesthetic appearance of the skin lesions. We report two new cases of Goltz syndrome in which the cutaneous findings remarkably improved with pulsed dye laser and carbon dioxide laser.
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Hipoplasia Dérmica Focal , Terapia a Laser , Aciltransferases/genética , Hipoplasia Dérmica Focal/diagnóstico , Hipoplasia Dérmica Focal/genética , Hipoplasia Dérmica Focal/patologia , Humanos , Proteínas de Membrana/genética , MutaçãoRESUMO
Patients with frontal fibrosing alopecia report higher rates of sunscreen use than control subjects. However, it is not known whether the higher use of sunscreens is a cause or a consequence of the alopecia. A greater use of sunscreens should be associated with a lower incidence of signs of actinic damage. The aim of this study is to assess the presence of actinic damage in patients with frontal fibrosing alopecia. A cross-sectional study was carried out on 101 patients with frontal fibrosing alopecia and 40 control subjects. The presence of actinic damage, in the form of solar lentigines, actinic keratoses, and basal and squamous cell carcinomas, was recorded in both groups, together with sunscreen use. Trichoscopy and skin biopsy were performed on patients. Actinic damage was present more frequently in patients with frontal fibrosing alopecia (69.3%) than in control subjects (50%) (p = 0.031). Patients used sunscreens more frequently than did control subjects (83.2% vs 62.5%, p = 0.008). However, the prevalence of trichoscopic inflammatory signs, peripheral alopecia, and inflammatory infiltrate and sebaceous gland involvement in skin biopsy, were similar in patients who used sunscreens and those who did not use them. In conclusion, patients with frontal fibrosing alopecia had greater actinic damage than did control subjects, and this is hypothesized as a reason for the higher use of sunscreens among patients. Thus, use of sunscreens may not be the trigger for frontal fibrosing alopecia that dermatologists have proposed.
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Líquen Plano , Protetores Solares , Alopecia/induzido quimicamente , Alopecia/diagnóstico , Alopecia/epidemiologia , Estudos Transversais , Humanos , Líquen Plano/induzido quimicamente , Pele/patologia , Protetores Solares/efeitos adversosRESUMO
ABSTRACT: We present a case of a 55-year-old man with a rash on his right foot that was biopsied and diagnosed as a Varicella Zoster virus infection with an accompanying positive immunohistochemical study with antiviral antibodies. He concomitantly suffered from a Varicella Zoster virus meningitis. The skin biopsies not only showed clear histologic signs of viral cytopathic effects but also showed intercellular IgG and C3 intraepidermal staining by direct immunofluorescence study, findings which are typically consistent with pemphigus vulgaris. However, the patient did not have any history of pemphigus; there was no mucosal involvement, and serum antibodies to desmoglein 1 and 3 were negative. After discharge, the patient continued to have right-sided foot pain, and he continued the acyclovir treatment.
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Varicela , Herpes Zoster , Pênfigo , Infecção pelo Vírus da Varicela-Zoster , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Varicela/complicações , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Humanos , Masculino , Pessoa de Meia-Idade , Pênfigo/patologia , Infecção pelo Vírus da Varicela-Zoster/complicações , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológicoRESUMO
ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is a benign vascular and fibrohistiocytic (probably reactive) proliferation with peculiar multinucleate cells which most authors interpret as degenerated macrophages. Several clinical variants of MCAH have been described, some of them with brownish-appearing lesions clinically. However, no histologically identified pigment has been described in the cytoplasm of the multinucleate cells so far. We present a pigmented MCAH with cytoplasmic brownish pigment, which was positive with a Masson-Fontana stain and negative with an iron stain, consistent with melanin, in a 33-year-old woman with multiple papules and plaques on the right elbow, right jawline, and left flank.
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Histiocitoma Fibroso Benigno , Neoplasias Cutâneas , Adulto , Feminino , Células Gigantes/patologia , Histiocitoma Fibroso Benigno/patologia , Humanos , Ferro , Melaninas , Neoplasias Cutâneas/patologiaRESUMO
ABSTRACT: Eruptive disseminated Spitz nevus is an uncommon presentation of Spitz nevi. Only a few tens of cases have been published and only 6 of them have genetic studies. We present an additional case of a 29-year-old woman with dozens of Spitz nevi which had appeared since she was aged 10 years. The nevi were located on arms, inner thighs, legs, and buttocks. Nine of them were biopsied. Four presented severe atypia. Immunohistochemistry was performed on 5 of the biopsied specimens and was negative for PRAME, ROS-1, PDL-1, pan-TRK, and ALK. Molecular studies on the largest lesion demonstrated no NTRK1, NTRK2, or NTRK3 fusions. FISH study for PTEN showed no alteration in that same lesion. Next-generation sequencing was also negative for any detectable mutations in numerous genes analyzed. In conclusion, it seems reasonable to be cautious when evaluating atypia, even if severe, in cases of eruptive disseminated Spitz nevus.
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Exantema , Nevo de Células Epitelioides e Fusiformes , Neoplasias Cutâneas , Feminino , Humanos , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Imuno-Histoquímica , MutaçãoRESUMO
INTRODUCTION: Gap junctions are channels between adjacent cells formed by connexins (Cxs). Cxs also form hemichannels that connect the cell with its extracellular milieu. These channels allow the transport of ions, metabolites, and small molecules; therefore, Cxs, and more specifically, connexin (Cx) 43 has been demonstrated to be in control of several crucial events such as inflammation and cell death. MATERIAL AND METHODS: We examined the immunostaining of Cx43 in the endothelia of the cutaneous blood vessels of biopsies from 28 patients with several variants of lupus erythematosus. RESULTS: In 19 cases (67.86%), staining of more than half of the dermal vessels including both vessels of the papillary and of the reticular dermis was identified. Only in 4 cases (14.28%), less than 25% of the vessels in the biopsy showed expression of the marker. CONCLUSIONS: Our results suggest a role of Cx43 in regulating the endothelial activity in lupus erythematosus, which also opens a door for targeted therapeutic options.
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Conexina 43 , Junções Comunicantes , Lúpus Eritematoso Sistêmico , Biópsia , Conexina 43/genética , Junções Comunicantes/metabolismo , Humanos , Lúpus Eritematoso Sistêmico/genéticaRESUMO
ABSTRACT: Pulse granulomas are uncommon reactions to vegetable exogenous matter characterized by the presence of hyaline rings. Although they are usually found in the oral cavity or along the gastrointestinal or respiratory tracts, there are a few cases described outside those regions. We present the first case of a granulomatous reaction with hyaline rings in the skin reaction after an accidental wound and suggest the term pulse granuloma-like to describe lesions that resemble pulse granulomas but with no connection to the gastrointestinal or respiratory tracts. Moreover, we provide a graphic comparison of the hyaline rings observed in our case and the histologic sections of some plants that could have been involved.