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Elevated leaf silicon (Si) concentrations improve drought resistance in cultivated plants, suggesting Si might also improve drought performance of wild species. Tropical tree species, for instance, take up substantial amounts of Si, and leaf Si varies markedly at local and regional scales, suggesting consequences for seedling drought resistance. Yet, whether elevated leaf Si improves seedling drought performance in tropical forests is unknown. To manipulate leaf Si concentrations, seedlings of seven tropical tree species were grown in Si-rich and -poor soil, before exposing them to drought in the forest understorey. Survival, growth and wilting were monitored. Elevated leaf Si did not improve drought survival and growth in any of the species. In one species, drought survival was reduced in seedlings previously grown in Si-rich soil, contrary to our expectation. Our results suggest that elevated leaf Si does not improve drought resistance of wild tropical tree species. Elevated leaf Si may even reduce drought performance, suggesting differences in soil conditions influencing leaf Si may contribute to soil-related variation of tropical seedling performance. Furthermore, our results are at odds with most studies on cultivated species and show that alleviative effects of Si in crops cannot be generalized to wild plants in natural systems.
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Plântula , Árvores , Secas , Silício/farmacologia , Folhas de Planta , SoloRESUMO
ABSTRACT: Syphilis is a sexually transmitted disease that can present a wide variety of clinical and histopathological manifestations. We present the case of a 75-year-old patient with a persistent maculopapular rash on the trunk and extremities, in which the biopsy showed an exclusively perifollicular granulomatous infiltrate. In the immunohistochemical staining with anti-Treponema pallidum antibodies, spirochetes scattered within the perifollicular inflammatory infiltrate were identified. These findings together with the serological analysis allowed the diagnosis of secondary syphilis. Folliculotropic nonalopecic syphilis is rare, and the pathogenic mechanisms that cause this specific tropism are unknown. On the other hand, granulomatous inflammation is a pattern typically described in tertiary syphilis but also occasionally found in secondary syphilis. We present a case of secondary syphilis with the combination of both histopathological findings, an uncommon constellation for dermatopathologists to consider.
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BACKGROUND AND OBJECTIVES: Previous work has demonstrated that hydrochlorothiazide (HCTZ) is a risk factor for squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) due to pro-photocarcinogenic effects. Atypical fibroxanthoma (AFX) and pleomorphic sarcoma (PDS), both ultraviolet-induced cancers, display a rare but rising cutaneous tumor entity. This study aimed to evaluate if the use of HCTZ is higher in patients with AFX/PDS than in patients with SCC/BCC and subsequently may be a risk factor for AFX/PDS-development. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, AFX/PDS cases and SCC/BCC controls were sex and age matched (1:3) over a time-period of 7 years (2013-2019) to evaluate the use of HCTZ, immunosuppressive medication, second malignancies, and presence of diabetes mellitus. RESULTS: Overall, 146 AFX/PDS and 438 controls (SCC/BCC) were included in the study. The use of HCTZ was significantly higher in patients with AFX/PDS (44.5%) compared to patients with SCC/BCC (25.3%). Additionally, the presence of diabetes mellitus was significantly higher in AFX/PDS patients. CONCLUSIONS: This study demonstrates a significantly higher use of HCTZ in patients with AFX/PDS compared to SCC/BCC. This result suggests that HCTZ may be a risk factor for AFX/PDS. Additionally, diabetes mellitus or its comorbidities may be associated with an increased risk for AFX/PDS.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Diabetes Mellitus , Histiocitoma Fibroso Maligno , Sarcoma , Neoplasias Cutâneas , Humanos , Hidroclorotiazida/efeitos adversos , Estudos Retrospectivos , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/complicações , Sarcoma/epidemiologia , Sarcoma/patologia , Carcinoma Basocelular/induzido quimicamente , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/complicaçõesRESUMO
BACKGROUND: Institutes of dermatopathology are faced with considerable challenges including a continuously rising numbers of submitted specimens and a shortage of specialized health care practitioners. Basal cell carcinoma (BCC) is one of the most common tumors in the fair-skinned western population and represents a major part of samples submitted for histological evaluation. Digitalizing glass slides has enabled the application of artificial intelligence (AI)-based procedures. To date, these methods have found only limited application in routine diagnostics. The aim of this study was to establish an AI-based model for automated BCC detection. PATIENTS AND METHODS: In three dermatopathological centers, daily routine practice BCC cases were digitalized. The diagnosis was made both conventionally by analog microscope and digitally through an AI-supported algorithm based on a U-Net architecture neural network. RESULTS: In routine practice, the model achieved a sensitivity of 98.23% (center 1) and a specificity of 98.51%. The model generalized successfully without additional training to samples from the other centers, achieving similarly high accuracies in BCC detection (sensitivities of 97.67% and 98.57% and specificities of 96.77% and 98.73% in centers 2 and 3, respectively). In addition, automated AI-based basal cell carcinoma subtyping and tumor thickness measurement were established. CONCLUSIONS: AI-based methods can detect BCC with high accuracy in a routine clinical setting and significantly support dermatopathological work.
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Carcinoma Basocelular , Carcinoma de Células Escamosas , Aprendizado Profundo , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Inteligência Artificial , Carcinoma de Células Escamosas/patologia , Sensibilidade e Especificidade , Carcinoma Basocelular/patologiaRESUMO
Accurate classification of melanocytic tumors is important for prognostic evaluation, treatment and follow-up protocols of patients. The majority of melanocytic proliferations can be classified solely based on clinical and pathological criteria, however in select cases a definitive diagnostic assessment remains challenging and additional diagnostic biomarkers would be advantageous. We analyzed melanomas, nevi, Spitz nevi and atypical spitzoid tumors using parallel sequencing (exons of 611 genes and 507 gene translocation analysis) and methylation arrays (850k Illumina EPIC). By combining detailed genetic and epigenetic analysis with reference-based and reference-free DNA methylome deconvolution we compared Spitz nevi to nevi and melanoma and assessed the potential for these methods in classifying challenging spitzoid tumors. Results were correlated with clinical and histologic features. Spitz nevi were found to cluster independently of nevi and melanoma and demonstrated a different mutation profile. Multiple copy number alterations and TERT promoter mutations were identified only in melanomas. Genome-wide methylation in Spitz nevi was comparable to benign nevi while the Leukocytes UnMethylation for Purity (LUMP) algorithm in Spitz nevi was comparable to melanoma. Histologically difficult to classify Spitz tumor cases were assessed which, based on methylation arrays, clustered between Spitz nevi and melanoma and in terms of genetic profile or copy number variations demonstrated worrisome features suggesting a malignant neoplasm. Comprehensive sequencing and methylation analysis verify Spitz nevi as an independent melanocytic entity distinct from both nevi and melanoma. Combined genetic and methylation assays can offer additional insights in diagnosing difficult to classify Spitzoid tumors.
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Melanoma , Nevo de Células Epitelioides e Fusiformes , Paraganglioma , Neoplasias Cutâneas , Variações do Número de Cópias de DNA , Diagnóstico Diferencial , Humanos , Melanoma/diagnóstico , Melanoma/genética , Melanoma/patologia , Metilação , Nevo de Células Epitelioides e Fusiformes/diagnóstico , Nevo de Células Epitelioides e Fusiformes/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , SíndromeRESUMO
Biogeochemical cycling in permafrost-affected ecosystems remains associated with large uncertainties, which could impact the Earth's greenhouse gas budget and future climate policies. In particular, increased nutrient availability following permafrost thaw could perturb the greenhouse gas exchange in these systems, an effect largely unexplored until now. Here, we enhance the terrestrial ecosystem model QUINCY (QUantifying Interactions between terrestrial Nutrient CYcles and the climate system), which simulates fully coupled carbon (C), nitrogen (N) and phosphorus (P) cycles in vegetation and soil, with processes relevant in high latitudes (e.g., soil freezing and snow dynamics). In combination with site-level and satellite-based observations, we use the model to investigate impacts of increased nutrient availability from permafrost thawing in comparison to other climate-induced effects and CO2 fertilization over 1960 to 2018 across the high Arctic. Our simulations show that enhanced availability of nutrients following permafrost thaw account for less than 15% of the total Gross primary productivity increase over the time period, despite simulated N limitation over the high Arctic scale. As an explanation for this weak fertilization effect, observational and model data indicate a mismatch between the timing of peak vegetative growth (week 26-27 of the year, corresponding to the beginning of July) and peak thaw depth (week 32-35, mid-to-late August), resulting in incomplete plant use of nutrients near the permafrost table. The resulting increasing N availability approaching the permafrost table enhances N loss pathways, which leads to rising nitrous oxide (N2 O) emissions in our model. Site-level emission trends of 2 mg N m-2 year-1 on average over the historical time period could therefore predict an emerging increasing source of N2 O emissions following future permafrost thaw in the high Arctic.
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Gases de Efeito Estufa , Pergelissolo , Regiões Árticas , Ecossistema , Gases de Efeito Estufa/metabolismo , Óxido NitrosoRESUMO
HINTERGRUND UND ZIELE: In den letzten Jahren konnten umfassende Erkenntnisse über die Pathogenese, Diagnostik und Behandlung von kutanen Sarkomen, insbesondere des atypischen Fibroxanthoms (AFX) und pleomorphen dermalen Sarkoms (PDS) gesammelt werden. Beide Entitäten zeigten innerhalb der letzten Dekade steigende Inzidenzraten. Die vorliegende Studie diente der Untersuchung, welchen Einfluss die neuen Erkenntnisse auf die Fallzahlen von AFX/PDS im Vergleich zu anderen Sarkom-Entitäten haben. PATIENTEN UND METHODIK: Diese retrospektive Studie wurde an vier deutschen Hauttumorzentren durchgeführt und alle von zertifizierten Dermatopathologen bestätigten histopathologischen Befunde von kutanen Sarkomen (AFX, PDS, Dermatofibrosarcoma protuberans, kutanes Leiomyosarkom, Angiosarkom und Kaposi-Sarkom) in einem Zeitraum von sieben Jahren (2013-2019) evaluiert. Zusätzlich wurde der Einsatz von immunhistochemischen Markern als diagnostische Hilfe (Panzytokeratin, S100, Desmin, CD34, CD10, Prokollagen-1, CD99, CD14 und CD68) erfasst. ERGEBNISSE: Insgesamt konnten 255 kutane Sarkome in die vorliegende Studie eingeschlossen werden. Die Zahl der kutanen Sarkome nahm kontinuierlich von 2013 bis 2019 zu (von 16 auf 52 Fälle im Jahr). Die Diagnose eines AFX/PDS konnte in 2019 4,6-mal häufiger als in 2013 gestellt werden. Das AFX stellte mit 49,3 % aller kutanen Sarkome den häufigsten Sarkom-Subtypen dar. Zusätzlich war der Anstieg von AFX/PDS mit dem Einsatz von Immunhistochemie assoziiert. Der Einsatz von spezifischen Immunhistochemischen Markern stieg von 57,1 % im Jahr 2013 auf 100 % in 2019. SCHLUSSFOLGERUNGEN: Diese retrospektive Studie von vier deutschen Hauttumorzentren demonstriert eine substanzielle Zunahme von AFX/PDS, wahrscheinlich infolge kürzlich etablierter beziehungsweise verbesserter diagnostischer und terminologischer Standards. Dieser Anstieg ist vermutlich mit dem vermehrten Einsatz von bestimmten immunhistochemischen Markern assoziiert. AFX/PDS treten wahrscheinlich häufiger auf als bisher vermutet und repräsentieren möglicherweise den häufigsten kutanen Sarkom-Subtyp.
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BACKGROUND AND OBJECTIVES: In recent years, considerable insight has been gained into the pathogenesis, diagnosis and treatment of cutaneous sarcomas, including atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS). Both entities have shown increasing incidence rates in the last decade. This study was initiated to evaluate how these new insights impact the number of diagnoses of AFX/PDS compared to other cutaneous sarcoma entities. PATIENTS AND METHODS: In a retrospective study of four German skin cancer centers, all histopathological reports of cutaneous sarcomas (AFX, PDS, dermatofibrosarcoma protuberans, cutaneous leiomyosarcoma, angiosarcoma, and Kaposi sarcoma) confirmed by board-certified dermatopathologists were analyzed during a time-period of seven years (2013-2019). Additionally, utilization of immunohistochemical markers (including pan-cytokeratin, S100, desmin, CD34, CD10, procollagen-1, CD99, CD14, and CD68) as an adjunct to diagnose AFX/PDS was recorded. RESULTS: Overall, 255 cutaneous sarcomas were included in the present study. The diagnosis of a cutaneous sarcoma has consequently risen from 2013 to 2019 (from 16 to 52 annual cases). The results of AFX/PDS revealed 4.6 times more diagnoses in 2019 than in 2013. Atypical fibroxanthoma represented the most common subtype, displaying 49.3 % of all diagnosed cutaneous sarcomas. Additionally, the increase of AFX/PDS was linked to the use of immunohistochemistry, with specific immunohistochemical markers used in 57.1 % of cases in 2013 compared to 100 % in 2019. CONCLUSIONS: This retrospective study of four German skin cancer centers demonstrates a substantial rise of AFX/PDS, possibly due to recently established diagnostic and terminology standards. This rise is probably linked to increased utilization of specific immunohistochemical markers. Atypical fibroxanthoma/PDS may be more common than previously thought and seems to represent the most frequent cutaneous sarcoma subtype.
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Histiocitoma Fibroso Maligno , Sarcoma , Neoplasias Cutâneas , Humanos , Estudos Retrospectivos , Sarcoma/diagnóstico , Sarcoma/epidemiologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Histiocitoma Fibroso Maligno/diagnóstico , Imuno-Histoquímica , Biomarcadores Tumorais/análise , Diagnóstico DiferencialRESUMO
Various studies showed a decrease of drought stress specific parameters of plants after silicon (Si) fertilization. But all studies differed in soil Si concentration between the control and Si treatments. As amorphous silica (ASi) was recently found to cause a strong increase of water holding capacity and plant available water in soils, a combined effect of soil moisture and plant response due to Si addition was assumed. In this study, the influence of the soil Si content was excluded by using the same Si enriched soil for treatments of two rice lines, lsi1 mutant defective in Si uptake and its wild-type rice. Most plant parameters, such as nutrient contents, biomass, specific leaf area, specific root length, leaf water content and C allocation did not differ significantly between the genotypes neither under flooded conditions, nor under drought conditions. Only photosynthesis and stomatal conductance were slightly higher for the wild type in both drought and flooded treatments. Overall, our data showed that Si accumulation within the plant tissues has only a minor effect on plant performance under drought stress. Hence, existing studies should be reinterpreted in light of the fact that Si additions may increase soil water availability.
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Secas , Oryza/fisiologia , Silício/farmacologia , Solo/química , Água/fisiologia , Silício/metabolismoRESUMO
Silicon (Si) accumulation is known to alleviate various biotic and abiotic stressors in plants with potential ecological consequences. However, for dicotyledonous plants our understanding of Si variation remains limited. We conducted a comparative experimental study to investigate (1) interspecific variation of foliar Si concentrations across 37 dicotyledonous forbs of temperate grasslands, (2) intraspecific variation in foliar Si concentration in response to soil Si availability, the influence of (3) phylogenetic relatedness, and (4) habitat association to moisture. Foliar Si differed markedly (approx. 70-fold) across the investigated forbs, with some species exhibiting Si accumulation similar to grasses. Foliar Si increased with soil Si availability, but the response varied across species: species with higher Si accumulation capacity showed a stronger response, indicating that they did not actively upregulate Si uptake under low soil Si availability. Foliar Si showed a pronounced phylogenetic signal, i.e., closely related species exhibited more similar foliar Si concentrations than distantly related species. Significant differences in foliar Si concentration within closely related species pairs nevertheless support that active Si uptake and associated high Si concentrations has evolved multiple times in forbs. Foliar Si was not higher in species associated with drier habitats, implying that in dicotyledonous forbs of temperate grasslands high foliar Si is not an adaptive trait to withstand drought. Our results demonstrated considerable inter- and intraspecific variation in foliar Si concentration in temperate forbs. This variation should have pervasive, but so far understudied, ecological consequences for community composition and functioning of temperate grasslands under land-use and climate change.
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Silício , Solo , Ecossistema , Filogenia , PoaceaeRESUMO
BACKGROUND: Tinea capitis is a highly contagious infectious disease caused by dermatophytes. In Central Europe, it is mainly caused by zoophilic dermatophytes, as, for example Microsporum (M) canis or Trichophyton (T) mentagrophytes and increasingly by anthropophilic fungi. T tonsurans was commonly related to the Tinea gladiatorum, where transmission occurred between infected persons or via contaminated floors. OBJECTIVE: Reporting the transmission of this highly contagious dermatophyte for the first time via beard shaving and hairdressing in barber shops in Germany. PATIENTS AND METHODS: 18 young male patients developed tinea capitis and/or barbae shortly after shavings of the beard and/or hair in a barber shop. Native, cultural and molecular diagnostics as well as tissue biopsies and resistance tests were performed of skin and hair samples. RESULTS: In all samples, T tonsurans could be identified. The medical history and the clinical picture suggest a transmission through contaminated hairdressing tools. The patients were treated with terbinafine or itraconazole in combination with or exclusively with topical antimycotics. CONCLUSION: The transmission and a resulting increase in the incidence of infections with T tonsurans may be due to shavings with direct skin contact of insufficiently disinfected hairdressing tools. This path of infection has already been observed in Africa and is now being described for the first time in Germany. Knowledge of the pathogen and its transmission ways are essential to interrupt the chain of infection.
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Barbearia , Cadeia de Infecção , Pisos e Cobertura de Pisos , Tinha/transmissão , Trichophyton/patogenicidade , Adolescente , Antifúngicos/uso terapêutico , Criança , Pré-Escolar , Alemanha , Cabelo/microbiologia , Humanos , Incidência , Masculino , Estudos Retrospectivos , Pele/microbiologia , Pele/patologia , Tinha/tratamento farmacológico , Tinha/microbiologia , Trichophyton/efeitos dos fármacos , Trichophyton/genética , Adulto JovemRESUMO
In flooded paddy soils, inorganic and methylated thioarsenates contribute substantially to arsenic speciation besides the much-better-investigated oxyarsenic species, and thioarsenate uptake into rice plants has recently been shown. To better understand their fate when soil redox conditions change, that is, from flooding to drainage to reflooding, batch incubations and unplanted microcosm experiments were conducted with two paddy soils covering redox potentials from EH -260 to +200 mV. Further, occurrence of thioarsenates in the oxygenated rice rhizosphere was investigated using planted rhizobox experiments. Soil flooding resulted in rapid formation of inorganic thioarsenates with a dominance of trithioarsenate. Maximum thiolation of inorganic oxyarsenic species was 57% at EH -130 mV and oxidation caused nearly complete dethiolation. Only monothioarsenate formed again upon reflooding and was the major inorganic thioarsenate detected in the rhizosphere. Maximum thiolation of mono- and dimethylated oxyarsenates was about 70% and 100%, respectively, below EH 0 mV. Dithiolated species dominated over monothiolated species below EH -100 mV. Among all thioarsenates, dimethylated monothioarsenate showed the least transformation upon prolonged oxidation. It also was the major thiolated arsenic species in the rhizosphere with concentrations comparable to its precursor dimethylated oxyarsenate, which is especially critical since dimethylated monothioarsenate is highly carcinogenic.
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Arsênio , Oryza , Poluentes do Solo , Oxirredução , Rizosfera , SoloRESUMO
Despite available vaccination, measles is one of the leading causes of death among young children in developing countries. In clinical practice, the spectrum of differential diagnoses of morbilliform exanthemas associated with fever is wide, and it can be hard to differentiate from other infectious eruptions, especially in adults or in atypical courses in immunocompromised patients. The goal of our study was to identify characteristic histomorphological and immunohistochemical patterns of measles exanthema through the study of 13 skin biopsy specimens obtained from 13 patients with this disease and a review of cases in the literature. Histopathological features of measles exanthema are quite distinctive and characterized by a combination of multinucleated keratinocytes, and individual and clustered necrotic keratinocytes in the epidermis with pronounced folliculosebaceous as well as acrosyringeal involvement. Immunohistochemical staining of skin biopsies with anti-measles virus (MeV) nucleoprotein and anti-MeV phosphoprotein can be of great value in confirming the diagnosis of measles. Both methods can serve as quick additional diagnostic tools for prompt implementation of quarantine measures and for providing medical assistance, even in patients in whom the clinician did not consider measles as a differential diagnosis of the rash due to the rarity of the disease in a putatively vaccinated community.
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Exantema/diagnóstico , Imuno-Histoquímica , Vírus do Sarampo/patogenicidade , Sarampo/diagnóstico , Sarampo/patologia , Nucleoproteínas/análise , Fosfoproteínas/análise , Dermatopatias Virais/diagnóstico , Pele , Proteínas Virais/análise , Adolescente , Adulto , Biópsia , Diagnóstico Diferencial , Exantema/metabolismo , Exantema/patologia , Exantema/virologia , Feminino , Humanos , Masculino , Sarampo/metabolismo , Sarampo/virologia , Pessoa de Meia-Idade , Proteínas do Nucleocapsídeo , Valor Preditivo dos Testes , Estudos Retrospectivos , Pele/química , Pele/patologia , Pele/virologia , Dermatopatias Virais/metabolismo , Dermatopatias Virais/patologia , Dermatopatias Virais/virologia , Adulto JovemRESUMO
An otherwise healthy 50-year-old woman was evaluated for the presence of 2 erythematous, and slightly pruritic plaques, involving both cheeks for 30 years. Left-side skin biopsy showed a diffuse proliferation of ductal structures horizontally arranged and involving the reticular dermis that resembled tubular adenoma embedded in a sclerotic stroma and surrounded by a peculiar periductal desmoplasia. Nuclear atypia or mitosis was not found. Contralateral biopsy showed identical findings. Differential diagnosis included microcystic adnexal carcinoma (MAC) and plaque-like syringoma and a peculiarly horizontally arranged tubular adenoma. We ruled out MAC as the lesions were long-standing, without infundibular cysts, solid strands, or perineural infiltration. Our case closely resembled those previously described as sweat duct proliferation associated with aggregates of elastic tissue and atrophoderma vermiculatum, although striking differences were observed, as our case did not present aggregates of elastic tissue, did not involve the papillary and superficial reticular dermis, and presented evidences of decapitation secretion as a sign of apocrine differentiation. We consider our case as a MAC simulator and we propose the descriptive name of bilateral facial apocrine fibrosing hamartoma.
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Dermatoses Faciais/patologia , Hamartoma/patologia , Neoplasias de Anexos e de Apêndices Cutâneos/patologia , Neoplasias Cutâneas/patologia , Doenças das Glândulas Sudoríparas/patologia , Diagnóstico Diferencial , Dermatoses Faciais/diagnóstico , Feminino , Hamartoma/diagnóstico , Humanos , Pessoa de Meia-Idade , Neoplasias de Anexos e de Apêndices Cutâneos/diagnóstico , Neoplasias Cutâneas/diagnóstico , Doenças das Glândulas Sudoríparas/diagnósticoAssuntos
Necrose , Humanos , Masculino , Pessoa de Meia-Idade , Diagnóstico Diferencial , Pele/patologiaRESUMO
CLINICAL PRESENTATION: A 77-year-old man presented to our skin cancer centre with various cutaneous tumours occurring in 2006-2017. Histopathology showed a 'hidradenocarcinoma' on the left upper back (2006) and a sebaceous adenoma (figure 1) on the left shoulder (2011). In 2017, he developed a sebaceous carcinoma on the middle upper back, which manifested as a slowly enlarging, asymptomatic nodule. Medical history was significant for curative resection of colorectal cancer in 1988.gutjnl;67/11/1957/F1F1F1Figure 1Clinical appearance of the sebaceous adenoma on the patient's left shoulder in 2011.The most recent lesion was subjected to extensive immunohistochemical assessment. The neoplastic cells were positive for cytokeratin 5/6, cytokeratin 7, cluster of differentiation antigen 10, adipophilin, androgen receptor, epithelial membrane antigen, KI67 antigen, MLH1 and PMS2, but stained negative for gross cystic disease fluid protein 15, prostate-specific antigen, carbohydrate antigen 19/9, CDX2 protein, hepatocyte-specific antigen, carcinoembryonic antigen, cluster of differentiation antigen 117 and cytokeratin 19. Given the variety of histological manifestations of the patient's skin neoplasms, further studies were performed. They revealed positive nuclear expression signals for MLH1, MSH6 and PMS2, whereas MSH2 expression was absent in almost all tumour cells (figure 2). Positron emission tomography (PET)/CT and colonoscopy did not detect any pathological findings. However, molecular genetic analysis of peripheral blood showed a heterozygous deletion of exon 7 of the MSH2 gene. Subsequently, several family members tested positive for MSH2 mutations and underwent genetic counselling.gutjnl;67/11/1957/F2F2F2Figure 2(A-D) Histopathological images of the patient's most recent lesion (diaminobenzidine, original magnification, ×100). The tumour cells demonstrated strong nuclear positivity for MLH1 (A) and PMS2 (B), but were essentially negative for MSH6 (C) and MSH2 (D). QUESTION: What is your diagnosis? DIAGNOSIS: Muir-Torre syndrome (MTS).
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Síndrome de Muir-Torre/diagnóstico , Proteína 2 Homóloga a MutS/genética , Pele/patologia , Idoso , Humanos , Masculino , Mutação , Glândulas Sebáceas/patologiaRESUMO
Atypical fibroxanthomas and pleomorphic dermal sarcomas are tumors arising in sun-damaged skin of elderly patients. They have differing prognoses and are currently distinguished using histological criteria, such as invasion of deeper tissue structures, necrosis and lymphovascular or perineural invasion. To investigate the as-yet poorly understood genetics of these tumors, 41 atypical fibroxanthomas and 40 pleomorphic dermal sarcomas were subjected to targeted next-generation sequencing approaches as well as DNA copy number analysis by comparative genomic hybridization. In an analysis of the entire coding region of 341 oncogenes and tumor suppressor genes in 13 atypical fibroxanthomas using an established hybridization-based next-generation sequencing approach, we found that these tumors harbor a large number of mutations. Gene alterations were identified in more than half of the analyzed samples in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter. The presence of these alterations was verified in 26 atypical fibroxanthoma and 35 pleomorphic dermal sarcoma samples by targeted amplicon-based next-generation sequencing. Similar mutation profiles in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter were identified in both atypical fibroxanthoma and pleomorphic dermal sarcoma. Activating RAS mutations (G12 and G13) identified in 3 pleomorphic dermal sarcoma were not found in atypical fibroxanthoma. Comprehensive DNA copy number analysis demonstrated a wide array of different copy number gains and losses, with similar profiles in atypical fibroxanthoma and pleomorphic dermal sarcoma. In summary, atypical fibroxanthoma and pleomorphic dermal sarcoma are highly mutated tumors with recurrent mutations in FAT1, NOTCH1/2, CDKN2A, TP53, and the TERT promoter, and a range of DNA copy number alterations. These findings suggest that atypical fibroxanthomas and pleomorphic dermal sarcomas are genetically related, potentially representing two ends of a common tumor spectrum and distinguishing these entities is at present still best performed using histological criteria.
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Caderinas/genética , Receptor Notch1/genética , Receptor Notch2/genética , Sarcoma/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Hibridização Genômica Comparativa , Inibidor p16 de Quinase Dependente de Ciclina/genética , Variações do Número de Cópias de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Regiões Promotoras Genéticas , Telomerase/genética , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Understanding the long-term effect of alemtuzumab on the immune system of multiple sclerosis (MS) patients is crucial. OBJECTIVE: To report a case of acute sarcoidosis (Löfgren's syndrome) in a relapsing-remitting MS patient, 1.5 years after the second course of alemtuzumab treatment. CASE REPORT: Sarcoidosis was confirmed dermatohistologically, radiologically, and serologically. Analysis of the lymphocyte subpopulations showed a persistent effect of alemtuzumab treatment (CD4/CD8 ratio increased, absolute lymphocyte count of CD19-positive cells increased while CD3/4/8-positive cells were decreased). CONCLUSION: Our case highlights the profound effect of alemtuzumab on the immune system and its possible risk for autoimmune complications.