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2.
Artigo em Inglês | MEDLINE | ID: mdl-34348236

RESUMO

BACKGROUND: Adrenal gland metastases (AGMs) are common in advanced-stage melanoma, occurring in up to 50% of patients. The introduction of immune checkpoint inhibitors (ICIs) has markedly altered the outcome of patients with melanoma. However, despite significant successes, anecdotal evidence has suggested that treatment responses in AGMs are significantly lower than in other metastatic sites. We sought to investigate whether having an AGM is associated with altered outcomes and whether ICI responses are dampened in the adrenal glands. PATIENTS AND METHODS: We retrospectively compared ICI responses and overall survival (OS) in 68 patients with melanoma who were diagnosed with an AGM and a control group of 100 patients without AGMs at a single institution. Response was determined using RECIST 1.1. OS was calculated from time of ICI initiation, anti-PD-1 initiation, initial melanoma diagnosis, and stage IV disease diagnosis. Tumor-infiltrating immune cells were characterized in 9 resected AGMs using immunohistochemical analysis. RESULTS: Response rates of AGMs were significantly lower compared with other metastatic sites in patients with AGMs (16% vs 22%) and compared with those without AGMs (55%). Patients with AGMs also had significantly lower median OS compared with those without AGMs (3.1 years vs not reached, respectively). We further observed that despite this, AGMs exhibited high levels of tumor-infiltrating immune cells. CONCLUSIONS: In this cohort of patients with melanoma, those diagnosed with an AGM had lower ICI response rates and OS. These results suggest that tissue-specific microenvironments of AGMs present unique challenges that may require novel, adrenal gland-directed therapies or surgical resection.

3.
J Cutan Pathol ; 48(9): 1173-1177, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33934378

RESUMO

Occlusive nonvasculitic vasculopathy is a process characterized clinically by retiform purpura and potential ulceration and necrosis of affected areas, secondary to blockage of small vessels without associated inflammatory vasculitis. Intravascular injection of foreign material is known to cause distal ischemia and necrosis due to thrombosis, local vasoconstriction, or microemboli formation. A 27-year-old male presented with retiform purpura and worsening distal fingertip necrosis of the right upper extremity accompanied by suspicious intravascular polarizable foreign material identified on skin, muscle, and vascular biopsies. We report a case that highlights concerning complications and dermatopathologic findings of intravascular injection of oral opioid tablets.


Assuntos
Analgésicos Opioides/efeitos adversos , Embolia/diagnóstico , Dermatopatias Vasculares/patologia , Vasculite/patologia , Adulto , Analgésicos Opioides/administração & dosagem , Biópsia , Embolia/etiologia , Fasciotomia/métodos , Evolução Fatal , Dedos/patologia , Corpos Estranhos/diagnóstico , Reação a Corpo Estranho/diagnóstico , Reação a Corpo Estranho/cirurgia , Humanos , Injeções Intravenosas , Masculino , Necrose/diagnóstico , Necrose/etiologia , Cooperação do Paciente/psicologia , Púrpura/diagnóstico , Púrpura/etiologia , Pele/patologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Transtornos Relacionados ao Uso de Substâncias/patologia , Comprimidos/administração & dosagem , Vasculite/cirurgia
5.
Cureus ; 12(7): e9054, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32782873

RESUMO

Dermatitis artefacta is a rare psychological disorder in which patients self-inflict cutaneous lesions to satisfy an emotional need. Due to the nature of this disease, patients can present with a wide array of sometimes very severe skin lesions. Here, we describe a case of dermatitis artefacta initially misdiagnosed as pyoderma gangrenosum and treated as such for eight years. The patient reported a long history of cutaneous ulcers on her extremities and trunk, with resultant extensive scarring. Upon presentation, she displayed rapidly progressing necrotizing skin lesions on her bilateral distal lower extremities. Both the skin manifestations and histologic sections were extremely atypical for pyoderma gangrenosum leading to extensive medical records review and subsequent diagnosis of dermatitis artefacta. This case represents the importance of the timely recognition and treatment of dermatitis artifacta to prevent its progression to severe harm and even death.

7.
Australas J Dermatol ; 60(4): e317-e321, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31144292

RESUMO

Heterogeneous lymphoproliferative disorders occurring in the post-transplant setting are considered together as post-transplant lymphoproliferative disorders and can rarely present as primary cutaneous lesions. These disorders are often Epstein-Barr virus-driven and in some cases need only be treated with reduction in immune suppressive medications. We present two cases of monomorphic post-transplant lymphoproliferative disorder, a plasmablastic lymphoma and a diffuse large B-cell lymphoma, and summarise common reported clinical and histopathological features.


Assuntos
Linfoma Difuso de Grandes Células B/patologia , Linfoma Plasmablástico/patologia , Neoplasias Cutâneas/patologia , Transplantados , Humanos , Masculino , Pessoa de Meia-Idade
9.
Cutis ; 101(6): 422-424, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30063770

RESUMO

Extramammary Paget disease (EMPD) is a malignant tumor typically found in apocrine-rich areas of the skin, particularly in the anogenital region. Some germinative apocrine-differentiating cells might exist on the trunk, preferentially in Asian individuals. Ectopic EMPD arises in nonapocrine-bearing areas, specifically the nongerminative milk line. We present a case of a 67-year-old Thai man with a slowly progressive, pruritic, erythematous to brown plaque on the right lower back of 30 years' duration. Histopathologic examination of 2 scouting biopsies revealed a proliferation of large cells with pleomorphic nuclei, prominent nucleoli, and abundant pale to clear cytoplasm within the epidermis. In one of the biopsies, tumor cells were found in the dermis with an infiltrative growth pattern. Immunohistochemically, the tumor cells were positive for cytokeratin 7, carcinoembryonic antigen, and gross cystic disease fluid protein 15. Based on these findings, a diagnosis of ectopic EMPD was made.


Assuntos
Doença de Paget Extramamária/diagnóstico , Neoplasias Cutâneas/diagnóstico , Idoso , Exantema/complicações , Exantema/patologia , Humanos , Masculino
11.
Am J Dermatopathol ; 39(8): 606-613, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28654465

RESUMO

Cutaneous injuries due to industrial high-pressure paint guns are well-documented in the literature; however, the histologic characteristics are uncommonly described, and facial involvement has not been previously reported. Histopathologic features of paint gun injuries vary depending on the time since injection and type of material. Early lesions display an acute neutrophilic infiltrate, edema, and thrombosis, with varying degrees of skin, fat, and muscle necrosis. More developed lesions (120-192 hours after injury) have prominent histiocytes and fibrosis around necrotic foci, possibly with the pitfall of muscle regenerative giant cells that could be mistaken for sarcoma. Continuing inflammation, swelling, and resultant vascular compression could explain ongoing necrosis months after the accident. The histopathologic differential diagnosis in the absence of clinical history includes paint in an abrasion, foreign body reaction to tattoo, giant cell tumor of tendon sheath, and various neoplasms. If available, radiologic studies can substitute for clinical photographs to indicate the extent of injury. The radiologic differential, uninformed by history, may include calcific periarthritis, gouty tophus, and tumoral calcinosis. Seven cases of injury due to high-velocity paint guns are presented with 4 additional cases mimicking paint gun injury and with review of the literature.


Assuntos
Pintura/efeitos adversos , Pele/lesões , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Melanoma Res ; 27(3): 189-199, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28296713

RESUMO

Mucosal melanomas are a rare subtype of melanoma, arising in mucosal tissues, which have a very poor prognosis due to the lack of effective targeted therapies. This study aimed to better understand the molecular landscape of these cancers and find potential new therapeutic targets. Whole-exome sequencing was performed on mucosal melanomas from 19 patients and 135 sun-exposed cutaneous melanomas, with matched peripheral blood samples when available. Mutational profiles were compared between mucosal subgroups and sun-exposed cutaneous melanomas. Comparisons of molecular profiles identified 161 genes enriched in mucosal melanoma (P<0.05). KIT and NF1 were frequently comutated (32%) in the mucosal subgroup, with a significantly higher incidence than that in cutaneous melanoma (4%). Recurrent SF3B1 R625H/S/C mutations were identified and validated in 7 of 19 (37%) mucosal melanoma patients. Mutations in the spliceosome pathway were found to be enriched in mucosal melanomas when compared with cutaneous melanomas. Alternative splicing in four genes were observed in SF3B1-mutant samples compared with the wild-type samples. This study identified potential new therapeutic targets for mucosal melanoma, including comutation of NF1 and KIT, and recurrent R625 mutations in SF3B1. This is the first report of SF3B1 R625 mutations in vulvovaginal mucosal melanoma, with the largest whole-exome sequencing project of mucosal melanomas to date. The results here also indicated that the mutations in SF3B1 lead to alternative splicing in multiple genes. These findings expand our knowledge of this rare disease.


Assuntos
Biomarcadores Tumorais/genética , Exoma/genética , Melanoma/genética , Mucosa/patologia , Mutação , Neurofibromina 1/genética , Fosfoproteínas/genética , Proteínas Proto-Oncogênicas c-kit/genética , Fatores de Processamento de RNA/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Mucosa/metabolismo , Prognóstico
13.
Int J Surg Pathol ; 25(1): 41-50, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27507675

RESUMO

Discrepancies between intraoperative consultations with frozen section diagnosis and the final pathology report have the potential to alter treatment decisions and affect patient care. Monitoring these correlations is a key component of laboratory quality assurance, however identifying specific areas for improvement can be difficult to attain. Our goal is to develop a standardized method utilizing root cause analysis and a modified Eindhoven classification schematic to identify the source of discrepancies and deferrals and subsequently to guide performance improvement initiatives. A retrospective review of intraoperative consultations performed at a tertiary level hospital and cancer center over a 6-month period identified deferrals and discrepancies between the intraoperative consult report and the final pathology report. We developed and applied a classification tool to identify the process errors and cognitive errors leading to discrepant results. A total of 48 (4.6%) discrepancies and 24 (2.3%) deferrals were identified from the 1042 frozen sections. Within the entire data set of frozen sections, the process errors (n = 26, 54.2%) were due to gross sampling (n = 16, 33.3%), histologic sampling (n = 8, 16.7%), and surgical sampling (n = 2, 4.2%). Interpretation errors (n = 22, 45.8%) included undercalls/false negatives (n=8, 16.7%), overcalls/false positives (n = 10, 20.8%), and misclassification errors (n = 4, 8.3%). Application of our classification tool demonstrated that the root cause of discrepancies and deferrals varied both between organ systems and by specific organs and that classification models may be utilized as a standardized method to identify focused areas for improvement.


Assuntos
Erros de Diagnóstico/prevenção & controle , Secções Congeladas , Patologia Cirúrgica/normas , Garantia da Qualidade dos Cuidados de Saúde , Humanos , Período Intraoperatório , Patologia Cirúrgica/métodos , Encaminhamento e Consulta , Estudos Retrospectivos
14.
Pigment Cell Melanoma Res ; 30(1): 53-62, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27864876

RESUMO

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations.


Assuntos
Proteínas do Domínio Armadillo/genética , Melanoma/classificação , Melanoma/genética , Proteínas de Fusão Oncogênica/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Rearranjo Gênico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade
16.
J Am Med Inform Assoc ; 23(4): 721-30, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27026619

RESUMO

OBJECTIVE: Currently, there is a disconnect between finding a patient's relevant molecular profile and predicting actionable therapeutics. Here we develop and implement the Integrating Molecular Profiles with Actionable Therapeutics (IMPACT) analysis pipeline, linking variants detected from whole-exome sequencing (WES) to actionable therapeutics. METHODS AND MATERIALS: The IMPACT pipeline contains 4 analytical modules: detecting somatic variants, calling copy number alterations, predicting drugs against deleterious variants, and analyzing tumor heterogeneity. We tested the IMPACT pipeline on whole-exome sequencing data in The Cancer Genome Atlas (TCGA) lung adenocarcinoma samples with known EGFR mutations. We also used IMPACT to analyze melanoma patient tumor samples before treatment, after BRAF-inhibitor treatment, and after BRAF- and MEK-inhibitor treatment. RESULTS: IMPACT Food and Drug Administration (FDA) correctly identified known EGFR mutations in the TCGA lung adenocarcinoma samples. IMPACT linked these EGFR mutations to the appropriate FDA-approved EGFR inhibitors. For the melanoma patient samples, we identified NRAS p.Q61K as an acquired resistance mutation to BRAF-inhibitor treatment. We also identified CDKN2A deletion as a novel acquired resistance mutation to BRAFi/MEKi inhibition. The IMPACT analysis pipeline predicts these somatic variants to actionable therapeutics. We observed the clonal dynamic in the tumor samples after various treatments. We showed that IMPACT not only helped in successful prioritization of clinically relevant variants but also linked these variations to possible targeted therapies. CONCLUSION: IMPACT provides a new bioinformatics strategy to delineate candidate somatic variants and actionable therapies. This approach can be applied to other patient tumor samples to discover effective drug targets for personalized medicine.IMPACT is publicly available at http://tanlab.ucdenver.edu/IMPACT.


Assuntos
Adenocarcinoma/genética , Exoma , Genes erbB-1 , Neoplasias Pulmonares/genética , Melanoma/genética , Mutação , Adenocarcinoma de Pulmão , Biologia Computacional , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Medicina de Precisão
18.
JAAD Case Rep ; 1(3): 166-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-27051719
20.
Mol Carcinog ; 54(4): 291-300, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24243690

RESUMO

Preventive measures against oral carcinogenesis are urgently warranted to lower the high morbidity and mortality associated with this malignancy worldwide. Here, we investigated the chemopreventive efficacy of grape seed extract (GSE) and resveratrol (Res) in 4-nitroquinoline-1-oxide (4NQO)-induced tongue tumorigenesis in C57BL/6 mice. Following 8 weeks of 4NQO exposure (100 µg/ml in drinking water), mice were fed with either control AIN-76A diet or diet containing 0.2% GSE (w/w) or 0.25% Res (w/w) for 8 subsequent weeks, while continued on 4NQO. Upon termination of the study at 16 weeks, tongue tissues were histologically evaluated for hyperplasia, dysplasia, and papillary lesions, and then analyzed for molecular targets by immunohistochemistry. GSE and Res feeding for 8 weeks, moderately decreased the incidence, but significantly prevented the multiplicity and severity of 4NQO-induced preneoplastic and neoplastic lesions, without any apparent toxicity. In tongue tissues, both 4NQO + GSE and 4NQO + Res treatment correlated with a decreased proliferation (BrdU labeling index) but increased apoptotic death (TUNEL-positive cells) as compared to the 4NQO group. Furthermore, tongue tissues from both the 4NQO + GSE and 4NQO + Res groups showed an increase in activated metabolic regulator phospho-AMPK (Thr172) and decreased autophagy flux marker p62. Together, these findings suggest that GSE and Res could effectively prevent 4NQO-induced oral tumorigenesis through modulating AMPK activation, and thereby, inhibiting proliferation and inducing apoptosis and autophagy, as mechanisms of their efficacy.


Assuntos
4-Nitroquinolina-1-Óxido/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Anticarcinógenos/uso terapêutico , Carcinógenos/toxicidade , Carcinoma de Células Escamosas/prevenção & controle , Extrato de Sementes de Uva/uso terapêutico , Estilbenos/uso terapêutico , Neoplasias da Língua/prevenção & controle , Proteínas Quinases Ativadas por AMP/análise , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/induzido quimicamente , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/patologia , Feminino , Marcação In Situ das Extremidades Cortadas , Camundongos , Camundongos Endogâmicos C57BL , Resveratrol , Língua/efeitos dos fármacos , Língua/patologia , Neoplasias da Língua/induzido quimicamente , Neoplasias da Língua/patologia
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