RESUMO
Mycosis fungoides (MF) represents the most common type of primary cutaneous T-cell lymphoma. Recognition of MF variants with divergent immunophenotypes is important for accurate diagnosis and appropriate management, as they can be confused with other lymphoma subtypes. We present a case of a 49-year-old male previously diagnosed with a cutaneous lymphoproliferative disorder with an unusual NK/T-cell phenotype. He presented with a 10-year history of pelvic girdle rash involving the right hip and upper thigh. The lesions were characterized as atrophic patches concentrated in sun-protected areas and involving 10% of the body surface area. Shave biopsies revealed an atypical epidermotropic infiltrate composed of hyperchromatic small to medium-sized lymphocytes with perinuclear halos and "tagging" along the dermal-epidermal junction. The immunophenotype was unusual in that the neoplastic lymphocytes showed complete loss of pan T-cell antigens along with expression of CD56, cytotoxic markers, and weak CD20. All other B-cell markers were negative. The combination of clinical findings, in addition to the histopathologic and immunophenotypic profile, were diagnostic of null T-cell phenotype MF with aberrant expression of CD56 and CD20. Null T-cell phenotype MF is very uncommon, can be diagnostically challenging, and can mislead the diagnosis of aggressive lymphoma subtypes.
Assuntos
Antígenos CD20 , Antígeno CD56 , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Micose Fungoide/metabolismo , Masculino , Pessoa de Meia-Idade , Antígeno CD56/metabolismo , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/metabolismo , Antígenos CD20/metabolismo , Imunofenotipagem/métodos , Fenótipo , Linfócitos T/patologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Diagnóstico Diferencial , Biomarcadores Tumorais/metabolismoRESUMO
BACKGROUND: The use of immunohistochemical (IHC) stains in dermatopathology is commonplace; however, little is known regarding utilization trends in melanoma diagnosis. Current Medicare local coverage determinations (LCDs) state that most pigmented lesions, including melanoma, can be diagnosed using H&E alone. METHODS: Histopathology reports for all biopsy-proven melanomas excised between January 1, 2017 and June 30, 2018, at a single dermatology clinic, were identified with the following parameters abstracted: laboratory/dermatopathologist rendering the diagnosis, whether IHC was performed, type/number of stains utilized, presence/depth of invasion, and melanoma subtype. The association of characteristics with IHC utilization was evaluated using χ2 test for categorical variables. RESULTS: Three hundred and fifty six eligible melanomas were identified. IHC was employed in 228 (64%) of the diagnoses. Invasive melanoma was diagnosed in 199 cases (55.9%) while 157 (44.1%) were identified as melanoma in situ (MIS). Of the 228 that utilized IHC, 117 were performed on invasive melanoma (58.8%) and 111 were performed on MIS (70.7%). CONCLUSION: Our findings suggest a higher IHC usage for the diagnosis of melanoma than previously reported. Existing LCDs regarding IHC utilization in melanoma do not reflect the current state of practice. Further investigation regarding IHC utilization and the development of appropriate-use criteria for melanoma IHC is necessary.
Assuntos
Imuno-Histoquímica/métodos , Medicare/estatística & dados numéricos , Melanoma/diagnóstico , Melanoma/metabolismo , Biópsia , Feminino , Humanos , Imuno-Histoquímica/estatística & dados numéricos , Antígeno MART-1/metabolismo , Masculino , Medicare/normas , Melanoma/patologia , Invasividade Neoplásica/patologia , Nevo Pigmentado/patologia , Estudos Retrospectivos , Fatores de Transcrição SOXE/metabolismo , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: BAP-negative melanocytic tumors were unrecognized in the medical literature until 2011. While the clinical significance of these tumors is poorly understood, there is concern such lesions represent processes in transition, and malignant degeneration is a concern. We investigated use of a 23-gene expression profiling (23-GEP) test for distinction from melanoma with the aim of better characterizing the biologic potential of such tumors. METHODS: Twenty BAP-negative melanocytic tumors, subjected to 23-GEP (Myriad Genetic Laboratories, Inc. [Salt Lake City, Utah]) testing, were retrospectively analyzed. RESULTS: Tumors exhibited varying degrees of atypia and aberrant immunohistochemical profiles. 23-GEP testing revealed a "malignant" genetic signature in four cases, a "benign" signature in 15 cases, and an "indeterminate" signature in one case. Array-based comparative genomic hybridization (aCGH) testing was performed for two cases with a "malignant" 23-GEP signature, but the aCGH result conflicted with 23-GEP, and supported benignity. Conversely, in one case with a "benign" 23-GEP result, aCGH testing supported assessment as melanoma. Moreover, evolving melanoma could not be wholly excluded by histopathological analysis in 2 "benign" cases. CONCLUSIONS: BAP-negative melanocytic tumors remain a diagnostic dilemma for dermatopathologists. A widely marketed 23-GEP test may not be useful in distinguishing these tumors from spitzoid melanoma, at least in comparison to aCGH technology.
RESUMO
BACKGROUND: The occurrence of lichenoid keratosis (LK) on the face is not well characterized, and the histopathologic distinction between LK and lupus erythematosus (LE) occurring on the face is often indeterminate. The authors aimed to describe differences between LE and LK occurring on the face by hematoxylin and eosin alone. METHODS: Cases of LK and LE were obtained using computer-driven queries. Clinical correlation was obtained for each lupus case. Other diagnoses were excluded for the LK cases. Hematoxylin and eosin-stained sections were reviewed. RESULTS: Forty-five cases of LK and 30 cases of LE occurring on the face were identified. Shared features included follicular involvement, epidermal atrophy, pigment incontinence, paucity of eosinophils, and basket-weave orthokeratosis. Major differences between LK and LE, respectively, included perivascular inflammation (11%, 90%), high Civatte bodies (44%, 7%), solar elastosis (84%, 33%), a predominate pattern of cell-poor vacuolar interface dermatitis (7%, 73%), compact follicular plugging (11%, 50%), hemorrhage (22%, 70%), mucin (0%, 77%), hypergranulosis (44%, 17%), and edema (7%, 60%). A predominate pattern of band-like lichenoid interface was seen more commonly in LK as compared with LE (93% vs. 27%). CONCLUSIONS: The authors established the occurrence of LK on the face and identified features to help distinguish LK from LE. Follicular involvement, basket-weave orthokeratosis, pigment incontinence, paucity of eosinophils, and epidermal atrophy were not reliable distinguishing features. Perivascular inflammation, cell-poor vacuolar interface, compact follicular plugging, mucin, hemorrhage, and edema favored LE. High Civatte bodies, band-like lichenoid interface, and solar elastosis favored LK.
Assuntos
Face/patologia , Erupções Liquenoides/patologia , Lúpus Eritematoso Discoide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Neurothekeoma represents a neoplasm of uncertain histogenesis that often occurs on the head and neck of younger individuals. Distinguishing neurothekeoma from other tumors, particularly malignancies such as melanoma, can be difficult given the variable presence of nuclear atypia, mitoses and extension into fat or skeletal muscle. KBA.62 represents an anti-melanoma monoclonal antibody that marks approximately 93% of melanomas. This study sought to evaluate KBA.62 expression in neurothekeomas, both as means of affirming the diagnosis and as a potential confounding factor in excluding a melanocytic process. METHODS: Eighteen neurothekeomas from 17 patients were analyzed by light microscopy and immunohistochemistry. Immunohistochemistry was performed with KBA.62, S100 and CD10 antibodies. The diagnosis of neurothekeoma was confirmed by at least two dermatopathologists. RESULTS: All cases showed similar light microscopic and immunohistochemical features. With the exception of two cases, cells expressed CD10 and exhibited morphologic features consistent with neurothekeoma. All 18 cases were S100 immunonegative. The epithelioid cells of all neurothekeomas were KBA.62 immunopositive, including both of two neurothekeomas occurring in the same patient. CONCLUSIONS: In this study 100% of neurothekeomas tested were KBA.62 positive, admittedly to varying degrees, suggesting the utility of this reagent as being supportive of the diagnosis of neurothekeoma.
Assuntos
Anticorpos Monoclonais/metabolismo , Melanoma/diagnóstico , Neurotecoma/diagnóstico , Neoplasias Cutâneas/diagnóstico , Adolescente , Adulto , Biomarcadores Tumorais/metabolismo , Criança , Pré-Escolar , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Masculino , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Neurotecoma/metabolismo , Neurotecoma/patologia , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Adulto JovemRESUMO
The expansion of telemedicine nationwide has resulted in many states adopting specific telemedicine regulations to avoid the issue of requiring a full medical license to practice telemedicine. How these laws and regulations relate to the practice of telepathology and teledermatology has not been well delineated. It is important to understand these regulations to avoid potential judicial penalties arising from non-compliance. This article aims to outline state-specific telemedicine regulations and penalties.
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Dermatologia/legislação & jurisprudência , Licenciamento/legislação & jurisprudência , Dermatopatias/patologia , Telemedicina/legislação & jurisprudência , Telepatologia/legislação & jurisprudência , Dermoscopia , Humanos , Fotografação , Estados UnidosRESUMO
Medications are commonly used during pregnancy; in fact, female patients take an average of 2.9 medications during pregnancy. Due to this high prevalence, malpractice litigation poses a high legal risk to dermatologists who prescribe medications to female patients who are or may become pregnant. This article introduces the medicolegal risks involved in prescribing dermatological medications to a pregnant patient and discusses ways for a dermatologist to mitigate those risks. International safety classification systems are reviewed, and potential high risk dermatologic medications prescribed in acne, psoriasis, atopic dermatitis, and connective tissue disease are discussed. In addition, the article summarizes resources available to patients as well as the important elements for dermatologists to include when documenting their discussion with the patient in the medical record.
Assuntos
Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/classificação , Dermatologia/legislação & jurisprudência , Doenças Fetais/induzido quimicamente , Imperícia/legislação & jurisprudência , Dermatopatias/tratamento farmacológico , Acne Vulgar/tratamento farmacológico , Alopecia/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Minoxidil/efeitos adversos , Gravidez , Psoríase/tratamento farmacológico , Retinoides/efeitos adversos , Estados UnidosRESUMO
A 44-year-old woman with a medical history of chronic pain syndrome presented with a 3-day history of a painful "rash" that started on her face and spread to her legs. Further history revealed that she recently started a new medication, varenicline, 7 weeks prior to admission and had a long-standing history of intranasal cocaine use. Review of systems was significant for rhinitis, nasal congestion, joint pain, and a febrile episode 2 days prior to admission. Physical examination revealed centrally violaceous, tender, stellate, and retiform purpuric patches and plaques on her extremities, nasal dorsum, and cheeks. Approximately 1.0-centimeter tender purpuric nodules were noted on her bilateral second proximal interphalangeal joints. She was afebrile. Initial laboratory data revealed a mild leukopenia, normal serum urea nitrogen and creatinine without hematuria, and an elevated erythrocyte sedimentation rate. Further analysis showed a normal complement level, negative antinuclear antibody, human immunodeficiency virus, rapid plasma reagin, and hepatitis panel. Trace cryoglobenemia and a positive anti-streptolysin O were noted, along with a positive antineutrophil cytoplasmic antibody (c-ANCA) (> 8.0 U) and perinuclear antineutrophil cytoplasmic antibodies, or p-ANCA (1.5 U). The hypercoagulable workup was negative. A skin biopsy taken from the left thigh was consistent with leukocytoclastic vasculitis. After several weeks of high-dose oral prednisone taper, the patient's symptoms improved, but flared upon discontinuation. On follow-up, she admitted to frequent relapses of cocaine abuse and had developed tender purpuric plaques on her nose, ears, and extremities, some with ulcerations (Figure 1 and Figure 2). She also had significant edema and joint pain that limited her ambulation. Further evaluation revealed normal chest x-ray results; however, computed tomography of her sinuses demonstrated thickened maxillary sinuses consistent with subacute/ chronic sinusitis. She also developed hematuria. Mass spectrometry analysis ofhair and urine samples tested positive for cocaine and levamisole. A presumptive diagnosis of levamisole-induced Wegener's vasculitis was made. She was restarted on high-dose prednisone and methotrexate with improvement and advised to discontinue cocaine use, so as to avoid exposure to both substances.
Assuntos
Antinematódeos/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína , Contaminação de Medicamentos , Granulomatose com Poliangiite/induzido quimicamente , Levamisol/efeitos adversos , Adulto , Fármacos Dermatológicos/administração & dosagem , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Granulomatose com Poliangiite/tratamento farmacológico , Humanos , Metotrexato/administração & dosagem , Prednisona/administração & dosagemRESUMO
BACKGROUND: Infantile acropustulosis (IA) is a recurrent, self-limited, vesicopustular disorder affecting young children. Most cases occur after scabies infestation. IA seems to be common in children adopted from orphanages overseas. OBJECTIVES: We sought to demonstrate the prevalence of IA in internationally adopted children and to examine the number of doctors seen for IA before a diagnosis, the frequency of misdiagnoses, specialists most likely to make the diagnosis of IA, and features of IA. METHODS: An Internet-based survey was posted on international adoption forums. Parent participation was voluntary, and specific inclusion criteria existed. Follow-up telephone questionnaire was then conducted. RESULTS: Seventeen children had been given a diagnosis of IA and 21 had classic presentations but no IA diagnosis. Birth countries included Vietnam, China, Ethiopia, Guatemala, and Russia. Pediatric dermatologists and pediatricians affiliated with international adoption clinics were most likely to diagnose IA; 53% of diagnoses occurred after patient prompting. Frequent misdiagnoses were recurrent scabies and hand-foot-mouth disease. Feet were affected in 100% of cases and hands in 94%. Over 50% of children in both the diagnosed and undiagnosed groups had coexistent atopic dermatitis. LIMITATIONS: Limitations are potential parent reporting bias, selection bias, recall bias, and low response rate. Electronic survey instrument requires technically savvy parents. CONCLUSIONS: IA appears to be common in internationally adopted children, who spent early childhood in crowded, unclean living conditions with a high prevalence of scabies infestation. IA is frequently misdiagnosed as recurrent scabies, resulting in unnecessary use of permethrin. This study demonstrated a coexistence of atopic dermatitis in over 50% of IA cases.
Assuntos
Dermatite Atópica/complicações , Psoríase/diagnóstico , Escabiose/complicações , Dermatopatias Vesiculobolhosas/diagnóstico , Adoção , Criança , China , Etiópia , Guatemala , Humanos , Orfanatos , Psoríase/etiologia , Escabiose/diagnóstico , Dermatopatias Vesiculobolhosas/etiologia , VietnãRESUMO
Intralesional agents have a role in the management of cutaneous malignancies. In this article, the efficacy, side effects, strengths, limitations, costs, and practical considerations regarding the use of intralesional agents to treat basal cell carcinoma, squamous cell carcinoma, selected cutaneous lymphomas, and even metastatic melanoma are reviewed. Intralesional administration of 5-fluorouracil, interferon, interleukin-2, bleomycin with electrochemotherapy, and aminolevulinic acid with photodynamic therapy are discussed as treatment modalities in basal cell carcinoma. Interferon (â¼1.5 M IU, 3 times weekly × 3 weeks) is perhaps the most widely used regimen for basal cell carcinoma. With regard to squamous cell carcinoma, treatment with 5-fluorouracil, methotrexate, interferon, and bleomycin are reviewed. Methotrexate (â¼0.3-2.0 mL of 12.5 or 25 mg/mL, two injections â¼2 weeks apart) was perhaps the most widely used agent. Interferon (3 M IU × 3 times weekly for â¼8.5 weeks) and rituximab (10-30 mg per lesion, 3 times weekly for 1 week, possibly repeated 4 weeks later) are sometimes used in the management of primary cutaneous B-cell lymphomas, whereas in primary cutaneous CD30(+) lymphoma intralesional methotrexate (0.4-0.5 mL of 50 mg/mL weekly for 2 weeks) has been used. Finally, the roles of BCG vaccine, cidofovir, rose bengal, and bleomycin with electrochemotherapy for the palliation of metastatic melanoma are reviewed. Intralesional management appears most useful when surgical intervention is not a viable option, for cases in which the cosmetic outcome may be superior, or for situations in which the side effects from systemic chemotherapeutic agents are to be minimized.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/administração & dosagem , Ácido Aminolevulínico/uso terapêutico , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/uso terapêutico , Bleomicina/administração & dosagem , Bleomicina/uso terapêutico , Carcinoma Basocelular/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Injeções Intralesionais , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Interleucina-2/administração & dosagem , Interleucina-2/uso terapêutico , Linfoma de Células B/tratamento farmacológico , Melanoma/tratamento farmacológico , Melanoma/patologia , Metotrexato/administração & dosagem , Metotrexato/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , RituximabRESUMO
Plasma cell cheilitis (PCC) is an uncommon condition characterized by mature plasma cell infiltration of the dermis of the mucosal lip. The condition often presents as a red-brown patch or plaque on the lower lip in older individuals that can progress to erosions and edema. Diagnosis can be delayed because clinical findings are nonspecific and can mimic neoplastic, infectious, and inflammatory conditions. We describe a patient with PCC who presented to our institution via teledermatology. Findings were equivocal on 2 early biopsies until the presentation evolved to dramatic ulceration and necrosis, which prompted a third biopsy that was diagnostic for PCC. Empiric therapy with a class I topical corticosteroid was successful.
Assuntos
Queilite , Idoso , Biópsia , Queilite/diagnóstico , Humanos , Lábio , PlasmócitosRESUMO
BACKGROUND: Nephrogenic systemic fibrosis (NSF) is a fibrotic disorder occurring in patients with renal dysfunction. Exposure to gadolinium (Gd)-based contrast agents (GBCAs) during renal impairment is associated with development of NSF. METHODS: A cross-referenced search of kidney transplantation and radiology databases at a single institution revealed the prevalence of NSF in the transplant population. Clinical records and skin biopsy specimens from 6 patients with kidney transplant given a diagnosis of NSF were reviewed to identify contributing factors. RESULTS: Between January 1999 and December 2006, NSF was diagnosed in 6 of 705 patients with kidney transplant (0.9%). Renal function was impaired in all patients. Of 33 patients with kidney transplant exposed to GBCAs, 5 (15.2%) developed NSF. Disease onset ranged from 7 days to 11 months after exposure to GBCAs. All 5 patients exposed to GBCAs who developed NSF were also treated with a beta-blocker and clinical improvement was observed with discontinuation. The sixth case NSF appeared unrelated to Gd, without a known exposure, and testing of tissue via mass spectrometry revealed no Gd. Symptoms of NSF in this patient disappeared after administration of darbepoetin was switched from subcutaneous to intravenous injection. One patient with NSF who manifested the highest Gd level in tissue died 22 months after disease onset. LIMITATIONS: The study represents the retrospective experience of only a single center. CONCLUSIONS: NSF can develop in kidney transplant recipients with altered graft function. In these patients, exposure to GBCAs appears associated with development of NSF. The role of beta-blockers in the course of the disease merits further investigation.
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Gadolínio/efeitos adversos , Transplante de Rim/estatística & dados numéricos , Dermopatia Fibrosante Nefrogênica/epidemiologia , Dermopatia Fibrosante Nefrogênica/etiologia , Adulto , Biópsia por Agulha , Meios de Contraste/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Imuno-Histoquímica , Incidência , Imageamento por Ressonância Magnética/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Dermopatia Fibrosante Nefrogênica/patologia , Prognóstico , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Nephrogenic systemic fibrosis is a fibrosing disorder associated with gadolinium (Gd)-based contrast agents dosed during renal insufficiency. OBJECTIVE: In two patients, Gd deposition in tissue affected by nephrogenic systemic fibrosis was quantified using inductively coupled plasma mass spectrometry. The presence of Gd was confirmed and mapped using synchrotron x-ray fluorescence spectroscopy. RESULTS: Affected skin and soft tissue from the lower extremity demonstrated 89 and 209 ppm (microg/g, dry weight, formalin fixed) in cases 1 and 2, respectively. In case 2, the same skin and soft tissue was retested after paraffin embedding, with the fat content removed by xylene washes, and this resulted in a measured value of 189 ppm (microg/g, dry weight, paraffin embedded). Synchrotron x-ray fluorescence spectroscopy confirmed Gd in the affected tissue of both cases, and provided high-sensitivity and high-resolution spatial mapping of Gd deposition. A gradient of Gd deposition in tissue correlated with fibrosis and cellularity. Gd deposited in periadnexal locations within the skin, including hair and eccrine ducts, where it colocalized to areas of high calcium and zinc content. LIMITATIONS: Because of the difficulty in obtaining synchrotron x-ray fluorescence spectroscopy scans, tissue from only two patients were mapped. A single control with kidney disease and gadolinium-based contrast agent exposure did not contain Gd. CONCLUSIONS: Gd content on a gravimetric basis was impacted by processing that removed fat and altered the dry weight of the specimens. Gradients of Gd deposition in tissue corresponded to fibrosis and cellularity. Adnexal deposition of Gd correlated with areas of high calcium and zinc content.
Assuntos
Gadolínio/metabolismo , Dermopatia Fibrosante Nefrogênica/metabolismo , Espectrometria de Fluorescência/métodos , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Nefropatias Diabéticas/metabolismo , Glândulas Écrinas/metabolismo , Feminino , Gadolínio DTPA , Humanos , Imageamento por Ressonância Magnética , Masculino , Insuficiência Renal Crônica/metabolismo , SíncrotronsRESUMO
Aim: Evaluate the accuracy of a 23-gene expression signature in differentiating benign nevi from melanoma by comparing test results with clinical outcomes. Materials & methods: Seven dermatopathologists blinded to gene expression test results and clinical outcomes examined 181 lesions to identify diagnostically uncertain cases. Participants independently recorded diagnoses and responses to questions quantifying diagnostic certainty. Test accuracy was determined through comparison with clinical outcomes (sensitivity and percent negative agreement). Results: Overall, 125 cases fulfilled criteria for diagnostic uncertainty (69.1%; 95% CI: 61.8-75.7%). Test sensitivity and percent negative agreement in these cases were 90.4% (95% CI: 79.0-96.8%) and 95.5% (95% CI: 87.3-99.1%), respectively. Conclusion: The 23-gene expression signature has high diagnostic accuracy in diagnostically uncertain cases when evaluated against clinical outcomes.
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Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Melanoma/diagnóstico , Adulto , Idoso , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Melanoma/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To use a rat model for nephrogenic systemic fibrosis (NSF) that was administered high-dose gadodiamide to determine whether the co-administration of erythropoietin (Epo) and intravenous iron potentiated development of skin lesions that are thought to be a marker for the development of NSF. MATERIALS AND METHODS: The local committee for animal research approved this study. High-dose gadodiamide was administered, 2.5 mmol per kilogram of body weight for 20 days, or 500 times the U.S. Food and Drug Administration-approved dose, to four groups of Hannover-Wistar rats: group A, gadodiamide only; B, gadodiamide and Epo; C, gadodiamide and intravenous iron; and D, gadodiamide, Epo, and intravenous iron. The animals were sacrificed 7 days after final injection, and the authors examined dermal histologic findings from each animal and measured metal deposition by using inductively coupled plasma mass spectrometry. To compare the effect of metal deposition and cellularity, a linear mixed effects model was used to fit the data within PROC MIXED modeled with rat-specific random effects, and subsequently a Dunnett adjustment was performed. RESULTS: Rats treated with gadodiamide and both Epo and intravenous iron (group D) had significantly worse skin lesions at gross and histologic analysis (P = .004) compared with the rate treated with gadodiamide only (group A). Group D also had increased levels of deposited gadolinium as measured by means of mass spectrometry (P = .012). CONCLUSION: With a rat model similar to those already existing in the literature, skin changes were more marked in animals exposed to gadodiamide, Epo, and intravenous iron, as opposed to those animals exposed to gadodiamide alone; this experiment suggests that great caution may be warranted when prescribing gadolinium-based contrast agents to patients receiving Epo and intravenous iron.
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Meios de Contraste/toxicidade , Eritropoetina/toxicidade , Gadolínio DTPA/toxicidade , Complexo Ferro-Dextran/toxicidade , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Animais , Cálcio/metabolismo , Meios de Contraste/administração & dosagem , Sinergismo Farmacológico , Epoetina alfa , Gadolínio DTPA/administração & dosagem , Injeções Intravenosas , Complexo Ferro-Dextran/administração & dosagem , Masculino , Dermopatia Fibrosante Nefrogênica/metabolismo , Dermopatia Fibrosante Nefrogênica/patologia , Ratos , Ratos Wistar , Proteínas Recombinantes , Pele/metabolismo , Pele/patologiaRESUMO
PURPOSE: To retrospectively assess the association between gadopentetate dimeglumine exposure at magnetic resonance imaging and the development of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: This HIPAA-compliant study had institutional review board approval. Informed consent was waived. A search of medical and pathologic records was performed to identify patients with NSF that was diagnosed between January 1998 and December 2007. Patients with known exposure to gadolinium-based contrast agents other than gadopentetate dimeglumine were excluded. Medical records were then reviewed for gadopentetate dimeglumine exposure, renal status, concomitant diseases, timing of NSF symptom onset, date of NSF diagnosis, and clinical outcome. Skin gadolinium deposition was assessed for those patients with adequate available tissue. Spearman rank correlations were estimated to assess the relationship between the dose of gadopentetate dimeglumine and the time to onset of NSF. RESULTS: Thirty-six patients (mean age, 62.6 years; range, 30-83 years) had been exposed to gadopentetate dimeglumine prior to NSF onset. All had stage 5 chronic kidney disease and all but one were undergoing dialysis at the time of exposure. NSF developed within 3 months after the last gadopentetate dimeglumine exposure (range, 1-59 months) in 21 (66%) of 32 patients. The patients had been exposed to median cumulative gadopentetate dimeglumine volumes of 35, 40, 85, and 117.5 mL over the 3, 12, and 24 months and up to 11 years preceding the onset of NSF, respectively. Patients who received higher cumulative and total gadopentetate dimeglumine doses had a higher risk of developing NSF than did those who received lower doses (odds ratio = 1.2). Twenty (56%) of 36 patients died, with a median interval of 18 months between NSF symptom onset and death. CONCLUSION: NSF develops in patients with renal impairment after exposure to gadopentetate dimeglumine in a dose- and time-dependent manner. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531082160/-/DC1.
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Meios de Contraste/efeitos adversos , Gadolínio DTPA/efeitos adversos , Imageamento por Ressonância Magnética , Dermopatia Fibrosante Nefrogênica/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Meios de Contraste/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Dermopatia Fibrosante Nefrogênica/epidemiologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Cimex lectularius (the "bedbug") is an insect that feeds nocturnally, taking a requisite blood meal from a sleeping human or other parasitized host. Immunological reactions to bedbug saliva vary, but typically, bites yield erythematous and pruritic papules. The face and distal extremities, areas uncovered by sleeping clothes or blankets, are preferentially involved. Until the late 1990s, bedbug infestations in the United States were declining. Resurgence is attributed to increased travel and resistance to insecticides. Although hepatitis or human immunodeficiency virus is not effectively transmitted by the bedbug, pruritus and the fear and perceived violation of an infestation can be debilitating. Bedbugs are small but robust, and their ability to remain ensconced in crevices within the bedroom makes eradication difficult. As more patients present with bedbug bites, physicians must possess the knowledge to diagnose, treat, and educate with regard to bedbug bites and bedbug infestations.
Assuntos
Percevejos-de-Cama/parasitologia , Mordeduras e Picadas de Insetos/terapia , Animais , Vetores Artrópodes/parasitologia , Roupas de Cama, Mesa e Banho/parasitologia , Eritema/parasitologia , Humanos , Mordeduras e Picadas de Insetos/diagnóstico , Prurido/parasitologia , Estados UnidosRESUMO
TP63 is frequently amplified or overexpressed in primary head and neck squamous cell carcinomas (HNSCC). Nevertheless, the role of TP63 in the initiation and progression of HNSCCs is not known. Using archival HNSCC tissue sections, we found that TP63 expression is often downregulated in late-stage human HNSCCs. To establish a causal link between TP63 loss and HNSCC tumorigenesis, we developed a genetically engineered mouse model in which Trp63 (the mouse homolog of human TP63) was ablated from head and neck epithelia. Upon exposure of the mice to a chemical carcinogen, we found that Trp63 ablation accelerated HNSCC initiation and progression. To determine whether these findings are relevant for human HNSCCs, we generated TP63 knockdown HNSCC cell lines. These cells were implanted into the tongue of athymic nude mice to generate orthotopic xenografts. We found that loss of TP63 promoted HNSCC progression and metastasis. Furthermore, we determined that tumor metastasis is dependent on MAPK activation in TP63 knockdown HNSCCs. The significance of these findings is underscored by our finding that pharmacologic inhibition of MAPK activity by trametinib drastically impaired HNSCC metastasis mediated by TP63 loss. In conclusion, our data provide novel mechanistic insights into the role of TP63 loss in HNSCC initiation and progression, and provide a rationale for the development of new therapeutic approaches specifically targeting TP63-dependent tumor pathways. IMPLICATIONS: Our findings uncover a novel functional role for TP63 loss in HNSCC metastasis and identify MAPK signaling as a potential therapeutic target for treating HNSCCs with low TP63 expression.
Assuntos
Neoplasias de Cabeça e Pescoço/genética , Metástase Linfática/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Animais , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Linfática/patologia , Camundongos , Camundongos Nus , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Nephrogenic systemic fibrosis (NSF) is a recently recognized clinicopathologic entity. It is believed to be related to exposure to gadolinium-containing magnetic resonance imaging agents with gadolinium deposition in the tissues, including skin and other organs. It mainly affects patients on dialysis therapy. Pregnancy in dialysis patients is a rare occurrence. We present a case of a dialysis patient who developed NSF after exposure to gadodiamide and went on to have a successful pregnancy while on hemodialysis therapy. The patient had marked clinical and histological improvement in NSF during and after her pregnancy. This also correlated with decreasing gadolinium levels in skin biopsy tissue specimens. We discuss the interplay of factors involved in the successful pregnancy and improvement in NSF lesions in this patient.