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BACKGROUND: Activating BRAF gene alterations are central to melanocytic tumor pathogenesis. A small, emerging subset of melanocytic tumors driven by BRAF fusions has distinct therapeutic implications and has been described to have Spitzoid morphology patterns. However, such morphological patterns do not encompass all cases, and little is known about the functional molecular events. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify melanocytic tumors with BRAF fusions. We reviewed clinical, histopathological, and genomic features. We further explored transcriptomic and protein-level findings. RESULTS: Histopathologic patterns varied, with many cases without a distinctive pattern. We identified novel and diverse BRAF gene fusion partners. Differential transcriptomic analysis between low-risk BRAF fusion tumors and reference BRAF V600E tumors showed no differentially expressed genes. However, quantitatively stronger MAPK pathway activation of BRAF fusion tumors over BRAF V600E tumors was demonstrated by statistically significant stronger staining of p-ERK immunohistochemistry. Gene-specific RNA analysis shows comparable BRAF transcript levels between the two groups. DISCUSSION AND CONCLUSION: The quantitatively stronger activation of the MAPK pathway of BRAF fusion tumors, instead of qualitatively different transcriptomes, may account for the morphology difference from conventional BRAF V600E tumors. BRAF fusions likely act through dysregulated protein function rather than RNA upregulation related to the characteristics of the fusion partners.
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BACKGROUND: Granular cell tumor (GCT) is a S100+ neoplasm with atypical and malignant variants. Similar to melanocytic neoplasms, the tumors make nests and can have junctional components raising a differential diagnosis of melanoma. Nevi and melanomas may also have granular cell cytoplasm. MelanA is useful in distinguishing melanocytic from granular cell lineage, but increasingly MelanA/SOX10 negative melanomas have been recognized by correlation with molecular methods. METHODS: We encountered several cases with morphologic overlap between melanoma and atypical GCT necessitating additional molecular workup. We sequenced two cases and searched our archive for similar cases of GCT with overlapping features of melanocytic lineage. RESULTS: In our two index cases, we excluded melanoma driver mutations and identified frameshift or premature stop codons in ATP6AP1/2 pathognomonic of granular cell lineage. Data retrieved from Cosmic identified 24 melanomas with missense single nucleotide variants (SNVs) in ATP6AP1 but no frameshift or premature stop codons. Twenty-one melanomas had missense SNVs in ATP6AP2. One melanoma had a premature stop codon in ATP6AP2, but this lesion also had a melanoma-associated driver mutation NRASQ61K. We found 1 of 23 additional cases of GCT in our archives with a junctional component and no additional cases with maturation. CONCLUSIONS: Atypical and malignant GCT can have histopathologic overlap with melanoma. Frameshift and premature stop codons in ATP6AP1/2 are specific for granular cell lineage, and capable of excluding melanoma, in the absence of known melanoma-associated driver mutations.
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Lipofibromatosis-like neural tumor is a recently described entity defined by a low-cellularity spindle cell infiltrate in the subcutaneous fat with admixed inflammatory cells. This tumor is histopathologically similar to lipofibromatosis, but unlike lipofibromatosis shows reactivity for S100 and has an NTRK-1 kinase fusion. These lesions are locally aggressive but appear to have a negligible metastatic potential. Subsequently, a more cellular variant has been described with generally low mitotic rate. This variant also displays S100 reactivity and kinase fusions (typically involving NTRK-1), but it has a low risk of metastasis. In this report, we describe a case that aligns with the more cellular variant of NTRK-1 kinase fusion tumors on histopathologic, immunohistochemical, and molecular grounds, but in addition has distinctive nodules with peripheral accentuation of cellularity, reminiscent of those present in epithelioid malignant peripheral nerve sheath tumors. This latter feature is previously undescribed in NTRK kinase fusion soft tissue tumors and offers further support for the presumed neural differentiation of this neoplasm.
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Neoplasias de la Mama , Neoplasias Cutáneas , Neoplasias de los Tejidos Blandos , Humanos , Femenino , Receptor trkA/genética , Neoplasias de los Tejidos Blandos/patología , Neoplasias Cutáneas/genética , Biomarcadores de TumorRESUMEN
BACKGROUND: Melanocytic tumors driven by MAP2K1 in-frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well-known second molecular "hits." Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with MAP2K1 in-frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single-nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations. RESULTS: Of 27 sequenced tumors, 6 (22%) showed a pathogenic MAP2K1 in-frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque-like or wedge-shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1-2/mm2 ). Five cases (83%) had a small component of nevic-looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in-frame deletion involving the p.I103_K104del locus while two cases (33%) showed in-frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the MAP2K1 gene locus. DISCUSSION AND CONCLUSION: Melanocytic tumors with MAP2K1 in-frame deletion could represent another spectrum of melanocytic tumors with close genotypic-phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with BRAF V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.
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Melanoma , Nevo de Células Epitelioides y Fusiformes , Neoplasias Cutáneas , Femenino , Humanos , Masculino , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Rayos Ultravioleta , Melanoma/patología , Neoplasias Cutáneas/patología , Nevo de Células Epitelioides y Fusiformes/genética , Aberraciones Cromosómicas , MAP Quinasa Quinasa 1/genéticaRESUMEN
BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
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Administración Oral , Antibacterianos/administración & dosificación , Enfermedades Óseas Infecciosas/tratamiento farmacológico , Artropatías/tratamiento farmacológico , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The Oral Versus Intravenous Antibiotics (OVIVA) Trial demonstrated that oral therapy, when used during the initial 6 weeks in the treatment in bone and joint infection (BJI), is noninferior to intravenous therapy. To date there are no reports describing reproducibility of these findings in a real-world setting. METHODS: We studied all patients diagnosed with BJI at our hospital 12 months pre- and postimplementation of the OVIVA trial findings into clinical practice. An infection consultant recommended antibiotic treatment and patients were followed up by an outpatient parenteral antibiotic therapy (OPAT) service. Prospective data from a local registry was used to analyze baseline clinical details, outcome, length of hospital stay (LOS), and costs. RESULTS: A cohort of 328 patients (145 pre- and 183 postimplementation) was analyzed. Postimplementation, 66.1% of patients were switched to a suitable oral antibiotic regimen. Definite failure at 1 year was 13.6% in the preimplementation group and 18.6% in the postimplementation group (Pâ =â .154). Postimplementation, definite failure was more common in patients requiring intravenous antibiotics due to lack of suitable oral options (intravenous, 26.7% and oral, 14.3%). Adverse drug reactions (ADRs) requiring closer monitoring or change to treatment were more common postimplementation (21.0% and 37.1%, respectively). ADR-related hospital readmissions were similar in both groups (2.1 and 2.2%). Comparing both groups, the postimplementation group showed a reduction of 4 days in the median LOS and a median cost reduction of £2764.28 per patient. CONCLUSIONS: The OVIVA trial findings can be safely implemented into clinical practice when patients on oral antibiotics are followed up by an established OPAT service. Two-thirds of patients were switched to a suitable oral antibiotic regimen. Implementation led to reductions in hospital LOS and antibiotic costs.
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Antibacterianos , Hospitales , Administración Intravenosa , Antibacterianos/uso terapéutico , Humanos , Estudios Prospectivos , Reproducibilidad de los ResultadosRESUMEN
Dedifferentiated metastatic melanoma can pose a significant diagnostic challenge, especially if the history of primary melanoma is not known or is remote. BRAF and NRAS mutations are common melanoma driver mutations that are usually sequenced to evaluate for treatment targets. We evaluated whether BRAF and NRAS mutational testing could contribute to the diagnosis of dedifferentiated metastatic melanoma when immunostains are negative. Seven patients with melanoma who had an additional diagnosis of poorly differentiated sarcoma with negative melanocytic immunostains were tested for BRAF and NRAS mutations. Three patients showed identical BRAF mutations in the melanoma and the poorly differentiated sarcoma and hence were re-classified as metastatic dedifferentiated melanoma. In these three patients, there was an average delay of 7 months before appropriate testing, workup and treatment for metastatic melanoma was initiated. Two of these patients currently have stable metastatic disease and show sustained therapeutic response to melanoma-specific treatment including BRAF inhibitors. BRAF mutational analysis should therefore be considered in cases of poorly differentiated sarcoma, especially if there is a known history of melanoma or with unusual localization of disease. The administration of melanoma-specific treatments in such dedifferentiated cases can show therapeutic response, highlighting the importance of rendering accurate diagnoses on such cases.
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Errores Diagnósticos , Melanoma/diagnóstico , Metástasis de la Neoplasia/diagnóstico , Proteínas Proto-Oncogénicas B-raf/genética , Sarcoma , Neoplasias Cutáneas/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/genética , Melanoma/terapia , Persona de Mediana Edad , Mutación , Metástasis de la Neoplasia/genética , Metástasis de la Neoplasia/terapia , Sarcoma/diagnóstico , Sarcoma/genética , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/terapiaRESUMEN
AIMS: The aim of this paper is to determine the rate of true anaphylaxis to teicoplanin. METHODS: A case-series including all suspected anaphylactic reactions attributed to teicoplanin anaphylaxis within a single institution over a 29-month period were categorised according to the probability of true IgE-mediated anaphylaxis using previously published criteria. The number of patients who received teicoplanin was determined and used to calculate the rate of IgE-mediated anaphylaxis. RESULTS: Approximately 18 800-19 600 patients received teicoplanin during the study period, during which there were 14 cases of suspected anaphylaxis attributed to the administration of teicoplanin: five were categorised as definite IgE-mediated anaphylaxis, four as probable, two as uncertain and three were excluded. Of the excluded cases, two were found to have positive intradermal skin testing to alternative agents (rocuronium and chlorhexidine), and one did not meet the published clinical criteria. We therefore calculated the rate of IgE-mediated anaphylaxis to be between 0.046% and 0.059% (equating to between 1:2088 and 1:1655). CONCLUSIONS: This is the first study to calculate a rate of IgE-mediated anaphylaxis to teicoplanin in clinical practice. Our case series suggests that these life-threatening reactions occur less commonly than reported by the manufacturers. Mast cell tryptase is unreliable when used to predict the likelihood of IgE-mediated anaphylaxis to teicoplanin.
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Anafilaxia/epidemiología , Profilaxis Antibiótica/efectos adversos , Hipersensibilidad a las Drogas/epidemiología , Teicoplanina/efectos adversos , Adolescente , Adulto , Anciano , Anafilaxia/inducido químicamente , Anafilaxia/inmunología , Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/inmunología , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Teicoplanina/uso terapéutico , Reino Unido/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Deep prosthetic infection is a potentially devastating complication after total elbow arthroplasty, with an incidence of up to 12%. This study examined the demographics, microbiologic profile, and outcomes of infected total elbow arthroplasty treated with 2-stage revision in a tertiary referral unit. METHODS: We identified 19 consecutive patients (mean age, 65 years) undergoing revision arthroplasty for deep prosthetic infection. All patients underwent a first-stage procedure with removal of implants, débridement, and insertion of an antibiotic-loaded cement spacer, followed by at least 6 weeks of intravenous antibiotics. Fourteen patients required a second-stage revision. RESULTS: Five patients did not undergo a second-stage procedure because of patient choice (n = 2), medical or surgical risk factors (n = 2), and death from an unrelated cause (n = 1). Of the 19 patients undergoing a first-stage procedure, 16 (84%) remained infection free, and 11 of the 14 patients (79%) undergoing reimplantation of an elbow prosthesis remained infection free. Six patients required further surgery (3 for recurrent infection, 3 for noninfective indications). The commonest infecting organism was Staphylococcus aureus (47%). A degree of postoperative ulnar nerve dysfunction occurred in 37% of patients, but all resolved fully without further treatment. CONCLUSIONS: Management of prosthetic joint infection using 2-stage revision can result in high rates of eradication, although rates of reoperation and transient ulnar nerve dysfunction are high.
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Antibacterianos/uso terapéutico , Artroplastia de Reemplazo de Codo/efectos adversos , Desbridamiento/métodos , Manejo de la Enfermedad , Prótesis de Codo/microbiología , Infecciones Relacionadas con Prótesis/terapia , Infecciones Estafilocócicas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infecciones Relacionadas con Prótesis/microbiología , Reoperación , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificación , Resultado del TratamientoRESUMEN
Cutaneous collagenous vasculopathy (CCV) is a rare benign microangiopathy of the superficial dermal vessels. Clinically, it is characterized by widespread, asymptomatic development of cutaneous telangiectasia in the absence of systemic symptoms. Morphologically, it most resembles generalized essential telangiectasia and other telangiectatic syndromes such as telangiectasia macularis eruptiva perstans (TMEP), ataxia telangiectasia, and hereditary hemorrhagic telangiectasia. It is distinctive in its histology, showing characteristic dilated thick-walled blood vessels in the superficial dermis. The thickened walls of these superficial dermal blood vessels demonstrate reduplication of the basement membrane on PAS staining. We report a 63-year-old man with CCV with this condition for 20 years, starting in 1996. He was diagnosed in the past as having essential telangiectasia. The development of the telangectasias occurred after coronary artery bypass grafting, also performed in 1996. This case not only demonstrates the characteristic clinical and histologic findings, but also suggests a possible mechanism. Moreover, it illustrates that cases of generalized essential telangiectasia may in fact be CCV that are misclassified.
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Puente de Arteria Coronaria/efectos adversos , Enfermedades de la Piel/patología , Telangiectasia/patología , Vasculitis/patología , Dermis/irrigación sanguínea , Dermis/patología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades de la Piel/etiología , Telangiectasia/etiología , Vasculitis/etiologíaRESUMEN
BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. FINDINGS: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. INTERPRETATION: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern. FUNDING: Royal Free London NHS Foundation Trust.
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Alanina/análogos & derivados , Antivirales/uso terapéutico , Ebolavirus/aislamiento & purificación , Fiebre Hemorrágica Ebola/diagnóstico , Meningoencefalitis/diagnóstico , Meningoencefalitis/virología , Ribonucleótidos/uso terapéutico , Carga Viral/efectos de los fármacos , Enfermedad Aguda , Adenosina Monofosfato/análogos & derivados , Adulto , Alanina/uso terapéutico , Enfermedades de los Nervios Craneales/virología , Brotes de Enfermedades , Drogas en Investigación/uso terapéutico , Ebolavirus/genética , Femenino , Genoma Viral , Fiebre Hemorrágica Ebola/tratamiento farmacológico , Humanos , Meningoencefalitis/complicaciones , Meningoencefalitis/tratamiento farmacológico , Enfermeras y Enfermeros , ARN Viral/sangre , ARN Viral/líquido cefalorraquídeo , ARN Viral/aislamiento & purificación , Radiculopatía/virología , Recurrencia , Escocia , Sierra LeonaRESUMEN
Here, we describe the first use of thromboelastography (TEG) in the management of 2 cases of Ebola virus disease. Early in their illness, both patients had evidence of a consumptive coagulopathy. As this resolved, TEG demonstrated that both developed a marked hypercoagulable state, which was treated with low-molecular-weight heparin.
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Trastornos de la Coagulación Sanguínea/diagnóstico , Fiebre Hemorrágica Ebola/complicaciones , Tromboelastografía , Adulto , Trastornos de la Coagulación Sanguínea/etiología , Femenino , HumanosRESUMEN
An epithelial sheath neuroma (ESN) is a rare benign process of unknown pathogenesis, which is characterized histologically by multiple enlarged peripheral nerve fibers ensheathed by mature squamous epithelium. The histologic features can elicit concern for carcinomatous perineural invasion. The process is limited to the superficial dermis and is surrounded by a loose myxoid stroma, lymphocytic infiltrate and sometimes prominent infundibular cysts. The etiology of this peculiar entity has been debated and theories include a benign neoplasm, a hamartoma or an unusual reactive hyperplasia. There are only seven prior cases reported of ESN in the literature. Our case presented here is the first report to show connection of the ESN to the overlying epidermis and reactive epidermal hyperplasia. This suggests that ESN is indeed an unusual form of benign reactive hyperplasia. In addition, the clinical setting in this case was of pruritus and scratching in a background of papular urticaria, supporting the previous notion that ESN is probably a response to an external stimulus such as rubbing.
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In this report, the authors present a case of diffuse dermal angiomatosis (DDA) with an underlying mass lesion of the breast, which proved to be a large calcified, thrombosed artery with adjacent fat necrosis. Histologically, DDA consists of hyperplastic vessels, which diffusely infiltrate the papillary and reticular dermis forming small vascular lumina. The condition is associated with various underlying conditions, many of which result in local tissue ischemia. In the past, DDA was most commonly reported on the lower extremities; however, it seems that this entity is more common on the breast than previously recognized. Various treatments have proven beneficial, including revascularization, oral corticosteroids, smoking cessation, and isotretinoin. In this case, our patient benefited from primary excision of the affected area.
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Angiomatosis/etiología , Arteriopatías Oclusivas/complicaciones , Enfermedades de la Mama/etiología , Necrosis Grasa/complicaciones , Enfermedades Cutáneas Vasculares/etiología , Piel/irrigación sanguínea , Trombosis/complicaciones , Calcificación Vascular/complicaciones , Anciano , Angiomatosis/diagnóstico , Angiomatosis/cirugía , Arteriopatías Oclusivas/diagnóstico , Arteriopatías Oclusivas/cirugía , Biopsia , Enfermedades de la Mama/diagnóstico , Enfermedades de la Mama/cirugía , Diagnóstico Diferencial , Necrosis Grasa/diagnóstico , Necrosis Grasa/cirugía , Femenino , Humanos , Inmunohistoquímica , Valor Predictivo de las Pruebas , Piel/patología , Enfermedades Cutáneas Vasculares/diagnóstico , Enfermedades Cutáneas Vasculares/cirugía , Trombosis/diagnóstico , Trombosis/cirugía , Resultado del Tratamiento , Calcificación Vascular/diagnóstico , Calcificación Vascular/cirugíaRESUMEN
Systemic targeted molecular therapy, in the form of a selective BRAF inhibitor with or without a MEK inhibitor, is a standard treatment for patients with BRAF V600 mutation-positive melanoma with unresectable stage III and IV disease. Patients with BRAF mutation-negative primary tumors may manifest BRAF mutation-positive metastatic disease. It is unclear whether all metastatic lesions carry the same BRAF mutation status found in the primary tumor and if discordancy exists, in what frequency it occurs. Primary and matched metastatic lesions in 25 melanoma patients were tested for the BRAF V600E/Ec, V600K, V600D, and V600R mutations using a BRAF RGQ PCR kit (Qiagen). Four patients (16%) had discrepancies between their primary and metastatic melanoma BRAF status. Of these patients, 2 (8%) had BRAF mutation-positive primary melanomas with BRAF mutation-negative metastatic lesions and 2 (8%) patient had BRAF mutation-negative melanoma with a BRAF mutation-positive metastatic lesion. In summary, discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma. It may be prudent in previously negative patients to determine BRAF mutation status of new metastatic tumors for proper allocation of BRAF inhibitor therapy. Discordant BRAF status may have a role in the varying patterns of response and inevitable resistance seen with BRAF inhibitor therapies.
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Melanoma/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Melanoma/patología , Melanoma/secundario , Persona de Mediana Edad , Terapia Molecular Dirigida , Neoplasias Cutáneas/patología , Adulto JovenRESUMEN
Primary apocrine adenocarcinoma (AA) is a rare malignant cutaneous neoplasm that typically arises in areas of high apocrine gland density such as the axillae and the anogenital region. Due to the nonspecific clinical manifestation of AA, the differential diagnosis may be broad. The rarity of this neoplasm has led to a relative lack of well-established histologic and immunohistochemical diagnostic criteria, further complicating the diagnosis of AA. We report the case of a 49-year-old man with primary AA of the left axilla and provide a review of the clinical and histologic findings, epidemiology, and treatment modalities of this rare cutaneous neoplasm.
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Adenocarcinoma/patología , Glándulas Apocrinas/patología , Neoplasias de las Glándulas Sudoríparas/patología , Adenocarcinoma/diagnóstico , Adenocarcinoma/terapia , Axila , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de las Glándulas Sudoríparas/diagnóstico , Neoplasias de las Glándulas Sudoríparas/terapiaRESUMEN
Malignant Peripheral Nerve Sheath Tumor (MPNST) is a rare soft tissue sarcoma that can occur in superficial locations. Histologically it is categorized into two variants: a conventional/spindled and an epithelioid variant. The latter one is very rare and can be confused histologically with malignant melanoma as it is diffusely positive for S100-protein. Herein we present a case that was initially misdiagnosed as malignant melanoma and discuss morphological and immunohistochemical clues to reach a correct diagnosis.
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Errores Diagnósticos , Melanoma/patología , Neoplasias de la Vaina del Nervio/patología , Neoplasias Cutáneas/patología , Adulto , Biomarcadores de Tumor/análisis , Femenino , Humanos , Inmunohistoquímica , Neoplasias de la Vaina del Nervio/cirugía , Neoplasias Cutáneas/cirugía , Melanoma Cutáneo MalignoRESUMEN
BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease.
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Antimaláricos/uso terapéutico , Malaria Falciparum/transmisión , Parasitemia/transmisión , Plasmodium falciparum/crecimiento & desarrollo , Viaje , Adulto , Portador Sano/transmisión , Femenino , Humanos , Malaria Falciparum/tratamiento farmacológico , Masculino , Parasitemia/tratamiento farmacológico , Plasmodium falciparum/efectos de los fármacos , Análisis de RegresiónRESUMEN
We herein describe 2 cases of adult multivisceral transplant patients who developed graft-versus-host disease manifesting predominantly as lichenoid skin papules and plaques. The diagnosis was supported by histopathology but ultimately corroborated by the utilization of the fluorescence in situ hybridization (FISH) technique using X and Y chromosome probes on unstained biopsy slides. In both cases, FISH revealed a high percentage of donor-derived cells as part of the inflammatory infiltrate in the skin biopsy. This report adds to the previous publications showing the utility of FISH in corroborating the diagnosis of graft-versus-host disease in transplant patients with unmatched sex donor.
Asunto(s)
Cromosomas Humanos X , Cromosomas Humanos Y , Pruebas Genéticas/métodos , Enfermedad Injerto contra Huésped/diagnóstico , Enfermedad Injerto contra Huésped/genética , Hibridación Fluorescente in Situ , Trasplante de Órganos/efectos adversos , Adulto , Anciano , Biopsia , Sondas de ADN , Resultado Fatal , Femenino , Marcadores Genéticos , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Enfermedad Injerto contra Huésped/inmunología , Enfermedad Injerto contra Huésped/patología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Valor Predictivo de las Pruebas , Piel/patología , Resultado del TratamientoRESUMEN
BACKGROUND: Infection is a devastating complication of endoprosthetic replacement (EPR) in orthopaedic oncology. Surgical treatments include debridement and/or one- or two-stage exchange. This study aims to determine the infection-free survival after surgical treatment for first and recurrent EPR infections and identify the risk factors associated with infection recurrence. METHODS: This single-centre cohort study included all patients with primary bone sarcomas or metastatic bone disease treated for infected EPR between 2010 and 2020. Variables included soft tissue status using McPherson classification, tumour type, silver coating, chemotherapy, previous surgery and microorganisms identified. Data for all previous infections were collected. Survival analysis, with time to recurrent infection following surgical treatment, was calculated at 1, 2 and 4 years. Cox regression analysis was used to assess the influence of different variables on recurrent infection. RESULTS: The cohort included 99 patients with a median age of 44 years (29-58 IQR) at the time of surgical treatment. The most common diagnoses were osteosarcoma and chondrosarcoma. One hundred and thirty-three surgical treatments for first or subsequent infections were performed. At 2 years of follow-up, overall success rates were as follows: two-stage exchange 55.3%, one-stage exchange 45.5%, DAIR with an exchange of modular components 44.6% and DAIR without exchange of modular components 24.7%. Fifty-one (52%) patients were infection-free at the most recent follow-up. Of the remaining 48 patients, 27 (27%) were on antibiotic suppression and 21 (21%) had undergone amputation. Significant risk factors for recurrent infection were the type of surgical treatment, with debridement alone as the highest risk (HR 4.75: 95%CI 2.43-9.30; P < 0.001); significantly compromised soft tissue status (HR 4.41: 95%CI 2.18-8.92; P = 0.001); and infections due to Enterococcus spp.. (HR 7.31: 95%CI 2.73-19.52); P = 0.01). CONCLUSIONS: Two-stage exchange with complete removal of all components where feasible is associated with the lowest risk of recurrent infection. Poor soft tissues and enterococcal infections are associated with higher risks of recurrent infection. Treatment demands an appropriate multidisciplinary approach. Patients should be counselled appropriately about the risk of recurrent infection before embarking on complex treatment.