RESUMEN
Recently, a novel group of CD34+ and S100+ spindle cell tumors with distinctive stromal and perivascular hyalinization showing recurrent gene fusions involving RAF1, BRAF, NTRK1/2/3, and RET has been identified. ALK rearrangements have been rarely reported in this group of tumors. We report a 24-year-old woman with a 1.5-cm pink mass of the scalp. The tumor was made of spindle cells organized in fascicles or haphazardly arranged in a patternless architecture, with areas of stromal and perivascular hyalinization. The tumor cells diffusely expressed CD34 and S100, without SOX-10 expression. The tumor showed diffuse immunopositivity for ALK. RNA sequencing using next-generation sequencing (NGS) detected an EML4-ALK fusion. This case extends the spectrum of this newly described group of CD34+/S100+ spindle cell tumors at the molecular-genetic level. Dermatopathologists should be aware of this recent entity, as it may fall in the differential diagnosis of many other spindle cell tumors with CD34 expression. NGS-based techniques should be performed when facing spindle cell tumors with similar morphology and immunophenotype. Identification of kinase fusions is essential for the precise classification and better knowledge of these tumors, and for targeted therapy in rare aggressive cases.
Asunto(s)
Antígenos CD34/metabolismo , Proteínas S100/metabolismo , Neoplasias de los Tejidos Blandos/metabolismo , Neoplasias de los Tejidos Blandos/patología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/patología , Diagnóstico Diferencial , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Hialina/metabolismo , Inmunohistoquímica/métodos , Proteínas de Fusión Oncogénica , Análisis de Secuencia de ARN/métodos , Neoplasias de los Tejidos Blandos/diagnóstico , Células del Estroma/metabolismo , Células del Estroma/patología , Negativa del Paciente al Tratamiento , Adulto JovenAsunto(s)
Cadenas Ligeras de Inmunoglobulina/análisis , Mieloma Múltiple/diagnóstico , Penfigoide Ampolloso/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Piel/inmunología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Biomarcadores/análisis , Biopsia , Diagnóstico Diferencial , Errores Diagnósticos , Resultado Fatal , Técnica del Anticuerpo Fluorescente , Humanos , Masculino , Microscopía Electrónica , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/inmunología , Mieloma Múltiple/patología , Valor Predictivo de las Pruebas , Piel/efectos de los fármacos , Piel/ultraestructura , Enfermedades Cutáneas Vesiculoampollosas/tratamiento farmacológico , Enfermedades Cutáneas Vesiculoampollosas/inmunología , Enfermedades Cutáneas Vesiculoampollosas/patología , Resultado del TratamientoRESUMEN
M. chelonae is a classical but uncommon etiology of nodular lymphangitis. We report 2 cases of nodular lymphangitis caused by M. chelonae occurring in immunocompromised hosts; both were cleared with antibiotic therapy.
Asunto(s)
Huésped Inmunocomprometido , Linfangitis/microbiología , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium chelonae , Administración Oral , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Claritromicina/administración & dosificación , Esquema de Medicación , Quimioterapia Combinada , Femenino , Humanos , Inyecciones Intravenosas , Linfangitis/patología , Masculino , Persona de Mediana Edad , Minociclina/administración & dosificación , Minociclina/análogos & derivados , Tigeciclina , Tobramicina/administración & dosificación , Resultado del TratamientoAsunto(s)
Investigación Biomédica , Competencia Dirigida , Atención Ambulatoria/economía , Atención Ambulatoria/legislación & jurisprudencia , Atención Ambulatoria/métodos , Investigación Biomédica/economía , Humanos , Revisión de la Investigación por Pares , Relaciones Médico-Paciente , Carga de TrabajoAsunto(s)
Cruz Roja/historia , Guerra , Atención a la Salud/historia , Historia del Siglo XIX , Humanos , SuizaRESUMEN
Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain. Those findings accorded gliptins extrinsic accountability in triggering MMP onset. Therefore, we examined gliptin intrinsic accountability in a cohort of 313 MMP patients. To do so, we (1) identified MMP patients with gliptin-treated (challenge) diabetes; (2) selected those whose interval between starting gliptin and MMP onset was suggestive or compatible with gliptin-induced MMP; (3) compared the follow-ups of patients who did not stop (no dechallenge), stopped (dechallenge) or repeated gliptin intake (rechallenge); (4) compared the clinical and immunological characteristics of suggestive-or-compatible-challenge patients to 121 never-gliptin-treated MMP patients serving as controls; and (5) individually scored gliptin accountability as the trigger of each patient's MMP using the World Health Organization-Uppsala Monitoring Center, Naranjo- and Begaud-scoring systems. 17 out of 24 gliptin-treated diabetic MMP patients had suggestive (≤12 weeks) or compatible challenges. Complete remission at 1 year of follow-up was more frequent in the 11 dechallenged patients. One rechallenged patient's MMP relapsed. These 17 gliptin-treated diabetic MMP patients differed significantly from the MMP controls by more cutaneous, less buccal, and less severe involvements and no direct immunofluorescence IgA labeling of the basement membrane zone. Multiple autoantibody-target antigens/epitopes (BP180-NC16A, BP180 mid- and C-terminal parts, integrin α6ß4) could be detected, but not laminin 332. Last, among the 24 gliptin-treated diabetic MMP patients, five had high (I4-I3), 12 had low (I2-I1) and 7 had I0 Begaud intrinsic accountability scores. These results strongly suggest that gliptins are probably responsible for some MMPs. Consequently, gliptins should immediately be discontinued for patients with a positive accountability score. Moreover, pharmacovigilance centers should be notified of these events.
Asunto(s)
Autoanticuerpos/inmunología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Membrana Mucosa/efectos de los fármacos , Penfigoide Benigno de la Membrana Mucosa/inducido químicamente , Penfigoide Ampolloso/inducido químicamente , Anciano , Anciano de 80 o más Años , Autoantígenos/inmunología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Penfigoide Benigno de la Membrana Mucosa/patología , Penfigoide Ampolloso/patología , Estudios Retrospectivos , Piel/inmunologíaAsunto(s)
Atención a la Salud/economía , Reforma de la Atención de Salud , Política , Humanos , SuizaAsunto(s)
Educación Médica/legislación & jurisprudencia , Necesidades y Demandas de Servicios de Salud/legislación & jurisprudencia , Legislación Médica , Selección de Profesión , Movilidad Laboral , Prueba de Admisión Académica , Emigrantes e Inmigrantes/legislación & jurisprudencia , Necesidades y Demandas de Servicios de Salud/tendencias , Humanos , Legislación Médica/estadística & datos numéricos , Legislación Médica/tendencias , Política , Competencia Profesional , Factores de TiempoRESUMEN
Systemic steroids, in association or not with cyclosporin, are indicated for the treatment of large or widespread Pyoderma gangrenosum (PG). We report the case of a 27-year-old woman with a 15-year history of severe Crohn's disease, who developed a severe and disseminated PG, refractory to multiple lines of treatment. Infliximab and adalimumab were contraindicated, either because of allergy or of ineffectiveness on Crohn's disease. The addition of certolizumab pegol to the baseline treatment, associating systemic steroids and tacrolimus, finally allowed the complete healing of PG. Oral prednisone was stopped and tacrolimus was decreased, without any cutaneous or digestive relapse. Certolizumab pegol could be an alternative therapy in the treatment of PG in case of intolerance or ineffectiveness of the other anti-tumor necrosis factor (anti-TNF) therapies.
Asunto(s)
Certolizumab Pegol/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Piodermia Gangrenosa/tratamiento farmacológico , Adulto , Enfermedad de Crohn/complicaciones , Femenino , Humanos , Prednisona/uso terapéutico , Piodermia Gangrenosa/etiología , Recurrencia , Inducción de Remisión , Tacrolimus/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
CONTEXT: Serum creatinine has been reported to increase in patients receiving Vemurafenib, yet neither the prevalence nor the mechanism of this adverse event are known. OBJECTIVE: We aimed to evaluate the frequency and the mechanisms of increases in plasma creatinine level in patients receiving Vemurafenib for advanced melanoma. METHODS: We performed a retrospective monocentric study including consecutive patients treated with Vemurafenib for an advanced melanoma. We collected clinical and biological data concerning renal function before introduction of Vemurafenib and in the course of monthly follow-up visits from March 2013 to December 2014. Cystatin C-derived glomerular filtration rate was evaluated before and after Vemurafenib initiation, as increase in serum cystatin C is specific to a decrease in the glomerular filtration rate. We also performed thorough renal explorations in 3 patients, with measurement of tubular secretion of creatinine before and after Vemurafenib initiation and a renal biopsy in 2 patients. RESULTS: 70 patients were included: 97% of them displayed an immediate, and thereafter stable, increase in creatinine (+22.8%) after Vemurafenib initiation. In 44/52 patients in whom Vemurafenib was discontinued, creatinine levels returned to baseline. Serum cystatin C increased, although proportionally less than serum creatinine, showing that creatinine increase under vemurafenib was indeed partly due to a renal function impairment. In addition, renal explorations demonstrated that Vemurafenib induced an inhibition of creatinine tubular secretion. CONCLUSION: Thus, Vemurafenib induces a dual mechanism of increase in plasma creatinine with both an inhibition of creatinine tubular secretion and slight renal function impairment. However, this side effect is mostly reversible when Vemurafenib is discontinued, and should not lead physicians to discontinue the treatment if it is effective.