RESUMEN
The differential diagnosis for neonatal primary lung masses includes developmental anomalies and congenital lung tumors. Fetal lung interstitial tumor (FLIT) is a rare benign mesenchymal lesion which presents either antenatally or within the first 3 months of age. FLIT is a circumscribed solid-cystic mass which histologically resembles the fetal lung during the canalicular stage at 20-24 weeks of gestation. It is composed of immature mesenchymal cells expanding the interstitium and irregular airspace-like structures. Of all published cases, only 1 identified an α2-macroglobulin (A2M)::anaplastic lymphoma kinase (ALK) fusion and all cases underwent surgical resection in the neonatal or infancy period. We present the second case of FLIT with an A2M::ALK fusion diagnosed postnatally in a neonate which partially regressed spontaneously during conservative management with interim resection at 39 months of age, and provide a review of the literature.
Asunto(s)
Neoplasias Pulmonares , alfa 2-Macroglobulinas Asociadas al Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Quinasa de Linfoma Anaplásico/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/congénito , Pulmón/patología , alfa-MacroglobulinasRESUMEN
Congenital cystic pulmonary lesions (CCPLs) are represented by the following entities: congenital pulmonary airway malformation (CPAM), formerly congenital cystic adenomatoid malformation, extra- and intralobar sequestration (EIS), congenital lobar emphysema (overexpansion), and bronchogenic cyst. The developmental model of CPAM histogenesis by Stocker proposed perturbations designated as CPAM type 0 to type 4 without known or specific pathogenetic mechanisms along the airway from the bronchus to the alveolus. This review highlights mutational events either at the somatic level in KRAS (CPAM types 1 and possibly 3) or germline variants in congenital acinar dysplasia, formerly CPAM type 0, and pleuropulmonary blastoma (PPB), type I, formerly CPAM type 4. The potential for overt malignant progression exists in the case of PPB type I and CPAM type 1 in some cases to well-differentiated mucinous adenocarcinoma. On the other hand, CPAM type 2 is an acquired lesion resulting from interruption in lung development secondary to bronchial atresia. The latter is also regarded as the etiology of EIS whose pathologic features are similar, if not identical, to CPAM type 2. These observations have provided important insights into the pathogenetic mechanisms in the development of the CPAMs since the Stocker classification.
Asunto(s)
Secuestro Broncopulmonar , Malformación Adenomatoide Quística Congénita del Pulmón , Neoplasias Pulmonares , Blastoma Pulmonar , Anomalías del Sistema Respiratorio , Humanos , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Malformación Adenomatoide Quística Congénita del Pulmón/genética , Pulmón/patología , Blastoma Pulmonar/diagnóstico , Blastoma Pulmonar/genética , Neoplasias Pulmonares/congénito , Anomalías del Sistema Respiratorio/diagnóstico , Anomalías del Sistema Respiratorio/genética , Secuestro Broncopulmonar/patologíaRESUMEN
Infantile choriocarcinoma (ICC) is a rare, highly malignant form of gestational trophoblastic neoplasia. Rapid diagnosis and initiation of treatment are paramount in reaching a successful outcome. Patients with these tumors typically present with a triad of anemia, hepatomegaly, and precocious puberty. Cutaneous manifestations of ICC are extraordinarily rare with few documented cases. Here, we describe a male neonate who presented to our Dermatology clinic with a rapidly growing, markedly vascular glabellar mass associated with abnormal laboratory values suggestive of Kasabach-Merritt phenomenon. The initial clinical impression of infantile hemangioma led to an initial treatment with propranolol. However, the mass continued to enlarge and a biopsy was obtained. Histology revealed a high-grade, poorly differentiated carcinoma. A robust immunohistochemical battery demonstrated tumor reactivity with Glut-1, GATA3, Glypican-3, CAM5.2, and ß-hCG establishing the diagnosis of metastatic choriocarcinoma. The diagnosis was further supported by the elevated serum ß-hCG. In addition to the glabellar mass, imaging demonstrated tumor foci in the liver and lung. Clinical investigation of the mother revealed no evidence of disease.
Asunto(s)
Coriocarcinoma/secundario , Hemangioma/diagnóstico , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Cutáneas/secundario , Coriocarcinoma/congénito , Coriocarcinoma/diagnóstico , Coriocarcinoma/patología , Diagnóstico Diferencial , Resultado Fatal , Hemangioma/congénito , Hemangioma/patología , Humanos , Lactante , Neoplasias Hepáticas/congénito , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patología , Masculino , Neoplasias Cutáneas/congénito , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patologíaRESUMEN
Primary lung tumors in children are rare, with a narrow range of diagnostic considerations. However, the overlapping imaging appearances of these tumors necessitate attention to key discriminating imaging and pathologic features. In the neonate and infant, the important considerations include pleuropulmonary blastoma (PPB), infantile fibrosarcoma, and fetal lung interstitial tumor. Among these tumors, imaging findings such as air-filled cysts in type 1 PPB and homogeneously low attenuation of fetal lung interstitial tumors are relatively specific. Key pathologic and genetic discriminators among this group of tumors include the DICER1 germline mutation found in PPB and the t(12,15)(p13;q25) translocation and ETV6-NTRK3 fusion gene seen in infantile fibrosarcoma. Primary lung tumors in older children include inflammatory myofibroblastic tumors (IMTs), carcinoid salivary gland-type tumors of the lung, recurrent respiratory papillomatosis, and other rare entities. IMT, a spindle-cell proliferation with inflammatory elements, is the most common lung tumor in children. Anaplastic lymphoma kinase, a receptor-type protein tyrosine kinase, is present in 50% of these tumors, and this finding may support an imaging diagnosis of IMT. Carcinoid tumors account for a substantial portion of childhood lung tumors, and their characteristic avid enhancement on images corresponds to the compressed fibrovascular stroma histologically. Furthermore, novel imaging agents used with somatostatin receptor analogs have an emerging role in the evaluation of carcinoid tumors. Although less common than mucoepidermoid carcinoma, adenoid cystic carcinoma tends to recur given the perineural spread seen histologically. Integrating radiologic and pathologic knowledge is critical to accurate diagnosis, treatment planning, and surveillance of primary lung tumors in children.
Asunto(s)
Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Niño , Preescolar , Diagnóstico Diferencial , Humanos , Lactante , Recién Nacido , Neoplasias Pulmonares/congénitoRESUMEN
A 13-year-old girl was referred by her general practitioner with acute worsening exertional dyspnoea and sudden onset of left-sided chest pain. There was no associated trauma, palpitations or syncope. Clinical examination revealed that the left lung was hyper-resonant on percussion with reduced air entry on auscultation. Chest X-ray showed a left tension pneumothorax. She was treated conservatively with chest drain. Follow-up X-ray revealed multiple bullae within her left lung. Unfortunately, she redeveloped a pneumothorax and was sent to a tertiary centre. She was under the care of the paediatric cardiothoracic surgeons who organised a CT thorax and performed a lobectomy to remove the bullae. She was discharged from the tertiary centre and currently being followed up under the care of the paediatrician in the district general hospital. She have not developed any further pneumothoraxes.
Asunto(s)
Síndrome del Nevo Basocelular/complicaciones , Vesícula/congénito , Neoplasias Pulmonares/congénito , Neumotórax/congénito , Adolescente , Femenino , HumanosAsunto(s)
Adenocarcinoma Mucinoso/congénito , Adenocarcinoma Mucinoso/genética , Malformación Adenomatoide Quística Congénita del Pulmón/genética , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Adenocarcinoma Mucinoso/patología , Malformación Adenomatoide Quística Congénita del Pulmón/patología , Femenino , Humanos , Recién Nacido , Neoplasias Pulmonares/patología , Embarazo , Diagnóstico PrenatalRESUMEN
BACKGROUND: The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. OBJECTIVE: The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. MATERIALS AND METHODS: We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10 years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. RESULTS: All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. CONCLUSION: The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible.
Asunto(s)
Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/diagnóstico por imagen , Pulmón/anomalías , Blastoma Pulmonar/congénito , Blastoma Pulmonar/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Segundo Trimestre del Embarazo , Estudios RetrospectivosRESUMEN
RATIONALE: Non-small-cell lung cancer (NSCLC)-associated malignant pleural effusions (MPEs) are sometimes the only available specimens for molecular analysis. OBJECTIVES: This study evaluates diagnostic yield of NSCLC-associated MPE, its adequacy for molecular profiling and the potential influence of MPE volume/cellularity on the analytic sensitivity of our assays. METHODS: Molecular results of 50 NSCLC-associated MPE cases during a 5-year period were evaluated. Molecular profiling was performed on cell blocks and consisted of fluorescent in situ hybridization (FISH) for ALK gene rearrangements and the following sequencing platforms: Sanger sequencing (for EGFR) and high-throughput pyrosequencing (for KRAS and BRAF) during the first 4 years of the study period, and targeted next-generation sequencing performed thereafter. RESULTS: A total of 50 NSCLC-associated MPE cases were identified where molecular testing was requested. Of these, 17 cases were excluded: 14 cases (28%) due to inadequate tumor cellularity and 3 cases due to unavailability of the slides to review. A total of 27 out of 50 MPE cases (54%) underwent at least EGFR and KRAS sequencing and FISH for ALK rearrangement. Of the 27 cases with molecular testing results available, a genetic abnormality was detected in 16 cases (59%). The most common genetic aberrations identified involved EGFR ( 9 ) and KRAS ( 7 ). Six cases had ALK FISH only, of which one showed rearrangement. MPE volume was not associated with overall cellularity or tumor cellularity (P = 0.360). CONCLUSIONS: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in 59% of samples with minimal risk of false negative.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Derrame Pleural Maligno/genética , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Humanos , Hibridación Fluorescente in Situ , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/congénito , Metástasis de la Neoplasia , Derrame Pleural Maligno/etiologíaAsunto(s)
Quiste Broncogénico/congénito , Quiste Broncogénico/cirugía , Secuestro Broncopulmonar/cirugía , Malformación Adenomatoide Quística Congénita del Pulmón/cirugía , Enfisema Pulmonar/congénito , Adulto , Quiste Broncogénico/diagnóstico , Secuestro Broncopulmonar/diagnóstico , Transformación Celular Neoplásica/patología , Preescolar , Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirugía , Embarazo , Diagnóstico Prenatal , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/cirugía , Factores de RiesgoRESUMEN
La hemangiomatosis capilar pulmonar es una entidad poco frecuente, caracterizada por la proliferación de capilares que infiltran paredes alveolares, septos interlobulillares, pleura e intersticio pulmonar, sin características de malignidad, con asociación casi constante a hipertensión pulmonar. Hasta el momento, solo se han reportado en la literatura, dos casos de presentación congénita; este es el tercer caso en un recién nacido y que no se asocia a hipertensión pulmonar. Esta se encuentra en la mayoría de los pacientes con dicha patología, con mayor incidencia entre los 20 y los 40 años de edad. Se presenta a un recién nacido pretérmino de 36 semanas de gestación con dificultad respiratoria progresiva, que requirió asistencia ventilatoria mecánica por desaturaciones constantes en su evolución clínica, sin signos clínicos, radiológicos o ecográficos de hipertensión pulmonar.
Pulmonary capillary hemangiomatosis is a rare entity characterized by the proliferation of capillaries into alveolar walls, interlobular septa, pleura and pulmonary interstitium, without malignant characteristics, with almost constant association with pulmonary hypertension. Until now two cases of congenital presentation have been reported in the literature. This is the third case in a newborn; he has not followed the usual pattern associated with pulmonary hypertension as occurs in most patients with this pathology; the highest incidence is among 20-40 years old. We report a preterm newborn patient of 36 weeks of gestation with progressive respiratory distress requiring mechanical ventilation by constant desaturation during his clinical evolution without clinical, radiological or ultrasonographic signs of pulmonary hypertension.
Asunto(s)
Humanos , Masculino , Recién Nacido , Hemangioma Capilar/congénito , Neoplasias Pulmonares/congénitoRESUMEN
BACKGROUND: Spinal metastasis is considered to have a worse prognosis in lung cancer than in other cancers, but recent clinical studies report improved overall survival of lung cancer. We compared the postoperative prognoses of vertebral metastatic tumors from lung with other types of cancer. METHODS: From 2011 to 2015, 31 Japanese patients (mean age 73 years, range 55-88 years; 19 males, 12 females) underwent surgery for spinal metastasis at our center. We observed patients retrospectively in March 2016, dividing them into groups by cancer type: lung (LK group, n = 10); prostate, breast, or thyroid (PB group, n = 12); and other (OT group, n = 9). We compared survival and revised Tokuhashi score, which provides a basis for choosing a treatment course. Neurologic status was graded before and after surgery using the Frankel system. RESULTS: Mean follow-up was 16.5 months (range 1-62 months). Only seven of 31 patients (22.6%) were alive at final follow-up. Frankel grade significantly improved postoperatively only in the LK (P = 0.01) and PB (P = 0.048) groups. Revised Tokuhashi score differed across groups (P < 0.0001), and was significantly lower in the LK group than in the PB group (P = 0.00) and OT group (P = 0.02). Postoperative survival was significantly shorter in the LK group than in the PB group (P = 0.01) but did not differ between the LK and OT groups. CONCLUSIONS: The revised Tokuhashi score may underestimate the survival of lung cancer patients, who may derive the same benefit from surgical intervention as those with vertebral metastasis from other cancer types.
Asunto(s)
Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/cirugía , Anciano , Anciano de 80 o más Años , Dolor de Espalda/etiología , Dolor de Espalda/patología , Dolor de Espalda/cirugía , Descompresión Quirúrgica/métodos , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/congénito , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos/métodos , Guías de Práctica Clínica como Asunto , Pronóstico , Estudios Retrospectivos , Fusión Vertebral/métodos , Neoplasias de la Columna Vertebral/complicacionesRESUMEN
Pulmonary capillary hemangiomatosis is a rare entity characterized by the proliferation of capillaries into alveolar walls, interlobular septa, pleura and pulmonary interstitium, without malignant characteristics, with almost constant association with pulmonary hypertension. Until now two cases of congenital presentation have been reported in the literature. This is the third case in a newborn; he has not followed the usual pattern associated with pulmonary hypertension as occurs in most patients with this pathology; the highest incidence is among 20-40 years old. We report a preterm newborn patient of 36 weeks of gestation with progressive respiratory distress requiring mechanical ventilation by constant desaturation during his clinical evolution without clinical, radiological or ultrasonographic signs of pulmonary hypertension.
La hemangiomatosis capilar pulmonar es una entidad poco frecuente, caracterizada por la proliferación de capilares que infiltran paredes alveolares, septos interlobulillares, pleura e intersticio pulmonar, sin características de malignidad, con asociación casi constante a hipertensión pulmonar. Hasta el momento, solo se han reportado en la literatura, dos casos de presentación congénita; este es el tercer caso en un recién nacido y que no se asocia a hipertensión pulmonar. Esta se encuentra en la mayoría de los pacientes con dicha patología, con mayor incidencia entre los 20 y los 40 años de edad. Se presenta a un recién nacido pretérmino de 36 semanas de gestación con dificultad respiratoria progresiva, que requirió asistencia ventilatoria mecánica por desaturaciones constantes en su evolución clínica, sin signos clínicos, radiológicos o ecográficos de hipertensión pulmonar.
Asunto(s)
Hemangioma Capilar/congénito , Neoplasias Pulmonares/congénito , Humanos , Recién Nacido , MasculinoRESUMEN
BACKGROUND: The management of congenital cystic lung lesions is controversial. Arguments for routine resection during infancy include the possibility of the lesion being Type I pleuropulmonary blastoma (PPB) rather than a cystic congenital pulmonary airway malformation (CPAM). We aimed to identify clinical and radiological features that might distinguish between CPAM and PPB and to develop a diagnostic algorithm based on these features. METHODS: All recorded cases of Type I PPB were retrieved from the International PPB Registry and compared with an institutional cohort of children undergoing resection of CPAM (2002-2013) that was noted at some stage to be at least partially cystic. Regression models were created to identify variables that might differentiate CPAM from PPB. Odds ratio (OR) and positive predictive value (PPV) were calculated for each variable and a decision algorithm developed. RESULTS: In 112 cases of Type I PPB and 103 of CPAM, factors favoring a diagnosis of CPAM included prenatal detection (OR 89.4), systemic feeding vessel (OR 61.7), asymptomatic (OR 8.0), and hyperinflated lung (OR 6.6). Factors favoring a diagnosis of PPB included bilateral or multisegment involvement (OR 2.4). A decision algorithm that helps to identify lesions requiring resection and those which can be safely observed is presented. CONCLUSION: Clinical and radiological features can help to differentiate between CPAM and PPB. Our algorithm allows identification of children at higher risk of PPB in whom we would recommend resection and those at low risk in whom continued close observation is safe.
Asunto(s)
Malformación Adenomatoide Quística Congénita del Pulmón/diagnóstico , Técnicas de Apoyo para la Decisión , Neoplasias Pulmonares/diagnóstico , Blastoma Pulmonar/diagnóstico , Algoritmos , Niño , Preescolar , Diagnóstico Diferencial , Femenino , Humanos , Lactante , Recién Nacido , Neoplasias Pulmonares/congénito , Masculino , Oportunidad Relativa , Valor Predictivo de las Pruebas , Blastoma Pulmonar/congénito , Sistema de Registros , Estudios RetrospectivosRESUMEN
A congenital peribronchial myofibroblastic tumor (CPMT) is a rare benign tumor arising from the lungs. Although CPMT is a benign tumor, it is characterized by rapid growth, and is easily misdiagnosed during the prenatal period when the symptoms are nonspecific. The authors present a rare case of CPMT in a premature infant, which was detected at 28 weeks on ultrasonography (US) but resolved at a later stage of pregnancy. The knowledge concerning the diagnosis and management of CPMT is reviewed. Herein, the authors report of a 30-minute-old premature newborn infant in whom a pulmonary mass was discovered 1 month before delivery. Maternal prenatal US demonstrated a 0.8 × 1 cm well-defined oval-shaped mass in the left hemithorax in the 28th week of gestational age. The pulmonary mass, however, was not apparent on repeat US examination at 32 weeks. The child was delivered by cesarean section at 34 weeks estimated gestational age. Chest radiography and computed tomography revealed a mass-like lesion in the left lower pulmonary lobe. The chest computed tomography characteristics of the tumor included large size (4 cm), an irregular margin, and surrounding ground-glass opacity, which led to misdiagnosis as a malignant tumor. The patient underwent a left inferior lung lobectomy and was pathologically diagnosed with CPMT. He is currently alive 12-month postresection with no evidence of disease recurrence.The authors report this rare case of CPMT, which was detected at 28 weeks and resolved at a later stage of pregnancy. Congenital peribronchial myofibroblastic tumor is an uncommon benign tumor. Lobectomy or pneumonectomy is often required. The prognosis after surgery is good.
Asunto(s)
Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/diagnóstico por imagen , Ultrasonografía Prenatal , Adulto , Femenino , Edad Gestacional , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Regresión Neoplásica Espontánea , EmbarazoRESUMEN
BACKGROUND: Congenital peribronchial myofibroblastic tumor (CPMT) is a rare, benign lung tumor of infants, with only 19 reported cases worldwide. It is often diagnosed by prenatal imaging or in the immediate postnatal period due to co-morbidities like polyhydramnios, fetal hydrops, respiratory distress, and heart failure. OBSERVATION: We report the oldest known infant (8 weeks old) diagnosed with CPMT, and present his clinical course including the relevant radiographic and histopathologic findings. CONCLUSIONS: CPMT is a rare tumor that should be considered among other primary lung tumors of infancy (developmental, benign, and malignant) even if not detected prenatally or in the immediate postnatal period.
Asunto(s)
Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/patología , Neoplasias de Tejido Muscular/congénito , Neoplasias de Tejido Muscular/patología , Humanos , Lactante , Neoplasias Pulmonares/diagnóstico por imagen , Masculino , Neoplasias de Tejido Muscular/diagnóstico por imagen , Radiografía TorácicaAsunto(s)
Enfermedades Fetales/diagnóstico , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/diagnóstico , Adulto , Femenino , Enfermedades Fetales/diagnóstico por imagen , Enfermedades Fetales/patología , Humanos , Hidropesía Fetal/diagnóstico por imagen , Hidropesía Fetal/patología , Inmunohistoquímica , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Embarazo , Ultrasonografía Prenatal/métodosRESUMEN
The multikinase inhibitor sorafenib is under clinical investigation for the treatment of many solid tumors, but in most cases, the molecular target responsible for the clinical effect is unknown. Furthermore, enhancing the effectiveness of sorafenib using combination strategies is a major clinical challenge. Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. We further show in a phase II clinical trial in KRAS mutant advanced non-small cell lung cancer (NSCLC) with single agent sorafenib an improved disease control rate in patients using the antidiabetic drug metformin. Consistent with this, sorafenib and metformin act synergistically in inhibiting cellular proliferation in NSCLC in vitro and in vivo. A synergistic effect of both drugs is also seen on phosphorylation of the AMPKα activation site. Our results provide a rationale for the synergistic antiproliferative effects, given that AMPK inhibits downstream mTOR signaling. These data suggest that the combination of sorafenib with AMPK activators could have beneficial effects on tumor regression by AMPK pathway activation. The combination of metformin or other AMPK activators and sorafenib could be tested in prospective clinical trials.
Asunto(s)
Proteínas Quinasas Activadas por AMP/fisiología , Antineoplásicos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/tratamiento farmacológico , Metformina/farmacología , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Transducción de Señal , Animales , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/antagonistas & inhibidores , Quinasa de la Proteína Quinasa Dependiente de Calcio-Calmodulina/fisiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos BALB C , Mutación , Niacinamida/farmacología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras) , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Sorafenib , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Proteínas ras/genéticaRESUMEN
Fetal lung interstitial tumor (FLIT) is a recently reported type of congenital lung lesion comprising solid and cystic components. The pathological features include unique interstitial mesenchyme-based cell proliferation, and differ from other neoplasms represented by pleuropulmonary blastoma or congenital peribronchial myofibroblastic tumor. FLIT is extremely rare and its gene expression profile has not yet been reported. We provide the first report of a novel chromosomal rearrangement resulting in α-2-macroglobulin (A2M) and anaplastic lymphoma kinase (ALK) gene fusion in a patient with FLIT. The tumor cells contained a t(2;12)(p23;p13) and were mesenchymal in origin (e.g., inflammatory myofibroblastic tumors), suggesting the involvement of ALK in this case of FLIT. Break apart fluorescence in situ hybridization demonstrated chromosomal rearrangement at ALK 2p23. Using 5'-rapid amplification of cDNA ends, we further identified a novel transcript fusing exon 22 of A2M to exon 19 of ALK, which was confirmed by reverse-transcription polymerase chain reaction. The corresponding chimeric gene was subsequently confirmed by sequencing, including the genomic break point between intron 22 and 18 of A2M and ALK, respectively. Discovery of A2M as a novel ALK fusion partner, together with the involvement of ALK, provides new insights into the pathogenesis of FLIT, and suggests the potential for new therapeutic strategies based on ALK inhibitors.
Asunto(s)
Neoplasias Pulmonares/genética , Proteínas de Fusión Oncogénica/genética , Proteínas Tirosina Quinasas Receptoras/genética , alfa-Macroglobulinas/genética , Cromosomas Humanos Par 2 , Exones , Humanos , Recién Nacido , Cariotipificación/métodos , Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/patología , MasculinoAsunto(s)
Neoplasias Pulmonares/congénito , Neoplasias Pulmonares/patología , Neoplasias de Tejido Muscular/congénito , Neoplasias de Tejido Muscular/patología , Adulto , Resultado Fatal , Femenino , Humanos , Recién Nacido , Neoplasias Pulmonares/diagnóstico , Masculino , Neoplasias de Tejido Muscular/diagnóstico , Parto/fisiologíaRESUMEN
We present a prenatal case of congenital peribronchial myofibroblastic tumor referred as a congenital pulmonary airway malformation (CPAM) with hydrops and polyhydramnios at 30 weeks' gestational age. US and fetal MRI findings did not fit with the referral diagnosis, raising the possibility of intrinsic lung tumor. Fetal hydrops worsened and the baby was successfully delivered by ex utero intrapartum treatment (EXIT) to resection at 31 weeks' gestational age. To the best of our knowledge, this is a unique case of congenital peribronchial myofibroblastic tumor that underwent comprehensive prenatal evaluation and EXIT procedure with good outcome.