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F. Guerrera
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MTE 11 - Mediastinal Tumors Including Thymic Tumors, Lymphoma, Germ-Cell Tumors: Biology, Diagnosis and Treatment (Ticketed Session) (ID 63)
- Event: WCLC 2015
- Type: Meet the Expert (Ticketed Session)
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 07:00 - 08:00, 201+203
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MTE11.03 - Mediastinal Tumors Including Thymic Tumors, Lymphoma, Germ-Cell Tumors: Biology, Diagnosis and Treatment (ID 1996)
07:00 - 08:00 | Author(s): F. Guerrera
- Abstract
- Presentation
Abstract:
The mediastinum is customarily divided into an anterior, middle (visceral) and posterior (bilateral paravertebral) compartment. Studies encompassing large series of patients indicate that more than half of the mediastinal masses arise in the anterior compartment (54-59%), up to 20% in the middle compartment, and 25% in the paravertebral (posterior) compartment. The general approach to a patient with a mediastinal mass include a thorough history and clinical examination. The type of a mediastinal tumor largely depends on the age of the patient and the presence of associated symptoms and/or paraneoplastic conditions. The most common symptoms are nonspecific and include cough, dyspnea, chest pain, arrhythmias, dysphagia, pleural effusion or, in more aggressive forms, superior vena cava (SVC) syndrome. Some tumor markers may be helpful in some forms (germ cell tumors). Chest radiography and CT scan can image the mass and can allocate it to one of the mediastinal compartments. The CT characteristics may somehow guide the clinician to a differential diagnosis and to the nature (benign or malignant) of the mass. In selected cases MRI may be useful to assess the relationship with the vascular structures and the heart. PET or integrated PET-CT have a role to define the activity of the tumor and the correct stage. Biopsy of the mass, either through a fine-needle aspiration (FNA) or core biopsy is indicated in case the imaging is not diagnostic. Very often, a surgical biopsy through an anterior mediastinotomy (Chamberlain procedure), mediastinoscopy or VATS is needed to provide sufficient tissue to the pathologist for a correct diagnosis. A brief description of the histologic types and the diagnostic workup for the most common mediastinal tumors in the three compartments will be presented. In conclusion, diagnostic workup of mediastinal masses include a careful medical history (age, duration and type of symptoms); imaging definition with CT scan is essential to precisely determine the mediastinal compartment, and cyto-histological confirmation is required in case of undetermined lesions. Differential diagnosis is crucial to provide optimal treatment. Anterior mediastinal tumors. They represent more than half of the mediastinal masses at any age. The most common types are thymic tumors (35%), lymphomas (25%), intrathoracic thyroid tumors (15%), germ cell tumors (20%, malignant 10% - teratomas 10%), other tumors (5%). According to age groups, in adults (> 40 years) thymic tumors are the most common type in men and women. Thyroid tumors are the second most common type in elderly patients. In adolescent/young adults (<40 years) lymphomas are the most common type (either Hodgkin or non-Hodgkin), while thymic tumors are the second most common in young adults, and germ cell (teratoma) in adolescents. Finally, in children (<10 years) a similar prevalence of thymic tumors, teratomas, and lymphomas is observed. The diagnosis of an anterior mediastinal mass is based on the duration and type of symptoms. Thymomas, thyroid goitres and teratomas are usually asymptomatic or indolent, Hodgkin lymphoma and seminomas are associated with an intermediate duration of symptoms, while non-seminomatous germ cell tumors (NSGCT) and lymphoblastic lymphomas have a rapid onset of severe symptoms (SVC syndrome is frequent in these patients). High alpha-feto protein (AFP) or beta-HCG levels are diagnostic of NSGCT, and high lactate dehydrogenase (LDH) suggest a diagnosis of lymphoma; the association of Myasthenia Gravis secures the diagnosis of thymoma. Cyto-histological diagnosis is indicated in undetermined forms, usually to differentiate lymphoma from thymic tumors for optimal subsequent treatment. The average sensitivity of needle biopsy (either FNA or core biopsy) in the diagnosis of lymphoma is around 50%, and in most cases a surgical biopsy is needed in suspected cases. Mediastinotomy is preferred to mediastinoscopy (which reaches the middle-visceral mediastinal compartment). Video-assisted thoracic surgery (VATS) is also a reliable technique, particularly in case of associated pleural effusion. Middle mediastinal tumors. The vast majority of middle (visceral) mediastinal masses are benign. Half of these are cysts (bronchogenic, esophageal duplication cysts). The remaining masses are most often from lymphnodes and can be either malignant (lymphadenopathy from lung cancer, lymphomas), or inflammatory/granulomatous (tuberculosis, sarcoidosis). A small percentage of these lesion (<10%) are miscellaneous (Castleman disease, paraganglioma, intrathoracic thyroid mass). Diagnosis is usually easily accomplished with CT scan, which reveals the liquid component of the cyst. MRI is required in undetermined solid lesions. Cyto-histologic diagnosis (FNA/core biopsy or mediastinoscopy/VATS) is sometimes required for undetermined adenopathy for the differential diagnosis between lymphoma and solid tumors. Almost all the benign lesions are asymptomatic or associated with mild nonspecific symptoms (cough, arrhythmias). In the malignant lesions most symptoms result from the underlying disease (lymphoma, lung cancer). Paravertebral mediastinal tumors. Almost all the tumors in the paravertebral compartment arise from the nervous structures (nerves and ganglia). The prevalence of the different types is different in adults and children/adolescents. In adults almost 90% of the masses are benign, including schwannoma (50%), ganglioneuroma (20%) and neurofibroma (15-20%). The little percentage of malignant neurofibrosarcomas are part of a familial neurofibromatosis. In these patients the clinical presentation includes severe symptoms (pleural effusion, chest pain, dyspnea) and a large tumor (> 10 cm.). Benign paravertebral masses without symptoms can be observed over time if there is no spinal extension. Diagnosis is quite easy using CT scan. Intraspinal extension can be documented with MRI. Resection is indicated in symptomatic forms or in case of intraspinal extension. Patients with familial neurofibromatosis and paravertebral mediastinal mass should receive surgery due to the demonstrated high rate of malignant shift. In children less than 4 years of age paravertebral masses are in high percentages malignant neuroblastomas or ganglioneuroblastomas (virtually 100%l in children < 1 year). The percentage of malignant forms decreases with increasing age. In neuroblastomas, serum levels of vanillylmandelic acid (VMA) and metanephrine are almost always elevated and therefore diagnostic.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-104 - Lung Cancer Patients Derived Xenografts: Prospective Molecular Profiling and Potential Evaluation of Drug Resistance (ID 1278)
09:30 - 17:00 | Author(s): F. Guerrera
- Abstract
Background:
The discovery of “driver mutations” such as the Epidermal Growth Factor Receptor (EGFR) and the Anaplastic Lymphoma Kinase (ALK) has led to a remarkable improvement in the outcomes of lung adenocarcinoma, which accounts 50% of the non-small cell lung cancer (NSCLC) diagnoses. Up today, no druggable molecular targets have been identified for squamous carcinoma or small cell lung cancer, which are still treated with the “one-fits-all” therapeutic approach, as it is for a relevant percentage of adenocarcinomas too. The precise definition of molecular profile and, possibly, the description of predictive factors are research priority in the thoracic oncology field. The vast majority of preclinical data are based on in vitro studies, but cell lines models do not entirely reflect tumour characteristics and are hampered by genetic divergence from primary tumours. Patient derived tumour xenografts (PDTX) are a valuable alternative to closely reproduce tumour biology and to prospectively characterize in vivo mechanisms of cancer growth and therapeutic response. Through the generation of a cohort of lung cancer xenopatients, the project aims to confirm the reliability of such models in this disease and to prospectively characterize its biomolecular features.
Methods:
Metastatic and early stages lung cancer cases are considered for the enrolment. Written informed consent is requested from each patient. Fresh tumour tissue from lung biopsies or lung resections is collected and kept in serum free medium (4° C), embedded in 20% matrigel and subcutaneously engrafted into NSG and NOD SCID mice, within 24 hours from sample collection. The exponentially growing tumours are passaged subcutaneously to other mice for a second passage after which they are archived for subsequent analyses (formalin fixed, snap frozen and RNA later). Each sample from surgical resection is also stored to create a DNA lung cancer bank.
Results:
Fourteen samples from TC-guided lung biopsies and sixty-six from radically resected NSCLC were engrafted in NSG and NOD SCID mice lineage in a 1:1 ratio. Due to the low engraftment rate and high morbidity observed in NGS mice in the first 73 samples, subsequent engraftments and expansions were performed in NOD SCID mice only. The overall engraftment rate in biopsy samples was 0 % in NGS and 7.14 % in NOD SCID mice as opposed to 0 % in NGS and 27,27 % in NOD SCID for surgical samples (50% adenocarcinomas, 44,45% squamous carcinomas and 5,55% sarcomatoid carcinomas). Nineteen samples underwent the second passage: of those, 10 samples have been archived after the second successful passage and will be used for further analyses.
Conclusion:
The trial is still ongoing and a longer follow-up is needed. In biopsy-derived samples, engraftment is deeply limited by the paucity of tissue. The results of this study will possibly confirm the reliability of PDTX in lung cancer and provide prospective biomolecular characterization for different histological types.
