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L. Fernandez



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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: 3
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      P1.04-020 - Adenocarcinoma Metastatic Gastrointestinal Origin and Lung Squamous Carcinoma Associated with HIV Disease: Case Report (ID 1284)

      09:30 - 09:30  |  Author(s): L. Fernandez

      • Abstract
      • Slides

      Background:
      Individuals infected with HIV have a higher predisposition to develop malignancies. The spectrum of neoplastic diseases in HIV-infected patients has changed after the introduction of antiretroviral therapy which decreased the AIDS defining malignancies such as Kaposi's sarcoma (KS) and non-Hodgkin lymphoma (NHL), but augmented other tumor types contributing to increased mortality of patients on chronic treatment. We report a patient with HIV on more than 10 years of antiretroviral treatment in whom diagnosis of a metastatic adenocarcinoma of gastrointestinal origin and a concomitant primary lung squamous carcinoma was made.

      Methods:
      Clinical History Revission

      Results:
      A 68-year-old man with a history of HIV on antiretroviral treatment (ART) since 2004, ex-smoker with COPD, osteoporosis and chronic malnutrition, who presents with cough, dyspnea and hemoptysis. On the chest CT-scan a right paravertebral mass associated with atelectasis, a parahilar mass extending to the left upper lobe, and a mass in the pancreatic head is observed. A bronchoscopy with biopsies is performed. The morphological and inmunophenotypic expression patterns of the right lower lobe show metastatic adenocarcinoma of gastrointestinal origin while the left lower lobe biopsy shows primary squamous cell lung carcinoma and the presences of Aspergillus. The patient continued with hemoptysis, developed refractory respiratory failure and died.

      Conclusion:
      With the widespread use of potent ART there was a dramatic decrease in the incidence of KS and NHL and a significant increase in the incidence of several other malignancies. Although the biology of malignancy in HIV-infected people is often more aggressive than in those without HIV infection, standard treatment is generally indicated and can be associated with a favorable outcome, depending upon the tumor type, stage, and comorbidity. In this case two advanced stage tumor lesions associated with hemoptysis were documented, which finally led to the death of the patient. Figure 1 Figure 2





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      P1.04-037 - Lung and Hypopharyngeal Angiosarcoma (AS) in a Renal Transplant Patient: Case Report (ID 1636)

      09:30 - 09:30  |  Author(s): L. Fernandez

      • Abstract
      • Slides

      Background:
      (AS) are rare malignant soft tissue tumors of endothelial cell origin representing 2% of all sarcomas. Most AS develops in the absence of precursor lesions. To date, only 20 cases of (AS) have been described after renal transplantation, occurring mostly on the skin or in a dialysis fistula, their pulmonary location is very rare. We report the case of a patient with a renal transplant who presents a hypo pharyngeal and a right lower lobe (RLL) lesion where a Angiosarcoma was documented.

      Methods:
      Clinical History Revision

      Results:
      A 78 years-old patient, ex-smoker, with end-stage renal failure received a cadaveric donor renal transplant in 2000. Immunosuppressed with relatively low doses of tacrolimus and steroids, graft function remained stable with a serum creatinine in 1,2 until January 2015 when he consults with dysphonia, dysphagia, cough, and mild hemoptysis. The patient had bilateral neck lymphadenopathy, bilateral basal crackles and the rest of the physical examination within normal parameters. Pulmonology evaluated the patient finding a hypopharyngeal mass and another with round morphology in RLL that were metabolically active in PET-CT. A hypopharyngeal biopsy is taken and a CT-guided transthoracic puncture, finding a high grade undifferentiated tumor of mesenchymal origin, expressing Vimenin and CD10, with vascular marker CD31 and gene C-Myc. Gene p53 and Ki-67 in 90% of the tumor. No lymphoid or epithelial line markers are expressed. The patient is currently in chemotherapy and immunotherapy.

      Conclusion:
      The use of potent immunosuppressive agents has significantly reduced the rates of acute rejection after renal transplantation. However, in­creased cancer incidence after renal transplan­tation has become an important problem. Skin tumors, post-transplant lymphoproliferative dis­eases and organ cancers are the most common malignant tumors seen in these patients. Angiosarcoma is rarely seen in this group of patients, and location in lung and hypopharynx without evidence elsewhere of commitment affectation is very rare. Figure 1 Figure 2





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      P1.04-043 - Pulmonary Lepidic Adenocarcinoma in a Patient with Prior Diagnosis of Breast Cancer: Case Report (ID 1289)

      09:30 - 09:30  |  Author(s): L. Fernandez

      • Abstract
      • Slides

      Background:
      The combined effect of improved cancer diagnosis and management has led to a marked increase in cancer survivors. Consequently, an appreciable proportion of cancer diagnoses are registered among patients who had already received a cancer diagnosis in the past, and more accurate diagnostic procedures lead to the identification of more than one cancer in a subset of patients. We present the case of a patient with breast cancer in whom a lepidic primary lung adenocarcinoma was discovered during a follow-up.

      Methods:
      Medical History Revission

      Results:
      A 68-years-old female with breast cancer EC EIII diagnosed in March / 2010, handled with lumpectomy and lymph node removal, solid mucinous ductal carcinoma Ki67 expression: 35% RH: E (+) 100%, P (-), HER 2 NEU negative, negative margins with angiolymphatic invasion 3/15. She received radiotherapy, tamoxifen and later anastrozole. In Dec / 2010 she presents tumor recurrence managed with radical mastectomy, received chemotherapy with Adriamycin and Cyclophosphamide. In April / 2013 she consults with two months of dry cough and dyspnea, normal physical examination, an unremarkable mammography, chest CT-scan with irregular right basal nodular lesion and mediastinal nodes. The patient underwent resection through thoracoscopy, pathology shows lepidic adenocarcinoma pattern with mutated EGFR exon 19 and exon 21 negative, with metastatic nodal involvement by the primary lung tumor and previous breast carcinoma.

      Conclusion:
      Patients that have been diagnosed with a cancer, have an increased lifetime risk for developing another de novo malignancy depending on various inherited, environmental and iatrogenic risk factors. Cancer patients could survive longer due to settling treatment modalities, and then would likely develop a new malignancy. The monitoring and evaluation procedures are especially useful for early detection of tumors associated when there’s a known tumor lesion. Figure 1Figure 2





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    P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P2.04-042 - Mutation of Epidermal Growth Factor Receptor (EGFR) in Patients with Non-Small Cell Lung Cancer (NSCLC) in a University Hospital in Latin America (ID 1457)

      09:30 - 09:30  |  Author(s): L. Fernandez

      • Abstract
      • Slides

      Background:
      The presence of activating gene mutations in the epidermal growth factor receptor of non-small cell lung cancer patients is predictive. It improved progression-free survival and improved response rate when treated with small molecule tyrosine kinase inhibitors. Together, exon 19 deletion and exon 21 L858R gene substitution are present in about 10% of Caucasian patients and in 20–40% of Asian patients. Moreover, guidelines now suggest EGFR gene mutation testing should be conducted in all patients with lung adenocarcinoma or mixed lung cancers with an adenocarcinoma component, regardless of characteristics such as smoking status, gender or race. The success of targeted therapies in non-small cell lung cancer patients has changed the treatment paradigm in metastatic non-small cell lung cancer. We describe the frequency of mutations in exons 19 and 21 of the EGFR gene in (NSCLC) in our hospital

      Methods:
      Between June 2013 and March 2015, 73 samples of lung tissue of patients with NSCLC were obtained in Fundacion Valle del Lili Cali-Colombia. Microdissection cuts on paraffin-embedded lung tissue was performed with the objective of increasing the amount of tumor DNA. DNA was extracted with DNA FFPE Tissue Kit QIAamo Kit (Qiagen), then amplified with PCR and exons 19 and 20 of EGFR mutations studied for amplification. Visualization was performed using microfluidic electrophoresis in the Agilent Bioanalyzer.

      Results:
      We analyzed tumor samples from 73 patients with NSCLC by PCR and RFLP. Good quantity and quality of DNA in 96% (70) cases was obtained. The average age was 65.6 years ± SD, 69% (48) women and 31% (22) men. EGFR mutations were observed in 21% (15) of the samples with 80% (12) in females. 47% of mutations were in exon 19 and 53% in exon 21. 80% of cases with mutations were adenocarcinomas. 53% of patients with mutations were in stage IV disease and 33% of patients received the tyrosine kinase inhibitor.

      Conclusion:
      In patients who are properly selected for EGFR-positive gene mutations, EGFR-TKIs have been shown to improve symptom control and quality of life, especially in frail elderly patients who desire to avoid the systemic side effects of cytotoxic chemotherapy while achieving a certain level of clinical efficacy. As more clinical trials for novel third-generation EGFR TKIs and other alternative therapies mature, better understanding may be gained through the use of these agents in improving treatment efficacy in adenocarcinoma or even squamous cell histology of metastatic NSCLC. Figure 1



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    P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P3.04-018 - Expression of Protein Kinase EML4-ALK Gene in Non-Small Cell Lung Cancer (NSCLC) in a University Hospital of Reference in Latin America (ID 1465)

      09:30 - 09:30  |  Author(s): L. Fernandez

      • Abstract
      • Slides

      Background:
      Lung cancer, the leading cause of cancer deaths worldwide, exists in two distinct entities: small and non-small cell lung cancer, representing 85% of lung cancers, and generally presents at diagnosis with locally advanced or metastatic disease. The rare genetic changes, anaplastic lymphoma kinase (ALK) gene rearrangements, most often consisting in a chromosome 2 inversion leading to a fusion with the echinoderm microtubule-associated protein like 4 (EML4) gene, results in the abnormal expression and activation of this tyrosine kinase in the cytoplasm of cancer cells. This rearrangement occurs in 2–5% of NSCLC, predominantly in young patients (50 years or younger), in non-smokers or former smokers with adenocarcinoma. This aberration most commonly occurs independent of EGFR and KRAS gene mutations. Inmunohistochemical analysis is a cost-effective alternative for the detection of ALK gene rearrangements and recent guidelines from the College of American Pathologists, International Association of the Study of Lung Cancer, and The Association for Molecular Pathology supports the use of IHC screening as long as it has been appropriately validated.

      Methods:
      Between November 2014 and March 2015, 20 tumor samples were obtained in the Fundacion Valle del Lili, Cali-Colombia. The Ventana anti-ALK (D5F3) assay was performed using OptiView DAB IHC detection kit and OptiView Amplification Kit, with external controls rated with positive and negative cell lines (H2228 and CALU-3 respectively), with appropriate expression.

      Results:
      We analyzed samples from 20 patients with NSCLC using immunohistochemistry. We found tumor cells in 100% of the samples. The average age was 62.8 years ± SD, 45% (9) women and 55% (11) men. The protein kinase expression of EML4-ALK gene was found in 20% of the cases (4),which included 3 females. Thirteen cases were adenocarcinoma and fourteen patients were diagnosed in stage IV. Fourteen of twenty patients received chemotherapy. At this time in our hospital began the Phase Three study of the molecule specific for this tumor rearrangement. The mortality in this group of patients was 3 of 20.

      Conclusion:
      Knowledge of cancer biology and oncogenic drivers has led to a better understanding of lung cancer and the development of very active targeted therapies. ALK rearrangements have been identified as oncogenic drivers for a subgroup of lung adenocarcinoma. The clinical benefit gained by targeted therapies has led to transition from a standardized therapeutic approach to a personalized approach based on molecular tumor characteristics in current clinical practice.Figure 1



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