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Most Common Types of Liposarcoma and Investigation of Prognostic Values to Disease Progression

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Most Common Types of Liposarcoma and Investigation of Prognostic Values to Disease Progression Lietuvos University of Health Sciences Faculty of Medicine Department of Pathological anatomy Sara García Coronel Final Master’s Thesis MOST COMMON TYPES OF LIPOSARCOMA AND INVESTIGATION OF PROGNOSTIC VALUES TO DISEASE PROGRESSION Thesis supervisor: dr. Lina Poškienė Kaunas, 2018 TURINYS SUMMARY ........................................................................................................................................ 3 ACKNOWLEDGEMENTS ................................................................................................................ 4 CONFLICT OF INTEREST ................................................................................................................ 4 CLEARANCE BY ETHICS COMMITTEE ....................................................................................... 4 ABBREVIATIONS ............................................................................................................................. 5 INTRODUCTION ............................................................................................................................... 6 AIM AND OBJECTIVES OF RESEARCH ....................................................................................... 7 1.LITERATURE REVIEW ................................................................................................................. 8 1.1.General characteristics of liposarcoma classification and its epidemiology ............................. 8 1.1.1.Atypical lipomatous tumor and its epidemiological patterns ............................................. 9 1.1.2.Dedifferentiated liposarcoma (DDLPS) and its epidemiological patterns ....................... 10 1.1.3.Myxoid liposarcoma (MLS), or round cell liposarcoma, and its epidemiological patterns ................................................................................................................................................... 10 1.1.4. Pleomorphic liposarcoma and its epidemiological patterns ............................................ 11 1.2.Morphologic characteristics of different types of liposarcomas ............................................. 12 1.2.1. Morphologic features of atypical lipomatous tumor ....................................................... 12 1.2.2. Morphologic features of dedifferentiated liposarcoma ................................................... 13 1.2.3. Morphologic features of myxoid liposarcoma................................................................. 13 1.2.4. Morphologic features of pleomorphic high grade sarcoma ............................................. 15 1.3.Prognosis factors and their impact on liposarcoma’s clinical course ...................................... 16 2.RESEARCH METHODOLOGY AND METHODS ..................................................................... 18 3.RESULTS OF RESEARCH ........................................................................................................... 19 4.DISCUSSION OF RESEARCH RESULTS .................................................................................. 26 CONCLUSIONS ............................................................................................................................... 29 LITERATURE .................................................................................................................................. 30 2 SUMMARY Author of master thesis: Sara García Coronel Master thesis: “Most common types of liposarcoma and prognostic values to disease progression” Supervisor of master thesis: dr. Lina Poškienė, MD Aim of research: to determine the characteristic features of the most common types of liposarcoma according to patient’s age, disease representation, liposarcoma’s anatomical localization and morphologic features. Objectives of research: 1. To evaluate the clinical characteristics of patients diagnosed with liposarcoma between 2006 and 2016. 2. To determine the most common types of liposarcoma from biopsy and surgical material examined by histological examination between 2006 and 2016. 3. To evaluate anatomical localization, morphologic features of liposarcoma diagnosed for patients between 2006 and 2016. 4. To evaluate clinical and morphologic characteristics of different liposarcoma types in recurrence cases of patients diagnosed with liposarcoma between 2006 and 2016. Methods: object of research – liposarcomas diagnosed for patients at the department of Pathological Anatomy of LUHSH Kaunas Clinics between 2006 and 2016. Retrospective investigation of pathology reports was performed evaluating patient’s clinical data, macroscopic and microscopic morphologic characteristics of different types of liposarcomas. Statistical analysis was performed by applying MS Excel and SPSS software. Statistical significance was p<0.05. Results: 65 patients with liposarcoma were evaluated by gender, age, anatomical localization, size and histological type of liposarcoma between 2006 and 2016. 52.3% of these patients were males and 47.7% were females. The average age of patients was 60±14 years old. The average size of liposarcoma was 15.018±10.79 cm. 16 (24.61%) of examined 65 patients were diagnosed with dedifferentiated liposarcoma, 23 (35.38%) cases – myxoid liposarcoma, 12 (18.46%) – pleomorphic liposarcoma and 14 (21.54%) cases of of overall examined patients were diagnosed with well- differentiated liposarcoma. According to anatomical localization, 6 (9.23%) cases were in the back, 26 (40%) cases were in the lower extremity, 4 (6.15%) cases were in the upper extremities, 1 (1.54%) case was in the mediastinum, 1 (1.54%) case was in the neck, 3 (4.2%) cases were not reported, 3 (4.62%) cases were in the pelvis, and 21 (29.2%) cases were retroperitoneal liposarcomas. There were no statistically significant differences by gender, age, anatomical localization, and liposarcoma type in tumor’s recurrence cases (p>0.05). Conclusions: 1. Liposarcoma affects almost equally males and females mean age being about 60 years old. 2. The most common type of liposarcoma was myxoid, followed by dedifferentiated, well-differentiated and pleomorphic. 3. The average size of liposarcoma was 15.018±10.79 cm, most common localization being lower extremity followed by retroperitoneal are. The less common localizations of tumor were back, upper extremity, pelvis, neck and mediastinum. 4. Overall recurrence of liposarcomas was 26.4% (19 out of 65 patients). There were no statistically significant differences by gender, age, anatomical localization, and liposarcoma type in tumor’s recurrence cases (p>0.05). 3 ACKNOWLEDGEMENTS This research is part of my integrated studies in the Lithuanian University of Health Sciences as a Final Master Thesis during my 6th year of medical studies. CONFLICT OF INTEREST The author of master thesis reports no conflict of interest. CLEARANCE ISSUED BY ETHICS COMMITTEE No. of approval by ethics committee: BEC-MF-85. Date of issue: 2017-11-24. 4 ABBREVIATIONS % – percentage ALT – atypical lipomatous tumour CDK4 – cyclin-dependant kinase 4 CDKN2A – cyclinc-dependant kinase inhibitor 2A cm – centimeter DDLPS – dedifferentiated liposarcoma EWS – Ewing sarcoma EWSR1-CHOP – fusion of genes: EWS RNA-binding protein 1 and CCAAT/Enhancer-Binding Protein Homologous Protein (CHOP), an activating protein of apoptosis FAP – fibroblast activating protein Fig. – figure FUS – gene encoding RNA-binding protein FUS/TLS (Fused in Sarcoma/Translocated in Sarcoma) HPF – hibernation promoting factor IHC – immunohistochemistry MDM2 – gene encoding mouse double minute 2 homolog MLS – myxoid liposarcoma STS – soft tissue sarcoma p16 – tumor suppressor protein RNA – ribonucleic acid TP53 – gene that provides instructions for making a protein called tumor protein p53 (or p53) WDL – well-differentiated liposarcoma WHO – World Health Organization 5 INTRODUCTION Soft tissue as described by anatomical terms is the tissue that connects, supports or surrounds other tissues. Examples include muscles, tendons, fat, fibrous tissue, synovial tissue, vessels, and nerves. In other words, soft tissue is ¨non-epithelial, extra skeletal mesenchyme exclusive of the reticuloendothelial system and glia. Soft tissue sarcoma (STS) is a cancer of these soft tissues that arise predominantly from the embryonic mesoderm(10) and can be classified according to the type of tissue they started in. They encompass a group of neoplasms of over 50 different types(31), that are anatomically and biologically diverse(9), a rare and heterogeneous group of malignant tumours of mesenchymal origin that comprise less than 1 percent of all adult malignancies with an estimated incidence of 4–5 neoplasms /100 000 per year in Europe and 12 percent of paediatric cancers. Even though the skeletal and soft tissue are the most abundant tissue in the human body, STS consists of only 1%(29). As classified by the World Health Organization (WHO), the group of STS includes more than 100 different histological subtypes according to the presumptive tissue of origin. The natural behavior and outcome of STS are dependent of the age of the patient, anatomical site and depth, size, and resectability of the tumor, as well as of histology, grade, nodal disease, and distant metastasis. Some predisposing factors have been identified: genetic alterations (neurofibromatosis type 1, Li – Fraumeni syndrome, FAP/Gardner syndrome, Beckwith – Wiedemann syndrome, hereditary retinoblastoma, Werner syndrome, Costello syndrome, Nijmegen breakage syndrome)(3) and exposure to radiation or chemical substances.
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