DISSERTATION ON HISTOMORPHOLOGICAL PATTERNS OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON ESTROGEN RECEPTOR & PROGESTERONE RECEPTOR EXPRESSION IN SURFACE EPITHELIAL TUMOURS Dissertation submitted to THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY in partial fulfilment of the requirement for the award of degree of MD BRANCH – III PATHOLOGY KARPAGA VINAYAGA INSTITUTE OF MEDICAL SCIENCES, MADURANTAGAM THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI, TAMILNADU. APRIL 2016 DISSERTATION ON HISTOMORPHOLOGICAL PATTERNS OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON ESTROGEN RECEPTOR & PROGESTERONE RECEPTOR EXPRESSION IN SURFACE EPITHELIAL TUMOURS Dissertation submitted to THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY in partial fulfilment of the requirement for the award of degree of MD BRANCH – III PATHOLOGY KARPAGA VINAYAGA INSTITUTE OF MEDICAL SCIENCES, MADHURANTHAGAM THE TAMIL NADU DR. M.G.R. MEDICAL UNIVERSITY, CHENNAI, TAMILNADU. APRIL 2016 CERTIFICATE Certified that this dissertation entitled “HISTOMORPHOLOGICAL PATTERNS OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON ESTROGEN RECEPTOR & PROGESTERONE RECEPTOR EXPRESSION IN SURFACE EPITHELIAL TUMOURS” is a bona fide work done by Dr. R.Madhumittha, Post graduate student, KarpagaVinayaga Institute of Medical Sciences, Madhuranthagam, during the academic year 2013 – 2016. Dr.A.R. Chakravarthy MBBS, MD, DGO, Prof.Dr. T.Chitra, M.D., Dean, Hod&Professor of Pathology, Karpaga Vinayaga Institute of Medical KarpagaVinayaga Institute of Medical Sciences, Sciences, Madhuranthagam Tk, MadhuranthagamTk, Kancheepuram Dist-603308, Kancheepuram Dist-603308, Tamilnadu, India. Tamilnadu, India. DECLARATION BY THE CANDIDATE I hereby declare that this dissertation entitled “HISTOMORPHOLOGICAL PATTERNS OF OVARIAN NEOPLASMS WITH SPECIAL EMPHASIS ON ESTROGEN RECEPTOR & PROGESTERONE RECEPTOR EXPRESSION IN SURFACE EPITHELIAL TUMOURS” submitted by me for the Degree of M.D is the record work carried out by me during the period from August 2013 to September 2015 under the guidance of Dr.A.B.Harke, Professor, Department of Pathology, Karpaga Vinayaga Institute of Medical Sciences and has not formed the basis of any degree, diploma or fellowship titles in this or any other University or other similar Institution of Higher learning. Place: Dr. R. Madhumittha, Date: Post-graduate student in Pathology. Signature of the guide Dr A.B.Harke, Professor, Department of Pathology, Karpaga Vinayaga Institute of Medical Sciences and Research Centre, Madhuranthagam ACKNOWLEDGEMENT I feel words can‘t express my gratitude for all those lovely people who have always been there for me and have stood beside me in all the phases of my life. I express my very sincere thanks to Dr. R. ANNAMALAI, Managing Director, Karpaga Vinayaga Institute of Medical Sciences for his kind-heartedness & providing me with all the available facilities to carry out this thesis work. I could never thank enough Dr. A.R. CHAKRAVARTHY, Dean Karpaga Vinayaga Institute of Medical Sciences for his student friendly nature, support and encouragement. I would like to express my sincere thanks to my guide Dr.A.B.HARKE, Professor, Department of pathology, Karpaga Vinayaga Institute of Medical Sciences, for being a tremendous mentor and letting me have a glimpse of his unsurpassed knowledge. I would like to thank him for patiently correcting my writing and also motivating me throughout the writing of this thesis. His remarkable patience and calmness have been invaluable in making me understand the basics of this subject. I am grateful to thank Dr.T.CHITRA, Professor and Head of Department of Pathology, Karpaga Vinayaga Institute of Medical Sciences, for her constant encouragement and support, extended to me throughout the course. With her friendly attitude creates a comfortable atmosphere in the department. I would like express my gratitude to Dr.E.SARAVANAN, Associate Professor, and Department of Pathology for his encouragement and caring attention. I would like to use this opportunity to also thank Dr. S. KARTHICK, Dr. B. SHOBANA and Dr.R.VIMAL, Assistant Professor of Pathology Karpaga Vinayaga Institute of Medical Sciences for their advices and helping me at times when I needed them the most. In the three years of my post graduation, I have completely understood the meaning of famous saying ―A Friend in need is a Friend indeed‖. I would like to thank my colleague and my juniors for their extreme warmth and care towards me and the infinite support they have given me. A very special thanks to all the lab technicians Mrs. DAISY, Mrs.JAYANTHI, Miss. DARWIN and other non teaching staffs for providing me with everything essential for my thesis and without which it would have remainded incomplete. I would like to thank Obstetrics & Gynaecology department for their help & constant support. Last but not least, I would like to convey my regards to my Dad who is my role model & hero; my Mom who is seeing me from heaven and my Brother and Sister for their blessings and warmth for that I have achieved what I wanted. I would like to end the acknowledgement with thanks to the almighty God. CONTENTS Sl.No CONTENTS Page No 1 Introduction ………………………….… 1 2 Aim and objectives …………………….. 3 3 Review of literature ……………………. 4 4 Methodology ………………..………….. 48 5 Results ………………………………… 49 6 Discussion ……………………………… 80 7 Conclusion ……………………………... 94 8 Annexures 9 Bibliography Introduction The ovaries are a couple of tiny organs in the female pelvic cavity situated on both the sides of the uterus, suspended in the pelvic cavity by the mesovarium, which is attached to the broad ligament1. In US the estimated number of new cases & deaths of ovarian tumors in 2015 is 21,290 & 14,180 respectively. One of 70 of women develops some type of tumors in the ovary in her lifetime. Ovarian neoplasm represents the 6th most common malignancy, fourth leading cause of death due to cancers in women and second most common site for female genital tract & is seen usually after 3 rd decade of life. The incidence of ovarian neoplasms varies in different parts of the world. The difference is also noted in the type of ovarian cancer seen in Western countries & Asian continents. Surface epithelial tumors being more common in the former and germ cell tumors in the latter2-4, 7. The survival rate is less than 50% because the screening test has not been developed & the disease is also not very symptomatic and hence called as silent killer3. However they are treatable tumors because of sensitivity to anticancer therapies5,6. Estrogen and progesterone receptor expression in surface epithelial type are useful for selecting women suffering from ovarian cancers to improve their therapeutic response and also their prognosis7. Ovarian neoplasms are difficult to diagnose using simple techniques like smears, biopsy/ curettage in an early stage as it is possible in other tumors of cervix and body of the uterus. So it poses a difficult diagnostic challenge in early diagnosis. The aim of the study is to estimate the incidence rate, histomorphological patterns & clinical correlation. AIMS & OBJECTIVES 1. To characterize ovarian tumors based on gross and histopathological findings. 2. To study the incidence of ovarian neoplasms. 3. To study the age-related occurrence of the same. 4. To carry out ER & PR status of surface epithelial tumors wherever possible. REVIEW OF LITERATURE EMBRYOLOGY The embryonic development of the ovary begins in an undifferentiated stage. The ovary develops from the gonadal ridge, a bulging from the surface of the coelomic cavity. The ridges are located one on each side of the midline between the dorsal mesentery & mesonephros. Eventually, the tissue of these two ridges forms the two almond-shaped structures. First the mesodermal cells at the surface of the developing ovary differentiate into a layer of epithelial cells covering the organ. In other sites in the coelomic cavity, surface cells differentiate into thinner mesothelial cells that line the peritoneal cavity. Second, beneath the covering epithelium, cords of cells similar to the covering cells appear among the stromal cells. This is reminiscent of the development of epithelial glands and a commonly held view is that cords of cells that appear in the cortex represent the down growth from the surface epithelium. Third, at the same time when developing cords of cells are seen, primordial germ cells make their appearance in the cortex along with the cells of the cords. It was earlier believed that primordial germ cells are from these epithelial cells. However, it became established that the primordial germ cells originate in the endoderm of the yolk sac from which they migrate to the developing ovary and move into its substance at the same time when cords are forming in the cortex. The female germ cells that migrate to the ovaries and gain entrance to their stroma are called oogonia. There are 2 millions of these in both the ovaries at birth, but by puberty large numbers get degenerated so that only 40, 000 remain9. ANATOMY: Ovaries are a pair of nodular bodies situated on either side the uterus closer to the lateral pelvic wall, attached to the broad ligament of the uterus posteriorly and behind & below to the uterine tubes. It is connected to the uterine cornua by the utero-ovarian ligament, to the broad ligament by the mesovarium & lateral pelvic wall by the Infundopelvic ligament 1,10. WEIGHT & SIZE: The size of each ovary is 4x2x1cm and average weight is 5-8 Gms during the reproductive age group and during menopause they shrink to half/even lesser. EXTERNAL FEATURES: Each ovary has two surfaces-lateral & medial, two poles-upper/tubal poles & lower/uterine pole. The ovary also has two borders-anterior & posterior. The ovarian parenchyma has two distinct zones- an outer cortex and inner medulla1. BLOOD SUPPLY: The ovaries are supplied by arteries coming from the main stem of abdominal aorta & are named as an ovarian artery. It divides into two branches one into the mesovarium which supplies the ovary and another branch continues into the uterine broad ligament, below the tube and supplies the same.