2023 Female Reproductive Tract Pathology 1 - Microscopic anatomy and neoplasia.pptx

Pathology of the Female Reproductive Tract Tony Williams Consultant Histopathologist Brighton and Sussex University Hospitals 2023 Module 203 • Microscopic anatomy of the female reproductive tract and terminology of neoplasia + endometriosis • Cervical intra epithelial neoplasia (CIN) and carcinom...

Pathology of the Female Reproductive Tract Tony Williams Consultant Histopathologist Brighton and Sussex University Hospitals 2023 Module 203 • Microscopic anatomy of the female reproductive tract and terminology of neoplasia + endometriosis • Cervical intra epithelial neoplasia (CIN) and carcinoma • Endometrial carcinoma – Virtual microscopy: Cervix & cervical carcinoma – Virtual microscopy: Endo/myometrium & endometrial carcinoma • The testis and spermatogenesis – Semen analysis Microscopic anatomy of the female reproductive tract & terminology of neoplasia • Describe the microscopic anatomy of the female reproductive tract • Explain the development of the cervical transformation zone • Define the terminology and classification of neoplasia (including dysplasia, benign and malignant neoplasms) as applied to the female reproductive tract • Describe and understand the pathology of endometriosis Learning outcomes To describe and understand the microscopic anatomy of the structures of the female reproductive tract, including the formation of the cervical transformation zone and to define terminology used in the classification of neoplasia, using examples from the female genital tract. Microscopic Anatomy • Normal anatomy informs pathology • Microscopic changes in cells and tissues are translated into clinical disease • Neoplasms originate from cellular components of tissues Vulva and Vagina L Majora skin with hair follicles and sweat glands L minora and vagina Mucosa with stratified squamous epithelium Vagina at puberty • Oestrogen secreted by the ovary stimulates maturation of squamous epithelial cells • Glycogen is formed within mature squamous epithelial cells • Glycogen in cells shed from the surface is a substrate for vaginal anaerobic organisms (dominated by lactobacilli) • Lactobacilli produce lactic acid keeping vaginal pH below 4.5 cervix • Ectocervix • Endocervix • Transformation zone cervix Ectocervix: stratified squamous epithelium cervix Endocervix: Single layer of tall, mucin producing columnar cells The endocervix has a deceptively large surface area • Columnar epithelium lines tiny blind ending channels (‘clefts’) • These radiate out from the endocervical canal into the surrounding stroma • The ectocervix is covered by stratified squamous epithelium • The endocervix is lined by columnar epithelium • The junction between the two is called the ‘squamo-columnar junction Formation of the transformation zone • • • • During puberty the cervix changes shape The lips of the cervix grow The distal end of the endocervix opens Endocervical mucosa becomes exposed to the vaginal environment cervix • The distal endocervical columnar epithelium is exposed to the acidic vaginal environment • It is not suited to this, so undergoes an adaptive change called metaplasia • Reserve cells in this area proliferate and mature to form squamous epithelium: This process is called squamous metaplasia Metaplasia A transformation of cell type from one kind of mature differentiated cell type to another kind of mature differentiated cell type This may be physiological (as in the cervix) or pathological (as in the distal oesophagus in Barretts oesophagus) The cervical transformation zone • At first, the metaplastic squamous epithelium is thin and delicate (lots of proliferation & maturation is incomplete) • With time, the metaplastic epithelium comes to be as strong and well formed as that on the ectocervix body of the uterus body of the uterus myometrium Bundles of smooth muscle, vasculature and nerves body of the uterus endometrium endometrium Proliferative phase (before ovulation) 1. Tubular glands 2. Specialised stroma 3. Blood vessels Mitoses in glands endometrium Secretory phase 1. Cork screw glands 2. Specialised stroma 3. Blood vessels Secretions in glands common pathological features of neoplasia In the female genital tract neoplasia: ‘new growth’ – abnormal, uncoordinated and excessive cell growth. persists following withdrawal of stimulus and associated with genetic alterations Nomenclature of Neoplasms • Different neoplasms have different behaviour • Accurate identification and naming therefore important for treating the patient Nomenclature of Neoplasms Neoplasms are classified according to their behaviour and histogenesis Behaviour: Benign or Malignant Histogenesis: According to the tissues from which the neoplasms arise and of which they consist Behaviour of Neoplasms Benign: Remains localised and doesn’t invade surrounding tissues Generally grow slowly Good resemblance of parent tissue Leiomyoma of the myometrium ‘ fibroid ’ • A benign neoplasm of smooth muscle • Localised • Slow growing Leiomyoma of the myometrium closely resembles parent tissue Bundles of smooth muscle tissue Consequences of benign neoplasms • • • • • Pressure on adjacent tissue Obstruction of lumen of a hollow organ Hormone production Transformation into a malignant neoplasm Particular symptoms for the patient Benign neoplasms, clinical problems Pressure on adjacent tissue – Bladder (frequency) Rectosigmoid (constipation) Obstruction to lumen of a hollow organ – Adjacent (ureters) Blocking endocervix Hormone production – ? Erythropoietin producing polycythaemia Transformation into a malignant neoplasm – Probably malignancy arises de novo Particular symptoms for the patient - Abnormal uterine bleeding, pain Behaviour of neoplasms Malignant: Invade into surrounding tissues Spread via lymphatics to lymph nodes and blood vessels to other sites (metastasis) May grow relatively quickly Variable resemblance to parent tissue Malignant neoplastic tissue looks different to normal tissue. loss of differentiation loss of cellular cohesion enlarged irregular dark nuclei increased numbers of mitoses and abnormal forms Compare normal tissue and a malignant neoplasm Consequences of malignant neoplasms • • • • • • Destruction of adjacent tissue Metastasis Blood loss from ulcerated surfaces Obstruction of a hollow viscera Production of hormones Weight loss and debility Histogenesis of neoplasms • Classification according to histological appearance • Determined by examining tissue under the microscope • Resemblance to parent tissue correlates with clinical behaviour Terminology of neoplasia • Neoplasms have the suffix – oma • Malignant epithelial tumours are carcinomas • Carcinomas are named for the epithelial cell type which they resemble • Carcinomas of glandular epithelium are called adenocarcinomas • Malignant stromal tumours are sarcomas Cell type Benign Malignant Epithelial Squamous squamous cell squamous cell papilloma carcinoma Glandular adenoma adenocarcinoma Mesenchymal (stromal) Smooth muscle leiomyoma leiomyosarcoma Striated muscle rhabdomyoma rhabdomyosarcoma Adipose tissue lipoma liposarcoma Blood vessel angioma angiosarcoma Bone osteoma osteosarcoma Cartilage chondroma chondrosarcoma Endometriosis • The presence of endometrium-like tissue outside the uterus • 10-15% women of reproductive age • True prevalence may be higher - definitive diagnosis requires surgical visualisation / biopsy. No specific biomarkers. • Chronic pelvic pain, dysmenorrhoea, deep dyspareunia, dysuria, dyschezia, fatigue, infertility. Risk of neoplasia low. Origin of endometriosis Retrograde menstruation • Risk associations with short menstrual cycle and obstructed menstrual flow • Cellular studies tracing somatic genetic mutations in eutopic endometrium and endometriosis • If retrograde menstruation common, other factors must be involved in ability for endometrial cells to adhere, proliferate and mature Coelomic metaplasia • Transformation of peritoneal mesothelium into glandular endometrium suggested in women with Mullerian duct defects Lymphatic/vascular metastasis • Proposed as origin of extrapelvic endometriosis Sites of involvement by endometriosis Common Less common Rare • Ovaries • Uterosacral, round and broad ligaments • Rectovaginal septum • Cul de sac • Serosa of uterus and fallopian tubes • Serosa of other pelvic organs • Large bowel, small bowel and appendix • Mucosa of cervix, vagina and fallopian tubes • Skin (scars, umbilicus, vulva, perineum, inguinal region) • Ureter, bladder • Omentum, pelvic lymph nodes, • • • • Lungs, pleura Soft tissues, breast Bone Upper abdominal peritoneum • Stomach, pancreas, liver • Kidney, urethra, prostate, paratesticular area • Sciatic nerve, subarachnoid space, brain Peritoneal Lesions and an Ovarian Endometrioma Due to Endometriosis Giudice L. N Engl J Med 2010;362:2389-2398 Giudice L. N Engl J Med 2010;362:2389-2398 Gland Stroma Gland Endometriosis involving the colon Microscopic anatomy of the female reproductive tract & terminology of neoplasia • Describe the microscopic anatomy of the female reproductive tract • Explain the development of the cervical transformation zone • Define the terminology and classification of neoplasia (including dysplasia, benign and malignant neoplasms) as applied to the female reproductive tract • Describe and understand the pathology of endometriosis