Pathology of Female Genital Tract 1 19.04.24.pptx

Pathology of Female Genital Tract 1: Cervix and Uterus Catherine Chinyama [email protected] 19 April 2024 1 Learning Objectives 1. To revise the pathology of precancerous lesions of the cervix and cervical cancer 2. To revise the menstrual cycle 3. To learn about fibroids/leiomyomas, the most co...

Pathology of Female Genital Tract 1: Cervix and Uterus Catherine Chinyama [email protected] 19 April 2024 1 Learning Objectives 1. To revise the pathology of precancerous lesions of the cervix and cervical cancer 2. To revise the menstrual cycle 3. To learn about fibroids/leiomyomas, the most common tumour the uterus (new subject) 4. To revise the pathology of endometrial cancer 5. To learn about pregnancy related pathology (new subject) 6. Interact effectively 2 3 Normal cervix and uterus Identify the structures: A. B. C. D. E. A B C D E 4 What type of epithelium lines the ectocervix? Choose the best answer a) Cuboidal epithelium b) Columnar epithelium c) Keratinising stratified squamous epithelium d) Non-keratinising stratified squamous epithelium e) Pseudostratified columnar epithelium Is this a nulliparous or multiparous cervix? The ectocervix Cervical Specimens Submitted to Pathology Laboratory Cervical brush sample for cytology Colposcopic biopsies following an abnormal smear or for symptoms related to the cervix e.g. post coital bleeding Large loop excision transformation zone (LLETZ) for treatment of cervical intraepithelial neoplasia (CIN) Hysterectomy for early cervical cancer 5 Non-keratinising stratified squamous epithelium of the ectocervix Can you think of other organs with similar microscopic appearance? 6 Non-keratinising squamous epithelium of the ectocervix vs keratinising squamous epithelium of the skin 7 The endocervical mucosa (T/F): a) Consists of columnar cells b) Secretes mucus c) Can differentiate to squamous epithelium in a process termed metaplasia d) Can develop into adenocarcinoma The endocervix 8 Note the difference between the stratified squamous epithelium and columnar epithelium. Can you think of two other sites which possess the squamocolumnar junction? Cervical squamocolumnar junction 9 1 0 The Transformation Zone New squamo-columnar Cervical intra-epithelial neoplasia (CIN) + HPV HPV assessment is now used for cervical screening What are the two most common high-risk HPVs ? What are the two most common low risk HPVs ? On histological and cytological examination the cells infected by HPV show clear cytoplasm a feature termed koilocytosis. 11 Koilocytosis consists of clear cells on the surface In CIN 1 the precancerous or dysplastic cells involve the lower third of the epithelium Dysplasia (Gk): dsy - bad; plasis - formation CIN 1 + Koilocytosis 12 CIN 2 + Koilocytosis; two thirds of epithelium involved by dysplastic epithelium 13 CIN 3 - Dysplastic cells involve the full thickness of the epithelium→ carcinoma in situ 14 1. What are the possible presenting symptoms? Advanced cervical cancer 2. What is most likely histology of the cervical cancer? 15 Pathogenesis of Squamous cell carcinoma (SCC) of the Cervix The ectocervix consists of non-keratinising squamous epithelium; the transformation zone is made up metaplastic squamous epithelium. When the metaplastic epithelium is infected by high-risk HPV, the epithelium develops CIN and subsequently invasive cancer. When the CIN3 progresses to invasive cancer, the cancer produces keratin to resemble SCC of the skin. Therefore, SCC of the cervix is classified as: well, moderate and poorly differentiated which depends on the amount of keratin produced as this resembles skin SCC. 16 Early SCC arising in CIN3 to illustrate the development of keratinization in LLETZ CIN 3 CELLS WITH PINK CYTOPLASM = SCC Differentiation Differentiation pertains to how closely the cancer resembles the cell of origin in this case how well the cancer produces keratin What occurs in the skin also occurs in the cervix Well differentiated - lots of keratin production Moderately differentiated - half of the cells produce keratin; the other half do not Poorly differentiated - the cells produce little or no keratin; associated with poor prognosis. 20 Well differentiated SCC of the skin with good prognosis Lots of keratin productio n Round base Minimal invasion of dermis 21 Moderately differentiated SCC of the skin; moderate prognosis Modera te amount of keratin Irregular base, more invasive than well dif SCC 22 Poorly differentiated SCC of skin, poor prognosis No keratin productio n 23 Poorly differentiated SCC of skin Irregular base 24 Higher power: poorly differentiated SCC infiltrating the stroma in haphazard manner 25 The Menstrual Cycle Under the influence of the hypothalamus -pituitary ovarian axis Ovaries are the main source of oestrogens Can you name other sites/organs which produce oestrogens? 26 Developing Ovarian or Graafian Follicle Proliferati ve Phase 27 2 8 The follicular phase in the ovary corresponds to proliferative phase endometrium This endometrium is approximately day 7 of the menstrual cycle The glands are tubular and the cells show mitotic activity The stroma is dense 2 9 Corpus Luteum Early secretory endometriu m 3 0 The presence of a corpus luteum in the ovary corresponds to secretory phase endometrium This is early secretory phase endometrium - day 15 to 16 The cells show subnuclear vacuolation ( the clear spaces in a row below the nuclei). 3 1 This patient underwent hysterectomy for menorrhagia. Note the thick secretory phase endometrium (→) What are the other indications for hysterectomy? 3 2 myometriu m endometri um Late secretory phase 3 3 Late Secretory Phase Endometrium The endometrial glands are long, tortuous and with luminal secretions ready for implantation What is the best time to sample the endometrium when investigating infertility, follicular or luteal phase ? Why? Dysfunctional Uterine Bleeding DUB) Most endometrial biopsies and curettings are submitted to the lab for DUB Most DUB is due to hormonal imbalance with no mechanical cause such as fibroids Important to provide date of LMP and menstrual cycle e.g. LMP = 12. 02. 24; 4/28 Examples of DUB: Menorrhagia Intermenstrual bleeding Polymenorrhoea Metrorrhagia 34 Specimens Submitted to Lab from the Uterus Pipelle endometrial sample/endometrial biopsy Endometrial curettings Subtotal hysterectomy Vaginal hysterectomy Hysterectomy + both tubes and ovaries 35 3 6 Pipel le samp le Endomet rial curetting s 3 7 Vaginal hysterectomy Hysterectom y & bilateral salpingooophrectomy The Fibroid Uterus    Most common tumour of the uterus More common in patients of African origin than Caucasians Located in different sites in uterus Submucosal: under the endometrium Intramural: within the myometrium Subserosal: under the peritoneum Sizes vary from minute to massive Variable presenting symptoms The fibroid consists of smooth muscle and is termed a leiomyoma Multiple leiomyomas are invariably benign Malignant smooth muscle tumour is a leiomyosarcoma 38 Clinical Presentation of Leiomyomas Can be asymptomatic Abnormal uterine bleeding Pain which may include dysmenorrhoea Bladder symptoms due to pressure effect e.g. Urinary frequency Impaired fertility, recurrent miscarriage Fibroid in pregnancy: preterm labour, abnormal lie, obstructed labour, pain if infarcted due to increased vascularity 39 36-year-old woman presented with heavy bleeding. What other symptoms can this fibroid produce? There is a white ‘string’ in the endometrial cavity attached to an intra uterine contraceptive system (IUS). How does this form of treatment work in DUB? What this appropriate treatment for this patient? Submucosal Fibroid (Slide 40) 40 Answers to slide 40: Submucosal Fibroid 41 Mirena in SITU 45-year-old woman: menorrhagia and distended abdomen; multiple fibroids with gross distortion of the uterus – 4,747g 43 Distortion of the endometrial cavity; fibroids have a white knobbly cut surface 44 35yr old woman had hysterectomy for a fibroid uterus, 4/12 post-partum; 4,146g specimen. What are the possible complications during pregnancy? (Slide 45) 45 Answers to slide 45: Fibroid in Pregnancy This a large subserosal fibroid and possible complications include: 46 During pregnancy the fibroid grew due to oestrogen stimulation and increased vascularity, then infarcted. She had a subtotal hysterectomy. What is the disadvantage of this procedure? (Slide 47) 47 Uteru Answers to slide 47: Fibroid in Pregnancy 48 Carcinoma of Endometrium (slide 49) A 68-year-old woman presented with post-menopausal bleeding (PMB) The biopsy showed endometrial cancer What investigations would you order and why? 49 Answers to slide 49: Investigations for carcinoma of the endometrium 50 MRI showed cancer in the endometrial cavity & involving over 50% of the myometrium 51 Hysterectomy Specimen The patient had a hysterectomy and the cavity was full of cancer The gross specimen supports the MRI findings The cancer involves > 50% of the depth of the myometrium (FIGO stage 1B) 52 Grading based on how the cancer resembles the normal endometrium i.e. forming glands Cancer is graded as: well, moderate and poorly differentiated This is a well differentiated endometrioid adenocarcinoma Histology 53 Extra Information: Grading in Cancer Cancers are graded according to how closely the cancer cells resemble the cell of origin Well-differentiated (Grade 1) - closely resemble the cell of origin; in this case endometrial forming glands Moderately differentiated (Grade 2) - some areas form glands and others do not Poorly differentiated (Grade 3) - no resemblance to endometrial glands Poorly differentiated cancers have a high rate of proliferation and therefore have an increased propensity to invade blood vessels and lymphatics and spread to the lymph nodes and other organs such as the lungs and liver i.e. they have poor prognosis 54 Staging in Gynaecological Cancers FIGO : Federation Internationale de Gynaecologie et de Obstetrique International Federation of Gynaecologists and Obstetricians; the main staging system DO NOT CONFUSE STAGE and GRADE 55 Staging in Cancer FIGO staging is used in Gynaecological cancers All cancers in the body use the TNM for staging; TNM can also be applied to gynaecological cancers T = Tumour size or depth of invasion depending on the organ → T1, T2, T3 & T4 N = Lymph node spread; prognosis depends on the number of lymph nodes involved → N0, N1, N2. The higher the number of lymph nodes with metastatic cancer, the poorer the prognosis M = Metastasis to liver, lung, brain, bone→ M0 or M1. You do not need to know the different stages by heart, but you should have a vague idea of the prognosis e.g. patients with Stage T1 cancers have roughly 95% five-year survival 56 Pathology of Pregnancy-related Specimens Submitted to the Lab Products of conception for miscarriage or termination of pregnancy Placentas:  Twin pregnancy  Intrauterine growth retardation  Antepartum haemorrhage (APH) placenta previa & abruptio placenta  Placenta accreta – morbidly adherent placenta , usually removed manually Hysterectomy for post-partum haemorrhage (PPH - rare) Ectopic pregnancy 57 APH due to abruptio placenta Fetal surfa ce Matern al surfac e 58 Blood clot in the placenta PPH 35yr old woman; 4 previous C/S ( arrow) Why is the lower uterine segment used for Caesarean section? (Slide 59) 59 Answers to slide 59 Lower uterine segment and C/section 60 Hysterectomy for PPH following C/Section (Slide 61) The myometrium did not contract (involute) to close off the blood vessels resulting in PPH 61 1. What is the most common cause of PPH? 2. What is a pathologically adherent placenta? Tubal ectopic pregnancy : 6 to7 week after LMP + positive pregnancy test and no gestational sac in the uterus INTACT BLEEDIN G 63 RUPTUR ED a medical Any problems get in touch [email protected]