Female Reproductive Pathology

• Define endometriosis.

  Presence of endometrial glands & stroma outside the uterus
• What are the common sites of endometriosis?


  Ovaries

  Uterine ligaments

  Rectovaginal septum

  Cul de sac

  Pelvic peritoneum

  Serosa of the large & small bowel and appendix

  Mucosa of the cervix, vagina, and fallopian tubes

  Laparotomy scars
• What are the clinical features of endometriosis?


  Dysmenorrhea (painful menstruation)

  Dyspareunia (pain during intercourse)

  Pelvic pain -> intrapelvic bleeding & periuterine adhesions

  Menstrual irregularities

  Infertility
• Endometriosis affects approx 10% of women in reproductive age group.
• What are the different theories for the pathogenesis of endometriosis?


  Regurgitation theory (retrograde menstruation)

  'Benign' metastasis theory -> spread through blood vessels & lymphatic channels

  Metaplastic theory -> coelomic epithelium (mesothelium) -> Mullerian ducts

  Extrauterine stem/progenitor cell theory -> from bone marrow, differentiate into endometrial tissue
• What are the possible complications/risks of endometriosis?


  Periodic/cyclical bleeding -> due to extrinsic (ovarian) & intrinsic hormonal stimulation

  Extensive fibrous adhesions in tubes, ovaries & obliteration of pouch of Douglas

  Large cystic masses on ovaries (chocolate cysts or endometriomas)

  Malignancy -> commonly endometrioid & clear cell carcinoma
• What is shown in the image?

  Endometriosis in mucosa of the colon

  
• What is adenomyosis?


  Presence of endometrial tissue within the uterine wall (myometrium)
• What is shown in the image?

  Adenomyosis

  
• What are the possible treatments for endometriosis?


  Hormonal treatments (OCP/progesterone/GNRH agonists) -> suppress oestrogen

  Surgery (preserve fertility) -> laparoscopic diathermy/laser ablation

  Surgery (completed) -> hysterectomy & bilateral salpingo-oophorectomy
• Cervical cancer screening programme

  Available to women & people with a cervix 25-64

  • 25-49 years -> every 3 years
  • 50-64 years -> every 5 years
• What is the strongest RF for cervical cancer?

  HPV (DNA oncogenic virus)

  Found in 99% of cervical cancers
• What are the common HPV subtypes which cause cervical carcinoma?


  HPV 16 -> 60% of cases

  HPV 18 -> 10% of cases
• NOTE: HPV can cause cancers at other sites (vagina, vulva, penis, anus, tonsil & other oropharyngeal locations)
• What are 2 important proteins in HPV?


  HPV E6

  • promotes telomerase expression
  • inhibits p53

  HPV E7

  • inhibits p21 & RB

  = immortalisation, increased cell proliferation & genomic instability
• What are the steps involvement in the cervical cancer screening programme?

  Cervical smear taking

  HR (high-risk) HPV testing (PCR)

  Cervical cytology

  Colposcopy with biopsy +/- cervical loop
• How are samples taken during a PAP smear?

  Using plastic spatula, endocervical brush or broom-like device

  360 rotation of brush 5 times in the transformation zone
• Primary HPV screening pathway (UK)

  
• What happens in cervical cancer screening if smear is HR HPV positive?

  Smears assessed under microscope

  Classified into...

  • negative (normal)
  • borderline changes
  • mild dyskaryosis
  • moderate dyskaryosis
  • severe dyskaryosis
• What is cervical glandular intraepithelial neoplasia (CGIN)?

  Precursor lesion to cervical adenocarcinoma

  Always grade & requires treatment

  • grade 1 -> mild dysplasia
  • grade 2 -> moderate dysplasia
  • grade 3 -> severe dysplasia
• 80% of cervical cancers are squamous cell carcinoma.

  15% -> adenocarcinoma & mixed adenosquamous carcinoma

  < 5% -> small cell carcinoma
• What are the RFs of endometrial cancer?


  Age

  Genetics (Lynch syndrome)

  Lifestyle factors
• What are the types of endometrial cancers?

  Type I

  Type II

  
• Fill in the blanks - development of endometrial cancer

  A) Proliferative endometrium

  B) Simple hyperplasia

  C) Complex hyperplasia

  D) Complex atypical hyperplasia

  E) Grade 1 uterine endometrial carcinoma

  
• What is endometrioid endometrial adenocarcinoma?

  Closely resemble normal endometrium

  Gland forming tumour

  Usually express oestrogen & progesterone receptors
• What is the transformation zone?

  Part of the cervix where squamous & glandular cells meet

  Where most cervical pre-cancers & cancers occur
• What is colposcopy?

  Procedure where cervix is visualised using type of binocular microscope (colposcope)
• What is shown in the image?

  Squamous carcinoma of the cervix

  
• Which grades of cervical intraepithelial neoplasia (CIN) are at high risk of progression to invasive carcinoma?

  CIN 2

  CIN 3

  -> require treatment
• What is the treatment of CIN 1?

  Surveillance

  Low grade lesion, can spontaneously resolve
• What is the treatment of CIN 2/3?

  Large loop excision of transformation zone (LLETZ)
• What procedure is shown in the image?

  Large loop excision of the transformation zone

  
• What does the HPV vaccine protect against?

  Cervical cancer

  Some mouth & throat cancers

  Some cancers of anus & genital areas
• What are the different grades of endometrioid endometrial adenocarcinoma?

  Grade 1 & 2 -> mild to moderate cytological atypia (low grade)

  Grade 3 -> high grade
• What is serous endometrial adenocarcinoma?

  Type of endometrial cancer

  Papillary architecture

  Mutations in TP53 genes
• What is clear cell endometrial adenocarcinoma?

  Type of endometrial cancer

  Can have solid, papillary & glandular architecture

  Characterised by presence of 'clear cells'

  Oestrogen receptor negative

  High grade aggressive tumour
• What is the treatment of endometrial cancer?

  Surgery

  • total hysterectomy with bilateral salpingo-oophorectomy
  • radical hysterectomy (also remove pelvic lymph nodes, surrounding tissues & top of vagina)

  Radiotherapy

  Chemotherapy

  Sometimes pts can have progesterone to slow progression
• What are the 3 normal cell types in the ovary?

  Epithelial cells

  Germ cells

  Sex cord stromal cells
• What are the 3 major histological subtypes of epithelial ovarian tumours?

  Serous

  Mucinous

  Endometrioid
• What are the RFs of high-grade serous ovarian cancer?

  BRCA1 & BRCA2 mutations

  Lynch syndrome

  HRT

  Smoking

  Obesity/overweight

  Asbestos exposure

  Early menarche & late menopause