Gynaecological Pathology Flashcards
What are infections of the female genital tract cause discomfort but no serious complications?
Candida: Diabetes mellitus, oral contraceptives and pregnancy enhance development of infection.
Tichomonas vaginalis: Protozoan.
Gardenerella: Gram negative bacillus causes vaginitis
What infections of the female genital tract have serious complications?
Chlamydia: Major cause of infertility.
Gonorrhoea: Major cause of infertility.
Mycoplasma: Causes spontaneous abortion and chorioamnionitis.
HPV: Implicated in cancer.
How do gonococci, chlamydia and enteric bacteria cause PID?
Usually starts from the lower genital tract and spreads upward via mucosal surface.
How do staph, strep, coliform bacteria and clostridium perfringens cause PID?
Secondary to abortion.
Usually start from the uterus and spread by lymphatics and blood vessels upwards.
Deep tissue layer involvement.
What are complications associated with PID?
Peritonitis
Bacteraemia
Intestinal obstruction due to adhesions
Infertility
What is the sequence of events with salpingitis?
Usually direct ascent from the vagina.
Depending on severity and treatment may result in resolution or complications.
What are complications associated with salpingitis?
Plical fusion
Adhesions to ovary
Tubo-ovarian abscess
Peritonitis
Hydrosalpinx
Infertility
Ectopic pregnancy
What is this?
Salpingitis
What are pathologies which can occur in the cervix?
Inflammation
Polyps
Dysplasia and carcinoma
Which HPV types are low risk?
Most common types: 6, 11
Other types: 40, 42, 43, 44, 54, 61, 72, 73, 81
Genital and oral warts.
Low grade cervical abnormalities.
Which HPV types are high risk?
Most common types: 16, 18
Other types: 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68,82
Low & high grade cervical abnormalities.
Cervical cancer.
Vulval, vaginal, penile, and anal cancer.
What is cervical intraepithelial neoplasia (CIN)?
This is the term for dysplasia in this site.
Epithelial cells have undergone some phenotypic and genetic changes which are premalignant and preinvasive.
Basal membrane immediately deep to the surface epithelium is intact.
Squamous epithelium is involved more often than glandular epithelium (CGIN).
What is cervical carcinoma?
Invasion through the basement membrane defines change from CIN to invasive carcinoma.
Two types of cervical cancer:
- Squamous cell carcinoma.
- Adenocarcinoma (20% of all invasive cases).
HPV dependent or independent.
What is this?
Squamous cell carcinoma (cervical carcinoma)
What is this?
Adenocarcinoma (cervical carcinoma)
How does HPV transform cells?
Two proteins E6 and E7 encoded by the virus have transforming genes. E6 and E7 bind to and inactivate two tumour suppressor genes:
- Retinoblastoma gene (Rb) (E7)
- P53 (E6)
Both effects interfere with apoptosis and increase unscheduled cellular proliferation both of which contribute to oncogenesis. Infection is either latent or productive.
What is the pathophysiology of HPV in non-productive/latent phases?
HPV DNA continues to reside in the basal cells.
Infectious virions are not produced.
Replication of viral DNA is coupled to replication of the epithelial cells occurring in concert with replication of the host DNA.
Complete viral particles are not produced.
The cellular effects of HPV infection are not seen.
Infection can only be identified by molecular methods.
What is the pathophysiology of HPV in productive viral infection stages?
Viral DNA replication occurs independently of host chromosomal DNA synthesis.
Large numbers of viral DNA are produced and result in infectious virions.
What are the screening intervals for cervical cancer?
25 years - First invitation
25-49 years - Every 3 years
50-64 years - Every 5 years
65+ - Only if one of last three was abnormal
What are endometrial indications for uterine biopsies?
Infertility
Uterine bleeding
Thickened endometrium on imaging
What are uterine indications for biopsies?
Lesion identified on imaging
As part of a wider resection
What are risk factors for endometrial cancer?
Nulliparity
Obesity
Diabetes mellitus
Excessive oestrogen stimulation
What are features of endometrioid carcinomas?
Are oestrogen dependent
Often associated with atypical endometrial hyperplasia
Low grade and high grade tumours
Develop through the accumulation of mutations of different genes.
What is this?
Endometrioid Carcinoma
What is this?
Endometrioid carcinoma
What are serous and clear cell carcinomas associated with?
Older, postmenopausal
Less oestrogen dependent
Arise in atrophic endometrium
High grade, deeper invasion, higher stage
Which mutations are associated with endometrial serous carcinomas?
P53 mutations in 90%
PI3KCA mutations in 15% Her-2 amplification
Which mutations are associated with endometrial clear cell carcinoma?
PTEN mutation
CTNNB1 mutation
Her-2 amplification
What is this?
Endometrial serous carcinoma
What is this?
Endometrial clear cell carcinoma
What is the 2009 FIGO Staging for Carcinoma of the Endometrium?
Stage I: Tumour confined to the corpus uteri.
Stage II: Tumour invades cervical stroma.
Stage III: Local and/or regional spread of the tumour.
Stage IV: Tumour invades bladder and/or bowel mucosa, and/or distant metastases.
What is this?
HMLH1 (A), PMS2 (B), MSH2 (C) and MH6 (D) show strong nuclear expression in tumour cells of endometrioid carcinoma.
What are mesenchymal tumours (leiomyoma)?
Smooth muscle tumour of myometrium.
Commonest uterine tumour
20% of women >35yrs
Lay term is fibroid
Usually multiple
May be intramural, submucosal or subserosal
What is this?
Leiomyoma
What are leiomyosarcomas?
Malignant counterpart of leiomyoma - rare.
Usually solitary.
Usually postmenopausal.
Local invasion and blood stream spread.
5yr survival 20-30%.
What is this?
Leiomyosarcoma
What is this?
Endometrial stromal sarcoma
What is this?
Endometrial stromal sarcoma
What is this?
Serous Epithelial Ovarian Tumour
What is this?
Mucinous Epithelial Ovarian Tumour
What is this?
Endometrioid Epithelial Ovarian Tumours
What is this?
Clear cell Epithelial Ovarian Tumours
What is this?
Brenner Epithelial Ovarian Tumours
What is this?
Serous borderline tumour
What is this?
Mucinous borderline tumour
What are high grade ovarian serous carcinomas?
Most common type of malignant tumours (80%).
Aggressive.
- Alteration in P53, in virtually all.
- BRCA1 or BRCA2 abnormalities (germline and somatic mutations; BRCA1 promoter methylation).
These genes encode proteins that play important roles in DNA repair (homologous recombination).
What are low grade ovarian serous carcinomas?
Distinct pathogenesis from high grade serous carcinoma.
Low grade, relatively indolent, arise de novo or from borderline ovarian tumours.
Mutations in KRAS, BRAF.
No association with BRCA mutations.
Where are common origin sites for secondary ovarian tumours?
Metastatic colorectal carcinoma:
- Ovaries, an anatomic site prone to involvement by metastatic colorectal adenocarcinoma.
- 4-10% of CRC go to ovary.
- Ovarian lesions are identified prior to the primary tumor in 14-32% of cases.
Krukenberg tumours:
- Bilateral metastases composed of mucin producing signet ring cells.
- Most often of gastric origin or breast.
What are different categories of sex-cord stromal tumours?
Pure stromal tumours: e.g. Fibroma, Thecoma, microcystic stromal tumour.
Pure sex cord cells: e.g. Adult type and juvenile granulosa cell tumour.
Mixed sex cord-stromal tumours: e.g. Sertoli Leydig cell tumour.
What is this?
Fibroblasts: Fibromas:
Benign, no endocrine production
What is this?
Granulosa cells: Granulosa cell tumor
Variable behaviour, may produce estrogen
What is DICER1 Syndrome?
Germline mutation in DICER1, a gene encoding an RNAse III endoribonuclease.
Familial multinodular goitre with sertoli/leydig cell tumour, and tumour susceptibility includes pleuropulonry blastoma in childhood.
Found in up to 60% of seroli-Leydig cell tumours.
What is Peutz-Jegher’s Syndrome?
Germline mutations of STK11
Sex cord stromal tumour with annular tubules
Cases occurring in PJS usually show indolent behaviour.
What are immature teratomas?
Indicates presence of embryonic elements.
Neural tissue particularly conspicuous.
A malignant neoplasm that grows rapidly, penetrates the capsule and forms adhesions to the surrounding structures.
Spreads in the peritoneal cavity by implantation.
Metastasis to lymph nodes, lung, liver and other organs.
What is this?
Dysgerminoma
What is this?
Yolk sac tumour
What is this?
Embryonal carcinoma
What is this?
Choriocarcinoma
