Gynae Onc Flashcards
Lynch Syndrome
1. Inheritance
2. Genes involved
3. Lifetime risk of Endometrial Ca
- Autosomal Dominant
- Defective DNA mismatch repair, which affects the MSH2, MLH1, MSH6 and PMS2 genes.
- 25-60% lifetime risk of EC and present at younger ages.
What pre op work up is required for Granulosa Cell tumour ?
Endometrial biopsy - this releases oestrogen which may result in endometrial changes.
Stromal cells include:
- Theca cells
- Fibroblasts
- Leydig cells
Granulosa cells and Sertoli cells are present in…
Gonadal primitive sex cords
Sex cord stromal tumours
a) pure sex cord tumours
b) pure stromal tumours
A) Pure sex cord tumours
- Granulosa cell tumour (adult type and juvenile type)
- Sertoli cell tumour
- Sex cord tumour with annular tubules
B) Pure stromal tumours
- Fibroma
- Thecoma
- Fibrosarcoma
- Leydig cell tumour
C) Mixed sex cord stromal tumours (Sertoli-Leydig tumours)
Germ Cell Tumour
- Teratoma
- Embryonal carcinoma
- Non gestational choriocarcinoma
- Dysgerminoma
- Yolk sac tumour
- Mixed germ cell tumour
Tumour markers to be performed in women under 40 with complex ovarian masses
- Ca125
- LDH
- AFP
- HCG
Tumour markets in postmenopausal women with complex ovarian mass?
- Ca125
- CEA
- Ca19.9
Can aid diagnosis and indicate the likelihood of mucinous or Krukenberg tumours (upper or lower GIT)
Overall 5 year survival rate for ovarian Ca?
< 35%
Ovarian cancer is ? commonest cancer in women in the UK?
5th
(After breast, colorectal, lung, uterine)
Lifetime risk of being diagnosed with Ovarian Ca?
Lifetime risk of a women having ovarian ca who had a first degree relative with Ovarian Ca?
1 in 48.
5% lifetime risk if 1st degree relative.
Ca 125 should be measured in primary care if a patient reports any of the following ?
- Persistent abdominal distension or bloating
- Feeling full and or loss of appetite
- Pelvic or abdominal pain
- Increased urinary urgency and or frequenct
How to calculate RMI?
RMI = U x M x Ca125
U = US Score
(Multilocular cysts, solid areas, ascites, bilateral lesions).
M = menopausal status (pre = 1,
Post = 3)
RMI > ? Should be referred to specialist cancer centre
> 250
Stage I Ovarian Cancer:
- stage Ia
- stage Ib
- stage Ic (1c1, 1c2, 1c3)
Stage Ia: Tumour limited to 1 ovary, capsule intact, no tumour on surface, negative washings.
Stage Ib: Tumour confined to both ovaries with ovarian capsule intact and no tumour on the surface of the ovary. Peritoneal cytology is negative.
Stage Ic: tumour confined to both ovaries:
- 1c1 = surgical spill
- 1c2 = capsule rupture before surgery or tumour on ovarian surface
- 1c3 = malignant cells in the ascites of peritoneal washings
Stage II Ovarian Ca
Tumour involves 1 or both ovaries with pelvic extension (below the pelvic brim) or primary peritoneal cancer.
IIa: Extension and/or implant on uterus and/or fallopian tubes
IIb: Extension to other pelvic intraperitoneal tissues.
Stage III Ovarian Cancer?
Tumour involves 1 or both ovaries with cytologically or histologically confirmed spread to the peritoneum outside the pelvis and/or metastasis to the retroperitoneal lymph nodes.
IIIa: +ve lymph nodes and or microscopic metastasis beyond the pelvis
IIIb: macroscopic, extrapelvic, peritoneal mets < 2cm +/- pos retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen.
IIIc: macroscopic, extrapelvic, peritoneal mets > 2cm +/- retroperitoneal lymph nodes. Included extension to capsule of liver/spleen.
Stage IV Ovarian Cancer?
Distant mets including peritoneal mets.
IVa: pleural effusion with pos cytology
IVb: Hepatic and /or splenic parenchymal mets, mets to extra abdominal organs (Inc lymph nodes and lymph nodes outside of the abdominal cavity)
Ovarian Ca: treatment options for well/moderately well differentiated Stage Ia/IIb?
- TAH + BSO + Omentectomy
- Under surface of diaphragm should be visualised and biopsied
- Pelvic and abdominal peritoneal biopsies and pelvic and para aortic lymph node biopsies are required and peritoneal washings should be obtained.
Ovarian Ca: treatment for poorly differentiated Ia/Ib - stage II
- Adjuvant Chemotherapy - carboplatin single agent has been shown to significantly improve survival from 74% - 82%.
- Women with high risk stage I disease (grade 3 or stage Ic) should be offered adjuvant chemotherapy consisting of 6 cycles of carboplatin.
Ovarian Ca: treatment of Stage III and Stage IV?
- TAH + BSO + omentectomy and debulking + chemotherapy
- The volume of disease left at the completion of the primary surgical procedure is related to patient survival.
Surface Epithelial Stromal Ovarian Tumours:
1. Subtypes
2. Age group
3. Account for what % of all ovarian tumours?
4. Originate from?
- Serous, mucinous, endometrioid, clear cell, transitional cell
- Middle age or older, rare before puberty
- Account for 60% of all ovarian tumours and 90% or malignant ovarian tumours
- Originate from the surface epithelium of the ovary. Can be benign, borderline or malignant
Serous Ovarian Tumour - formed by cells resembling what?
Internal lining of the fallopian tube.
Types of serous ovarian tumour?
- Benign - serous cystadenoma
- Borderline serous tumour
- Malignant - serous cystadenocarcinoma
Serous Cystadenoma features ?
- Benign serous ovarian tumour.
- Thin wall cyst with straw coloured fluid. Int lining of the cyst is usually flat but may display a few course papillary projections.
- Account for 25% of all benign ovarian tumours and 66% of all ovarian serous tumours.
- 4th and 5th decade
- Bilateral in up to 20% of patients
Borderline Serous Ovarian Tumours
- More exuberant and finer papillary projections within the cyst cavity.
- Small tumourlets may be found within the abdomen or pelvis in up to 40% of patients.
- 10-15% of all ovarian serous tumours.
- 5th decade of life.
- 1/3 are bilateral.
Borderline serous ovarian tumour 5 year survival?
70 - 95% - treatment is surgical
Malignant serous cystadenocarcinoma features?
- Partially cystic with loculations, solid areas and delicate papillae the project into the cyst cavities
- Make up 33% of all ovarian serous tumours and 50% of all malignant ovarian tumours
- 6th decade
- 2/3rds are bilateral
- Most are widely disseminated at time of diagnosis
5 year survival rate for malignant serous cystadenocarcinoma? (Stage I-IV)
Stage 1 - 76%
Stage 2 - 56%
Stage 3 - 25%
Stage 4 - 9%
Mucinous ovarian tumours - formed from cells resembling what?
Endocervical or intestinal epithelium
Benign mucinous ovarian tumours?
- Multiloculated cysts filled with opaque, thick, mucoid material.
- 25% of all benign ovarian tumours and 75-85% of all mucinous ovarian tumours.
- 3rd to 5th decade
- Rarely bilateral
Borderline mucinous ovarian tumour ?
- Similar to benign tumours but have solid regions and exhibit papillae projecting into the cyst chambers.
- 10-14% of all ovarian mucinous tumours.
- 4th to 6th decade of life.
Malignant Mucinous Tumour
Contain more papillary projections within the cyst cavities, larger solid areas and larger areas of necrosis and haemorrhage.
5-10% of all malignant ovarian neoplasms.
6th decade.
Malignant Mucinous Tumour of the Ovary - 5 year survival? (Stage I - IV)
Stage 1 - 83%
Stage 2 - 55%
Stage 3 - 21%
Stage 4 - 9%
Late extraperitoneal recurrences, particularly in the lungs are characteristic of malignant mucinous tumours.
Endometrioid ovarian tumours are associated with what cell type?
Cells that resemble the endometrium.
May be associated with endometriosis,
Endometrial hyperplasia or carcinoma.
Clear cell tumour of the ovary - associations ?
2/3rds are Nulliparous
50-70% have endometriosis
Which tumour marker may be elevated with Dysgerminoma?
LDH
Commonest germ cell tumour. 10-15% are bilateral.
Endodermal sinus tumour (yolk sac tumour)- which tumour markers may be elevated?
AFP and LDH
Which tumour marker may be elevated in the presence of Granulosa cell tumour?
Serum Inhibin.
Granulosa cell tumour
1. Age groups
2. Presenting symptoms
- 5% pre pubertal girls, 50% in post menopausal bleeding
-> produce Oestrogen.
Associated with hyperplasia and carcinoma.
Present with precocious puberty, menorrhagia, irregular bleeding, PMB or acute abdominal pain because of tendency to rupture.
RMI score and risk of cancer ?
< 25
25 - 250
> 250
< 25 - 3%
25 - 250 - 20%
> 250 - 75%
CTAP should be performed
On all postmenopausal women who have ovarian cysts and RMI > 200.
Asymptomatic, simple, unilateral, unilocular ovarian cyst, < 5cm diameter.
- Risk of malignancy?
- Follow up?
- <1% and 50% resolve spontaneously within 3 months.
- In the presence of a normal Ca125, can be managed conservatively with rpt evaluation in 4-6 months.
Discharge from follow up after 1 year if the cyst remains unchanged or reduced in size with normal
ca125.
Women with RMI < ? Are suitable for laparoscopic management?
200!
Where possible, avoid intraperitoneal spillage.
BRCA1 - breast Ca pathology?
- Young age
- Invasive ductal carcinoma
- Higher tumour grade, lymphocytic infiltration and ‘pushing’ margins.
- Triple negative phenotype (compared with sporadic breast cancers)
BRCA2
- ER status
- HER2 status
- ER positive
- HER 2 negative
Prevalence of Lynch Syndrome in women with endometrial cancer?
3%
What is the most frequently used first line adjuvant chemotherapy following primary surgery for ovarian cancer ?
Paclitaxel and Carboplatin
6 cycles
3 weekly intervals
What % of patients with Ovarian Ca initially respond to first line chemotherapy?
75%
In ovarian cancer, Define:
- Complete response to chemotherapy
- Partial response to chemo
- Malignant disease not detectable for at least 4 weeks
- Tumour size reduced by at least 50% for more than 4 weeks
In advanced ovarian ca, what is an indication for neoadjuvsnt chemo followed by IDS?
- Bulky supracolic omental disease
- Liver Mets
Ovarian Ca:
- Platinum resistant disease
- Platinum refractory disease
- Platinum sensitive disease
- Platinum Resistant- Patients who develop recurrent disease within 6 months of receiving their last dose of platinum.
- Platinum Refractory - patients who develop resistance while receiving chemotherapy.
- Platinum sensitive - patients who develop recurrence beyond 6 months after completing the last dose of platinum.
Platinum free interval and response rate to second line chemotherapy?
Platinum sensitive > 12 months = 40-75%
Partially platinum sensitive 6-12 months = 25-30%
Platinum resistant < 6 months = 10-20%
Platinum refractory = < 10%
What is recommended to reduce risk of cancer in patients with Lynch Syndrome ?
Aspirin - reduces risk of all cancer types in lynch syndrome carriers.
When should surgery be offered to women with Lynch syndrome who have completed child bearing?
1. MLH1 and MLH2
2. MSH6
3. PMS2
Offer TAH BSO by:
1. Age 35
2. Age 40
3. Age 50
What % of endometrial cancers and ovarian epithelial cancers are hereditary?
5% endometrial cancers
20% epithelial ovarian cancers
BRCA1
1. Lifetime risk of ovarian ca by age 70
2. Lifetime risk of Breast ca by age 70
- Ovarian Ca 63%
- Breast Ca 85%
BRCA2
1. Lifetime risk of ovarian ca?
2. Lifetime risk of breast ca?
- 27% by age 70
- 84% by age 70