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56 Cards in this Set
- Front
- Back
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What are BRCA1 and BRCA 2 genes?
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they are actually tumour supressor genes whose protein products are BRCA1 and 2
the 2 proteins interact with recombination/DNA repair proteins to preserve intact chromosomal structure |
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what is the risk of potential ovarian cancer or breast cancer if
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BRCA 1- risk of ovarian cancer- 39-46%
BRCA 2 - risk of ovarian cancer 12-20% overall risk of breast cancer for one or the other: 64-74% |
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how are BRCA 1 and 2 genes inherited?
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autosomal dominant with variable penetrance
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what is the false negative rate of BRCA gene testing?
what types of results may come back with BRCA gene testing |
10% - false negative
unclassified variants - variety of mutations that are not frameshifts, but hard to know what they mean positive- most common is jewish founder mutations (ashkenazi population) |
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when should BRCA positive women undergo prophylatic BSO?
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usually at the end of childbearing or after age 35
in these patients, there tends to show occult malignancy |
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what if a patient has HNPCC - what should they have removed prophylactically?
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you should remove do a TAH-BSO
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what are the 2 features that distinguish benign cysts from borderline tumours or LOW Malignant Potential tumours
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nuclear atypia
stratification of the epithelium microscopic papillary projections cellular pleomorphism mitotic activity |
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what is the key difference between borderline tumours and frank carcinoma?
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there is NO stromal invasion of borderline tumours
borderline tumours can have some micro-invasion - foci measuring 3 mm in diameter and less than 5% of the tumour |
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what is the best treatment option for women with tumours of low malignant potential?
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it is reasonable to do fertility sparing surgery - USO - oophorectomy - cystectomy and leave the contralateral ovary and uterus
for post-menopausal - should do TAH BSO |
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what additional surgery would you consider if the tumour has a mucinous histology?
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appendectomy
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what is the 5-year survival for patients with borderline tumours? stage I - IV
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I- 99%
II- 98% III - 96% IV - 77% 80% have stage I disease |
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what is the rate of recurrence for stage I disease after TAH - BSO
what about stage 1 disease with fertility sparing surgery? |
rare - almost never occurs
15% recurrence rate in the contralateral ovary - but highly curable with re-operation and resection |
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what is the most reliable prognostic indicator for stage IV LMP tumours?
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invasive peritoneal implants - this starts to be treated like frank epithelial carcinoma
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what tumour histology are most borderline tumours?
what is the mainstay of treatment and recurrence? |
most of them are serous histology
surgery is the mainstay of treatment - chemotherapy is reserved for those with ascites, rapid tumour growth, or significant changes in the histology of the tumour |
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What are the RAS family of oncogenes and what do they do?
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the protein products help in cell cycle regulation and control cell proliferation
there is inhibition of cellular apoptosis |
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what is p53?
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p53 is a tumour suppressor gene that doesn't allow cells to go into cellular division and halts tumour replication
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Why are BRCA mutations so dangerous?
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because who have them only need ONE more hit before they are set up for a cancer -
Cancer usually occur 15 years earlier then expected there is some association between BRCA tumours and p53 inactivation |
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what are the 3 tumorigenic events that set women up for epithelial ovarian cancer?
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1. K-ras mutations
2. BRCA - p53 mutations - some fallopian tube association 3. cortical inclusion cysts (CICs) - invaginate into the ovary |
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what are some characteristics of physical findings of malignant tumours?
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fixed, solid, nodular
ascites - with fluid wave |
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what are characteristics findings on CBC/lytes results that show malignant transformation?
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thrombocytosis - a platelet count of >400
(malignant cells stimulate a cytokine release that causes platelet proliferation) hyponatremia - 125 - 130 - tumours secrete a vasopressin-like substance suggestive of SIADH |
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what tumour markers are elevated with mucinous tumours
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CA 19-9 or CEA may be more likely to elevated
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what is OVA1 and what is the utility?
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it's a biomarker blood test -
only to be done to reassure yourself that you have a benign mass if you are already going to refer to gyne-onc for worrisome features, then its not useful |
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what type of imaging should a women with ovarian cancer have?
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ultrasound to start may be helpful in characterizing and identifying masses, but its not perfect if the mass is large
CXR may be indicated for patients to rule-out pleural effusions - but should always listen to the chest first CT scans may aid in surgical planning and may help to identify un-resectable disease - BUT not absolutely necessary prior to referral |
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what are the different histologic sub-types of tumours?
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Epithelial tumours represent 80% of ovarian cancer:
1.Serous adenocarcinoma - (fallopian tube) 2. mucinous (appendix / endometrial ca) -adenocarcinoma -pseudomxyoma peritonei 3. endometriod tumours (uterus) -adenocarcinoma -malignant mixed mullerian tumour (MMMT) 4. Clear Cell adenocarcinoma (endometriosis) 5. Transitional cell tumours -malignant brenner -transitional cell carcinoma (Bladder) 6. Squamous cell carcinoma 7. Mixed carcinoma 8. undifferentiated 9. Small cell carcinoma |
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what are the pathognomonic histological features for epithelial ovarian cancer?
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Psammoma bodies -ovarian type with serous histology
collection of calcified material 'psammoma' means sand |
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in the case of an endometrioid ovarian tumour what is the chance of a co-existant uterine tumour?
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15-20% of cases
usually characterized as a syndronous tumour |
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what is an MMMT?
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malignant mixed mullerian tumour- carcinosarcoma
mixed with epithelial and mesenchymal components |
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how do advanced stages mucinous tumours compare with serous tumours?
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they have a worse prognosis
mucinous tumours tend to be resistant to platinum chemotherapy |
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What is pseudomyxoma peritonei?
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when a very thick abundant mucoid or gelatinous material is found in the abdomen surrounded by thin fibrous capsules
it's rare that ovarian mucinous tumours excrete this type of material --> usually always metastatic in this case NEED to remove the appendix to exclude primary appendiceal origin |
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what is disseminated peritoneal adenomucinosis?
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when the epithelial peritoneal cells are benign or borderline - protracted but indolent course
if they are malignant then the course is fatal |
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what is the origin for a clear cell cancer and how do the behave?
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generally clear cell is only 5-10% of epithelial cancers
clear cell cancer usually arise from endometriosis similar to those that develop sporadically from uterus, vagina, and cervix They are usually confined to the ovary and often cured by surgery alone |
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what if you have an advanced clear cell carcinoma ? what is the prognosis?
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20% of clear cells will be advanced and platinum resistant
this carries worse prognosis |
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what are hobnail cells?
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they are the cells seen on histology that are associated with clear cell carcinoma
almost pathognomonic |
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how are brenner tumours characterized?
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dense and unusually abundant stroma with embedded nests of transitional epithelium
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how are transitional cell carcinomas different from brenner tumours?
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they are in the same transitional family BUT they DO NOT have the fibrous brenner component
they look like transitional cell of the bladder, BUT have immunohistochemistry that shows ovarian origin |
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what is the source of a squamous cell carcinoma in the ovary?
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Rare and a new category - where does it come from?
- metastatic cervical cancer -malignant transformation in dermoid -ovarian endometrioid variants with squamous differentiation |
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what are the types of small cell cancer?
what is the prognosis? |
they are very RARE and VERY malignant
Hypercalcemic type - young women in their 20s, unilateral, 2/3 with hypercalcemia that resolve post-op pulmonary type - look like oat cell carcinoma of the lung - in older women 1/2 with bilateral ovarian disease usually die within 2 years of diagnosis |
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what are the criteria for diagnosing primary peritoneal carcinoma when the ovaries are present?
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-both ovaries normal in size - or enlarged by benign process
-extra-ovarian site involvement must be more than the involvement of either ovary ovarian involvement is only on surface or only involving 5x5 mm |
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how do you distinguish a fallopian tube lesion from a primary carcinoma?
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tumor located macroscopically within the tube or its fimbriated end
uterus/ovary must not contain carcinoma- or if not, then must be clearly differentiated from fallopian tube lesion |
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what is a krukenberg tumour?
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almost universally bilateral
looks like metastatic signet ring cell adenocarcinoma originates from GI origin tumour - usually the stomach (remember the stomach also has signet rings) |
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what is the usual pattern of spread of ovarian cancer?
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usually exfoliation - it circulates in the abdomen in the usual path of peritoneal fluid
usually DOES NOT invade into the visceral organs and exist as surface implants mostly lymphatic dissemination- follow the drainage of the ovarian blood supply - along the IP and terminating in the para-aortic lymph nodes --> lymphatics may also follow the chain through broad ligament and parametrium to external iliac, obturator, hypogastric nodal chains --> may also round ligaments to the inguinal nodes direct extension of tumour into adjacent structures |
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how is ovarian cancer staged?
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surgically
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what is the most prognostically important step, but one that we don't do for ovarian cancer staging?
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pelvic and para-aortic lymphadenectomy
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in what group of patients can you be treated with just surgery alone?
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Stage IA/IB, grade 1 and 2
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what patients will go on to need adjuvant chemotherapy?
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Stage IC, II, III, IV
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what is the usual chemotherapy regimen that is used for adjuvant ovarian cancer treatment?
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carboplatinum and taxol
between 3 to 6 cycles |
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even for early stage patients, what is the recurrence rate for ovarian cancer?
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20% and unfortunately specific treatments like maintenance palitaxel doesn't make a difference
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what is the surveillance schedule for patients after treatment for their early stage cancer?
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every 2-4 months for 2 years, the twice yearly for the remaining 3 years, then annually
follow-up should be complete history and physical may consider CA 125 if it was initially elevated |
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what is the goal for optimal debulking for ovarian cancer patients?
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Less than 1 cm of disease at any one site
of course if you can get it to less than 1.5, less than 1, less than 0.5 then outcomes are better |
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what are the 5 main reasons that tumour debulking works?
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1. removes large volumes of chemo-resistant tumour clones
2. removing necrotic masses helps to give drug to well-vascularized cells 3. small residual tumour implants are fast growing, so more susceptible to chemo 4. less cancer cells, mean less chemo needs to be given 5. removal of bulky disease enhances immune system |
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what is the benefit of neoadjuvant interval debulking?
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Allows those patients with initially unresectable tumour (bulky upper abdominal disease or those with lots of residual disease that wasn't initially resected by a gyne-onc
to have best chance to completely resect all their tumour |
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what is avastin?
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bevicizumab - was tried in first line chemotherapy and as a maintenance agent and only shoed modest improvement in progression free survival
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who are patients who are NOT candidates for IP chemotherapy?
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patients with lots of residual bulky disease
stage IV patients those who can't tolerate the toxicity related to IP chemo (more toxic) those who end up having catheter related problems |
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what are the most favourable prognostic factors for ovarian cancer?
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younger age
good performance status cell type other than mucinous and clear cell well-differentiated tumour smaller disease volume prior to surgical debulking absence of ascites smaller residual tumour following primary cytoreductive therapy |
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what are the overall five-year survival rates of ovarian cancer compared with uterine or cervical?
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ovarian cancer- 45% 5-year survival
uterine cancer - 84% 5-year survival cervical cancer - 73 % 5-year survival |
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what does platinum-refractory and platinum-resistant mean?
platinum-sensitive? |
platinum-refractory- meaning progression on primary chemotherapy
platinum resistant means progressing within 6 months platinum sensitive - meaning didn't relapse until 6 months or a year after treatment |
