Repro 4 Aging & Neoplasia Flashcards
Perimenopausal Pelvic Mass
Ddx
QUESTIONS TO ASK:
• Physiologic vs Pathologic?
• Benign vs Malignant
NOTE: Any adnexal mass in pre-menarchal
or post menopause has a high probability of being malignant
►OVARY
– Malignancy (Ovarian Carcinoma)
– Benign Cysts
►FALLOPIAN TUBES
– Infection (PID) CT & NG
– Malignancy (primary or metastases)
– Hydrosalpinx
►UTERUS
– Malignancy (Sarcoma)
– Fibroid
– Cervical Cancer
►GI – Inflammatory (IBD) – Infectious – Malignancy (primary or metastases) – Diverticulosis / Diverticulitis – Colonic Carcinoma
►GU
– Bladder Distension
– Benign & Malignant Masses
– Pelvic Kidney
►PARATUBAL
– Embrylogical Remnants
Mrs T presents with pelvic mass concern to gynecologist.
It take a Hx. Need to do a physical.
How am I going to say this?
So Mrs T, we will need to do a full physical exam and pelvic exam to investigate the mass that your family doctor found.
Abdomen
Breast
Pelvic Exam
Bimanual Exam
Cervical Motion Tenderness
What is it?
aka “cervical excitation”
- suggestive of pelvic pathology
- Classically present in the setting of pelvic inflammatory disease (PID), ectopic pregnancy, and is of some use to help differentiate PID from appendicitis
- Helps differentiate PID from Appendicitis
Cervical Motion Tenderness
What is the colloquial name?
►”Chandelier sign”
due to the pain being so excruciating upon bimanual pelvic exam that it is as if the patient reaches up to motion the grabbing of a ceiling-mounted chandelier.
PID
Pelvic Inflammatory Disease
- Infection of upper genital tract in females that involves any combination of the uterus, endometrium, ovaries, fallopian tubes, pelvic peritoneum and adjacent tissues
- consists of ascending infection from the lower to upper genital tract.
PID
Bacterial Causes?
- Neisseria gonorrhoeae (GC)
- Chlamydia trachomatis (CT)
- Trichomonas vaginalis
- Mycoplasma genitalium
- Mycoplasma hominis
- Ureaplasma urealyticum
- Bacterial vaginosis (BV)
PID
Predisposing Risk Factors
- sexual contact
- Hx of STI
- multiple sexual partners
• upper female genital tract instrumentation:
– D&C
– recent IUD insertion
– therapeutic abortion
PID
What are the cardinal signs?
►lower abdominal pain – usually bilateral
►abnormal bimanual pelvic exam that includes:
– adenexal tenderness (ovaries)
– fundal tenderness
– cervical motion tenderness
Patient Summary Outline
►ID & CC
►Hx
►Px Findings
Ovarian Carcinoma
Risk Factors?
- Advanced Age
- Smoking
- Infertility
►Menstruation Hx:
• Early Menarche
• Late Menopause
►Familial Cancers
• Lynch Syndrome
• BCRA Mutations
Why is it important to ask about menarche & menopause timing?
A major risk factor for ovarian cancer is the number of lifetime menstrual cycles which a woman has.
We think it is related to ascending inflammatory mediators present during menstruation.
Tumor Markers in presence of pelvic mass
►CEA Colon
(carcinoma embryonic Ag)
►Ca-124 Ovary
►Ca-19-9 Pancreas
►Ca-15-3 Breast
What features on a pelvic U/S are suggestive of malignancy?
►Large Size
>6-8 cm
►Solid/Complex
– contains both solid & cystic qualities
►Bilateral
– Associated with Ascites
►Extra-ovarian Masses
– suggestive of metastasis
We have performed pelvic U/S on our patient have confirmed the presence of a mass. This supports a diagnosis of Ovarian Carcinoma
What should we do know?
CT
Has it spread???
Ovarian Cancer
How does it spread?
Spreads by exfoliation of malignant cells into the peritoneal cavity, but may also spread directly, lymphatically, or hematogenously
Ovarian Cancer
Staging
►STAGE 1 Confined to Ovary • 1a - one ovary • 1b - both ovaries • 1c - rupture of tumor on surface
►STAGE 2
Confined to pelvis (uterus & tubes)
►STAGE 3
Confined to abdomen
►STAGE 4
Distant Metastasis
Ovarian Cancer
What is required for diagnosis?
What is required for staging?
Biopsy for definitive Dx
Traditionally, ovarian cancer is surgically staged
What are the 3 cell lines that Ovarian Cancer may originate from?
►Epithelial Cells
– 80-90% of all ovarian cancer
– aka “ovarian carcinoma”
– (eg) High Grade Serous Carcinoma → most common malignant tumor
►Gonadal / Stromal Cells
– 3-5%
– provide structural support and produce hormones
►Germ Cells
– 10-15%
– normally become oocytes but can mutate from teratomas (dermoid cysts) → most common benign tumor
– Dysgerminoma
Recent BC research has actually shown that the majority of serous ovarian cancers actually originate from the nearby fimbriae of the fallopian tube
What are STICs?
“Serous Tubal Intra-epithelial Cells”
When fallopian cells accumulate genomic alterations (p53), them may become STICs.
These cells then have the ability to exfoliate and implant on the ovarian surface and can progress to invasive and metastatic malignancy.
What are the 5 subtypes of Ovarian Carcinoma
Epithelial Tumors
►High Grade Serous Carcinoma
70% & most deadly
►Clear Cell Carcinoma
10%
►Endometrial Carcinoma
10%
►Low Grade Serous Carcinoma
<5%
What is the most common type of Ovarian Carcinoma?
►High Grade Serous Carcinoma
70% & most deadly!
Our patient’s lab & imaging suggests that the mass in her pelvis is likely ovarian carcinoma which has spread to her abdomen.
What stage is this?
STAGE 3
Remember …
►STAGE 1
Confined to Ovary
►STAGE 2
Confined to pelvis (uterus & tubes)
►STAGE 3
Confined to abdomen
►STAGE 4
Distant Metastasis
How do we share this bad news?
SPIKES
►Setting
►Perception
►Invitation
►Knowledge
►Emotion / Empathy
►Strategy / Summary
Given our patient’s clinical picture, what is the most appropriate treatment steps?
►Surgical removal of mass and all visible metastasis.
– to pathology for definitive diagnosis.
►Post-operative Chemotherapy
– for Tx of any residual microscopic malignant tissue
What type of surgery would be required?
Hysterectomy with BSO and omentectomy
BSO = Bilateral Salpingoophorectomy
Why is the prognosis of Ovarian Cancer so poor?
►asymptomatic presenting at an advanced stage
►vague Sx – abdominal discomfort – loss of appetite – urinary urgency – ascites – pleural effusion
What are red flags for pelvic mass on U/S?
> 8cm
complex
solid
bilateral
associated with ascites and masses outside the ovaries
Repro Age Pelvic Mass DDx
►OVARY
– Malignancy (Ovarian Carcinoma)
– Benign Cysts
►FALLOPIAN TUBES
– Infection (PID: CT & NG)
– Malignancy (primary or metastases)
– Ectopic Preg
►UTERUS
– Malignancy (Sarcoma)
– Fibroid
– Endometriosis
►GI
– Inflammatory (IBD)
– Infectious
– Malignancy (primary or metastases)
►GU
– Bladder Distension
– Benign & Malignant Masses
– Pelvic Kidney
►PARATUBAL
– Embrylogical Remnants
What questions could we ask to rule in / out malignancy?
B-Sx
– Fever
– Nightsweats
– Weight Loss
Other Sx: – Increased Abdominal size – Bloating – Weight Gain (from fluid) – Early satiety
21 y/o Famle healthy R adnexal mass not tender asymptomatic
What is the DDx?
►Ectopic Pregnancy (MUST RULE OUT)
►Not pregnant?
Benign Ovarian Cysts
Benign Ovarian Cyst in Reproductive Age
DDx
►FUNCTIONAL / PHYSIOLOGICAL • Influenced by normal menstrual hormones • can become • usually <10cm. • asymptomatic unless bleeding or torsion occurs • resolve on own within a few weeks – Follicular cysts – Corpus luteal cysts
►NON-FUNCTIONAL – PCOS – Theca lutein cysts (respond to ßHCG) – Dermoid Cysts (aka teratomas or germ cell cysts) – Endometriosis
Follicular Cysts
- most common benign ovarian cysts
- occur when the follicle in the ovary does not rupture and continues to grow
- U/S: appear smooth and thin walled
Corpus Luteum Cyst
- can form if Corpus Luteum does not degenerate as usual after 5-9 days
- grossly yellow
- U/S: appear complex
- can become hemorrhagic
What is the most frequent endocrine abnormality of repro age?
PCOS
• causes excess androgens which inhibit ovulation
• results in numerous immature follicles forming “cysts” in the ovaries
Theca Lutein Cysts
• originate from theca lutein cells which abnormally respond to ßHCG during pregnancy or molar pregnancy
Dermoid cysts
aka “teratomas”
- benign growth
- usually composed of all 3 germ cell layers
- have potential to grow any cell type (pluripotent)
- “Screw Blueprints, I’M going to make a human”
AS A RESULT …
• they are able to make any tissue in the body, including skin, teeth, hair
Endometriosis
- common
- cells that ordinarily line the uterus grow outside of the uterine cavity
- frequently results in blood filled endometriotic cysts
Dermoid cysts
aka “teratomas”
- benign growth
- usually composed of all 3 germ cell layers
- have potential to grow any cell type (pluripotent)
- “Screw Blueprints, I’M going to make a human”
AS A RESULT …
• they are able to make any tissue in the body, typically ectodermal in nature including skin, teeth, hair, sebaceous glands
Dermoid cysts
Who gets them?
- most common ovarian tumor
- common in the children and young adults (median age 30)
- BUT, can be encountered throughout reproductive life and after menopause
- 10-15% are bilateral
Dermoid cysts
• Benign 98% of time
However, what are complications?
►Torsion Mass effect can lead to ... • infarction • perforation • hemoperitoneum • autoamputation
►Spontaneous Perforation
• Sudden? → acute abdomen
• Slow? → granulomatous peritonitis
►May become cancerous
– Very rarely (<2% of all dermoid cysts)
– most often squamous cells
– risk increases with age
– Dr McGuiness never saw one become malignant
Dermoid cysts
Tx?
Surgical Removal
– usually well encapsulated
– get it out
– these can look gross: tissue, hair, teeth, whatever, could even look like a mini mutated human
What are the top 4 cancers in women?
- breast
- lung
- colorectal
- endometrial
What is the 5 year survival of Endometrial Cancer?
70%
Overview of Gynecological Cancers
Endometrial Cancer
Endometrial Cancer
►Type I (“low-risk”)
►Type I (“low-risk”)
Age~62 (20% < age 50)
►Estrogen-related – Obesity – PCOS – Type 2 diabetes – Tamoxifen (adjunct for breast cancer Tx)
►Endometrioid histotype
►Usually grade 1, early stage
(good prognosis)
Endometrial Cancer
►Type II (“high risk”)
►Type II (“high risk”)
Age~70
Classification
►Not estrogen-related
– More likely to have normal BMI
►Non-endometrioid
– Serous
– Clear cell
– Malignant mixed mullerian tumour (carcinosarcoma)
►All high grade (grade 3)
Endometrial Cancer
How will the majority of patients present?
Abnormal Uterine Bleeding!
Speculum exam is critical in ANY woman with abnormal uterine bleeding
Dysplasia
When do we use the term in gynecological cancers?
We use this term for cervical cancer, but not for endoemtrial cancer.
For endometrial cancer we use the term “hyperplasia”
Abnormal Vagninal Bleeding
Ddx
►Premenopausal – Fibroids – Polyps – Anovulatory cycles (including PCOS) – Cervical cancer (post- coital)
►Postmenopausal – Atrophy (50%) – Polyps – Cervical cancer – Endometrial hyperplasia – Endometrial cancer (10%)
How informative is U/S?
It is informative as it tells us if the endometrial lining is thick or thin.
However, it is NOT diagnostic by itself.
We are suspecting endometrial cancer. We perform a speculum exam and the cervix appears normal.
What does that tell us about the possible stage of the cancer if in fact the pateint has it?
At the most, the patient has Stage 1
Remember: ►Stage I - confined to uterus ►Stage II - cervix ►Stage III - adnexae, uterine serosa, vagina, lymph nodes ►Stage IV - bowel, bladder, distant
Endometrial Cancer
Dx?
►Surgery
• Hysterectomy + bilateral salpingo-oophorectomy
• +/- lymphadenectomy
►Adjuvant therapy
• Pelvic radiation - local
• Chemotherapy – distant
• Hormone therapy – adv differentiated (grade 1)
What are Prognostic factors in Endometrial cancer?
- Grade (poorly differentiated/grade 3)
- Depth of myometrial invasion (>50%)
- Cervical stromal involvement
We recommend adjuvent therapy for these patients. Why is it coming back if we have removed the uterus? We don’t know, maybe because some cells have escaped.
Follow-up for endometrial cancer
►To detect recurrence
– Pelvic exam q6/12 for 2-3 years, then annually
– Screening tests NOT useful. No use for Pap smear, CXR, blood tests, imaging)
– Most are symptomatic (vaginal bleeding)
►To maximize survivorship
– Reduce risk of other cancers – Quality of life
Women who have had Endometrial Cancer have a high risk of other kinds of cancers?
What are these other cancers?
►Breast cancer
• 2x higher risk
• Estrogen
• 1-2% in next 5 years
►Colorectal cancer
• 3-7x higher risk
• Obesity, radiotherapy, Lynch Syndrome
• 1-2% in next 5 year
We need to educate these women about their increased risk for these 2 cancers and screen them diligently for these in the GP’s office.
How do we screen for these two cancers?
►Breast cancer
• easy!
• Any female can call up the “Screening Mammography Program” and book their own appt.
• Age 50-79
►Colorectal cancer
• FIT test
• every 2 years
• age 50-74
What is HNPCC?
Lynch Syndrome
• Inherited mutation in DNA mismatch repair (MMR) gene
• named after Henry Lynch, an internist. Crazy story, falsified ID to join military, became a pro boxer and then went to med school. Famous for researching genetics in cancer.
HNPCC
It has been proven that women who have Lynch Syndrome also have increased risk of endometrial & ovarian cancer.
Women with HNPCC are now recommended to get a hysterectomy & bilateral oopherectomy.
When should they have this?
Earlier the better, but typically in early 40s to allow for family planning.
Hormone replacement therapy afterwards
NOTE: these women do not have an increased risk of breast cancer.
Who should be tested for Lynch syndrome?
Amsterdam II criteria (3-2-1 rule)
• 3 family members
• 2 generations
• 1 under age 50
BUT … Fam Hx is not enough! There is more to it! The problem is that the Amsterdam Criteria is discriminatory against those women who do not have a large family or do not know they Hx.
Immunohistochemistry (IHC)
To detect 4 MMR proteins • MLH1 • MSH2 • MSH6 • PMS2
Lack of staining suggests gene mutation
Any women who has an endometrial cancer will have an IHC performed to detect the four MMR proteins.
What next?
80% of those tested will be normal
20% will be abnormal → Refer to Hereditary Cancer Program
Why identify Lynch Syndrome in women with endometrial cancer?
- They are still at risk for colorectal cancer
* Their unaffected family members will benefit
Obesity & Diabetes are both associated with an increased risk of Endometrial Cancer.
OBESITY
• 3-10x increased risk of endometrial cancer
• Endometrial biopsy if abnormal bleeding, regardless of age
DIABETES
• 2-3 x risk
• Hyperinsulinemia is independent risk factor
• Endometrial biopsy if abnormal bleeding, regardless of age or BMI
Do all women with endometrial cancer need a hysterectomy?
Progestins as alternative to surgery for young women (Megace, Provera)
Grade 1 endometrioid tumours, no myometrial invasion (on MRI)
A/E weight gain, edema, hyperglycemia, HTN, DVT
Response rate 60-70% - need regular surveillance (endometrial biopsy, D&C)
Do all young women with endometrial cancer need a BSO?
YES
• Concurrent ovarian pathology
• Synchronous ovarian primary (low grade endometrioid tumour), up to 25% (good prognosis)
• Ovarian metastases less likely (~3%)
NO
• Morbidity and mortality from early BSO
• Osteoporosis, CHD, lu and colorectal cancers
What are the consequences of receiving a premature oopherectomy?
For every 8 women who have a BSO and not receive HT, 1 will have adverse effect.
In other words, for HT, our NNT = 8
Is HT safe after endometrial cancer?
No difference in recurrence rates
Should women on tamoxifen be screened for endometrial cancer?
- Endometrial cancer risk ~ 2/1000 (2x)
- Other pathology more common
- Asymptomatic endometrial thickening >8mm
- Polyps
Annual screening not warranted if asymptomatic
Who is at decreased risk?
Multiparity OC >5 yrs Exercise Coffee Smoking (crazy but true)
Why is OC protective against Endometrial Cancer?
Progestin component of OC is protective
Pound in the point … what should Endometrial cancer tissue be evaluated for?
Lynch Syndrome
IHC
(immunohistochemistry)
What is the difference between XR for diagnostic vs therapeutic?
Diagnostic • Low dose • single exposure • Low energy • no change on tissue
Therapeutic • Dose is about 100x higher! • 1-35treatments/course • High energy • changes tissue
20 year-old G1P0 presents with abnormal vaginal bleeding
• “I think I am having a miscarriage”
• 9 weeks pregnant by LMP dating
• Significant nausea and vomiting over past month
• 14 week gestational size uterus
• No fetal heart heard
• Speculum exam reveals some blood in vagina, cervix closed.
Must consider Molar Pregnancy
