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11/11- Ovarian Neoplasms/Pathology Flashcards

1
Q

What is DDx for pelvic pain and ovarian mass?

A
  • Ectopic pregnancy
  • Ovarian cancer
  • Endometriosis
  • Many more
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2
Q

What do you need to determine in the patient history?

  • Age criteria
A

Who

  • Patient history
  • Age (pre vs. post-menopausal)
  • Past medical/surgical history
  • Menstrual history (including LMP)

Symptoms:

  • Pain, bloating, bowel habits, etc.

When/how long

  • Duration of symptoms Why - History (past med/surg, family)
  • Lab studies
  • Routine labs (CBC, Chem 7)
  • Tumor markers
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3
Q

What parts of the physical exam are especially important in OB/GYN?

A
  • Pelvic exam
  • Rectovaginal exam
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4
Q

What are best imaging modalities for ovaries?

A
  • Ultrasonography
  • MRI (CT scan not so great)
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5
Q

What are main considerations in adnexal symptoms you want to determine/rule out?

A
  • Ectopic pregnancy
  • Infection

ALWAYS RULE THESE OUT

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6
Q

What factors increase the risk of malignancy in ovarian masses?

A
  • Large size
  • Bilaterality
  • Solid vs. cystic
  • Radiologic appearance:
  • Complex, papillary, high density, low pulsatility of blood flow
  • Age of pt. outside reproductive span
  • Ascites
  • Elevated serum tumor markers (CA125)
  • Not specific for ovarian cancer (benign neoplasm, endometriosis, PID…)
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7
Q

What are some gynecologic conditions which increase CA125? (don’t memorize)

A
  • PID
  • Adenomyosis
  • Benign ovarian neoplasm/cyst
  • Endometriosis
  • Menstruation
  • Ovarian hyperstimulation
  • Fibroids
  • Cancer
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8
Q

What are some non-gynecologic conditions which increase CA125? (don’t memorize)

A
  • Hepatitis/liver disease/cirrhosis
  • Pancreatitis
  • CHF
  • Diverticulitis
  • Lupus
  • Pneumonia
  • Mesothelioma
  • Metastatic cancer
  • Tuberculosis
  • ANY condition which irritates peritoneal lining
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9
Q

In women under __ yo, elevated CA125 is associated with malignancy less than ___% of the time

A

In women under 50 yo, elevated CA125 is associated with malignancy less than 25% of the time

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10
Q

What is the general treatment algorithm for ovarian masses?

A
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11
Q

What are indications for surgery with adnexal masses?

A
  • Cyst > 5 cm (persistent)
  • Solid
  • Papillary appearance on sonography
  • Initial size > 10 cm
  • Ascites
  • Age of patient outside reproductive range
  • Torsion or rupture suspected
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12
Q

What is the DDx for benign neoplasms? (don’t memorize)

A
  • Functional or corpus luteal cysts
  • Theca lutein cyst
  • Dermoid/cystic teratoma
  • Paraovarian cyst
  • Serous or mucinous cystadenoma
  • Endometrioma
  • Adenofibroma
  • Brenner tumor
  • Polycystic ovary
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13
Q

What is the DDx for malignant tumors? (don’t memorize)

A
  • Serous or mucinous cystadenocarcinoma
  • Endometrioid carcinoma
  • Immature teratoma
  • Dysgerminoma
  • Endodermal sinus tumor
  • Granulosa cell tumor
  • Sertoli-Leydig tumor
  • Choriocarcinoma
  • Malignant Brenner tumor
  • Malignant gonadoblastoma
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14
Q

What is the flowchart for management of adnexal mass in reproductive age females?

A

Rule out pregnancy and infection!!

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15
Q

What is the flowchart for management of adnexal mass in postmenopausal females?

A
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16
Q

What are some benign ovarian masses (covered in this lecture)?

A
  • Functional (Follicular) cysts
  • Polycystic Ovarian Syndrome (PCOS)
  • Corpus luteum cysts
  • Endometrioma
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17
Q

What is the most common cystic mass in women of reproductive age?

A

Functional (follicular) cyst

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18
Q

Describe functional (follicular) cysts

  • Benign vs. malignant
  • Size
  • Types
  • Prognosis
  • Treatment
A
  • Benign ovarian mass
  • Most common cystic mass in reproductive-age women
  • Rarely >6 cm
  • Cystic follicles very common (< 2cm )
  • Follicular cyst > 2 cm
  • Pelvic pain
  • Multiple cysts can be seen in polycystic ovarian syndrome

Prognosis

  • Spontaneously resolve
  • May rupture or undergo torsion

Prevention: hormonal contraception

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19
Q

What is seen here?

A

Functional (Follicular) cysts

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20
Q

What is seen here?

A

Functional (Follicular) cysts

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21
Q

What is seen here?

A

Functional (Follicular) cysts

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22
Q

What is Polycystic Ovarian syndrome?

  • Aka
  • Prevalence
  • Symptoms
  • Associated conditions
A
  • Formerly called “Stein Levinthal syndrome”
  • 6-10% of reproductive age women
  • Hyperandrogenism, menstrual abnormalities, chronic anovulation, decreased fertility
  • Associated with obesity, Type 2 diabetes
  • Polycystic ovaries: multiple cystic follicles
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23
Q

What is seen here?

A

Polycystic ovaries

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24
Q

What is seen here?

A

Polycystic ovary

  • Many follicular cysts in different stages of development
  • Medulla is the internal part with many blood vessels
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25
Q

What are corpus luteum cysts

  • Age group
  • Size
  • Prognosis
  • Appearance
A
  • Seen in reproductive age women
  • Usually < 5 cm
  • Self-resolving
  • May hemorrhage or undergo torsion
  • Yellow rim
  • May have central hemorrhage
  • May become large, rupture and cause a peritoneal reaction
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26
Q

What is seen here?

A

Corpus luteum cysts

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27
Q

What is seen here?

A

Corpus luteum

  • Luteinized granulosa cells
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28
Q

What is an endometrioma (broadly)?

A

Cysts associated with endometriosis

  • Can fill with blood and become “chocolate cyst”
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29
Q

What is seen here?

A

Endometrioma

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30
Q

What is endometriosis?

  • Definition
  • Age group
  • Location
  • Signs/symptoms
A

Definition: Endometrial glands and stroma outside the uterus

  • Reproductive age group
  • Sites: Ovary, cul-de-sac, peritoneal surfaces, bowel wall, distant sites

Signs and symptoms:

  • Dysmenorrhoea
  • Pelvic pain
  • Infertility
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31
Q

What tumor types arise in endometriosis?

A
  • Endometrioid carcinoma
  • Clear cell carcinoma
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32
Q

What is seen here?

A

Chocolate cyst of the ovary

  • Ovary distended and filled with blood; chronic process
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33
Q

What is seen here?

A

Triad of endometriosis

  1. Endometrial glands
  2. Stroma
  3. Hemosiderin-laden macrophages
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34
Q

Ovarian cancer is the #__ cancer cause of death in women

A

Ovarian cancer is the #5 cancer cause of death in women

(1. lung, 2. breast, 3. colorectal, 4. pancreas)

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35
Q

Epidemiology of ovarian cancer

  • General risk of development
  • Burden of disease
  • Incidence increases with ___
  • Stage of presentation
A
  • General risk of developing ovarian cancer: 1.8% (1:56 women)
  • Burden of disease is greater in developed countries
  • Incidence increases with age
  • Almost 75% of cases present with advanced stage III / IV disease
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36
Q

T/F: Incidence of ovarian cancer has increased in recent history

A

False

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37
Q

What ethnic group is most affected by ovarian cancer?

A

Caucasians

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38
Q

What are risk factors for ovarian cancer?

A
  • Age; peak age: 56-60 years old
  • Family history of ovarian cancer (important)
  • BRCA mutation
  • Never pregnant or given birth
  • Incessant ovulation
  • History of endometriosis
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39
Q

What are the clinical features/symptoms of ovarian cancer?

A

Very vague; that’s why they’re typically diagnosed so late stage

  • Abdominal distention
  • Ascites
  • Abdominal pain/discomfort
  • Bowel obstruction
  • Nausea/vomiting
  • Altered bowel habits
  • Urinary frequency/retention
  • Bloating
  • Early satiety
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40
Q

Describe the growth pattern of ovarian cancer

  • Methods of spread
A
  • Main mode of spread is by implantation on peritoneal surfaces
  • Lymphatic spread also important
  • Omentum usually involved
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41
Q

How is diagnosis of ovarian cancer performed?

A
  • Physical exam
  • Pelvic US/CT scan
  • Tumor markers: CA125, CEA
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42
Q

What are the different types of ovarian cancer?

A
  • Surface epithelium-stroma (95%)
  • Serous, mucinous, endometrioid, clear cell, transitional cell
  • Germ cells
  • Dysgermimoma, yolk sac, embryonal carcinoma, choriocarcinoma, teratoma
  • Sex cord (spindle cell)-stroma
  • Granulosa cell, thecoma, fibroma*, Sertoli cell, Sertoli-Leydig, steroid
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43
Q

What are the main types of primary ovarian neoplasms in the surface epithelial category?

A

Surface epithelial

  • Serous (resembles Fallopian tube)
  • Mucinous (mucin in cytoplasm)
  • Endometrioid (resembles endometrial ep)
  • Clear cell (clear cytoplasm)
  • Transitional cell (resemble cells of urothelium)

Further subdivided into:

  • Benign
  • Borderline
  • Malignant
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44
Q

What are the main types of primary ovarian neoplasms in the sex cord stromal category?

A

Sex cord stromal

  • Granulosa cell tumor
  • Sertoli-Leydig cell tumor
  • Fibrothecoma
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45
Q

What are the main types of primary ovarian neoplasms in the germ cell category?

A

Germ cell

  • Teratoma
  • Dysgerminoma
  • Yolk sac tumor
  • Mixed
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46
Q

What is the most common form of ovarian cancer?

A

Epithelial (85-90%)

(other slide said 95%)

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47
Q

Describe epithelial ovarian cancer

  • Signs
  • Associated with what
  • Age of diagnosis
  • Stage of diagnosis
A
  • Most common form (85-90%)
  • Elevated CA125
  • Associated with hereditary/genetic syndromes
  • Diagnosed between 40-65 yo
  • Usually diagnosed at advanced stages due to non-specific symptoms
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48
Q

Define the following categories of surface epithelial tumors of the ovary:

  • Benign
  • Borderline
  • Malignant
A
  • Benign: no or minimal cell proliferation
  • Borderline: cellular proliferation and atypia but no stromal invasion
  • Malignant: stromal invasion
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49
Q

What percentage of surface epithelial tumors of the ovary are benign?

A

80%

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50
Q

The majority of malignant epithelial tumors of the ovary are what type?

A

High grade serous carcinomas

  • Poor prognosis – due to late detection
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51
Q

Who is screened for ovarian cancer?

A

Patients with family history

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52
Q

Describe serous tumors of the ovary

  • __% of all ovarian tumors
  • __% of all ovarian cancers
  • Uni or bilateral
  • Subtypes
  • Malignant types
A
  • 30% of all ovarian tumors
  • 40% of all ovarian cancers
  • Bilateral in up to 60% patients
  • Benign, borderline, malignant

Malignant

  • Low grade serous carcinoma
  • High grade serous carcinoma
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53
Q

The low-grade serous carcinoma arises how? High grade?

A

- Low grade:

  • Cystadenoma/endometriosis
  • Progresses to borderline tumor and then low-grade serous carcinoma

- High grade arises de novo;

  • Fallopian tube forms STIC and get into ovary during ovulation to form inclusion cyst
  • No borderline or benign precursor
54
Q

What is seen here?

A

Serous cystadenoma

55
Q

What is seen here?

A

Serous borderline tumor

  • Epithelial proliferation but no stromal invasion
56
Q

Compare/contrast low grade vs. high grade serous carcinomas: age

A
  • Low grade: reproductive age
  • High grade: post-menopausal
57
Q

Compare/contrast low grade vs. high grade serous carcinomas: origin

A
  • Low grade: borderline tumors
  • High grade: de novo/STIC; arises from fallopian tube/cortical inclusion cysts of ovary
58
Q

Compare/contrast low grade vs. high grade serous carcinomas: histology

A

Low grade:

  • Mild atypia and pleomorphism
  • Low mitotic count
  • Psammoma bodies

High grade:

  • Marked atypia and pleomorphism
  • High mitotic count
  • Psammoma bodies
  • Multinucleation
  • Necrosis
59
Q

Compare/contrast low grade vs. high grade serous carcinomas: behavior

A

Low grade:

  • Progress slowly
  • Chemoresistant

High grade:

  • Progress rapidly
  • Chemosensitive
60
Q

Compare/contrast low grade vs. high grade serous carcinomas: molecular pathogenesis

A

Low grade

  • KRAS
  • BRAF
  • ERBB2 mutations

High grade:

  • TP53 mutations
  • BRCA1 and BRCA2 mutations (inherited)
61
Q

What is seen here?

A

Low grade serous carcinoma

62
Q

What is seen here?

A

Bilateral high grade serous carcinoma

63
Q

What is seen here?

A

High grade serous carcinoma

  • Pink areas are necrosis
  • Loses differentiation; no longer looks like Fallopian tube epithelium
64
Q

Compare serous and mucinous tumors of the ovary in terms of their uni/bilaterallity

A
  • Most serous tumors (especially the malignant ones) are bilateral
  • Most mucinous tumors are unilateral
65
Q

Describe mucinous tumors of the ovary

  • ___% of all ovarian tumors
  • Uni or bilateral
  • Size
  • Subtypes
  • Location
  • Spread
  • Molecular pathogenesis
A
  • 10-25% of all ovarian tumors
  • Majority are unilateral (>95%)
  • Largest of all ovarian tumors
  • Benign, borderline, malignant
  • Confined to the ovary in most cases
  • Mucinous carcinomas that spread outside the ovary tend to be fatal
  • Harbor KRAS mutations
66
Q

What is seen here?

A

Mucinous (?)

67
Q

What is seen here?

A

Mucinous borderline tumor

68
Q

What is seen here?

A

Mucinous carcinoma

  • Apical mucin
  • Very abnormal nucleus
  • Stromal invasion
69
Q

Describe endometrioid tumors of the ovary

  • __% of all ovarian tumor
  • Uni or bilateral
  • Subtypes
  • Associations
  • Mutations
A
  • 10-15% of all ovarian tumors
  • Bilateral in 40% (so more unilateral)
  • Benign and borderline tumors uncommon
  • Endometrioid carcinoma resembles endometrioid carcinoma of the endometrium
  • Associated with endometriosis in 15-20% cases
  • Mutations similar to those seen in endometrioid endometrial carcinomas
  • Synchronous tumors can occur (involving endometrium of uterus and ovary)
70
Q

What is seen here?

A

Endometrioid adenocarcinoma (of the ovary)

  • Glands will give rise to squmous epithelium (VERY unique to endometrioid tumors)
71
Q

Describe clear cell tumors of the ovary

  • Subtypes (and how common)
  • Associations
  • Microscopic features
A
  • Benign and borderline extremely rare
  • Carcinoma is usually seen
  • 1/3 arise in endometriosis

Microscopy:

  • Solid, cystic, tubular and papillary growth patterns
  • Cells with clear cytoplasm, marked atypia
72
Q

What is seen here?

A

Clear cell carcinoma

73
Q

Describe Transitional cell tumors of the ovary

  • Subtypes
  • Gross and microscopic appearance
A
  • Brenner tumor: composed of neoplastic cells resembling urothelium
  • Borderline and malignant Brenner extremely rare (most commonly benign)
  • Gross: solid and yellow
  • Microscopy: Nests of transitional cells in a fibrous stroma
74
Q

What is seen here?

A

Brenner tumor

75
Q

Recall: what are the subtypes of sex cord stromal tumors?

A
  • Granulosa cell
  • Sertoli-Leydig cell
  • Fibrothecoma
76
Q

Describe sex cord stromal tumors of the ovary

  • Prevalence
  • Age group
  • Production
  • Symptoms
A
  • Rare malignancies
  • More common in younger women
  • May elaborate hormones
  • Patients may have effects of hormone production
  • Virilization with androgens
  • Precocious puberty, endometrial hyperplasias and carcinoma with estrogens
77
Q

Describe sex cord tumors of the ovary

  • Uni or bilateral
  • Cystic or solid
  • Therapy
  • Tumor marker
A
  • Unilateral in >95% patients
  • Usually solid tumors
  • Very chemosensitive
  • Fertility sparing surgery in young women
  • Tumor marker: Inhibin (granulosa cell tumor)
78
Q

What are the 2 types of granulosa cell tumors?

A
  • Adult (peri-postmenopausal women): 95%
  • Juvenile (adolescents)
79
Q

Describe granulosa cell tumors

  • Production
  • Solid or cystic
  • Cell appearance
  • Recurrence potential
  • Lab markers
A
  • May produce estrogen, less commonly androgens
  • Can be solid or cystic
  • Cells resemble granulosa cells of the ovarian follicle (CALL–EXNER bodies)
  • Cells uniform with grooved nuclei “coffee bean appearance”
  • Can have malignant behavior
  • Potential for late recurrences
  • Increased levels of serum INHIBIN
80
Q

What is seen here?

A

Granulosa cell tumor

  • Call-Exner body (very diagnostic for granulosa cell tumors
  • Grooves in center of cell (coffee bean apperance)
81
Q

Describe Sertoli-Leydgi cell tumor

  • Prevalence
  • Symptoms
  • Age group
  • Gross appearance
  • Histology
  • Prognosis
A
  • Rare, often functional
  • Masculinization, defeminization
  • Younger women, 3rd and 4th decade
  • Solid: yellow or golden- brown
  • Histology: Dual cell population
  • Sertoli cells and Leydig cells
  • 5% recur or metastasize
82
Q

What is seen here?

A

Sertoli-Leydig cell tumor

  • Sertoli tubules
  • Leydig cells: more eosinophilic

Two cell population + masculinization of pt is strongly diagnostic for this tumor

83
Q

Describe fibroma and thecoma

  • Age group
  • Benign vs. malignant
  • Uni vs. bilateral
  • Gross appearance
  • Production
  • Microscopic appearance
A
  • Older women
  • Benign solid firm tumors
  • Unilateral
  • Grossly:
  • White: fibroma
  • Yellow: thecoma
  • Mixed: fibro-thecoma
  • Fibroma is hormonally inactive; thecoma may produce estrogen
  • Microscopically:
  • Fibroma: Fibrous tissue with collagen
  • Thecoma: Spindle cells with lipid
84
Q

What is seen here?

A

Fibroma-thecoma (?)

85
Q

What is seen here?

86
Q

What is seen here?

87
Q

Recall: what are the subtypes of germ cell ovarian tumors?

A
  • Teratoma
  • Dysgerminoma
  • Yolk sac tumor
  • Mixed
88
Q

Describe germ cell tumors of the ovary

  • Prevalence
  • Main subtype
  • Age group
  • Symptoms
  • Treatment
A
  • 15-20% of all ovarian neoplasms
  • Majority are mature cystic teratoma seen in women of reproductive age group
  • Remainder seen in children and young women; tend to be malignant (5%)
  • Patients present with abdominal/pelvic pain, mass
  • Very chemosensitive
89
Q

What serum tumor markers are elevated in different germ cell tumors?

A
  • LDH – Dysgerminoma
  • HCG – Choriocarcinoma, embryonal carcinoma
  • AFP – endodermal sinus tumor, embryonal carcinoma
90
Q

What are the different lines of differentiation for germ cell tumors:

  • Towards oogonia
  • Towards extraembryonic yolk sac
  • Towards placenta
  • Towards multiple germ layers
A
  • Towards oogonia: dysgerminoma
  • Towards extraembryonic yolk sac: yolk sac tumor
  • Towards placenta: choriocarcinoma
  • Towards multiple germ layers: teratoma
91
Q

What are the subtypes of teratoma?

A
  • Mature (usually benign)
  • Immature (malignant)
  • Monodermal/highly specialized
92
Q

What are features of mature/benign teratomas?

A
  • Mature elements from all 3 germ cell layers
  • Rare somatic malignancies eg. Squamous cell carcinoma
93
Q

What are features of immature/malignant teratomas?

A

Immature elements usually immature neuroepithelium

94
Q

What are features of monodermal/highly specialized teratomas?

A

Most common types

  • Struma ovarii (thyroid predominant)
  • Carcinoid
95
Q

What is seen here?

A

Mature cystic teratoma

96
Q

What is seen here?

A

Dermoid cyst

97
Q

What is seen here?

A

Mature teratoma

  • MANY different tissue types (cartilage, thyroid tissue, adipose, salivary gland, respiratory epithelium…)
98
Q

What is seen here?

A

Immature teratoma

  • Immature elements (neuroepithelium)
99
Q

Describe dysgerminoma

  • Seen in what pts
  • Gross and microscopic appearance
  • Lab markers
  • Treatment
A
  • Ovarian counterpart of testicular seminoma
  • Most common malignant germ cell tumor
  • Seen in patients with gonadal dysgenesis
  • Gross: Solid fleshy tumor
  • Microscopy:
  • Large cells with abundant cytoplasm, large nuclei and prominent nucleoli
  • Lymphocytic infiltration
  • Serum LDH levels markedly increased
  • Excellent response to chemotherapy
100
Q

What is seen here?

A

Dysgerminoma

101
Q

What is seen here?

A

Dysgerminoma

102
Q

Describe yolk sac tumors

  • Aka
  • Prevalence
  • Age group
  • Symptoms
  • Gross and microscopic appearance
  • Lab markers
  • Treatment
A
  • aka endodermal sinus tumor
  • Rare neoplasm seen in children and young women
  • Rapidly enlarging pelvic mass
  • Gross: solid fleshy tumor
  • Microscopy:
  • Variety of histologic patterns
  • SCHILLER-DUVAL BODY
  • Serum α- fetoprotein levels (AFP) markedly increased
  • Excellent response to chemotherapy
103
Q

What is seen here?

A

Yolk sac tumor

  • Schiller-Duval body: central space filled with blood surrounded by cells that radiate outward
  • Anastomosing channels filled with blood
104
Q

What are the most common metastases to the ovary:

  • Mullerian origin
  • Extra-Mullerian origin
A

Most are Mullerian!

  • Uterus
  • Tubes
  • Peritoneal surfaces

Extra-Mullerian: may precede detection of primary, may mimic primary ovarian tumors

  • Colon
  • Breast
  • Appendix
  • Stomach (esp young women)
  • Pancreas and biliary tract
105
Q

What is a Krukenberg tumor (broadly)?

A

Unique pattern of mets involving bilateral ovaries

106
Q

Describe Krukenberg tumor

  • Age group
  • Origin
  • Histologically
  • Method of spread
  • Prognosis
A
  • Young women
  • Mostly gastric origin
  • Mucin-producing signet ring cells
  • Trans-coelomic route of spread
  • Death within one year of diagnosis
107
Q

What is seen here?

A

Krukenburg tumor

  • Bulky, white/opaque masses
108
Q

What is seen here?

A

Krukenberg tumor

  • Signatory cells filled with mucin (giving pale blue color)
109
Q

What is the treatment for ovarian cancer?

A

Surgery

  • Hysterectomy/BSO/Staging
  • Tumor reduction (residual tumor ≤1 cm in maximum diameter)
  • Consider fertility sparing surgery for young women

Chemotherapy

  • Neoadjuvant or Adjuvant
  • Salvage for recurrent disease

Radiation

  • Limited role
110
Q

Describe staging of ovarian cancer

A
  • Stage I: confined to ovaries (20%)
  • Stage II: confined to pelvis (5%)
  • Stage III: confined to abdomen/lymph nodes (58%)
  • Stage IV: distant mets (17%)
111
Q

CA125 is more helpful in what age groups with suspected tumor?

A

Post-menopausal (it’s more a marker of epithelial tumors; others may be more possible in younger population)

112
Q

What is the rate or survival for the stages of ovarian cancer?

A
  • Stage I: 89%
  • Stage II: 66%
  • Stage III: 34%
  • Distant mets: 18%
113
Q

__% of ovarian cancer is familial

  • Hereditary ovarian cancer occurs approximately ____ than non-hereditary tumors
A

8-10% of ovarian cancer is familial

  • Hereditary ovarian cancer occurs approximately 10 yrs earlier than non-hereditary tumors
114
Q

What are some inherited syndromes of ovarian cancer?

A
  • Lynch Syndrome
  • Hereditary Breast and Ovarian Cancer Syndrome (HBOC)
115
Q

What is Lynch syndrome?

  • Aka
  • What cancers are involved
  • __% lifetime risk of ovarian cancer
  • Accounts for __% of all ovarian cancers
  • Mutations to look for
A

Aka HNPCC (hereditary non-polyposis….)

  • Early onset colon, uterine, and ovarian cancers
  • 3-14% lifetime risk of ovarian cancer
  • Accounts for 1% of all ovarian cancers
  • Evaluate for MSH2, MLH1, PMS1, or PMS2 mutations
116
Q

What is Hereditary Breast-Ovarian Cancer Syndrome (HBOC)?

  • Incidence
  • __% of ovarian cancers are due to __ mutations
  • Pattern of inheritance; penetrance
  • Genes/mutations involved and associated risks
A

Incidence

  • General: 1/500-1000
  • Ashkenazi Jewish: 1/40 10-14% of ovarian cancers due to BRCA mutations Genetics:
  • Autosomal dominant inheritance with 85% penetrance
  • BRCA1 – up to 44% risk of ovarian cancer
  • BRCA2 – up to 27% risk of ovarian cancer
  • BRCA 1 and 2 – 65-75% risk of breast cancer
117
Q

What are the mechanisms of inherited syndromes of ovarian cancer?

A
  • BRCA regulates p53 (tumor suppressor gene)
  • Loss of BRCA allows DNA damage to accumulate via loss of function of p53
  • Other mechanisms involving different pathways
  • Loss of function of at least one BRCA somatic allele in 30-70% sporadic breast/ovarian CA
118
Q

Describe methods for BRCA testing

  • When should it be done
A

Mouth swab or blood test

  • Family or personal history of breast cancer
119
Q

What is Lynparza (Olaparib)?

A

First FDA approved PARP inhibitor for pts with BRCA-mutated advanced ovarian cancer who have been treated with 3+ lines of chemotherapy

120
Q

What screening should be done for ovarian cancer?

A

No recommended screening tool exists

  • Physical exam: most ovarian cancer not detected before Stage III or IV
  • Imaging: no imaging technique can definitively diagnose or rule out ovarian malignancy
  • Serologic testing: no serum marker with sufficiently high sensitivity or specificity, especially in early stage cancer
121
Q

What screening studies have been done for ovarian cancer? Ongoing?

A
  • Prostate, Lung, Colon, Ovarian Cancer Screening (PLCO) trial: NCI (CA-125 + TV-US)
  • Many false positives
  • Too many underwent unneeded surgery
  • Thus CA125 and TVUS is not great for screening general population
  • Risk of Ovarian Cancer Algorithm (ROCA)
  • Looking at CA125 levels and trends (rather than cutoff value)
  • If high risk features in pts, following CA125 trend could help find ovarian cancer early
  • Study not too robust

In progress:

  • UK Collaborative Trial of Ovarian Cancer Screening (TV-US vs. multimodal – ROCA screening)
  • Other tumor biomarkers – HE4, MMP7, CA72.4
122
Q

Describe cancer screening for BRCA individuals

A
  • CA125 with pelvic ultrasound between:
  • 30-35 yo OR
  • 5-10 yrs prior to earliest age of ovarian cancer in family
  • Clinical breast exam 2X/yr with annual mammogram and breast MRI at age 25 or sooner based on earliest age onset in family
123
Q

What are methods of cancer prevention in BRCA individuals?

A
  • Remove ovaries by 40 years old or upon completion of childbearing -> reduces risk of ovarian cancer by 85-90% and breast cancer by 40-70%
  • Prophylactic mastectomy decreases risk by 90-95%
124
Q

What are protective factors against ovarian cancer?

A
  • Pregnancy
  • Use of birth control pills for >5 years
  • Breast feeding
  • Tubal ligation/hysterectomy
  • Bilateral salpingectomy
  • Prophylactic oophorectomy
125
Q

Case 1)

  • 23 yo female presents with 2 days of sharp cramping pelvic pain.
  • Pelvic exam notes a 3 cm mobile left adnexal mass.

What is your next step?

A. CT scan

B. Surgery

C. UPT

D. Observation

E. Ultrasound

A

A. CT scan

B. Surgery

C. UPT- in young reproductive-aged women, always rule out pregnancy first!

D. Observation

E. Ultrasound

126
Q

Case 1 cont’d)

  • US describes a 2.5 cm cystic mass arising from the L ovary, suggestive of a benign endometrioma. Her pain improves with ibuprofen.

What are your treatment recommendations?

A. Immediate surgery since she is having pain

B. Repeat US in 4-6 wks

C. Referral togyn oncologist

D. CT scan to confirm endometrioma

A

A. Immediate surgery since she is having pain

B. Repeat US in 4-6 wks- this is okay since pain is controlled

C. Referral togyn oncologist

D. CT scan to confirm endometrioma

127
Q

Case 1 cont’d)

  • She presents to your office 4 wks later with pain that has ben worsening over the past 5 days, not relieved with ibuprofen.
  • UPT is negative
  • Repeat US notes a 5 cm complex L adnexal mass with moderate free fluid in pelvis. She has rebound and guarding on pelvic exam.

What is your next step? Why?

A. Narcotic medicaiton and see if her pain improves

B. Surgery

C. Reassure, send home, and return in 4 wks

A

A. Narcotic medicaiton and see if her pain improves

B. Surgery- this is probably benign, but now a cyst or something has ruptured; due to pain and rebounding guarding with other symptoms, need surgery

C. Reassure, send home, and return in 4 wks

128
Q

Case 2)

  • 56 yo present with abdominal bloating and pain
  • Abdominal exam notable for fluid wave
  • CT scan is concerning for omental caking and bilateral adnexal masses

Which tumor marker is most likely to be elevated?

129
Q

Case 2 cont’d)

  • She is taken to surgery
  • Shows bilateral masses
  • (Need picture)

What is your diagnosis?

A. Metastatic gastric carcinoma

B. Dysgerminoma

C. Sertoli Leydig tumor

D. High grade serous ovarian carcinoma

A

A. Metastatic gastric carcinoma

B. Dysgerminoma- more unilateral

C. Sertoli Leydig tumor- mixture of populations

D. High grade serous ovarian carcinoma- poorly differentiated epithelial cells

130
Q

Case 2 cont’d)

  • Surgery confirms stage IIIC high grade srous ovarian carcinoma
  • Post-op she asks you how she coudl have prevented. SHe is worried about her 2 sisters and her daughter

What screening tests do you recommend?

A. Annual pelvis US

B. Annual CA125

C. Pelvic US and CA125 testing every 1-2 yrs

D. None. There are no definitive screening tests at this time

A

A. Annual pelvis US

B. Annual CA125

C. Pelvic US and CA125 testing every 1-2 yrs

D. None. There are no definitive screening tests at this time

  • Although now recommended that all ovarian cancer pts udnergo BRCA testing regardless of family history
131
Q

Case 2 cont’d)

  • She tests positive for BRCA

What do you recommend for sisters and daughters?

A. BRCA testing

B. MSH/MLH testing of her tumor

C. ckit tumor testing

D. BCR/ABL mutation testing

A

A. BRCA testing- if positive, can take methods to reduce risks

  • Semiannual breast exams
  • Annual mammogram/breast MRI
  • CA125/US screaning
  • More…

B. MSH/MLH testing of her tumor

C. ckit tumor testing

D. BCR/ABL mutation testing

a_GYNGU (17 decks)

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