✓ 33- Benign and Malignant Ovarian Conditions Flashcards
What is the management/follow up plan for ovarian masses?
- < 5 cm → Doesn’t recquire follow up [likely physiological]
- 5-7 cm → Yearly US
- > 7 cm → further imaging and surgical intervention
What are the general types of ovarian masses?
- Functional
- Inflammatory
- Neoplastic
- Other
What are the functional ovarian masses?
- Follicular cyst
- Corpus Luteum cyst
- Theca Lutein cyst
What are the inflammatory ovarian masses?
- Tubo-ovarian masses
- Abscess
What are the neoplastic ovarian masses?
- Benign ovarian mass
- Borderline ovarian mass
- Malignant ovarian mass
What are the “other” type of ovarian masses?
Endometrima
Enlarged PCO
Parovarian cyst
Epidemiology of Ovarian Tumors
- 80% are benign
- cmost 20-45 yrs.
- High mortality in malignancies
- accounts for 27% of gynecologic cancer
- and accounts for 53% of deaths
- 75% are diagnosed with advanced stage
What are the risk factors for ovarian carcinoma?
- Nulliparity
- Family history
- Childhood gonadal dysgenesis
- Clomiphene
- Inheredited
What genes are responsible for Familial Ovarian Cancers?
BRCA1 [39%]
BRCA 2 [11%]
HNPCC- Mutations in mismatch repair genes
- MLH1
- MSH2
- MSH6
What cancers are associated with BRCA1 mutations?
- Breast
- Ovary
- Fallopian tube
- Colorectal
- Prostate
What cancers are associated with BRCA2 mutations?
- Breast
- Ovary
- Fallopian tube
- Pancreatic
- Gallbladder
- Bile Duct
- Gastric
- Melanoma
- Male Breast
- Prostate
What is the risk of Hereditary ovarian cancer in women? [General population, BRCA1, BRCA2, HNPCC]
- General Population: 1/70
- BRCA1: 20-40% [65%]
- BRCA2: 20-25%
- HNPCC: 9%
What are the different classification of Primary ovarian tumors?
- Surface/Mullerian Epithelial tumors
- Germ cell tumors
- Sex cord-stromall tumors
What is the frequency of each type of ovarian tumors?
- Surface/Mullerian Epithelial tumors
- 65-70%
- Germ cell tumors
- 15-20%
- Sex cord-stromall tumors
- 5-10%
- Metastasis
- 5%
What are the different types of Surface epithelial cell tumor?
- Serous [75-80%]
- Mucinous [8-10%]
- Endometrioid [10%]
- Clear cell [<1%]
- Brenner [<1%]
- Cystadenofibrma
What are the different types of Germ cell tumor?
- Teratoma
- Dysgerminoma
- Endodermal sinus
- Choriocarcinoma
What are the different types of Sex-cord stroma tumor?
- Fibroma
- Granulosa-theca cell tumor
- Sertoli-Leydig cell tumor
Describe the gross and microscopic features of borderline surface epithelial tumors?
Gross: cystic /solid foci
Microscopic:
- Papillary complexity
- Stratification
- Nuclear atypia
- No stromal invastion
Describe the gross and microscopic features of benign surface epithelial tumors?
Gross: mostly cystic
Microscopic:
- Cuboidal-Columnar epithelium
- Fine Papillae
- No stratification
- No nuclear atypia
- No stromal invastion
Describe the gross and microscopic features of malignant surface epithelial tumors?
Gross: mostly solid, and hemorrhage/necrosis
Microscopic:
- Papillary complexity
- Stratification
- Nuclear atypia/ Malignany cells in glandular pattern
- High mitotic activity
- Psammoma bodies
- Stromal invastion
What does the lining epithelium of serous tumors resemble?
Fallopian tube
What does the lining epithelium of mucinous tumors resemble?
- Intestinal → gastrointestinal mucosa
- Müllerian → endocervix
What does the lining epithelium of endometrioid tumors resemble?
Endometrial glands
What does the lining epithelium of brenner tumors resemble?
Bladder [transitional epithelium]
What does the lining epithelium of clear cell tumors resemble?
Mesonephric [renal cell]
General epidemiology of Serous tumors
- Most common in 4th/5th decades of life
- Most common cystic neoaplasm of ovary
- accounts for 75% of epithelial ovarian tumors
What are the different types of serous tumors and the incidence of each?
- Benign / Cystadenomas[60%]
- Borderline [15%]
- Malignant / Cystadenocarcinoma [25%]
How likely would both ovaries be affected in the different types of serous tumors
- Benign → 20%
- Borderline → 30%
- Malignanct → 65%
What factors would determine the prognosis of serous tumors?
- Stage of disease
- presence of peritoneal implants
Prognosis of Borderline Serous Cystadenoma
- Age: 20-50 yrs
- Bilaterally: 30%
- Prognosis: 100% 5yrs survival
Describe the histological appearance of ovarian cystadenofibroma
Well differentiated glands are embedded within a dense fibrous stroma
What type of ovarian tumors is the largest?
Mucinous tumors [mall fill entire abdominal cavity]
What is the condition may be associated with Endometrioid tumors?
Endometrial cancers [15-20%]
Describe the Gross and Morphological appearance of Endometrioid tumors
- May be cystic or solid
- Content tends to be hemorrhagic rather than serous or mucinous
T/F: Endometrioid tumors are benign.
False, almost all cases of Endometrioid tumors are malignant
What two other condition may be found in a patient with Endometrioid tumor?
- Concurrent endometrioisis [10-20%]
- Endometrial cancer [15-20%]
Describe clear cell tumors , in terms of its grade, malignancy and incidence
- Uncommon
- Agressive tumor
- Invariable high grade
- Mostly malignant
Describe the appearance of Clear cell tumors
clear, peg-like or hobnail-like cells
What is the precurosr of clear cell tumors?
in 1/4 of cases they arise from lining of benign endometrioid cyst
What other condition may a patient with clear cell tumor also complain of?
50-70% have endometriosis
What is the average age of incidence of Brenner tumor?
50 years
What signs maybe found in patients with Brenner Tumors?
- Sign of Hyperestronsim
- Post-menopausal bleeding from endometrial hyperplasia
- Ascites [rarely]
Describe the gross appearance of Brenner Tumor
- white to tan-yellow whorled cut surface
- Cystic spcaes and calcification [possible]
Describe the microscopic appearance of Brenner Tumors
- Epithelial cells: solid and cystic nests
- Resemble transitional epithelium
- Surrounded by abundant stroma.
T/F: Brenner tumor is described as a large and fast growing malignant tumor
False, its mostly benign and its slow growing with a variable size of 1-30 cm
What is the treatment of Borderline Brenner tumors?
Surgical removal
Define Malignant Brenner tumor
benign or borderline when coexisting with invasive transitional cell carcinoma
What are the prognostic factors in ovarian cancer?
- Stage of disease
- Volume of Residual disease post surgery
- Histological type and Grade of Tumor
- Age at presentation
What are the different complications of Ovarian tumors?
- Torsion
- Rupture
- Haemorrhage
- Infection
- Pseudomyxoma peritonei
- Malignancy
Describe the hematogenous spread of ovarian tumors?
- This spread at the time of diagnosis is uncommon
- Spead to lungs and liver in 2-3%
Describe the Lymphatic spread of ovarian tumors
- Pelvic LN: via broad ligament
- Inguinal LN: Retrograde dissemination via lymphatics → round ligament to → Inguinal LN
- Advanced stage disease
- Precaval/Paraaortic LN: follows ovarian vein
Describe the Transcoelomic pattern of spread of Ovarian tumors
- Most common & earliest mode by exfoliation of cells which implant along surfaces of peritoneal cavity
- Metastasis typically seen on POD, paracolic gutters, right hemidiaphragm, liver capsule, peritoneal surface of intestine & mesenteries, omentum
- It seldom invades intestinal lumen, but progressively agglutinates loops of bowel - functional intestinal obstruction and carcinomatous ileus
What is the tumor markers for Serous tumors?
- CEA
- CA-125
What are the tumor markers for Mucinous tumors?
- CA19-9
What are the tumor marker for Dysgerminoma?
- LDH
- ß-hCG
What are the tumor marker for Sertoli-Leydig tumors?
Testosterone
What are the tumor markers for Endodermal sinus tumors?
AFP
What are the tumor markers for Choriocarcinoma?
ß-hCG
What are the tumor markers for Teratomas?
AFP
What tumor markers are important for screenign gynecological malignancies?
- CA19-9
- CA-125
- CEA
When is CA-125 useful to use as a tumor marker?
Whn non-mucinous epithelial cancers are present
- found in 85% of patients with epithelialc ovarian cancers
Relevance of Ca-125 to cancer treatment
used to monitor response to therapy
What conditions are associated with a rise in CEA?
- Colonic carcinoma
- Ovarian carcinoma
What imaging modality is most useful to investigate ovarian tumors?
US is the most useful non invasive test for suspected malignancy
What is the indication for FNA as an investigative option for ovarian tumor?
For patients with advanced ovarian cancer who are medically unfit to undergo surgery permitting initiation of neoadjuvant chemotherapy (NACT)
What is the common origin of metastatic tumors of the ovary?
- Stomach [70%]
- Large bowel [15%]
- Breast [6%]
Describe the appearance of Krukenberg tumors
Bilateral tumors
Grossly:
- Smooth surface, slightly bossed, freely movable in pelvis
- No infiltration through the capsule
- No tendency to form adhesions
- Tumour retains the shape of normal ovary, with solid waxy consistency
Microscopic:
- cellular or myxomatous stroma, scattered “signet ring” mucin- secreting cells
What are the signs and symptoms of Sertoli-Leydig cell tumors?
Clinical virilisation in 70-85%
Signs of virilisation/defeminizing:
- oligomenorhoea
- amenorrhoea
- breast atrophy
- acne
- hirsuitism
- clitoromegaly
- deepening of voice
- receding hair line
What causes the virulizing effects seen in sertoli-leydig cell tumor?
The androgen produced by tumor cells
Epidemiology of Sertoli-Leydig cell tumor
- Rare (0.2% of ovarian cancers)
- Occur most frequently in 3rd or 4th decade [75% in women < 40 yrs]
- Unilateral
What is another name for Sertoli-Leydig cell tumors?
ARRHENOBLASTOMA
Describe the morphology of Sertoli-Leydig cell tumor
- Unilateral
- Recapitulates development of testis with tubules or cords and plump pink Leydig cells
What is Meig’s Syndrome?
Triad of:
- Solid ovarian mass
- Ascite
- Pleural effusion
Investigation of Thecomas
- Inhibin
- Oil Red O fat stains
T/F: Fibromas and Thecomas are both hormonally active tumors that secrete androgens.
False:
- Fibromas are hormonally inactive
- Thecomas secrete estrogen
Malignancies of Thecoma-Fibroma group
- Thecoma: pure thecomas are always benign
-
Fibroma: generally benign
- malignant transformation in 1% of cases
What group of woman would thecomas be found in?
Post-menopausal women in their 60s
What group of woman would fibromas be found in?
In perimenopausal and menopausal women
Describe the clinical picture of patients with Fibromas
- Ascites [40%]
- Meig’s syndrome [1%]
Describe the clinical picture of Thecomas
- Abnormal bleeding
- Pelvic mass
- Cystic disease of breast
What is the origin of fibromas?
Arises from spindle stromal cells that form collagen
Describe the appearance of thecomas
Cells resemle thecal cells
Adult GC
- common in postmenopausal
- Avg age is 50years
- Associated with ESTROGEN production.
- Endometrial hyperplasia ( 25-50%)
- endometrial Carcinoma (5-10%)
Juvenile GC
- 90% before puberty
- Mean age at diagnosis is 13 years.
- Menstrual irregularities
- amenorrhea
- precocious puberty.
- True GC tumors are low grade; confined to one ovary with EXCELLENT PROGNOSIS
- long term survival 75-90 %
T/F: Granulosa cell tumors are bilateral in 98% of cases
False only bilateral in 2% of cases
Describe the morphology fo Granulosa Cell tumors
Grossly:
- solid can be cystic
- cut surface is soft and yellow-tan
Microscopically:
- Mixture of cuboidal granulosa cells
- Scant cytoplasm
- “COFFEE BEAN” grooved nuclei
- spindled or plump lipid- laden theca cells
- Call-Exner bodies
What is the most common complication of Mature cystic Teratomas?
Torsion
What is Rokitansky’s protuberance?
A solid protuberance projecting from an ovarian cyst in the context of mature cystic teratoma. It often contains calcific, dental, adipose, hair, and/or sebaceous components
Malignancy and Mature Teratomas
< 1% undergo malignant transformation (commonly squamous cell ca)
Epidemiology of Mature Teratomas
- Almost 20% of all ovarian neoplasms:
- App 95% of all ovarian teratomas
- Age < 20 years
What are immature teratomas?
Malignant ovarian germinal tumor composed of mixture of immature embryonal and mature adult tissue derived from all three germ layers.
Epidemiology of Immature Teratomas
Usually children and adolescents
What determines the grade of immature teratomas?
Quantity of immature neural tissue alone determines grade
Describe Grade I and III of Immature teratomas
- Grade I: mature teratoma with only rare immature foci
- Grade III: large portion embryonal tissue with atypia and mitotic activity
Describe the appearance of immature teratomas
- immature neuroepithelium forming rosettes
- Maybe solid with a few cysts
- Rarely bilateral
What is struma ovarii?
Thyroid tumor group that can be either benign or malignant
- Dominant growth of thyroid tissue in a teratoma, sometimes to exclusion of other components
Epidemiology of Dysgerminoma
- Commonest malignant germ cell tumor (30 to 40% )
- 75% seen at 10 to 30 years of age
- Rare after 50yrs.
- Occur with gonadal dysgenesis
- Unilateral in 80%–90%
What pathology in the testis is similar to Ovarian Dysgerminoma?
Testicular seminoma
Malignancy and Dysgerminomas
All malignant- 1/3 metastasize
Treatment of Dysgerminomas
80% cure rate
- All radiosensitive and chemosensitve
What is Dysgerminoma?
Consists of germ cells that have not differentiated to embryonic or extraembryonic structures
Describe the morphology of Dysgerminomas
- Sheets or cords of large clear cells
- stroma may contain lymphocytes and occasional granulomas
What is the significance of AFP in endodermal sinus tumors?
correlates extent of disease & monitoring treatment
Epidemiology of Endodermal Sinus tumor
- 3rd most frequent malignant GCT
- Median age 16 – 18 yrs
- Unilateral in 100 %
Clinical picture of Yolk sac tumor
- Abdomen or pelvic pain (75 %)
- Asymptomatic pelvic mass (10%)
Malignancies of Endodermal sinus tumors
Highly aggressive, and associated with other GCT
Describe the morphology of Yolk Sac tumors
Gross:
- Soft-Grayish brown mass with cystic areas
Microscopic:
- Schillar Duval bodies with central capillary and mantle of endoderm
- Extracellular hyaline droplet
Choriocarcinomas
- Malignant tumor of the ovary with trophoblastic differentiation composed of syncytiotrophoblast and cytotrophoblast
- Resistant to chemotherapy
- High HCG
Embryonal carcinomas
- Most malignant but rare (4%)
- Homologous to the embryonal carcinoma of adult testis.
- 47% prepubertal at diagnosis
- 43% may present with hormonal abnormalities
- precocious puberty, vaginal bleeding etc
What is pseudomyxoma peritonei?
Mucinous tumors may involve the peritoneal surface with collection of extensive mucinous material resembling cystic contents within the peritoneal cavity.
- A rare condition
- Seen with primarily borderline or malignant neoplasms.
Describe the gross and microscopic morphology of Malignant Mucinous tumors
Gross:
- Solid with some mucin-containing cystic spaces
- Thickened cyst wall
- Hemorrhage + necrosis
Microscopic:
- Cell atypia
- Increased layering
- Gland complexity
- Papillae
- Areas of stromal invasion
Epidemiology of Malignancy Mucinous tumors
Age:c40-70 yrs
Bilateral: 5-15%
Describe the gross and microscopic appearance of benign mucinous tumor
Gross:
- Multiloculated
- Mucoid fluid
Microscopic:
- Lined by a single layer of tall columnar mucinous epithelium without cilia.
What complications arise from rupture of mucinous ovarian tumors?
- pseudomyxoma peritonei
- adhesion formation
What type of epitheliums line mucinous tumors?
- intestinal epithelium (intestinal type) - more frequently
- columnar epithelium (mullerian mucinous tumors)
Describe the gross appearance of mucinous tumors
- Honey cob appearance [cut surface]
- Cystic tumor
What genes are mutated in Lynch Syndrome?
HNPCC- Mutations in mismatch repair genes
- MLH1
- MSH2
- MSH6
Lynch Syndrome
- ~7% of hereditary ovarian cancer cases
- Predominance of early onset proximal colon cancer, ca ovary and endometrium.
Inherited vs. Sporadic Ovarian cancers
Inherited familial ovarian cancers occur 10 years younger than sporadic
What is the pattern of inheritance of familial ovarian cancers?
AD
