Ovarian Cancer and Ovarian Cysts😊

Types of Ovarian Cancer (WHO Classification)

Metastatic tumor:

p53 and Gyne Cancers

• Ca Cervix
• E6 → P53
• E7 → Rb gene

• Ca Ovary
• Serous cystadenocarcinoma
• p53 (90%) m/c
• BRCA1 (10%)

• Type 2 Endometrial Ca

m/c ovarian tumor a/w

• Endometriosis:
• Clear cell Ca > endometrioid tumor.
• Endometriosis → Clear the problem

• Endometrial Ca:
• Endometrioid tumor > granulosa cell tumor.
• Oid → tumor

Note

• Only 2 solid benign tumors of ovary
• Brenner
• Fibroma

• Mnemonic: Solid FiBre (Fibroma, Brunners)

Screening of Ovarian Cancer

• Not done universally.

• Indication:
• H/o familial ovarian Ca (10%).
• Family history (1st degree relative):
• Occurs a decade earlier (5th decade).
  ↓

• BRCA gene 1/2 testing
  
  ↓ (if positive)

• Perform TAH + BSO once family is complete OR
  patient >40 years of age.
  
  ↓

• Screening with TVS + CA 125 annually.

Protocol for Adnexal Mass on P/V

• TVS (Next step).

• Features suggestive of malignancy:
1. Solid component.
2. Bilateral.
3. Papillary excrescences.
4. Thick septa.
5. Increased vascularity in septa.
6. Ascites/LN involvement/matted bowel loop.

Types of Ovarian Tumors

Epithelial Ovarian Tumors

• m/c ovarian tumors.

• m/c type: Serous cystadenoma Ca.

• Seen in >60 years.

• Mostly unilateral.

• Mutations:
• Low grade tumors: KRAS/PTEN.
• High grade tumors: p53.

• Ovarian Ca a/w pseudomyxoma peritonei: mucinous tumor.

Prognosis

• Not good.

• Non-specific signs & symptoms initially.

• Present in advanced stage directly.

Pseudomyxoma peritonei

• Causes:
• Appendix Ca (m/c).
• Mucinous ovarian tumor.
• Mucocele of appendix.

• ↑↑ recurrence rate: Bad prognosis.

Syndromes a/w Ascites & Right Side Pleural Effusion

Meigs's syndrome:

• Any 1 of the following
• Fibroma >>
• Granulosa cell tumor.
• Brenner tumor (Solid benign tumor).
• Thecoma.

• Mnemonic:
• The (thecoma) Baby (Brennur) in Family (Fibroma) Guy (Granulosa)

Pseudo Meig Syndrome

• When associated with any other condition
• (Eg: Fibroids, mucinous ovarian tumors).

Brenner's Tumor

Features

• Epithelial cell type

• Solid consistency
• Mnemonic: FiBre (Fibroma, Brunner)

• Unilateral (U/L)

• Benign tumor

Histopathology (HPE)

• Coffee bean nucleus present

• Walthard cell nest present

Epithelium

• Transitional epithelium

• Mnemonic:
• Valathi kili cell nest (Walthard cell nest) → Bru coffee (Coffe bean)
• BBBB → Bruners, Bladder epi, bfenign, Bean (coffee bean)

Germ Cell Tumor (GCT)

Demographics

• Common age group: 10–30 years

Laterality

• Mostly unilateral (U/L)
• Always U/L:
• Yolk sac tumor
• Mnemonic: Yolk → Y → Yuni → unilateral
• Bilateral (B/L) in:
• 2-10% of dermoid cysts
• 15-20% of dysgerminomas

Most Common GCT

• Dermoid cyst / mature teratoma

Most Common Malignant GCT

• Immature teratoma

Prognosis

• Good prognosis
• Due to detection at early age

• Best prognosis:
• Dysgerminoma

• Worst prognosis:
• Yolk sac tumor

Progression

• Rapid progression:
• Yolk sac tumor
• Presents with acute abdomen

Note on Radiosensitivity

• Most radiosensitive organ: Ovaries

• Ovarian CA are radioresistant

Teratoma/Dermoid Cyst

Features

• Most common benign ovarian tumor in women of reproductive age.

• Found in reproductive age & pregnancy

• During pregnancy, it’s the most common persistent (non-functional) ovarian tumor.
• First trimester cyst → Corpus luteum cyst
• Later persistent cyst → Dermoid cyst (most common benign tumor during pregnancy)
• Most common complication → Torsion
• Preferred time for elective surgery → Second trimester (16–20 weeks)

• Mostly unilateral (U/L)

• Bilateral (B/L) in 10%

• Mostly benign

Types:

• Mature Teratoma:
• Benign.

• Immature Teratoma:
• Malignant (cancer in protuberance possible).

Monodermal Teratoma:

• Contains only one type of tissue.



• Struma Ovarii: 
• Thyroid gland tissue in ovary.
• Grossly:
• Appears golden brown colored.
• Microscopy:



• Shows areas with pink colloid.
• Functional: Produces T3/T4, potentially causing hyperthyroidism.

• A/w Totipotent stem cell

Stem Cell Type	Potency	Ability	Function / Fate
Totipotent	Highest	Differentiate into all cell types — embryonic and extraembryonic	Can form a complete organism (e.g. zygote, 2-cell, 4-cell stage)
Pluripotent	High	Differentiate into 3 germ layers: ectoderm, mesoderm, endoderm	Form all embryonic tissues, but not extraembryonic tissues
Multipotent	Moderate	Differentiate into multiple, but closely related cell types	Give rise to a specific tissue lineage (e.g. hematopoietic → blood cells)
Lineage Stem Cells	Low	Differentiate into specific lineages only	Limited to a defined differentiation pathway

Grossly:

• Contains tissues from multiple germ layers (bone, skin, hair, teeth).

• Most common component: Ectodermal tissue

• Features a Rokitansky protuberance (solid area for cancer examination).

Malignancy

• Risk: 0.2-2%

• Common site of malignancy: Rokitansky protuberance

• Common malignant type: Squamous Cell Carcinoma

USG Findings in Teratoma Ovary

• Tip of iceberg appearance

• Dot & dash appearance

• Rokitansky protuberance visualization

CT Scan of Pelvis Teratoma ovary

• Mass with Calcification (white) + Fat (dirty black)
• indicates a Teratoma/Dermoid.

Management (mx)

• Cystectomy recommended
• Due to maximum risk of torsion

• Oophorectomy performed
• If family is complete

Dysgerminoma
(Seminoma in testes)

• Tumor markers: LDH, PLAP are increased.

Features

• Usually unilateral (U/L)

• GCT with highest risk of bilaterality:
• 15-20% of cases
• Mnemonic: Germs are both sides, germs are radiosensitive

Grossly:

• Looks like a "cut potato".
• Solid tumor
• Fleshy consistency
• Lobulated shape
• Tan in color

Microscopy: 

• Nests of cells
• Separated by fibrous septa
• Lobules with Septa infiltrated by lymphocytes and plasma cells

• "Fried egg appearance",

• Mnemonic: Potato () um fried egg () um cut chyth vachapo → Germ (dysgerminoma) keri

Yolk Sac Tumor / Endodermal Sinus Tumor

• Commonly seen in children.

• Tumor markers: Alpha-fetoprotein (AFP), Alpha 1 antitrypsin.

Features

• Most malignant GCT
• Note: m/c malignant GCT → Malignant Teratoma
• Most rapidly progressing tumor
• GCT with worst prognosis

• Can present as acute abdomen

• Always unilateral (100% U/L)

Histopathology (HPE)

• Schiller Duval bodies present
• Similar to glomeruloid bodies
• central blood vessel → two layers of tumor cells → space in between.

Choriocarcinoma

• Grossly: Appears hemorrhagic and necrotic.

• Tumor marker: hCG (Human Chorionic Gonadotropin).

• Microscopy: Two cell types:
• Cytotrophoblast: Cells with one nucleus.
• Syncytiotrophoblast: Cells with multiple nuclei (cluster).

• Mnemonic:
• Chori comes alone (Cyto) or in groups (synsitio)
• Chori attack → full of blood

Sex Cord Stromal Tumors

Granulosa Cell Tumor

• Typically seen in postmenopausal patients.

• Releases much estrogen → hyperestrogenism.

• Presence: Any age.

• Gene Defect: FoxL2 gene.

• Estrogen Production:
• Increased risk of endometrial carcinoma.
• Requires endometrial biopsy.

• Presentation:
• Puberty: Puberty menorrhagia.
• Reproductive/Perimenopausal Age: Abnormal Uterine Bleeding (AUB).
• Menopausal: Postmenopausal bleeding.

• Microscopy:
• Coffee bean nuclei.
• Call-Exner bodies (round bodies with pink material).

• Tumor marker: Inhibin.

• CD marker: CD99 positive.

• Granny story Mnemonic
• Cystic BRAIN TUMORS
• Craniopharyngioma
• JPA

Marker	Positive In	Mnemonic / Note
Cytokeratin (CK)	Carcinoma	C for C
Vimentin	Sarcoma	ㅤ
CD45 / LCA Leucocyte Common Antigen	Lymphoma	L for L
HMB45 S 100	Melanoma	M for M
CD1A	Langerhans Cell Histiocytosis (LCH)	ㅤ
CD99	Granulosa Cell Tumor (ovary)	99-year-old granny
(MIC2)	Ewing Sarcoma (bone)	Mitu → childhood tumor
Glial Fibrillary Acidic Protein (GFAP)	Tumor markers in glioma (Astrocytoma, Glioblastoma multiforme)	ㅤ
Lamin	Progeria: Disorder of premature ageing (Hutchinson Gilford)	ㅤ

• Mnemonic:
• Sarcoma
• Vimal Sar
• Also remember Rape (Rhabdomyosarcoma) Syn (Synovial) Mnemonic
• Car
• Sit (Cytokeratin) inside Car
• Remember car → bike → took another route
• Helmet (HCC → Fibrolamellar)
• Rc book (RCC)
• Phone (Follicular CA)
• Granulosa cell tumor mnemonic
• 99 year old granny ex ne vilikkan poi.
• (99 (CD 99) year old granny → hyper estrogenism () → Called Ex (Call exner) → offered coffee (coffee bean) → she shouldve inhibited (inhibin) her)
• Ewings sarcoma Mnemonic:
• Mittu (MIC2) (11 year old) → Onion () kazhichapo wings () vannu → to Wings to Fly (EWS-FLI1) in Right (Homer wright) direction to get Pasta (Pas +ve).
• Mittu thirichu vannapo 22 vayassai (t(11:22))













Condition	Feature
NF1	Chromosome 17
NF2	Chromosome 22
DermatoFIBROSARCOMA protrubans	t (17;22)
Nodular Fascitis	t (22;17)

Sertoli-Leydig Cell Tumor / Pure Leydig Cell Tumor

• Microscopy:
• Presence of Reinke's crystalloids (characteristic of Leydig cells).

• Mnemonic: Renga (Reinke) annante Lady (leidig)

Fibroma

• Associated with Meigs Syndrome:
• Pelvis: Fibroma of ovaries.
• Abdomen: Ascites.
• Chest: Right-sided hydrothorax.

• Associated with Gorlin Syndrome (for INIC aspirants): BBB Mnemonic
• Bilateral fibromas (both ovaries).
• Basal cell carcinoma (facial).
• Blastoma (desmoplastic medulloblastoma in brain).
• PTCH → Tumor Suppressor Gene

• Gore Appearance for Halloween
• Brain middle (Medulloblatoma) cut
• Cut on face (BCC)
• Fibre around neck (B/L Fibroma)

Krukenberg Tumor

• Type: Metastatic tumor of ovary.

CDH gene (E-cadherin):

• Chromosome 16

• "Glue" for cell-to-cell connection.

Loss/mutation

• Mnemonic: Kadich (CDH) → Breastlum Vyarilum

• "Golu" tumors/Kadicha tumors
1. Diffuse Gastric Cancer

Lauren's Classification	Intestinal Lauren's Classification	Diffuse Lauren's Classification
Epidemiological	Environmental	Familial
Pathology	Gastric atrophy, intestinal metaplasia	Blood Group A
Sex	m > F	F > M
Age	↑ Incidence with ↑Age	Younger age
Morphology	Gland formation Round glands	Poorly differentiated
Cell Type	ㅤ	• Gross: Linitis plastica  ("leather bottle appearance"). • Microscopy: Signet ring cells.
Genetics	APC gene mutations, Microsatellite instability p53, p16 inactivation	Loss of E-cadherin (↓ E-cadherin) p53, p16 inactivation
Invasion	Hematogenous spread	Transmural/Lymphatic spread

2. Lobular Carcinoma Breast
• Indian File/Single File Pattern

• Mnemonic: File (Indian file) of Breast Ca patients
3. Claudin low → EMT positive breast cancer

---

• Krukenberg tumor
• Stomach > Breast/ Colon
• Signet Ring Cells
• Retrograde lymphatic spread

---

NOTE: Miscellaneous one liners

• Most common primary source: 
• Stomach CA (Pyloric end).
• Also in breast and colon

• Route of Spread: 
• Retrograde lymphatics.

• Bilateral Involvement: 
• 80% cases.

• Characteristics:
• Symmetrical ovarian enlargement.
• Shape retained.
• Waxy.
• Mobile.
• Intact capsule.

• On HPE: Signet ring cells.
• Filled with mucin.
• Nuclei pushed to periphery by large mucin vacuole.

Management of Ovarian Cancer

Staging Laparotomy/Surgical Staging

• Performed in all cases.

• Steps:
1. Ascitic fluid/peritoneal wash sample.
2. Multiple peritoneal biopsies.
3. Infracolic omentectomy (Not omental biopsy)
4. Total Abdominal Hysterectomy (TAH) + Bilateral Salpingo-Oophorectomy (BSO).
5. Pelvic & para-aortic lymph node dissection (LND).

Clinical Approach to Epithelial Ovarian Cancer

• Investigation: CT scan to stage tumor.

Based on Tumor Stage:

• Early Stage (1 or 2):
• Staging laparotomy.
• Post-operative/Adjuvant Chemotherapy (CT):
• Carboplatin + Paclitaxel (6 cycles).
• Add-on Drugs:
• Bevacizumab (both BRCA positive/negative).
• Olaparib (if BRCA positive).
• Mnemonic: Olaparambu → Bra
• Maintenance: PARP inhibitors (Olaparib, Niraparib) + Bevacizumab.

• Advanced Stage (3 or 4):
• Resectable Tumor:
• Debulking/Cytoreductive surgery.
• Adjuvant Chemotherapy (CT):
• Carboplatin + Paclitaxel (6 cycles).
• Maintenance:
• PARP inhibitors + Bevacizumab.
• Tumor Not Resectable:
• Neoadjuvant Chemotherapy (3 cycles):
• Carboplatin + Paclitaxel.
• Re-assessment Post-Chemo:
• If Resectable:
• Debulking surgery.
• Remaining 3 cycles of CT.
• If Still Not Resectable:
• Remaining 3 cycles of CT without surgery.

• Mnemonic:
• Car (Carboplatin) Park (Paclitaxel) cheythu → Ola (Olaparib) de mukalil Walk (Bevacizumab) cheythu
• Sis Flu (5 FU) → Cervix
• Sis (Cisplatin) Pack (Paclitaxel) → Uterus

Features of Non-Resectable Tumors:

• Peritoneal caking.

• Involves vital organs:
• Stomach, liver, great vessels, intestine, mesentery.

Management of Germ Cell Tumors

• Surgery: 
• Unilateral salpingo-oophorectomy (typically for young females).

• Chemotherapy:
• Given for all stages.
• Bleomycin, Etoposide, Cisplatin.
• Exception: 
• Dysgerminoma Stage I (may not need chemo).

Surveillance During Treatment (Platinum Free Interval)

↑↑ in CA 125 Levels while on surveillance:

• While on Platinum-Based CT:
• Refractory to Drugs
• DOC: Pegylated Liposomal Doxorubicin (PLD).

• After Stopping CT:
• Platinum free interval (PFI)
• < 6 months.
• Platinum Resistant Relapse
• DOC: Paclitaxel, Bevacizumab.
• > 6 months.
• Platinum Sensitive Relapse
• DOC: Carboplatin, Paclitaxel.

• Note: Partial platinum resistance does not exist.

CASE 1

Functional Ovarian Cysts

• Most common type of cyst

• Occurs due to hormonal disturbances

• Temporary, typically resolves spontaneously
• Specific treatment is not usually required

Types of Functional Ovarian Cysts

1. Follicular Cyst
• Most Common
• Size of follicle is ≥ 3 cm.
• Presentation
• Unilocular, Thin walled, Anechoeic cyst
• Mobile tender cystic adnexal mass
• Lower Abdominal pain
• Reproductive age group
• Recurrent Cyst
• OCPs

2. Corpus Luteum Cyst
• Most common cyst to rupture.

Stage of Pregnancy	Most Common Cyst Type
First trimester	Corpus luteum cyst
Second & third trimester [Overall]	Dermoid cyst (mature cystic teratoma)

3. Theca Lutein Cyst
• Occurs due to ↑↑ HCG levels.
• Seen in:
• Molar pregnancy
• Twin pregnancy
• Infertility treatment:
• Clomiphene
• HMG

4. Hemorrhagic cyst
• Reticular / Fish Net Pattern

5. Endometrioma (Chocolate Cyst)
• Thick walled
• First investigation:
• TVS (rules out other disorders)
• Ground glass echogenicity
• Homogenous Internal Echoes


• If patient desires pregnancy:
• Do not treat (conservatively managed)
• Pregnancy rates
• 60% in moderate disease
• 35% in severe disease
• If patient does not desire pregnancy:
• Asymptomatic and <5 cm:
• Follow-up with USG
• Asymptomatic and ≥5 cm or symptomatic cyst:
• Laparoscopic cystectomy + HPE

6. Malignant cyst
• Solid cyst
• Thick septae
• Papillary excrescences
• ↑ Vascularity in septae

7. Abscess
• Internal echoes
• Heterogenous
• ↑ Vascularity → ↑ Doppler flow

8. Ovarian Torsion
• Twisted pedicle
• ↓ Vascularity

9. Dermoid cyst
• Shows calcification
• Rokitansky Protuberance

10. Serous cystadenoma
• Unilocular

Ovarian Cysts Without Features of Malignancy on Ultrasound

Important Notes

• Malignant Transformation of Ovarian Masses:
• 30% in postmenopausal.
• 7% in premenopausal.

• CA 125
• Reproductive Age Group:
• ≥ 200 IU: Significant (suggests malignancy).
• Postmenopausal
• ≥35 IU: Significant

Approach

• Reproductive Age Group:

Size	Action
< 5 cm	Watch
5-7 cm	Serial ultrasound monitoring
> 7 cm	Surgical excision if risk of torsion

• Extremes of Age
• Post-menopausal
• Check CA 125,
• Pre-pubertal
• Suspect dysgerminoma
• AFP, HCG, LDH levels.
• If abnormal, consider malignancy.

CASE 2

Ovarian Cysts in Pregnancy

• Clinical Approach Based on Symptoms
• Symptomatic Cyst:
• Surgery irrespective of gestational age.
• Asymptomatic Cyst:
• 1st Trimester:
• Wait & watch (mostly corpus luteal cyst).
• 2nd/3rd Trimester:
• Surgery if
• malignant features OR
• size ≥ 10 cm on ultrasound.

Important Notes

• Most Common Benign Tumor: Dermoid cyst.

• Most Common to Undergo Torsion: Dermoid cyst.

• Most Common at End of 1st Trimester/During Puerperium: Dermoid cyst.

• Most Common Ovarian Cancer in Pregnancy: Dysgerminoma.