Gynaecology Marrow Pg 249-258 (Gynaecological Oncology)

Sex Cord Stromal Tumors

• Sex cord tumors can produce estrogen (feminizing) or androgen (virilizing) hormones.
• Granulosa cell tumors are estrogen-producing.
• Sertoli-Leydig cell tumors, Leydig cell tumors, and Hilus cell tumors produce androgens.
• Reineke's crystals are a characteristic histological feature.
• Stromal tumors include fibroma, thecoma, and fibrothecoma.
• Sex cord stromal tumors have a better prognosis than germ cell tumors and epithelial cell tumors.

Granulosa Cell Tumors

• Originate from granulosa cells.
• Produce estrogen and inhibin.
• Antimullerian hormone is a tumor marker.
• Present with excessive bleeding (atypical uterine bleeding, postmenopausal bleeding, precocious puberty).
• Ovarian cancers associated with endometrial cancer include endometrioid tumors and granulosa cell tumors.
• Endometrial sampling is mandatory in all cases with granulosa cell tumors.

Genetic Syndromes

• Lynch syndrome is associated with a high risk of colorectal cancer and endometrial cancer, with a 20% risk of ovarian cancer.
• BRCA1 mutation carries a maximum risk of 40% for ovarian cancer and an increased risk of endometrial cancer.
• BRCA2 mutation carries a 15% risk of ovarian cancer.

Hereditary vs Sporadic Ovarian Cancer

• Hereditary ovarian cancer affects younger women (under 50 years old) and accounts for about 5-10% of all ovarian cancers.
• Sporadic ovarian cancer is most common in women aged 60-70 years old.

Screening

• Women with a first-degree relative with hereditary ovarian cancer or a BRCA mutation need to be assessed for sporadic ovarian cancer.
• Annual screening with transvaginal sonography (TVS) and CA 125 is recommended for women aged 35-40 years old.

WHO Classification & Epithelial Ovarian Tumors

• Epithelial ovarian tumors are the most common (90%), followed by germ cell tumors (5-8%), then sex cord stromal tumors (3-5%).
• Serous cystadenoma is the most common overall, while dermoid cysts are most common in reproductive age.
• Serous cystadenocarcinoma is the most common type of ovarian cancer.

Types of Epithelial Ovarian Tumors

• Serous tumors are the most common.
• Other types include mucinous, Brenner's, endometrioid, and clear cell tumors.
• Most common age for epithelial ovarian cancer is 60 years old.
• Most commonly bilateral.
• Prognosis is poor due to non-specific symptoms.
• Psammoma bodies are a characteristic histological feature.
• Mutations include KRAS, PTEN, and p53.

Serous vs. Mucinous Tumors

• Serous tumors are more commonly benign (60% are serous cystadenoma) and often bilateral.
• Mucinous tumors are more commonly benign (80% are mucinous cystadenoma) and mostly unilateral.
• Serous tumors are associated with BRCA1, BRCA2, and p53 mutations.
• Mucinous tumors are associated with KRAS mutation.
• Mucinous tumors are linked to smoking, while serous tumors are not.
• Serous cystadenocarcinoma is the malignant counterpart of serous cystadenoma.
• Mucinous cystadenocarcinoma is the malignant counterpart of mucinous cystadenoma.
• CA 125 is the tumor marker for serous tumors.
• CEA and CA 19-9 are the tumor markers for mucinous tumors.
• Psammoma bodies are present in serous tumors.
• Mucinous tumors present with a honeycomb appearance on gross examination due to multiloculated cysts filled with mucinous material.

Dysgerminoma

• The second most common germ cell tumor (GCT).
• Most common in women of childbearing age.
• 15-20% are bilateral, with the highest risk of bilaterality among GCTs.
• Typically appears fleshy, solid, lobulated, and tan-colored.
• Has the best prognosis among GCTs.
• Only radiosensitive ovarian tumor.
• Histologically characterized by nests of cells separated by fibrous septa with lymphocyte infiltration.
• USG features include tip of iceberg sign and dot & dash appearance.
• Management includes cystectomy or oophorectomy depending on family plans.

Yolk Sac Tumor

• The most malignant GCT with the worst prognosis due to rapid progression.
• Histologically characterized by Schiller Duval bodies (glomeruloid bodies).
• Can present with acute abdomen.
• Typically unilateral (100%).
• Histologically shows central capillaries surrounded by tumor cells within cystic spaces.

Ovarian Pathologies in Pregnancy

• Management:
  • Benign ovarian tumor cysts are most likely to undergo torsion, especially at the end of the first trimester or during the puerperium.
  • Dysgerminoma is the most common ovarian cancer in pregnancy.
• 1st Trimester:
  • Corpus luteum is the most common type of ovarian cyst and usually resolves spontaneously.
  • Removal of cysts in the first trimester could lead to decreased progesterone and abortion.
• 2nd Trimester:
  • Symptomatic cysts (rupture or torsion) or cysts with malignancy features on USG (>10 cm) should be removed regardless of gestational age.

Factors Related to Ovarian Cancer

• Proven Risk Factors:
  • Excessive estrogen
  • Early menarche
  • Late menopause
  • Genetic syndromes (Lynch syndrome, BRCA1, BRCA2)
  • Exposure to carcinogens
  • Nulliparity
  • Asbestos
• Controversial Risk Factors:
  • Polycystic Ovarian Syndrome (PCOS)
  • Hormone Replacement Therapy (HRT)
  • Obesity
  • Endometriosis
  • Infertility and ovulation-inducing drugs
  • Talc
  • Smoking (mucinous adenocarcinoma)

Protective Factors

• Related to Estrogen:
  • Physical exercise
  • Oral contraceptive pills (OCP)
  • Breastfeeding
• Related to Ovulation:
  • Anovulation
  • Multiparity
  • OCP
• Surgeries:
  • Hysterectomy
  • Tubal ligation
  • Salpingectomy

Tumor Markers

• Used to diagnose and monitor GCTs.
• GCTs: LDH, HCG, PLAP (Placental alkaline phosphatase)
• Dysgerminoma: LDH, HCG
• Yolk Sac Tumor: AFP, LDH
• Embryonal Cancer: AFP, HCG
• Choriocarcinoma: HCG
• Teratoma: No tumor marker

Germ Cell Tumors (GCT)

• Most common in young girls (10-30 years old).
• Typically occur unilaterally.
• Types include teratoma (mature cystic teratoma/dermoid cyst, immature teratoma, struma ovarii), dysgerminoma, yolk sac tumor, embryonal cancer, choriocarcinoma, and mixed types.
• Have a better prognosis than other ovarian cancers due to early diagnosis.

258

• Histological feature of granulosa cell tumor, characterized by central acidophilic material surrounded by follicle-like cells with coffee bean nuclei.

Fibroma

• Unilateral, benign, solid tumor.
• Histologically characterized by well-differentiated fibroblasts.
• Associated with Meig's syndrome.

Meig's vs. Pseudo-Meig's Syndrome

• Meig's syndrome is characterized by a fibroma/thecoma/Brenner's tumor/granulosa cell tumor, ascites, and pleural effusion.
• Pseudo-Meig's syndrome is characterized by any other ovarian tumor (mucinous cystadenoma) or any other condition (fibroid), ascites, and pleural effusion.
• Removing the tumor in Meig's syndrome resolves ascites and pleural effusion.

Metastatic Tumors of the Ovary

• Most commonly originate from the stomach.
• Other common primary sources include gastrointestinal tract and breast carcinoma.
• Krukenberg tumors are metastatic tumors from stomach cancer (pyloric end), which spread through retrograde lymphatics to the ovaries.
• Bilateral (80%) and symmetrical enlargement of ovaries.
• The shape and capsule of the ovary are retained.
• Mobile and waxy consistency.
• Histologically characterized by signet ring cells with mucin-filled cytoplasm pushing the nucleus to one side.

Ovarian Cysts & Ovarian Cancer

• Functional ovarian cysts are the most common type, occurring due to hormonal disturbances.
• They are usually temporary and resolve spontaneously, requiring no specific treatment.
• Types include follicular cyst, corpus luteal cyst, and theca lutein cyst.
• Follicular cysts are the most common type and are more likely to rupture.
• Theca lutein cysts are associated with increased HCG levels and are seen in cases like molar pregnancy, twin pregnancy, and fertility treatments with clomiphene and HMG.

Features of Ovarian Cancers

• Rare, therefore screening is not routinely performed.
• Present with vague symptoms like nausea, vomiting, loss of appetite, and adnexal masses.
• Imaging of the ovaries (IOC) with a transvaginal sonography (TVS) is crucial for diagnosis.

Benign vs. Malignant Adnexal Masses

• Benign Adnexal Masses:
  • More common in reproductive age.
  • Pain is usually present due to inflammation.
  • No specific history.
  • Unilateral.
  • Cystic consistency.
  • Tenderness.
• Malignant Adnexal Masses:
  • More common in extreme age groups (pre-pubertal/menopausal).
  • Often no pain.
  • Rapid progression and weight loss are common.
  • Bilateral.
  • Solid consistency.
  • No tenderness.

Ultrasound Features

• Benign:
  • Unilateral
  • Anechoic
  • Unilocular
• Malignant:
  • Bilateral
  • Solid components >10 cm
  • Variable consistency (Solid components)
  • Thick septa with papillary outgrowths (Excrescenes).
  • Highly vascular.
  • Evidence of ascites, enlarged lymph nodes, and matted bowel loops.

Management of Ovarian Cysts

• Reproductive Age Group:*
  • 3-5 cm: Wait and Watch.
  • 5-7 cm: Follow up with serial ultrasounds.

  • 7 cm: Surgery for torsion or rupture.

• Extremes of Age:*
  • Post-menopausal (CA125 ≥ 35 IU): Further investigations and surgery.
  • Pre-pubertal: If elevated markers (AFP, HCG, LDH) are present, further investigations and surgery.

Features Suggestive of Ovarian Malignancy on Ultrasound (USG)

• Papillary excrescences
• Thick >3mm septations
• Mural nodularity
• Papillary projections
• Frank solid components

Notes

• CA-125 has limited value in the reproductive age group.
• Important: This document is a summary. Seek medical advice for diagnosis and treatment.