10- MALIGNANT TUMORS OF OVARY AND TUBES Quiz
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Questions and Answers

Which mutation is associated with a higher prevalence in fallopian tube carcinoma cases?

  • KRAS mutation
  • TP53 mutation
  • BRAF mutation
  • BRCA1 mutation (correct)

    • What is the Latzko triad associated with the presentation of fallopian tube carcinoma?

  • Weight loss, fever, and night sweats
  • Abdominal pain, bloating, and vaginal discharge (correct)
  • Anemia, cough, and chest pain
  • Fatigue, jaundice, and hematuria

    • Which imaging finding is characteristic of a fallopian tube mass in a patient with carcinoma?

  • Solid round mass
  • Pancake appearance
  • Stringy appearance
  • Sausage shape or cog-and-wheel appearance (correct)

    • What symptom is particularly alarming as it may suggest either endometrial or fallopian tube carcinoma?

    <p>Postmenopausal vaginal bleeding</p> Signup and view all the answers

    Which type of fallopian tube carcinoma is most commonly identified?

    <p>Serous type carcinoma</p> Signup and view all the answers

    Which of the following tumor types is classified as being malignant?

    <p>Serous (hgsoc)</p> Signup and view all the answers

    Which factor has been shown to lower the risk of developing epithelial ovarian tumors?

    <p>Use of oral contraceptives</p> Signup and view all the answers

    What is the percentage range of genetic predisposition in the cases of patients with ovarian cancer?

    <p>5-10%</p> Signup and view all the answers

    Which of the following risk factors is NOT associated with epithelial ovarian tumors?

    <p>Having children at an older age</p> Signup and view all the answers

    What is the role of BRCA1 and BRCA2 genes in relation to ovarian cancer?

    <p>They are tumor-suppressor genes associated with an increased risk of the disease.</p> Signup and view all the answers

    Which of the following best describes the categorization of epithelial ovarian tumors?

    <p>Benign, borderline (low malignant potential), and malignant</p> Signup and view all the answers

    At what age is the risk of developing ovarian cancer notably increased?

    <p>Over 40 years</p> Signup and view all the answers

    What is the recommended procedure if a suspicious lesion is found in the other ovary?

    <p>Biopsy the lesion and preserve the ovarian tissue</p> Signup and view all the answers

    What surgical procedure is indicated in cases of dysgenetic gonads carrying a Y chromosome?

    <p>Bilateral oophorectomy with preservation of the uterus</p> Signup and view all the answers

    What is the typical spread pattern for dysgerminomas?

    <p>Through the lymphatic system, particularly affecting aortic lymph nodes</p> Signup and view all the answers

    In managing a pregnant patient with a tumor, how is stage II and III treated?

    <p>Conservative surgery followed by chemotherapy, considering gestational age</p> Signup and view all the answers

    Which factor does NOT indicate a high risk of recurrence for a patient with ovarian tumors?

    <p>No lymphatic involvement</p> Signup and view all the answers

    What is the average age of onset for ovarian cancers in individuals under 20?

    <p>18 years</p> Signup and view all the answers

    What classification grade of immature teratoma indicates immature cells in more than 3 areas?

    <p>Grade III</p> Signup and view all the answers

    Which statement regarding immature teratomas is incorrect?

    <p>They are the most common type of benign ovarian tumor.</p> Signup and view all the answers

    How is chemotherapy applied to patients with stage I immature teratomas?

    <p>Chemotherapy is not typically required for all stage I tumors.</p> Signup and view all the answers

    What percentage of gastrointestinal-derived metastatic ovarian tumors are diagnosed during the reproductive period?

    <p>50%</p> Signup and view all the answers

    Which screening strategy has primarily been focused on detecting ovarian cancer in women with average risk?

    <p>CA125 biomarker</p> Signup and view all the answers

    What is a characteristic feature of primary fallopian tube carcinoma?

    <p>Papillary pattern of tubal mucosal involvement</p> Signup and view all the answers

    What is the recommended method of choice for the differential diagnosis of suspected metastatic ovarian tumors?

    <p>Laparoscopy</p> Signup and view all the answers

    Which cell type is associated with Krukenberg tumor?

    <p>Signet ring cells</p> Signup and view all the answers

    What is the main goal of risk-reducing surgery in women with high genetic risk for ovarian cancer?

    <p>To reduce the likelihood of future cancer development</p> Signup and view all the answers

    Which hormone is associated with the effects of Sertoli-Leydig cell tumors?

    <p>Androgens</p> Signup and view all the answers

    What is a common misconception regarding screening for ovarian cancer?

    <p>Effective screening strategies exist for all women</p> Signup and view all the answers

    Which feature is NOT indicative of granulosa cell tumors?

    <p>Significant virilization symptoms</p> Signup and view all the answers

    What is the average age range for the diagnosis of tubal cancer?

    <p>60 to 69 years</p> Signup and view all the answers

    Which histological type is NOT associated with fallopian tube carcinoma?

    <p>Small cell</p> Signup and view all the answers

    What proportion of gynecological malignancies does fallopian tube cancer represent?

    <p>1% to 2%</p> Signup and view all the answers

    Which of the following is a demonstrated diagnostic criterion for tubal carcinoma?

    <p>Demonstrable transition from benign to malignant epithelium</p> Signup and view all the answers

    Which demographic factor is most associated with primary fallopian tube cancer?

    <p>Race and age, particularly in white women aged 50 to 60</p> Signup and view all the answers

    Which of the following therapies is suggested to have a higher risk for primary fallopian tube cancer?

    <p>Postmenopausal progestin-based hormonal therapies</p> Signup and view all the answers

    In what context is diagnosis of tubal cancer most often made?

    <p>In advanced stages, mostly postoperatively</p> Signup and view all the answers

    What is the reported annual incidence rate for fallopian tube cancer?

    <p>0.41 per 100,000</p> Signup and view all the answers

    What is the significance of the Sedlis et al modified Hu criteria in diagnosing tubal cancer?

    <p>It outlines criteria for the transition from benign to malignant epithelium</p> Signup and view all the answers

    Which cancer type shares clinical and histopathologic features with fallopian tube carcinomas?

    <p>Primary peritoneal carcinoma</p> Signup and view all the answers

    Study Notes

    Ovarian and Tubal Tumors

    • Asena Ayar Madenli, MD, Asst. Prof.
    • ISU Medical School (2024-2025)
    • Liv Hospital Vadi Istanbul
    • Department of Obstetrics and Gynecology

    Ovarian Cancers

    • Epithelial (90%):
      • Serous (HGSOC, LGSOC)
      • Mucinous
      • Brenner
      • Endometrioid
      • Clear cell
    • Germ Cell:
      • Dysgerminoma
      • Yolk sac
      • Choriocarcinoma
      • Teratoma
      • Embryonal carcinoma
    • Sex Cord Stromal:
      • Granulosa cell
      • Sertoli-Leydig cell
      • Thecoma
      • Fibroma
    • Metastatic:
      • Krukenberg

    Epidemiology

    • Epithelial ovarian cancers are a significant cause of mortality worldwide.
    • In developed countries, there are ~190,000 new cases and ~114,000 deaths annually.
    • They account for ~3% of all cancers.
    • They rank 5th among cancer-related deaths (after lung, breast, colorectal, and pancreatic).
    • Ovarian cancer is the second most common gynecological malignancy (~23% of gynecological cancers).
    • Estimated lifetime risk of a woman developing ovarian cancer is between 1.4% and 1.7%. (1/70)
    • Average age of diagnosis is 63.

    Epidemiology- Continued

    • Tumors may occur at any age, with variations in histologic subtypes by age.
    • Germ cell tumors predominate in women under 20.
    • Borderline tumors typically occur in women in their 30s and 40s.
    • Invasive epithelial ovarian cancers mostly occur after the age of 50.

    Epithelial Ovarian Cancer (EOC)

    • Originate from the coelomic epithelium
    • Account for 90% of ovarian cancer cases.
    • Subtypes:
      • Serous (high-grade serous ovarian cancer, low-grade serous ovarian cancer)
      • Mucinous
      • Brenner
      • Endometrioid
      • Clear cell
    • Classification: Benign, borderline (low malignant potential), malignant.

    Carcinogenesis

    • Surface epithelium
    • Inclusion cysts
    • Metaplasia occurring in inclusion cysts
    • Genetic predisposition in ~5-10% of cases.

    Risk Factors

    • Age (>40 years)
    • Reproductive history: nulliparity, infertility, fertility medications (HRT >10 years)
    • Personal history of breast cancer
    • Race
    • Family history (hereditary nonpolyposis colorectal cancer (HNPCC)-Lynch 2 syndrome)
    • Early menarche-late menopause
    • Environmental factors
    • Genetic predisposition (BRCA mutations)
    • For epithelial ovarian tumors:
      • Reproductive risk factors: women who have never had children are twice as likely to develop the disease.
      • First pregnancy at an early age, early menopause, and the use of oral contraceptives have been associated with lower risks.
      • No clear relationship to fallopian tube cancer.

    BRCA 1 and 2

    • These are two tumor-suppressor genes.
    • BRCA1 is located on chromosome 17q21. Patients with a mutation have a dramatically elevated risk of developing ovarian cancer (39-46%).
    • BRCA2 is located on chromosome 13q12 and generally leads to a less likely risk of ovarian cancer (12-20%).
    • Mutations can skip generations.
    • Prophylactic bilateral salpingo-oophorectomy (BSO) is recommended in BRCA1 or BRCA2 carriers. BSO may be performed upon completion of childbearing or by age 40.
    • Prophylactic BSO reduces the risk of developing breast cancer by ~50%.

    Protective Factors

    • Multiparity
    • Oral contraceptives
    • Lactation
    • Hysterectomy
    • Tubal ligation
    • BSO (bilateral salpingo-oophorectomy)

    Staging Ovarian, Fallopian Tube, and Peritoneum

    • Stage I: Tumor confined to the ovaries or fallopian tubes (T1-No-Mo)
      • IA: Tumor limited to 1 ovary, no tumor on ovarian or fallopian tube surface, no malignant cells in ascities or peritoneal washings
      • IB: Tumor limited to both ovaries, no tumor on ovarian or fallopian tube surface, no malignant cells in ascities or peritoneal washings
      • IC: Tumor limited to 1 or both ovaries or fallopian tubes with the following:
        • IC1: Surgical spill
        • IC2: Capsule ruptured before surgery or tumor on ovarian or fallopian tube surface -IC3: Malignant cells in the ascities or peritoneal washings
    • Stage II: Tumor involves one or both ovaries or fallopian tubes with pelvic or extra pelvic extension
    • Stage III: Involvement of peritoneum
    • Stage IV: Distant metastases (excluding peritoneal metastases)

    Symptoms

    • Irregular bleeding in premenopause
    • Pressure symptoms
    • Lower abdominal distension
    • Dyspareunia
    • Acute pain
    • Distension due to ascites
    • Distension related to omental and intestinal metastasis
    • Postmenopausal bleeding

    Physical Findings

    • Pelvic examination reveals a solid, irregular fixed mass
    • Upper abdominal mass
    • Ascites
    • Palpable ovaries in postmenopausal patients
    • Pleural effusion

    Diagnostic Evaluation

    • Physical examination
    • Ultrasound, MRI, CT
    • Tumor markers (CA 125, CA 15-3, CA 19-9)
    • Cervical cytology
    • Endometrial sampling(for patients with irregular menstruation and postmenopausal bleeding complaints)
    • Investigation of liver and pancreatic pathologies (in patients without pelvic masses with ascites)
    • Laparotomy/Laparoscopy for definitive diagnosis

    Why a Successful Screening is Difficult?

    • Anatomical localization of ovaries
    • No well-defined precursor lesion
    • No specific validated diagnostic method that would reduce unnecessary intervention.

    CA 125

    • Malignant: Increases in endometrial, fallopian tube, germ cell, cervical, pancreatic, breast, and colon cancers.
    • Benign: Increases in endometriosis, fibroids, PID, adenomyosis, functional ovarian cysts, and pregnancy
    • Also increases in other diseases (kidney, heart, liver)
    • High in ~1% of normal women
    • Normal value <35. In very few benign conditions >100-200.

    Treatment

    • Surgery
    • Chemotherapy
    • Radiotherapy
    • Immunotherapy
    • Hormone therapy

    Treatment-Specific to particular Tumors

    • Borderline tumors: Resection of the primary tumor
    • Stages IA and IB G1 tumors: Surgery alone is sufficient(Fertility-sparing surgery can be performed)
    • Stages IA and IB G2-3 and Stage IC tumors: Surgery plus chemotherapy is required
    • Advanced stages: Cytoreductive surgery (debulking) plus chemotherapy is indicated.
    • Germ cell tumors: Optimal surgical staging, unilateral salpingo-oophorectomy, Chemotherapy.

    Cytoreductive Surgery

    • The goal is to achieve a state where there are no residual tumors larger than 1 cm, as this is the best indicator of survival in advanced-stage disease.
    • It is not the volume of the remaining tumor cells that determines prognosis, but rather the diameter of the largest residual tumor.

    Favorable Prognostic Factors

    • Younger age
    • Good performance status
    • Cell type other than mucinous and clear cell
    • Well-differentiated tumor
    • Smaller disease volume prior to surgical debulking
    • No ascites
    • Smaller residual tumor after primary cytoreductive surgery

    Non-Epithelial Ovarian Tumors

    • Germ cell tumors
      • Mature teratoma
      • Immature teratoma
      • Dysgerminoma
      • Embryonal carcinoma
      • Endodermal sinus tumor
      • Choriocarcinoma
      • Gonadoblastoma
      • Koruyokarsinom

    Germ Cell Ovarian Tumors

    • The most important feature is that they originate from primitive germ cells and account for ~70% of ovarian tumors seen before the age of 20.
    • After the third decade, it is very rare.
    • The most commonly seen malignant germ cell tumor is dysgerminoma (~40% of all germ cell tumors).
    • When diagnosed, ~60-75% are in stage I.

    Dysgerminoma

    • Accounts for 1-3% of ovarian cancers and 30-45% of all germ cell tumors.
    • Observed in individuals between the ages of 10 and 30, and constitute 20-30% observed during pregnancy.
    • Along with dysgerminoma, other germ cell tumors are observed.
    • Immature teratoma is the most common.
    • 5% of dysgerminomas are associated with abnormal gonads.
    • Seen in patients with gonadal dysgenesis and androgen insensitivity.
    • 10-15% is bilateral.
    • 75% of cases are stage I when diagnosed.

    Tumor Markers in Germ Cell Tumors

    • Dysgerminoma: AFP (-) β-hCG (-/+) CA 19-9 (-) LDH (-)
    • Chorionic carcinoma: AFP (-) β-hCG (+) CA 19-9 (-) LDH (+)
    • Immature teratoma: AFP (-) β-hCG (-) CA 19-9 (+) LDH (+)
    • Endodermal sinus tumor: AFP (+) β-hCG (-) CA 19-9 (+) LDH (-)
    • Embryonal carcinoma: AFP (+) β-hCG (-) CA 19-9 (-) LDH (+)

    Treatment of Germ Cell Tumors

    • The most commonly encountered germ cell ovarian cancer occurs in 75% of cases between the ages of 10 and 30, with 75% being in stage I
    • Treatment outlines that preserve the patient's fertility as much as possible and provide the longest survival include:
      • Optimal surgical staging
      • Unilateral salpingo-oophorectomy
      • Chemotherapy

    Treatment: Other considerations

    • Examine the other ovary if a suspicious lesion is found.
    • Resect the suspicious lesion while preserving normal ovarian tissue.
    • If fertility is not desired, consider radical surgery.
    • If there are dysgenetic gonads, perform bilateral oophorectomies, while preserving uterus.
    • Is pelvic/para aortic lymphadenectomy necessary?
    • Dysgerminomas most often spread through the lymphatic system (near the renal vein). Since dysgerminoma is sensitive to chemotherapy, sampling is sufficient.
    • How should management be in a pregnant patient?
      • Stage IA: Remove the tumor, pregnancy continues
      • Other stages: Treat based on gestational age. Conservative surgery is performed(followed by chemotherapy)
    • Which patients have highest risk of recurrence?
      • Under age 20
      • Mass larger than 15 cm
      • Rupture of mass during surgery
      • Lymphatic involvement

    Immature Teratoma

    • They account for 20% of germ cell ovarian tumors.
    • Ovaries account for 10-20% of cases in women under 20.
    • Responsible for over 30% of deaths from ovarian cancer in this age group.
    • Average age of onset is 18
    • In 70% cases, stage I upon diagnosis.
    • Rare in bilateral cases.
    • 5% of cases contain benign cystic teratoma in the other ovary, resulting in potential errors regarding metastasis.

    The Importance of "Grade" in Immature Teratoma

    • Histological classification based on neural tissue maturation
      • Grade I: 0–1 immature cells
      • Grade II: Immature cells in less than 3 areas
      • Grade III: Immature cells in more than 3 areas
    • Grade III tumors which contain malignant squamous components have worse prognoses.
    • Treatment: Surgical staging & unilateral salpingo-oophorectomy, biopsy of the other ovary not necessary. Chemotherapy for all tumors other than stage I.

    Endodermal Sinus Tumor

    • Accounts for 20% of germ cell ovarian tumors
    • 15% ipsilateral ovary, 5% opposite ovary with dermoid cyst.
    • Average age of onset is 18
    • 75% of cases involve pelvic pain.
    • Treatment: Unilateral salpingo-oophorectomy.
    • Total abdominal hysterectomy(TAH) will not affect prognosis.
    • AFP is a good tumor marker.

    Granulosa Cell Tumors

    • They make up 70% of sex cord stromal cell tumors.
    • Seen in every period from childhood to senility.
    • Two types: adult and juvenile.
    • Adult type in 95% all cases, juvenile type in the prepubertal period.
    • Tumors with low malignant potential
    • 30% associated with endometrial hyperplasia
    • 10% associated with endometrial cancer.
    • 80-90%- Stage I on diagnosis.
    • (2–5%) Bilateral tumors.

    Granulosa Cell Tumors (Juvenile Type)

    • At the time of diagnosis, approximately 90% are stage IA-IB.
    • Childhood brain tumors account for 5-7% of all tumors.
    • 5% bilateral.
    • Observed before ~90% of puberty.
    • Associated with peripheral precocious puberty (pseudo-precocious puberty)
    • E2, progesterone, testosterone ↑; FSH-LH↓
    • 10% of cases with acid, 10% with tumor rupture.

    TM Markers

    • E2
    • Inhibin
    • Follicle regulatory protein (FRP)
    • Müllerian inhibiting factor (MIF)

    Treatment-Prognosis

    • Treatment for granulosa cell tumors is adjusted according to the age at diagnosis and desire for fertility.
    • Fractional curettage is essential in perimenopausal and postmenopausal periods.
    • If fertility is to be preserved. USO + surgical staging.
    • 5-year survival (adult type): Stage I (92–100%), Stage II–III (33–53%).
    • 10-year survival (juvenile type): Stage I (97%).
    • Prognosis is better in cases with false precocious puberty (early diagnosis).

    Fibro-Thecoma

    • Considered benign.
    • Almost always one-sided
    • Conservative surgery performed.
    • Associated with endometrial hyperplasia and cancer.
    • May cause Meigs syndrome and Gorlin syndrome.

    Sertoli-Leydig Cell Tumors

    • Very rare (~0.5% of all ovarian tumors)
    • Average age of onset is 25; 10% seen after age 50
    • 1% bilateral
    • Feminization/masculinization in ~75-85% of cases.
    • Treatment with USO + surgical staging is sufficient.
    • Poor prognosis if tumor contains a "reticular" pattern, or extra-ovarian spread at time of diagnosis or heterologous mesenchymal differentiation.

    Metastatic Tumors of the Ovary

    • Ovaries are the most frequently metasized organs among genital organs
    • Can originate from thyroid, stomach, breast, colon, and gallbladder
    • ~10% of all ovarian tumors are metastatic tumors.

    Metastatic Tumors of the Ovary (continued)

    • ~50% of cases from gastrointestinal system and ~83% of those from breast, are in reproductive period on diagnosis.
    • Young patients with ascites, either bilateral or unilateral ovarian lesions, should be evaluated for potential metastatic ovarian involvement.
    • Laparoscopy is the method of choice for differential diagnosis.

    Common Metastatic Sites

    • Gastric
    • Primary colorectal
    • Breast
    • Gynecologic carcinomas
    • Krukenberg tumor

    Screening

    • Effective screening strategies for the early detection of ovarian cancer do not exist.
    • Women with high risk of developing ovarian cancer (germline mutations in BRCA1 or BRCA2) may undergo risk-reducing surgery (bilateral salpingo-oophorectomy).
    • Screening strategies in women with average risk use CA125, and transvaginal ultrasonography. These methods may detect early stage cancers, but don't improve patient mortality.

    Primary Fallopian Tube Carcinoma (FTC)

    • Tumors primarily located in the fallopian tube, arising from endosalpinx.
    • Papillary pattern of tubal mucosal involvement, with identifiable transition from benign to malignant epithelium.
    • Can be concurrent in ovaries or endometrium, but should be smaller than those in the fallopian tube.
    • Approached and managed similarly to ovarian cancers due to similar clinical and histologic features.

    Fallopian Tube Carcinoma (continued)

    • Two-thirds of cases occur in the postmenopausal period.
    • Average age is 60-69.
    • Histological types:
      • Serous
      • Mucinous
      • Endometrioid
      • Undifferentiated
      • Transitional carcinomas

    Diagnostic Criteria

    • Diagnosis in advanced stages, mostly postoperatively.
    • The main tumor arises from the endosalpinx.
    • The histologic pattern resembles tubal mucosa.
    • Transition from benign to malignant tubal epithelium is demonstrable.
    • If both tube and ovary affected, larger part of tumor is in the tube.

    Incidence

    • Fallopian tube carcinomas have clinical and histopathologic features similar to primary peritoneal and high-grade serous carcinomas.
    • They represent 1-2% of all gynecologic malignancies.
    • Incidence is reported at 0.41 per 100,000 annually.

    Epidemiology and Risk Factors

    • Primary fallopian tube cancer thought to emerge from chronic tubal inflammation.
    • Data on risk factors are limited.
    • Postmenopausal progestin-based hormonal therapies (estradiol combined with levonorgestrel-releasing intrauterine system) and sequential estradiol-progestin therapy are associated with higher risk.
    • Demographic risk factors: age and race (majority of cases in white women aged 50-60).
    • Family history of fallopian tube cancer, BRCA 1 mutations, and Lynch syndrome are also associated with increased risk.
    • Use of birth control pills and an increased number of pregnancies are likely protective factors.

    Risk Factors (continued)

    • BRCA1 and BRCA2 mutations in primary FTC (11% and 5% of cases respectively)
    • Chronic tubal inflammation
    • Infertility
    • Tubal endometriosis
    • Tuberculous salpingitis
    • Families with high risk of breast and ovarian cancer
    • Ethnicity (Ashkenazi Jews)

    Signs and Symptoms

    • Presenting symptoms are vague but can include: abdominal bloating, fullness, difficulty eating, bowel or bladder changes, pelvic/abdominal pain, and bleeding or watery vaginal discharge (Latzko triad)
    • Postmenopausal vaginal bleeding, which may suggest fallopian tube or endometrial carcinoma.
    • Watery vaginal discharge (hydros tubae profluens) in ~5% of cases.

    Diagnosis

    • Imaging, blood work (CA-125), and biopsy confirm.
    • Sausage-shaped or cog-and-wheel appearance on imaging.
    • Diagnosis can be delayed up to 48 months.
    • Ovaian malignancy algorithm(ROMA) to assist in distinguishing malignant from benign masses(assesses CA-125, human epididymis protein 4 (HE4), and menopausal status.)

    Staging and Grading

    • Shows similarity to ovarian carcinoma, using FIGO staging system (most recently updated in 2014).
    • Categorized as low-grade or high-grade serous carcinoma.
    • High-grade types are associated with advanced stage and TP53 and BRCA mutations..
    • Low-grade types are less common and associated with KRAS and BRAF mutations.

    Treatment

    • Surgical resection is the primary treatment, with adjuvant therapy required in some cases
    • TAH + BSO + omentectomy + pelvic and paraaortic lymphadenectomy

    Keynotes for FTC

    • Triad of pain, metrorrhagia and leukorrhea are considered pathognomonic for FTC.
    • BRCA1 and BRCA2 carriers should undergo extensive fallopian tube-sectioning during risk-reducing surgery.
    • Serous Tubal Intraepithelial Carcinoma is a precursor lesion to high-grade serous carcinoma.
    • Early salpingectomy with delayed oophorectomy currently being studied for potential high-risk women.

    Genetic Screening

    • American Cancer Society recommends genetic testing for:
      • Individuals with known familial history of BRCA mutations.
      • Individuals with ovarian, pancreatic, or a family history of breast cancer at a younger age.
      • Those with more than one family member with breast cancer
      • Individuals with male breast cancer.

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