TUBA CANCER
• It is a rare tumor (0.3%) that behaves like ovarian cancer. It usually occurs between the ages of 50-60. They are often metastatic rather than primary tumors. The presence of tubal epithelial dysplasia is required to call tubal carcinoma primary. In order of frequency, the most frequently metastasized tumors are ovarian, endometrial, gastrointestinal system and breast cancer.
• However, it is thought that primary tubal cancers are more common than previously thought. Today, it is accepted that the most common high-grade serous carcinoma is mostly caused by fimbria and tuba uterina, and its etiological origin is tuba uterine and peritoneal cancer.
• Almost all primary tubal cancers are cancers of epithelial origin and serous cancers are the most common. The presence of BRCA1 and BRCA 2 gene mutations is a high risk factor for the development of tubal cancer.
Clinic
• Although it is known with the classic triad of profuse watery vaginal discharge, pelvic pain, and pelvic mass, this triad is seen only in 15% of cases. On the other hand, vaginal discharge and bleeding are the most common symptoms (50%).
• 60% of the patients have a pelvic mass, and if this mass is pressed during the examination, this mass is felt to be getting smaller and smaller with an excessive watery vaginal discharge. This is called hydrops tuba profluens and is pathognomonic.
• Elevated Ca 125 levels are frequently observed in advanced cancers.
Spread
• Spread is most commonly in the form of peritoneal implantations by the transcoemic route. Lymphatic spread is also common, paraaortic lymph nodes are involved in 33% of cases.
Prognosis
• The prognosis depends on the stage of the disease.
Staging
• Staging is surgical and the same as for ovarian cancer.
Treatment
• TAH+BSO+ pelvic-paraaortic lymph node dissection+infracolic omentectomy is performed surgically. The most effective postoperative chemotherapy agents are alkylating agents and cisplatin (paclitaxel+carboplatin).
ovarian tumours
Gynecological malignancies with the highest mortality
Histopathological Classification
Epithelial Tumors (Occurring from Coelomic / Germinal Epithelium) (65-90%)
► Serous tumors; Benign, borderline, malignant (46%)
► Mucinous tumors; Benign, borderline, malignant (36%)
► Endometrioid tumors; Benign, borderline, malignant (8%)
► Clear cell (mesonephroid) tumors; Benign, borderline, malignant (3%)
► Brenner tumor (Transitional); Benign, borderline, malignant (2%)
► Undifferentiated tumors (2%)
► Mixed epithelial tumors; Benign, borderline, malignant (3%)
Germ Cell Tumors (5-15%)
► Primitive germ cell tumors
0 Dysgerminoma (30-40%) (most common malignant germ cell tumor)
0 Yolk sac tumor (endodermal sinus tumor) (10%)
0 Embryonal carcinoma (4%)
0 Polyembryoma
0 Choriocarcinoma (nongestational)
0 Mixed germ cell tumors
► Biphasic / Triphasic teratomas
0 Immature teratoma (10-20%)
0 Mature teratoma (most common germ cell tumor)
- Solid teratoma
- Cystic teratoma (dermoid cyst, fetiform teratoma-homunculus)
► Monodermal teratomas and somatic tumors associated with dermoid cyst
0 Struma ovarii (thyroid tissue)
0 Carcinoid (neurosecretory tissue)
0 Neuroectodermal tumor
0 Other; Melanocytic, carcinoma, sarcoma, sebaceous tumors, pituitary type tumor
Sex cord stromal (mesenchymal) tumors (5-8%)
► Granulosa-stromal cell tumors
0 Granulosa cell tumor; Adult and juvenile type
0 thecoma- fibroma group
- thecoma
- Fibroma
- Other; Cellular fibroma, Fibrosarcoma, Sclerosing stromal tumors, Signet ring cell stromal tumors, fibrothecoma
► Sertoli-stromal cell tumors
0 Sertoli-Leydig cell tumor group (Androblastoma)
0 Sertoli cell tumor
0 Stromal-Leydig cell tumors
► Mixed or unclassified sex cord stromal tumors
0 Sex cord stromal tumor containing annular tubules (may be associated with Peutz-Jeghers Syndrome)
0 Gynandroblastoma (components must be specified)
0 Unclassified sex cord stromal tumors
► Steroid cell tumors
0 Leydig cell tumor group
- Hilar cell tumors
- Nonhilar type Leydig cell tumors
- Leydig cell tumors not otherwise named
0 Steroid cell tumor not otherwise named
Metastatic Tumors (5-6%)
Bilaterality rate in ovarian tumors
Epithelial Tumors
- Serous cystadenocarcinoma ----------------------------------------------- --- ► 33-66%
- Endometrioid carcinoma ----------------------------------------------- ------ ► 13-30%
- Mucinous cystadenocarcinoma -----------------------------------------------► 10-20%
- Serous cystadenoma ----------------------------------------------- ----------------► 10%
- Benign Brenner tumor ---------------------------------------------- ---------► 6%
- Mucinous cystadenoma ----------------------------------------------- -----------► 5%
Germ Cell Tumors
- Benign cystic teratoma ---------------------------------------------- --------► 12%
- dysgerminoma ------------------------------------------------ -------------------►5-10%
- immature teratoma------------------------------------------------ ---------------►2-5%
- Other malignant germ cell tumors -------------------------------------------------rare
sex cord stromal tumors
- Tekoma ------------------------------------------------ --------------------------- ► Rare
- Sertoli-Leydig cell tumor ------------------------------------------ - ► Rare
- Granulosa-theca cell tumor------------------------------------------ ► Rare
Staging
Staging of ovarian tumors is surgical.
|
FIGO
staging |
|
|
1 |
Tumor limited to the ovary or ovaries |
|
1A |
Tumor limited to one ovary; Capsule intact, no tumor
on the ovarian surface, no acid and/or washing liquid containing malignant
cells |
|
1B |
Limited tumor in both ovaries; Capsule intact, no
tumor on the ovarian surface, no acid and/or flushing cyst containing
malignant cells |
|
1C |
Limited tumor in one or both ovaries accompanied by
any of the following |
|
2 |
Tumor involving one or both ovaries with pelvic
extension |
|
2A |
Tumor that has spread and/or implanted to the uterus
and/or tuba |
|
2B |
Tumor spreading to other pelvic intraperitoneal
tissues |
|
3 |
Tumor involving one or both ovaries outside the
pelvis with cytological or histologically demonstrated peritoneal spread
and/or metastasis to retroperitoenal lymph nodes |
|
3A |
Retroperitoneal lymph node metastasis and/or
microscopic extrapelvic peritoneal involvement |
|
3A1 |
Positive retroperitoneal lymph nodes only
(cytologically or histologically proven) |
|
3A2 |
Microscopic extrapelvic peritoneal involvement with
or without retroperitoneal lymph node metastasis |
|
3B |
Macroscopic extrapelvic peritoneal metastasis s 2 cm
in size with or without retroperitoneal lymph node metastasis |
|
3C |
Macroscopic extrapelvic peritoneal metastasis > 2
cm with or without retroperitoneal lymph node metastasis (includes
liver/spleen capsule involvement) |
|
4 |
Distant metastases other than peritoneal metastases |
|
4A |
Pleural effusion with cytology positive |
|
4B |
Extra-abdominal organ metastases, including
involvement of lymph nodes outside the abdominal cavity and inguinal lymph
nodes. (Includes liver/spleen parenchymal metastasis) |
Depth of invasion has no role in staging ovarian cancer.
Capsular spread of the tumor to the omentum, spleen or liver is Stage IIIC, while isolated spleen or liver parenchymal metastasis is Stage IVB.
In the presence of transmural intestinal infiltration or umbilical tumoral deposits, it is stage IVB.
Epithelial Ovarian Tumors
• The most common ovarian tumors are epithelial ovarian tumors.
90% originate from the coelomic (germinal) epithelium or mesothelium. Each histologic type of epithelial ovarian tumor is further categorized as benign, borderline (tumor of low malignant potential), or malignant.
• The most common malignant epithelial ovarian tumors are serous cancers (75-80%), less frequently endometrioid (10%), mucinous (5%), clear cell (5%), Brenner (transitional) (<1%) and undifferentiated carcinoma (<1%) is observed.
• Each subtype of epithelial ovarian tumors is histologically similar to the lower genital system epithelium.
characteristics of epithelial ovarian tumors
histological type
• serous
• Endometrioid
• mucinous
• Clear cell
• Brenner
cellular type
• Endosalpingeal
• Proliferative endometrium
• Endocervical, Intestinal
• Müllerian, secretory or gestational endometrium
• Transitional
Risk factors
|
Risk factors
of Epithelial Ovarian Cancers |
Relative
risk |
|
Family history (especially mother, daughter or
sister) and hereditary genetic predisposition |
3--4 |
|
early menarche |
1,5 |
|
late menopause |
1,5--2 |
|
nulliparity |
2--3 |
|
infertility |
2--5 |
|
old age |
3 |
|
The white race |
1,5 |
|
History of chronic perineal talcum powder use |
1,5--2 |
|
Pelvic inflammatory disease |
|
|
Postmenopausal hormone replacement therapy
(long-term estrogen therapy alone) |
3--5 |
|
Living in industrialized western countries; North
America and Northern Europe |
2--5 |
|
High socioeconomic or cultural level |
1,5--2 |
|
BMI height and height; In particular, there is an
increase in endometrioid type ovarian cancer. |
|
Genetic Risk and Hereditary Ovarian Cancers in Epithelial Ovarian Cancers
► 10% of all epithelial ovarian cancers are hereditary. Hereditary ovarian cancers occur an average of 10 years earlier than non-hereditary ones. Because these mutations are inherited in an autosomal dominant manner, a complete pedigree analysis of the patient should be performed. The risk of ovarian epithelial cancer doubles in women who have had breast cancer.
► More than 90% of hereditary ovarian cancers are associated with BRCA1 and BRCA 2 mutations. About 2/3 of all hereditary ovarian cancers are located on chromosome 17. While the (17q21) BRCA-1 tumor develops as a result of a mutation in the suppression gene, approximately 1/3 of hereditary ovarian cancers are located on the 13th chromosome.
(13q12) It develops as a result of mutation in the BRCA-2 tumor suppression gene. Mutations in these two genes increase the predisposition to both ovarian and breast cancer. Patients with ovarian cancer with BRCA1 and BRCA 2 gene mutations are more likely to survive than those without mutations.
► MSH2, MLH1, MSH6 in Hereditary Nonpolyposis Colorectal Cancer Syndrome {Lynch Syndrome) which is another hereditary disease and progresses with Multiple adenocarcinomas (colon, endometrium, ovary, gastrointestinal (stomach), genitourinary system (ureter) tumors and skin tumors) There are mutations in genes responsible for repairing mutations such as PMS1 and PMS2. The gynecological malignancy with the highest increased risk in women with Lynch syndrome is endometrial cancer (40-60%), and there is an increased risk of ovarian cancer (2-5%). The mean age of ovarian cancer in women with Lynch syndrome is 40 years and the clinical features are better than sporadic cases.
Approach to women at high risk of ovarian cancer
1. BRCA1 and BRCA2 gene mutations should be investigated in high-risk patients.
2. Patients who want to preserve their fertility capacity or delay prophylactic surgery should be screened with TVUSG every 6 months.
3. Oral contraceptives should be offered to young women when they are not planning pregnancy.
4. Women who do not want to preserve their fertility or who have completed their family should be offered prophylactic bilateral salpingooopherectomy after the age of 35 (The risk is reduced by 96%)
5. In women with a strong family history of breast or ovarian cancer, annual breast screening should be started by combining MRI, mammography and ultrasonography from the age of 30.
6. In patients diagnosed with Lynch Syndrome, prophylactic hysterectomy and bilateral salipingooopherectomy should be recommended after completion of fertility desire. Endometrial biopsy and TVUSG evaluation of the ovaries can be considered between the ages of 30-35 in those with fertility problems. Colonoscopy should be started between the ages of 20-25 or 10 years before the age of diagnosis of the youngest patient in the family and should be repeated every 1-2 years.
Conditions that reduce the risk of ovarian cancer
1. Multiparity (having at least 1 child reduces the risk by 30-40%)
2. Use of combined oral contraceptives (5 years reduces the risk by 60%)
3. History of tubal ligation or hysterectomy
4. Breastfeeding
5. Prolonged amenorrhea
Scanning
► There is no effective screening method for ovarian cancers. The combined use of pelvic examination, tumor markers, and color Doppler ultrasound is beneficial.
Ca-125
► Since the CA-125 value increases due to many gynecological reasons, its specificity is very low, especially in women of reproductive age. Since it has been shown that CA-125 and transvaginal USG do not reduce mortality due to ovarian cancer, they should not be routinely used in ovarian cancer screening, especially in reproductive age.
► In the postmenopausal period, a CA-125 level of >200 IU/ml has a 96% positive predictive value.
► The upper limit of the normal value of CA-125 is 35 IU/ml.
► Malignant causes of Ca-125 elevation
0 Non-mucinous epithelial ovarian cancers
0 Tubal cancer
0 Endometrial cancer
0 Cervical cancer
0 Pleural, pericardial and peritoneal cancers
0 Pancreatic cancer
0 Breast cancer
0 Colon cancer
0 Lung cancer
0 Liver
0 stomach
ROMA index (risk of ovarian malignancy algorithm)
► Another tumor marker that can be used is human epididymal protein-4.
{HE4) and is used to determine the ROMA (risk of ovarian malignancy algorithm) index together with Ca-125. In most benign conditions that increase Ca125 level (especially in endometriosis), HE4 level is lower. Therefore, false positivity in screening for ovarian cancer is lower.
Color Doppler Ultrasonography
► Neovascularization and low resistance index in color Doppler USG
(<0.4) is in favor of malignancy.
Clinic
► Invasive epithelial cancers are most common between the ages of 56 and 60, and 80% of them are observed in the postmenopausal period.
► It can remain silent for a long time. The most common symptoms are swelling, tension and pain in the abdomen. Constipation or incontinence symptoms may occur as a result of compression.
► The most important finding is the detection of a pelvic mass. Solid, irregular and fixed pelvic mass is highly suspicious for ovarian cancer. In addition, if there is an upper abdominal mass and ascites, the diagnosis of ovarian cancer is almost certain.
Spread
► Transcoelomic: It occurs by the implantation of exfoliated cells on the peritoneal cavity surfaces. It is the most common and earliest way of spread.
► Lymphatic: Spread to the pelvic and paraaortic lymph nodes is common, especially in the advanced stages of the disease.
► Hematogenous: Rare.
Prognosis
Prognostic Factors
1. The stage of the disease; It is the most important prognostic factor in advanced cancers.
2. Histological grade; It is an important prognostic factor in early stage cancers and is a strong predictor for occult metastases.
3. Acid volume
4. Malignant peritoneal cytology
6. Extent of residual tumor after primary surgery
7. Age
8. Performance status; Survival was significantly reduced in patients with low Karnofsky index.
9. Histological type; The prognosis is worse in advanced clear cell and mucinous cancers.
10. biomarkers
• Aneuploidy (50-80%); It is the most important determinant of survival.
• S phase / proliferative phase
• Abnormal oncogene expression and tumor suppressor gene mutation
- HER-2/neu; Associated with poor prognosis
- p53; It is the most common mutation in ovarian cancers (50%).
- K-ras; Common in borderline serous tumors and mucinous tumors
- BRAF; Berderline serous tumors are observed in 20%.
- PTEN
- Cyclin E amplification; Associated with poor prognosis
- Myc amplification
Prognostic Factors in Early Stage Epithelial Ovarian Cancers
High risk
• High grade
• Tumor beyond the capsule
• There is surface involvement
• There is acid
• Peritoneal cytology (+)
• Preoperative rupture
• Aneuploid tumor
• Presence of dense adhesion
low risk
• Low grade
• Intact capsule
• No surface involvement
• No acid
• Peritoneal cytology (-)
• Absence of rupture or intraoperative rupture
• Diploid tumor
• Absence of dense adhesion
In early stage ovarian tumors, intraoperative iatrogenic rupture of the tumor does not have a poor prognostic effect.
Histological Types of Epithelial Ovarian Cancers
Serous Cystadenocarcinoma (75-80%)
It is the most common tumor among epithelial ovarian tumors. Papillary formations are seen in 80% of these tumors.
0 Psammoma bodies seen in areas of intussusception are associated with a good prognosis and are found in the primary tumor focus while being in the metastasis focus.
0 Composed of tubal epithelium (endosalpingeal}-like columnar ciliated epithelium
0 Most common bilateral epithelial ovarian tumor (50%)
0 Although it is believed that epithelial ovarian cancers arise from the surface epithelium of the ovary, increasing evidence indicates that some high-grade serous ovarian cancers arise from the fimbrial end of the Fallopian tube rather than the ovary. Therefore, serous epithelial ovarian tumors are divided into two different groups as type I (low grade) and type II (high grade) according to their cell origin, molecular pathogenesis and biological behavior.
Types of Serous Ovarian Cancer
TYPE I Serous Ovarian Cancer
• Has a slower developmental stage.
• Includes serous borderline tumors and low grade serous carcinomas.
• They are genetically stable tumors.
- • It is characterized by K-ras and B-raf mutations.
TIP 2 serous Ovarian Cancer (More Common)
• They are highly aggressive and mostly advanced stage tumors that grow rapidly, lack well-defined precursor lesions.
• They start from the fimbrial end of the fallopian tube.
• They are not genetically stable.
• They contain p53 and BRCA mutations.
Primary peritoneal tumors are histologically indistinguishable from serous tumors of the ovary.
Endometrioid Cystadenocarcinoma (10%)
0 Endometriosis can be observed in the pelvis or ovary in most of the cases (up to 40%).
0 These are tumors that are similar to grade I or 2 endometrioid adenocarcinomas in the uterine corpus. It is the most common ovarian tumor associated with endometrial cancer and is accompanied by endometrial adenocarcinoma in 15-20% of cases (synchronous multifocal disease).
Mucinous Cystadenocarcinoma (5%)
0 These tumors are the largest of the ovarian tumors (16-17 cm).
0 Well-differentiated tumors resemble mucin-secreting intestinal or endocervical epithelium. Therefore, it may be difficult to distinguish it from gastrointestinal carcinoma metastasis only histologically without clinical correlation. High-grade primary ovarian mucinous cancers are rare and metastasis must be excluded.
Pseudomyxoma peritonei can be seen in mucinous tumors, but the most common cause of this condition is appendiceal mucinous neoplasm or other primary gastrointestinal tumors. Therefore, appendix or other intestinal foci should be investigated and appendectomy should be performed in all cases.
Transitional Cell Carcinoma (Brenner tumor) ( < 1%)
0 99% of cases are benign and malignant Brenner tumor is extremely rare. It is transitional cell (similar to bladder epithelium). Coffee bean cells and Walthard islets are seen.
Clear Cell Carcinoma (Mesonephroid carcinoma) ( < % 1)
0 They are usually seen between the 5th and 7th decades and 2/3 of the cases are nulliparous women. Most are unilateral. It is often grade 3 and no grading is required.
0 There is a risk of developing hypercalcemia, hyperpyrexia or pelvic venous thrombosis paraneoplastically.
0 More than 50% of the cases are associated with ovarian or pelvic endometriosis. Focal endometriosis foci are common within the tumor, and mixed clear cell and endometrioid carcinomas may be seen.
Histologically, it is identical to clear cell carcinomas of the vagina and uterus that occur in young women as a result of inutero exposure to DES. Tumors lined with cells resembling mullerian epithelium histologically. Clear cells and hobnail cells are typical in tumors.
Typically, the tumor is limited to the ovary, but 20% of cases are advanced-stage tumors that are resistant to platinum-based chemotherapy and have a worse prognosis than serous carcinomas.
Borderline Epithelial Ovarian Cancers (Low Malignant Potential Tumors)
0 It is the most common type of epithelial ovarian cancer in the reproductive age. It is commonly seen in premenopausal women and younger age. The average age of onset is 46. The prognosis is usually very good.
Diagnosis of borderline epithelial ovarian tumors criteria
1. Mild nuclear atypia
2. Slightly increased mitotic activity
3. Microscopic papillary projection (micropapillary and cribriform structure)
4. Epithelial stratification; Epithelial hyperplasia with pseudostratification
5. Cellular pleomorphism and discrete cell clusters
6. Absence of destructive stromal invasion (no tissue destruction)
0 At diagnosis, the tumor is usually confined to the ovary and more than 80% of all cases have stage I disease. Rarely, peritoneal implants can be seen and these implants can be invasive or noninvasive.
0 Resection of the primary tumor is sufficient for treatment.
Treatment in Epithelial Ovarian Cancers
► In general, primary treatment in early stage cancers is total abdominal hysterectomy + bilateral salpingooopherectomy and staging surgery. In advanced disease, cytoreductive surgery should be performed if the patient is medically stable. In other words, it is aimed to remove all of the tumor and metastatic masses as much as possible (Debulking). Residual tumor diameter It should be < 1 cm.
► Platinum-based adjuvant chemotherapy is used after optimal surgery in epithelial ovarian cancers. All cases are given adjuvant chemotherapy, except for stage 1A or IB, grade 1 or 2 cancer. Commonly used chemotherapy regimen Paclitaxel + Carboplatin.
► PARP inhibitors (Niraparib, olaparib) can be used in platinum-sensitive epithelial ovarian cancers, especially in patients with BRCA mutations.
Germ Cell Ovarian Tumors
• 1/3 of all ovarian neoplasms are germ cell tumors. The most common germ cell ovarian tumor is mature cystic teratoma (dermoid cyst), and 95% of all germ cell tumors are benign. Germ cell tumors only
3% of them are malignant and they constitute 5% to 1% of all ovarian cancers. The most common malignant germ cell ovarian tumors are dysgerminoma, yolk sac tumor and immature teratoma.
• They originate from the primordial germ cells of the ovary. Due to the peculiarity of the migration pathway of germ cells in the embryological period, malignant germ cell tumors can also be seen in the mediastinum and retroperitoneum extragonadally.
• These tumors are tumors of the first 2 decades, but they can rarely be seen in the third decade. Most patients are diagnosed in stage I. Due to their sensitivity to chemotherapy, their prognosis is excellent even in advanced disease.
• Most of the signs and symptoms of germ cell tumors are related to tumor growth and hormone production. Germ cell tumors grow quite rapidly in contrast to epithelial ovarian tumors. They are usually manifested by subacute pelvic pain due to stretching of the capsule, hemorrhage or necrosis of the tumor. Hormonal changes are frequently observed in these tumors. They can cause irregular and excessive menstrual bleeding.
• 2 cm in the premenarchal age group. and above adnexal masses usually require surgical exploration. Preoperative hCG, AFP, LDH and Ca 125 levels should also be checked in young patients. Since germ cell tumors can develop from a dysgenetic gonad background, preoperative karyotype analysis should be performed in young patients with suspected germ cell tumors and in all premenarchal patients to determine whether both gonads should be removed.
• Classification of germ cell tumors is made according to histological features and the presence of tumor markers immunohistochemically.
|
Tumor
Markers in Germ Cell Ovarian Tumors |
|
|
dysgerminoma |
AFP (-), hCG (±), LDH (+) Plasental ALP(+) |
|
Endodermal Sinus Tumor |
AFP(+), hCG (-) |
|
immature teratoma |
AFP(±), hCG (-) |
|
choriocarcinoma |
AFP(-), hCG (+) |
|
Embryonal Carcinoma |
AFP(+), hCG (+) |
|
polyembryoma |
AFP(±), hCG (±) |
|
Mixed germ cell tumor |
AFP(±), hCG (±) |
Dysgerminoma (30-40%)
► It is the most common malignant germ cell ovarian tumor. 75% of the cases are between the ages of 10-30. It is the most common malignant ovarian tumor in pregnancy (20-30%)
► It is the most common malignant germ cell ovarian tumor with bilaterality. (10-15%)
► It develops from benign gonadoblastoma. Homologous to seminoma in males.
► Histologically, fibrous septa, granuloma and diffuse necrosis are found within the lobules. Therefore, it is confused with tuberculosis. Sometimes they may contain syncytiotrophoblastic giant cells, in which case precocious puberty or virilization is seen.
► The most common symptom is rapid enlargement of the abdomen.
► LDH and placental alkaline phosphatase (PLAP) levels increase in 95% of cases. AFP never rises in dysgerniomas. hCG is usually negative, but hCG levels may be elevated, typically < 100 IU, due to syncytiotrophoblasts in approximately 5% of cases.
► The most common form of spread is lymphatic spread and the most common lymphatic spread is ovarian tumor.
► Treatment is conservative surgery and the minimum surgery for dysgerminoma is unilateral salpingooopherectomy. In metastatic disease, adjuvant chemotherapy is applied. The most commonly used chemotherapeutic regimen is the BEP (bleomycin, etoposide, cisplatin) protocol.
► It is the only ovarian tumor sensitive to radiotherapy, but the superiority of chemotherapy over radiotherapy has been clearly demonstrated.
► Dysgerminoma is the tumor with the best prognosis among all malignant germ cell ovarian tumors.
Gonadoblastomas contain germ cells and sex cord stroma. They are defined as germ cell/sex cord stromal tumors according to the WHO classification.
Teratomas
Immature Teratoma (10-20%)
0 They arise from embryonic cells and contain immature embryonal structures and typically contain immature neuroepithelials. 50% of immature teratomas are seen between the ages of 10-20.
0 Tumor markers are often negative. In some pure teratomas, AFP may be elevated, but hCG will not. In some cases, there may also be elevated CA125, CA19-9 and CEA. The most common site of spread is peritoneal spread.
0 The most important prognostic factor is the grade of the tumor. The amount of immature neuroepithelial tissue is used to determine the grade and is associated with survival time.
0 Treatment consists of unilateral oophorectomy and marginal surgical staging for tumors confined to a single ovary in premenopausal patients. Routine contralateral wedge resection is not necessary, as they are rarely bilateral. Total abdominal hysterectomy + bilateral salpingooopherectomy and surgical staging should be performed in postmenopausal patients.
Mature Cystic Teratoma (Dermoid cyst)
It is the most common teratoma (95%). It also accounts for 10-25% of all ovarian neoplasms and 60% of all benign ovarian neoplasms. It is the most common non-functional ovarian tumor in the 2-3 decade. However, unlike other germ cell ovarian tumors, there is a wide age distribution.
10% shows bilaterality.
They contain endo, ecto and mesodermal components. The most common are the components of ectodermal origin (hair follicle, sebaceous and sweat glands). The karyotype is observed as 46 XX in all mature cystic teratomas. There is a risk of malignancy over the age of 40, but the incidence is low (1%).
0 The most common cancer of teratoma, which is completely benign at the beginning, is squamous cell carcinoma.
0 The most common complication is torsion and the most common torsion is ovarian tumor (15%).
0 Mature cystic teratomas are the most common benign ovarian tumors in pregnancy.
0 Cystectomy is sufficient for treatment, rarely oophorectomy.
Monodermal Tratoma
0 Struma ovarii is a benign teratoma. Its main component is the parenchymal tissue of the thyroid and gives clinical signs of hyperthyroidism. Treatment is simple surgical excision.
0 Carcinoid tumors arise from the gastrointestinal and respiratory epithelium within the teratoma. Most of the cases are postmenopausal. There is 5-HIAA excretion in the urine. The treatment is surgical excision.
Endodermal Sinus Tumor (EST) (Path Sac Tumor) (10%)
► It develops from the primitive vitelline sac and originates from the extraembryonic tissues. The mean age at diagnosis is 18 years and 1:3 of cases are in the premenarchal period.
► Very rapid growth is the characteristic finding. Abdominal or pelvic pain is the most common symptom (75%).
► Most tumors secrete AFP. The prevalence of the disease is also correlated with the level of AFP. The hCG level is normal. In a small proportion, detectable levels of alpha-I antitrypsin are secreted.
► Microscopically characteristic structures are Schiller-Duval bodies.
► Treatment is unilateral salpingooopherectomy. Surgical staging is not necessary for every patient, as every patient must receive absolute chemotherapy (BEP). There is no bilaterality and biopsy from the other ovary is strictly contraindicated as they are always unilateral.
► The most deadly malignant germ cell tumor is endodermal sinus tumor.
Embryonal Carcinoma
► They are primitive tumors consisting of undifferentiated epithelial cells, which are the precursors of many germ cell tumors and resemble cells in the embryonic disc structure. It is distinguished from choriocarcinoma by the absence of cyto and syncytiotrophoblast.
► Patients are characteristically younger than other germ cell ovarian tumors and the mean age at diagnosis is 14 years.
► They can sequester estrogen and accordingly, pseudopuberty precox and irregular bleeding can be observed.
► They secrete AFP and hCG
► Its treatment is unilateral salpingooopherectomy followed by combined chemotherapy (BEP).
polyembryoma
► It is a tumor in which embryoid bodies are observed and mimics early embryonic differentiation (endoderm, mesoderm, ectoderm).
► It has high AFP, and hCG levels.
► It tends to occur in very young, premenarchal girls and in premenarchal patients
may cause symptoms of pseudopuberty.
► It is very sensitive to chemotherapy.
Choriocarcinoma
► It originates from extraembryonic tissues.
► The vast majority are patients younger than 20 years of age. Rarely, it can be bilateral.
► There are high hCG levels. Premenarchal patients with high hCG levels have isosexual precocious puberty at 50%. In women of reproductive age, it can cause irregular and heavy menstrual bleeding.
► Since most of the patients have organ parenchymal metastases at the time of diagnosis,
The prognosis is very poor.
Mixed Germ Cell Tumors
► The most common coexisting structures are dysgerminoma (80%) and endodermal sinus tumor (70%). In addition, immature teratoma (53%), choriocarcinoma (20%) and embryonal carcinoma (16%) may accompany dysgerminoma.
► Depending on the type of their components, AFP and hCG may be secreted or none of them may be secreted.
► The most important prognostic factor is tumor size and the rate of presence of the most malignant component.
► Treatment should be determined according to the component other than dysgerminoma. BEP chemotherapy should be preferred after surgery in treatment.
There is no indication for adjuvant chemotherapy in stage IA dysgerminoma and stage IA, grade I immature teratomas. Adjuvant chemotherapy (BEP) should be given in all other and more advanced germ cell ovarian tumors.
Sex Cord-stromal Tumors
• This group of tumors originates from the sex cords of the gonad and the ovarian stroma (or mesenchyme). At the time of diagnosis, they are usually limited to one ovary and most of them have low malignant potential, and the primary treatment is surgical resection. Relapses are infrequent and recurrences are usually seen late and in the abdomen or pelvis.
• Almost all (90%) of these tumors produce hormones, and affected patients typically have symptoms and signs related to estrogen or androgen release.
• Unlike epithelial ovarian cancers and malignant germ cell ovarian tumors, they can be seen in all age groups.
|
Tumor
Markers in Sex Cord Stromal Ovarian Tumors |
|
|
Granulosa cell tumor (adult or juvenile) |
Inhibin A and Inhibin B |
|
Sertoli-Leydig cell tumor |
Inhibin A and Inhibin B |
|
Sex cord stromal tumor with annular tubules |
inhibin A and inhibin B |
|
Steroid cell, not otherwise named |
steroid hormones |
Immunohistochemical staining with inhibin is used to differentiate ovarian sex cord stromal tumors from epithelial, germ cell and other spindle cell neoplasms.
Modified WHO Classification of Sex Cord Stromal Ovarian Tumors
A) Pure Stromal Tumors
Fibroma/fibrosarcoma
thecoma
sclerosing stromal tumor
Leydig cell tumor
steroid cell tumor
B) Pure Sex Cord Tumors
Granulosa cell tumor; Adult and juvenile type
Sertoli cell tumor
Sex cord stromal tumor containing annular tubules
C) Mixed Sex cord-stromal tumors
Sertoli-Leydig cell tumor
sex cord stromal tumors, NOS; Tumors not otherwise named
Granulosa Cell Tumor
► It is the most common malignant sex cord stromal tumor. There are adult (95%) and juvenile (5%) types.
► 20 cm to millimeter dimensions. Only 2% of cases are bilateral.
► DNA ploidy of the tumor is associated with survival and is an independent prognostic factor.
Adult type
0 It is most common in the 45-55 age group (immediately after menopause). 20 cm from millimeter dimensions. as much as they can.
0 Somatic point mutations are observed in the gene encoding FOXL2 (forkheaf box protein L2) in all adult type tumors. However, it is not available in juvenile form.
0 They usually secrete estrogen. Most patients in the reproductive period have menstrual irregularities or amenorrhea. Abnormal uterine bleeding is a common symptom in postmenopausal women. The most common causes of endometrial hyperplasia (25-50%) and endometrial cancer (5%) are ovarian tumors. For this reason, endometrial biopsy should be performed first for a premenopausal patient with a granulosa cell tumor in the ovary.
0 Granulosa cell tumors tend to be hemorrhagic and often rupture, causing hemoperitoneum.
0 Characteristic Call-Exner bodies are found
0 Inhibin is released from granulosa cell tumors and is a very useful marker in diagnosis and follow-up.
0 The adult type has a long natural course and is prone to late relapse.
0 If there is a desire to have children in early stage tumors, conservative surgery (unilateral salpingooopherectomy) is sufficient. Hysterectomy and bilateral salpingooopherectomy should be performed in perimenopausal and postmenopausal women.
juvenile type
0 They are the most common functional tumors in childhood. Affected patients often have menstrual irregularity or amenorrhea. In prepubertal patients, they typically cause isosexual pseudopuberty precox (75%) due to estrogen secretions.
0 Acute abdomen due to hemoperitoneum resulting from preoperative rupture is seen in 5-10% of the cases.
0 Concomitantly, Olier's Disease or Maffuci Syndrome may be seen.
0 Call-Exner bodies are rarely observed.
0 Less aggressive than the adult type. However, in advanced stage tumors, they are more aggressive than the adult type, and the relapse time and time of death are shorter.
0 Conservative surgery (unilateral salpingooopherectomy) is sufficient for early stage tumors.
thecoma
0 They are rarely malignant and typically occur in postmenopausal women (mid 60s). Bilateral ovarian involvement is rare (2-3%).
0 Among the sex cord stromal tumors, they are the most hormonally active tumors and generally secrete estrogen. Therefore, abnormal vaginal bleeding may occur. 78% of the cases are associated with endometrial hyperplasia and 21% with endometrial cancer.
0 They are clinically benign tumors and surgical excision is curative.
Endometrial biopsy should be taken in cases of granulosa cell ovarian tumor and thecoma, especially if fertility-sparing surgery is planned.
Fibroma
► They can be seen in all age groups, but are often seen in perimenopausal and menopausal women. They are hormonally inactive
► It is of mesothelial origin. They are rarely bilateral. They are solid and usually benign tumors.
► The presence of pleural effusion (hydrothorax) and ascites in the abdomen is called Meigs Syndrome. Fibromas are benign and in case of paracentesis, no malignant cells are seen in the ascitic fluid.
► Gorlin Syndrome, on the other hand, is a syndrome characterized by the presence of basal cell nevi and some hereditary anomalies in the early stages of life, usually characterized by bilateral ovarian fibromas.
► Treatment is unilateral salpingooopherectomy in benign fibroma
Sertoli Cell Tumor
► They are known as well-differentiated androblastoma. They are usually unilateral and the average age of onset is 30.
► Most of these tumors are clinically nonfunctional, but 25% of the cases may cause estrogenic or androgenic findings. Menstrual irregularity, postmenopausal bleeding, isosexual precocious puberty or increased libido may be observed due to estrogenic activity, as well as virilization due to androgenic activity.
► Rarely, the picture accompanies hyperaldosteronism, hypokalemia and hypertension.
► Conservative surgery is used in the treatment.
Sertoli Leydig Cell Tumor
► More than 90% of the cases occur in the reproductive age (usually in the 3rd and 4th decades), and 75% of the cases are under the age of 40. Their malignancy potential is low.
► They typically secrete androgens and virilization is seen in 70%-SS of patients. They are the most common virilizing tumors in women of reproductive age. Virilization findings; amenorrhea, breast atrophy, acne, hirsutism, clitoromegaly, deepening of the voice, and thinning of hair following oligomenorrhea. Plasma testosterone and androstenedione levels are increased, DHEA-S level is within normal limits or slightly elevated. Rarely, estrogenic activity can be seen.
► In women of reproductive age, unilateral salpingooopherectomy and evaluation of the contralateral ovary are usually sufficient. In older women, hysterectomy and bilateral salpingooopherectomy are appropriate approaches.
gynandroblastoma
► It is the rarest sex cord stromal ovarian tumor.
► Contains granulosa-theca and Sertoli-Leydig cell components. They are generally unilateral, small and benign.
► It can be estrogenic and/or androgenic as well as hormonally neutral.
► Contains intracytoplasmic Reinke crystals from Leydig cell components. It contains Call Exner bodies from granulosa cell components.
► Treatment is conservative surgery (unilateral salpingooopherectomy).
Steroid cell Tumor
Leydig Cell Tumor (hilar or nonhilar)
► It is a clinically benign tumor and typically occurs in postmenopausal women.
► Inclusions called intracytoplasmic Reinke crystalloids are characteristic
► They secrete testosterone and are often (3/4) associated with androgenic effects.
Steroid cell tumor (NOS) not otherwise classified
► It is characteristically seen in young women of reproductive age.
► Typically associated with androgen production (50% of cases) but overproduction of estrogen or cortisol (Cushing's Syndrome) has also been reported.
► 1/3 of the cases are clinically malignant and their prognosis is poor.
Sex Cord Tumors with Annular Tubules
► These tumors are divided into two subgroups according to whether they are accompanied by gastrointestinal polyposis and oral-cutaneous melanin pigmentation (Peutz-Jeghers Syndrome).
Those associated with Peutz-Jeghers Syndrome;
► 1/3 of cases. They are typically small, bilateral, and clinically benign tumors. The average age of onset is 27. In 15% of cases, adenoma malignum (a rare and well-differentiated adenocarcinoma) develops in the cervix. Treatment is conservative.
Those unrelated to Peutz-Jeghers Syndrome;
► It is 2/3 of the cases. Typically, this group is large, unilateral, and has a 15-20% rate of carrying a clinical malignancy. The average age of onset is 34. Surgical staging and TAH + BSO must be performed in the treatment.
Sclerosing stromal tumor
► They are rarely seen and the average age of occurrence is 20 years. They are clinically benign tumors and are typically unilateral. To the hormonal are inactive tumors.
► Contains histologically prominent areas of sclerosis.
Staging in Sex Cord Stromal Ovarian Tumors
Surgical
A) Staging Surgery IS REQUIRED
Granulosa cell tumor; Adult or juvenile type Fibrosarcoma
Sertoli-Leydig cell tumor (moderate or poorly differentiated type) Sex cord stromal tumor with annular tubules (type unrelated to Peutz-Jeghers Syndrome)
steroid cell tumor
B) Staging Surgery is NOT Necessary
• Tekoma
• Fibroma
• Sclerosing stromal tumor
• Gynandroblastoma
• Sertolileydig cell tumor (well-differentiated type),
• Sex cord stromal tumor with annular tubules (type associated with Peutz-Jeghers Syndrome)
Lipoid cell ovarian tumor; It is a tumor originating from adrenal cortex remnants at the edge of the ovary. It is often associated with virilization. Rarely, corticosteroid secretion is observed and may be accompanied by obesity, hypertension and glucose intolerance.
Small cell ovarian cancer; There are hypercalcemic and pulmonary types. Hypercalcemia is observed in 2/3 of hypercalcemic type tumors and is associated with SMARCA4 gene mutation.
Metastatic Ovarian Tumors (5-6%)
• Approximately 5-6% of ovarian tumors develop as a result of metastasis from other organs. These metastases often originate from the genital tract, breast, or gastrointestinal tract. Metastases to the ovary occur by direct adjacency, hematogenous lymphatic or transcoelomic routes.
Gynecological Metastases
► The most common cancer that metastasizes to the ovary is endometrial cancer. Although 5% of endometrial cancers spread directly to the ovary, the probability of synchronous coexistence of the two cancers is much higher than this figure (often endometrial adenocarcinoma + ovarian endometrioid adenocarcinoma).
► Tubal cancers can spread through the direct neighborhood and can also involve the ovary secondary in 13% of cases.
► Secondary spread of cervical cancers to the ovary is extremely rare (<1%). Most of these cases are adenocarcinoma or advanced stage cases.
Non-gynecological Metastases
The most common source of nongynecological metastatic carcinoma is the tubular gastrointestinal tract, especially colon cancer, followed by the breast and pancreatobiliary tract.
► Metastases of breast cancers to the ovary are very common and 80% of these cases were found to be bilateral.
► 30-40% of ovarian metastatic cancers are Krukenberg tumors
These tumors arise from the stroma of the ovary and classically contain signet ring cells filled with mucin. The primary tumor is most often in the stomach, less often in the colon, appendix, breast, or biliary tract. Very rarely, the primary tumor may also be in the cervix or bladder. Krukenberg tumors are also mostly bilateral.
► Colon cancer and, less frequently, pancreatic-biliary tract, appendix and small intestine cancers are among the other GIS-derived metastases that are not included in the Krukenberg group.
► Metastases of malignant melanoma and carcinoid tumors to the ovary are very rare. In lymphoma and leukemia, the ovaries can also be involved, which is usually bilateral. The most common lymphoma that metastasizes to the ovary is Burkitt lymphoma.
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Pathognomonic
microscopic markers in ovarian tumors |
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Histological Type |
Pathognomonic Microscopic Marker |
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serous |
psammoma body |
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mucinous |
goblet cell |
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Clear cell (mesonephroid tumor) |
Clear cells and hobnail cells |
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Brenner |
Walthard islets |
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Endodermal sinus tumor |
Schiller-Duval bodies |
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Granulosa cell tumor |
Call Exner body |
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Leydig cell tumor |
intracytoplasmic Reinke crystals |
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Krukenberg tumor |
stone body cell |
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carcinoid tumor |
respiratory epithelium |
Pregnancy and Ovarian Tumors
• Pregnancy does not affect the prognosis of many ovarian tumors; however, complications such as torsion or rupture are common and lead to spontaneous abortion and preterm labor frequently.
• Torsion is the most common complication of ovarian tumors during pregnancy. More than half of the torsions are either in the 8-16th week, when the uterus enlarges rapidly. It happens during the puerperal involution of the uterus.
Pregnancy and Ovarian Tumors
Bening ovarian tumors (95%)
• Mature cystic teratoma (dermoid) (most common)
• Serous cystadenoma
• mucinous cystadenoma
Malignant ovarian tumors (5%)
• Malignant epithelial tumors (most common)
• Dysgerminoma (most common alone)
• Malignant sex-cord stromal tumors