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Novak 33. Ovarian ca Novak 33. Ovarian ca Nonepithelial Ovarian Can Nonepithelial Ovarian Can cers cers 부부부부부 부부부부 부부부부부 부부부부 R2 R2 부부부 부부부

Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

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Page 1: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Novak 33. Ovarian caNovak 33. Ovarian ca

Nonepithelial Ovarian CancersNonepithelial Ovarian Cancers

부산백병원 산부인과부산백병원 산부인과R2 R2 박영미박영미

Page 2: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Nonepithelial Ovarian Cancers Nonepithelial Ovarian Cancers

Compared with epithelial ovarian cancers, Compared with epithelial ovarian cancers, other malignant tumors of the ovary are other malignant tumors of the ovary are uncommon uncommon

about about 10%10% of all ovarian cancers of all ovarian cancers

1. malinancies of germ cell origin, 1. malinancies of germ cell origin, sex cord-stromal cell origin, sex cord-stromal cell origin, 2. metastatic carcinoma to ovary 2. metastatic carcinoma to ovary 3. extremely rare ovarian cancers 3. extremely rare ovarian cancers (sarcoma, lipoid cell tumors) (sarcoma, lipoid cell tumors)

Page 3: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies

Page 4: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell Malignancies Germ-Cell Malignancies

                                    

Page 5: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies

◆ ◆ Serum tumor markers in malignant germ cell tumors Serum tumor markers in malignant germ cell tumors : can be clinically useful in the diagnosis of a pelvic mass and : can be clinically useful in the diagnosis of a pelvic mass and in monitoring course of patient after surgery in monitoring course of patient after surgery

α-fetoprotein(AFP), human chorionic gonadotropin(hCG)α-fetoprotein(AFP), human chorionic gonadotropin(hCG) : secreted by germ cell malignancy : secreted by germ cell malignancy

Placental alkaline phosphatase (PLAP), Placental alkaline phosphatase (PLAP), lactate dehydrogenase(LDH) lactate dehydrogenase(LDH) : produced by dysgerminoma : produced by dysgerminoma

Page 6: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies

◆◆ SymptomsSymptoms Germ-cell malignancies grow rapidlyGerm-cell malignancies grow rapidly,, in contrast to the relatively slowin contrast to the relatively slow growing epithelial growing epithelial ovarian tumors ovarian tumors : often are characterized by subacute pelvic pain : often are characterized by subacute pelvic pain related to capsular distension, hemorrhage, or related to capsular distension, hemorrhage, or necrosis necrosis : may produce pressure symptoms on the bladder or : may produce pressure symptoms on the bladder or rectum rectum

Page 7: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies

In menarchal patients, In menarchal patients, menstrual irregularities may also occur menstrual irregularities may also occur

Some young patients may misinterpret the early symptoms of a nSome young patients may misinterpret the early symptoms of a neoplasm as pregnancy eoplasm as pregnancy

--> This can lead to a delay in the diagnosis--> This can lead to a delay in the diagnosis

Acute symptoms associated with torsion or rupture of the Acute symptoms associated with torsion or rupture of the adnexa adnexa

In more advanced cases, In more advanced cases, ascites and abdominal distension may developascites and abdominal distension may develop

Page 8: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies ◆◆ DiagnosisDiagnosis

Adnexal masses will usually require surgical explAdnexal masses will usually require surgical exploration oration 2 cm or larger in premenarchal patient 2 cm or larger in premenarchal patient 8 cm or larger in other premennopausal patient 8 cm or larger in other premennopausal patient

Predominantly cystic lesions up to 8cm in diametPredominantly cystic lesions up to 8cm in diameters in postmenarcheal patients ers in postmenarcheal patients : may be observed or given oral contraceptives for: may be observed or given oral contraceptives for two menstrual cycles two menstrual cycles

Page 9: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Germ-Cell MalignanciesGerm-Cell Malignancies For young patient For young patient

Blood testBlood test - serum hCG and AFP titers, CBC, LFT - serum hCG and AFP titers, CBC, LFT Chest x-rayChest x-ray - evaluation for metastasis to the - evaluation for metastasis to the lung or mediastinum lung or mediastinum Karyotype - Karyotype - preoperatively for all premenarcheal preoperatively for all premenarcheal girl because of the propensity of these girl because of the propensity of these tumors to arise in dysgenetic gonads tumors to arise in dysgenetic gonads CTCT or or MRIMRI - may document retroperitoneal - may document retroperitoneal lymphadenopathy or liver metastases lymphadenopathy or liver metastases

but, such expensive and time- consuming but, such expensive and time- consuming evaluation is unnecessary because the patientsevaluation is unnecessary because the patients require surgical exploration require surgical exploration

Page 10: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

◆◆ Clinical CharacteristicsClinical Characteristics

The most common malignant germ-cell The most common malignant germ-cell tumor (30-40%) tumor (30-40%) 1-3% of all ovarian cancer 1-3% of all ovarian cancer 5-10% of ovarian cancers in patients younger 5-10% of ovarian cancers in patients younger

than 20 years of age than 20 years of age

* 5% : before the age of 10 years, * 5% : before the age of 10 years, * 75% : between the ages of 10 and 30 * 75% : between the ages of 10 and 30

years years * rarely occur after 50 years of age * rarely occur after 50 years of age

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DysgerminomaDysgerminoma

20-30% of ovarian malignancies associated with pregnan20-30% of ovarian malignancies associated with pregnancy are dysgerminomascy are dysgerminomas

Found in both sexes and may arise in gonadal or extragoFound in both sexes and may arise in gonadal or extrago

nadal sites nadal sites

Size varies widely, but usually 5-15cm in diameter Size varies widely, but usually 5-15cm in diameter

Capsule is slightly bosselated, the cut surface consistencCapsule is slightly bosselated, the cut surface consistency is spongy, the color is gray-browny is spongy, the color is gray-brown

Page 12: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

The histologic charactThe histologic characteristicseristics

The large round, ovoid, The large round, ovoid, or polygonal cells or polygonal cells

abundant, clear, very pabundant, clear, very pale staining cytoplasm, ale staining cytoplasm, large and irregular nucllarge and irregular nuclei, and prominent nuclei, and prominent nucleolieoli

Page 13: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

Approximately 5% of dysgerminomas are discoverApproximately 5% of dysgerminomas are discovered in phenotypic females with abnormal gonads.ed in phenotypic females with abnormal gonads.

pure gonadal dysgenesis (46XY, bilateral streak gonadpure gonadal dysgenesis (46XY, bilateral streak gonads), s),

mixed gonadal dysgenesis (45X/46XY, unilateral streamixed gonadal dysgenesis (45X/46XY, unilateral streak gonad, contralateral testis), k gonad, contralateral testis),

androgen insensitivity syndrome (46XY, testicular femiandrogen insensitivity syndrome (46XY, testicular feminization)nization)

∴ ∴ the karyotype should be determined in the karyotype should be determined in premenarcheal patients with a pelvic mass premenarcheal patients with a pelvic mass

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DysgerminomaDysgerminoma

About 75% of dysgerminomas are stage I at diaAbout 75% of dysgerminomas are stage I at diagnosis gnosis : 85-90 % are confined to one ovary : 85-90 % are confined to one ovary : 10-15% are bilateral : 10-15% are bilateral

- Dysgerminoama is the only germ-cell malignancyDysgerminoama is the only germ-cell malignancy that has this significant rate of bilaterality that has this significant rate of bilaterality - Other germ-cell tumor are rarely bilateral Other germ-cell tumor are rarely bilateral

Contralateral ovary has been preservedContralateral ovary has been preserved : diseases can develop in 5-10% of the retained: diseases can develop in 5-10% of the retained gonads over next 2 years gonads over next 2 years

Page 15: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

In the 25% of patients who present with metastatIn the 25% of patients who present with metastatic diseaseic disease

the tumor most commonly spreads via lymphatic systethe tumor most commonly spreads via lymphatic system m

Metastases to the lungs, liver, brain Metastases to the lungs, liver, brain : with long standing or recurrent disease: with long standing or recurrent disease Metastasis to the mediastinum and supraclavicular lyMetastasis to the mediastinum and supraclavicular ly

mph nodesmph nodes : a late manifestation of disease: a late manifestation of disease

Page 16: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

◆◆ TreatmentTreatment

The treatment of early dysgerminoma The treatment of early dysgerminoma : primarily surgical, including resection of the : primarily surgical, including resection of the primary lesion and proper surgical staging primary lesion and proper surgical staging

Chemotherapy or radiation is administered to patChemotherapy or radiation is administered to patients with metastatic disease ients with metastatic disease - Special consideration must be given to the preservatioSpecial consideration must be given to the preservatio

n of fertility n of fertility - because the disease principally affects girls and young because the disease principally affects girls and young

women women

Page 17: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma Surgery Surgery

Minimum operation : unilateral oophorectomy Minimum operation : unilateral oophorectomy

If there is a desire to preserve fertility, If there is a desire to preserve fertility, even in the presence of metastatic diseaseeven in the presence of metastatic disease : contralateral ovary, fallopian tube, and: contralateral ovary, fallopian tube, and uterus should be left in situ uterus should be left in situ : because of the sensitivity of the tumor to : because of the sensitivity of the tumor to chemotherapychemotherapy

If fertility need not be preservedIf fertility need not be preserved : TAH and BSO with advanced disease : TAH and BSO with advanced disease

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DysgerminomaDysgerminoma

Karyotype analysis reveals a Y chromosome Karyotype analysis reveals a Y chromosome --> both ovaries should be removed--> both ovaries should be removed

Dysgerminoma is the only germ-cell tumor that tends tDysgerminoma is the only germ-cell tumor that tends to be bilateral o be bilateral

--> bisection of the contralateral ovary and--> bisection of the contralateral ovary and excisional biopsy of any suspicious lesion excisional biopsy of any suspicious lesion

If a small contralateral tumor is foundIf a small contralateral tumor is found --> resect it and preserve some normal ovay --> resect it and preserve some normal ovay

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DysgerminomaDysgerminoma

Radiation Radiation

Dysgerminoma are very sensitive to radiation therapyDysgerminoma are very sensitive to radiation therapy

Doses of 2500-3500cGy may be curativeDoses of 2500-3500cGy may be curative

Loss of fertility is a problem Loss of fertility is a problem • radiation should rarely be used as first-line treatment radiation should rarely be used as first-line treatment

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DysgerminomaDysgerminoma

ChemotherapyChemotherapy

Metastatic dysgerminomas with systemic chemotheraMetastatic dysgerminomas with systemic chemotherapypy• the treatment of choicethe treatment of choice• preservation of fertility preservation of fertility

The most frequently used regimensThe most frequently used regimens• BEP (bleomycin, etoposide, cisplatin)BEP (bleomycin, etoposide, cisplatin)• VBP (vinblastine, bleomycin, cisplatin)VBP (vinblastine, bleomycin, cisplatin)• VAC (vincristine, actinomycin, cyclophosphamide) VAC (vincristine, actinomycin, cyclophosphamide)

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DysgerminomaDysgerminoma Cysplatin-based combination chemoTx Cysplatin-based combination chemoTx

• Advanced stage, incompletely resected dysgerminoma have aAdvanced stage, incompletely resected dysgerminoma have an excellent prognosisn excellent prognosis

• The best regimen : Four cycles of BEPThe best regimen : Four cycles of BEP

Macroscopic disease has all been resected at the priMacroscopic disease has all been resected at the primary operation mary operation

-> No need to perform a second-look laparotomy -> No need to perform a second-look laparotomy

Extensive macorscopic residual disease at the start of Extensive macorscopic residual disease at the start of chemotherapy chemotherapy

-> a second-look operation could be used -> a second-look operation could be used • effective second-line therapy is availableeffective second-line therapy is available• the earlier persistent disease is identified, the better the progthe earlier persistent disease is identified, the better the prog

nosisnosis

Page 22: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

Page 23: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

◆◆ Recurrent DiseaseRecurrent Disease

About 75% of recurrences occur within the About 75% of recurrences occur within the first year after initial treatment first year after initial treatment

most common site most common site : peritoneal cavity, retroperitoneal LN : peritoneal cavity, retroperitoneal LN

Patients with recurrent disease who have Patients with recurrent disease who have had no therapy other than surgery had no therapy other than surgery

-> should be treated with chemotherapy -> should be treated with chemotherapy

Page 24: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

If prior chemotharapy with BEP regimenIf prior chemotharapy with BEP regimen

POMB-ACE may usedPOMB-ACE may used• Vincristine, bleomycin, cisplatin, etoposide, actinomycin D, cyVincristine, bleomycin, cisplatin, etoposide, actinomycin D, cy

clophosphamideclophosphamide

The use of high-dose chemotherapy The use of high-dose chemotherapy • Carboplatin, etoposideCarboplatin, etoposide

Radiation therapy is effective for this disease ; major Radiation therapy is effective for this disease ; major disadvantage is loss of fertility disadvantage is loss of fertility

Page 25: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma◆ ◆ PregnancyPregnancy

Dysgerminomas tend to occur in young patient Dysgerminomas tend to occur in young patient -> may coexist with pregnancy -> may coexist with pregnancy

Stage Ia Stage Ia the tumor can be removed intact & the pregnancy continuedthe tumor can be removed intact & the pregnancy continued

More advanced diseases More advanced diseases continuation of the pregnancy depend on gestational agecontinuation of the pregnancy depend on gestational age

Chemotherapy Chemotherapy in 2nd & 3rd trimesterin 2nd & 3rd trimester in the same dosages as given for the nonpregnant patients in the same dosages as given for the nonpregnant patients without apparent detriment to the fetus without apparent detriment to the fetus

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DysgerminomaDysgerminoma

◆ ◆ PrognosisPrognosis

Stage IaStage Ia (unilateral encapsulated dysgerminoma) (unilateral encapsulated dysgerminoma) -> unilateral oophorectomy alone -> unilateral oophorectomy alone : 5yr disease-free survival rate of greater than 95% : 5yr disease-free survival rate of greater than 95%

Higher tendency to recurrence Higher tendency to recurrence lesions larger than 10-15 cm in diameter lesions larger than 10-15 cm in diameter age younger than 20 years age younger than 20 years a microscopic pattern that includes numerous mitosea microscopic pattern that includes numerous mitose

s, anaplasia, medullary pattern s, anaplasia, medullary pattern

Page 27: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

DysgerminomaDysgerminoma

In the past,In the past,

Surgery for advanced disease followed by pelvic Surgery for advanced disease followed by pelvic and abdominal radiation and abdominal radiation resulted in a 5-year survival rate of 63-83%, resulted in a 5-year survival rate of 63-83%,

NowNow

With the use of VBP or BEP combination With the use of VBP or BEP combination chemotherapychemotherapy cure rates of 85-90% for this same group cure rates of 85-90% for this same group

Page 28: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Immature teratomas Immature teratomas Fewer than 1% of all ovarian cancerFewer than 1% of all ovarian cancer

2nd most common germ-cell malignancy 2nd most common germ-cell malignancy

10-20% of all ovarian malignancy in younger than 20 year10-20% of all ovarian malignancy in younger than 20 years ago of ages ago of age

30% of deaths from ovarian cancer in younger than 20 ye30% of deaths from ovarian cancer in younger than 20 years ago of agears ago of age

About 50% of pure immature teratoma in women between About 50% of pure immature teratoma in women between 10 and 20 years 10 and 20 years

Rarely occur postmenopausal women Rarely occur postmenopausal women

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Immature teratomasImmature teratomas- Pathology –- Pathology –

- Neural tissues : demonstrate most clearly the importance Neural tissues : demonstrate most clearly the importance of the ability to matureof the ability to mature

Immature teratomas are classified Immature teratomas are classified : according to a grading system based on : according to a grading system based on the degree of differentiation and the the degree of differentiation and the quantity of immature neural tissuequantity of immature neural tissue

Grade 1 tumor Grade 1 tumor : <1 LPF contains immature neural elements : <1 LPF contains immature neural elements Grade 2 tumor Grade 2 tumor : 1-3 LPFs with immature elements : 1-3 LPFs with immature elements Grade 3 tumor Grade 3 tumor : >3 LPFs with these elements : >3 LPFs with these elements

Page 30: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Immature teratomasImmature teratomas

The prognosis can be correlated with the grade of these iThe prognosis can be correlated with the grade of these immature neural elements mmature neural elements

With a higher grade, there is a poorer prognosis With a higher grade, there is a poorer prognosis

Malignant change in benign cystic teratomasMalignant change in benign cystic teratomas occuring in 1-2% of casesoccuring in 1-2% of cases usually after the 40 years of age usually after the 40 years of age

Page 31: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Immature teratomasImmature teratomas

- Diagnosis -- Diagnosis -

Some of these lesions will contain calcification similar to Some of these lesions will contain calcification similar to mature teratomas mature teratomas

Calcification can be detected by an x-ray of the abdomen Calcification can be detected by an x-ray of the abdomen or by ultrasonography or by ultrasonography

Tumor markers are negative unless a mixed germ-cell tuTumor markers are negative unless a mixed germ-cell tumor is present mor is present

Page 32: Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미

Immature teratomasImmature teratomas- Treatment -- Treatment -

Surgery Surgery

For premenopausal patient, confined to a single ovaryFor premenopausal patient, confined to a single ovary : unilateral ooporectomy and surgical staging : unilateral ooporectomy and surgical staging

For postmenopausal patients For postmenopausal patients : TAH and BSO : TAH and BSO

Contralateral involvement is rare and routine resection Contralateral involvement is rare and routine resection or wedge biopsy of the contralateral ovary is unnecessor wedge biopsy of the contralateral ovary is unnecessary ary

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Immature teratomasImmature teratomas ChemotharapyChemotharapy

Stage Ia, grade 1Stage Ia, grade 1 : an excellent prognosis: an excellent prognosis : no adjuvant therapy is required : no adjuvant therapy is required

Stage Ia,Stage Ia, grade 2 or 3 grade 2 or 3 : adjuvant chemotherapy should be used: adjuvant chemotherapy should be used

Ascites Ascites : Chemotherapy is also indicated regardless of : Chemotherapy is also indicated regardless of tumor grade tumor grade

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Immature teratomasImmature teratomas

Regimen Regimen : VAC (most frequently used in the past): VAC (most frequently used in the past) : BEP, VBP (the newer approach) : BEP, VBP (the newer approach)

• the BEP regimen is superior to the VAC regimen in the treatmthe BEP regimen is superior to the VAC regimen in the treatment of completely resected nondysgerminomatous germ cells ent of completely resected nondysgerminomatous germ cells tumors of the ovarytumors of the ovary

The switch from VBP to BEP The switch from VBP to BEP • replacement of vinblastine with etoposide replacement of vinblastine with etoposide • a better therapeutic index, especially less neurologic and gasta better therapeutic index, especially less neurologic and gast

rointestinal toxicity rointestinal toxicity

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Immature teratomasImmature teratomas

Radiation therapy Radiation therapy

Generally not used in the primary treatment Generally not used in the primary treatment

No evidence that the combination of No evidence that the combination of chemotherapy and radiation has a higher rate chemotherapy and radiation has a higher rate of disease control than chemotherapy alone of disease control than chemotherapy alone

For patients with localized persistent disease For patients with localized persistent disease after chemotherapyafter chemotherapy

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Immature teratomasImmature teratomas- Second-Look Laparotomy -- Second-Look Laparotomy -

The need for second-look operation has been questioned The need for second-look operation has been questioned

It seems not to be justified in patient who have received It seems not to be justified in patient who have received chemotherapy in an adjuvant setting, because chemotherchemotherapy in an adjuvant setting, because chemotherapy in these patients is so effective apy in these patients is so effective

Sampling of any peritoneal lesions and the retroperitoneaSampling of any peritoneal lesions and the retroperitoneal lymph nodesl lymph nodes

Only mature elements : chemoTx should be discontinuedOnly mature elements : chemoTx should be discontinued Persistent immature elements : alternative chemoTxPersistent immature elements : alternative chemoTx

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Immature teratomasImmature teratomas- Prognosis- Prognosis - -

The most important prognostic feature The most important prognostic feature : the grade of the lesion : the grade of the lesion

the stage of disease and the extent of tumor at the stage of disease and the extent of tumor at the initiation of treatment the initiation of treatment

-> have an impact on the curability-> have an impact on the curability

the 5-year survival rate the 5-year survival rate all stage : 70-80%all stage : 70-80% surgical stage I : 90-95 % surgical stage I : 90-95 %

The 5yr survival rates for all stages with grade 1, The 5yr survival rates for all stages with grade 1, 2, 3 2, 3

: 82%, 62%, 30%: 82%, 62%, 30%

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Endodermal Sinus Tumor Endodermal Sinus Tumor

Yolk sac carcinomaYolk sac carcinoma

3rd most frequent malignant germ-cell 3rd most frequent malignant germ-cell tumortumor

Median age ; 16-18 yearMedian age ; 16-18 year

Abdominal or pelvic painAbdominal or pelvic pain The most frequent initial symptom The most frequent initial symptom about 75%about 75%

Asymptomatic pelvic massAsymptomatic pelvic mass In 10%In 10%

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Endodermal Sinus Tumor Endodermal Sinus Tumor

- Pathology -- Pathology -

The gross : soft grayish-brownThe gross : soft grayish-brown

Cystic areas : degeneration of the rapidly Cystic areas : degeneration of the rapidly growing lesionsgrowing lesions

The capsule is intact The capsule is intact

Unilateral in 100%Unilateral in 100% Biopsy of the opposite ovary in such young Biopsy of the opposite ovary in such young

patients is contraindicatedpatients is contraindicated

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Endodermal Sinus TumorEndodermal Sinus Tumor

Schill-Duval bodySchill-Duval body

Microscopically, the chMicroscopically, the characteristic featurearacteristic feature

The cystic space is lineThe cystic space is lined with a layer of flattend with a layer of flattened or irregular endotheled or irregular endothelium ium

into which projects a glinto which projects a glomerulus-like tuft with omerulus-like tuft with a central vascular core a central vascular core

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Endodermal Sinus TumorEndodermal Sinus Tumor

Most EST secrete AFPMost EST secrete AFP

There is a good correlation between the There is a good correlation between the extent of disease and the level of AFP extent of disease and the level of AFP

AFP is useful in monitoring the patient's AFP is useful in monitoring the patient's response to treatment response to treatment

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Endodermal Sinus TumorEndodermal Sinus Tumor- Treatment -- Treatment -

SurgerySurgery

Unilateral salpingo-oophorectomy and a frozen Unilateral salpingo-oophorectomy and a frozen section for diagnosis section for diagnosis

Any gross metastases should be removedAny gross metastases should be removed

Surgical staging is not indicated Surgical staging is not indicated • All patients need chemotherapyAll patients need chemotherapy

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Endodermal Sinus TumorEndodermal Sinus Tumor

The tumors tend to be solid and largeThe tumors tend to be solid and large• In size from 7 to 28 cm (median 15 cm)In size from 7 to 28 cm (median 15 cm)

Bilaterality is not seenBilaterality is not seen

Most patients have early stage diseaseMost patients have early stage disease• Stage I : 71%Stage I : 71%• Stage II : 6%Stage II : 6%• Stage III : 23%Stage III : 23%

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Endodermal Sinus TumorEndodermal Sinus Tumor ChemotherapyChemotherapy

All patients with EST are treated with either adjuvant oAll patients with EST are treated with either adjuvant or therapeutic chemotherapyr therapeutic chemotherapy

VBP regimen VBP regimen • more effective regimen in the treatment of measurable of incomore effective regimen in the treatment of measurable of inco

mpletely resected tumor mpletely resected tumor

POMB-ACE regimenPOMB-ACE regimen• Primary therapy for patients with liver or brain metastases Primary therapy for patients with liver or brain metastases • Moderately myelosuppressive Moderately myelosuppressive • the intervals between each course can be kept to a maximum the intervals between each course can be kept to a maximum

of 14days (usually 9 to 11 days)of 14days (usually 9 to 11 days)

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Endodermal Sinus TumorEndodermal Sinus Tumor Cisplatin-containing combination chemotherapy, BEP oCisplatin-containing combination chemotherapy, BEP o

r POMB-ACE r POMB-ACE

• primary chemotherapy for ESTprimary chemotherapy for EST

• 3 cycles 3 cycles : stage I & completely resected disease: stage I & completely resected disease

• 2 further cycles after negative tumor marker status 2 further cycles after negative tumor marker status : macroscopic residual disease before : macroscopic residual disease before chemotherapy chemotherapy

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Endodermal Sinus TumorEndodermal Sinus Tumor

- Second-Look Laparotomy -- Second-Look Laparotomy -

The value of a second-look operation has yet to bThe value of a second-look operation has yet to be established in patients with EST e established in patients with EST

It seems reasonable to omit the operation It seems reasonable to omit the operation Pure low stage lesionsPure low stage lesions AFP values return to normalAFP values return to normal Remain normal for the balance of their treatmentRemain normal for the balance of their treatment

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Embryonal CarcinomaEmbryonal Carcinoma

Extremely rare tumorExtremely rare tumor

Distinguished from a choriocarcinomaDistinguished from a choriocarcinoma By the absence of syncytiotrophoblastic and cytotrophBy the absence of syncytiotrophoblastic and cytotroph

oblastic cellsoblastic cells

The patients are very youngThe patients are very young Between 4 and 28 years (median 14yr)Between 4 and 28 years (median 14yr)

Estrogen secretion Estrogen secretion precocious pseudopubertyprecocious pseudopuberty Irregular bleeding Irregular bleeding

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Embryonal CarcinomaEmbryonal Carcinoma

The primary lesions tend to be largeThe primary lesions tend to be large

About two-thirds are confined to one ovary at the About two-thirds are confined to one ovary at the time of diagnosistime of diagnosis

The treatment of embryonal carcinoma is the saThe treatment of embryonal carcinoma is the same as for the ESTme as for the EST Unilateral oophorectomy followed by combination cheUnilateral oophorectomy followed by combination che

motherapy with BEPmotherapy with BEP

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Choriocarcinoma of the OvaryChoriocarcinoma of the Ovary

Extremely rare tumorExtremely rare tumor

The same appearance as gestational choriocarciThe same appearance as gestational choriocarcinoma metastatic to the ovariesnoma metastatic to the ovaries

Most patients are younger than 20 yearsMost patients are younger than 20 years

High hCGHigh hCG Isosexual precocity in about 50% of patients before mIsosexual precocity in about 50% of patients before m

enarcheenarche

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Choriocarcinoma of the OvaryChoriocarcinoma of the Ovary

MAC regimen MAC regimen : complete responses have been reported: complete responses have been reported

MethotrexateMethotrexate Actinomycin DActinomycin D CyclophosphamideCyclophosphamide

The prognosis has been poorThe prognosis has been poor Most patients having metastases to organ parenchymMost patients having metastases to organ parenchym

a at the time of diagnosisa at the time of diagnosis

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PolyembryomaPolyembryoma

Extremely rare tumorExtremely rare tumor

Composed of embryoid bodiesComposed of embryoid bodies

Very young & premenarcheal girls Very young & premenarcheal girls PseudopubertyPseudopuberty Elevated AFP & hCG Elevated AFP & hCG

VAC regimen : effective VAC regimen : effective

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Mixed Germ Cell TumorsMixed Germ Cell Tumors

The most common component of a mixed malignThe most common component of a mixed malignancyancy Dysgerminoma in 80%Dysgerminoma in 80% EST in 70%EST in 70% Immature teratoma in 53%Immature teratoma in 53% Choriocarcinoma in 20%Choriocarcinoma in 20% Embryonal carcinoma in 16%Embryonal carcinoma in 16%

The most frequent combination The most frequent combination Dysgerminoma and ESTDysgerminoma and EST

Combination chemotherapy BEPCombination chemotherapy BEP

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Mixed Germ Cell TumorsMixed Germ Cell Tumors

Second look laparotomy Second look laparotomy Macroscopic desease was present at initiation of cheMacroscopic desease was present at initiation of che

motherapymotherapy

The most important prognostic featuresThe most important prognostic features The size of the primary tumorThe size of the primary tumor

• Stage IA, samller than 10cm : survival is 100%Stage IA, samller than 10cm : survival is 100%

The relative size of most malignant componentThe relative size of most malignant component• Less than one-third EST, choriocarcinoma,Less than one-third EST, choriocarcinoma, grade 3 immature teratoma : excellent prognosisgrade 3 immature teratoma : excellent prognosis

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Sex Cord-Stromal TumorsSex Cord-Stromal Tumors

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Sex Cord-Stromal TumorsSex Cord-Stromal Tumors

5-8 % of all ovarian malignancies 5-8 % of all ovarian malignancies derived from the sex cords and the ovarian stromderived from the sex cords and the ovarian strom

a or mesenchyme a or mesenchyme

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

- granulosa cell tumor -- granulosa cell tumor -

low-grade malignancy low-grade malignancy

secrete estrogen secrete estrogen

seen in womon of all ages seen in womon of all ages

bilateral in only 2% of patients bilateral in only 2% of patients

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

- Pathology -- Pathology -

range from a few millimeters to 20cm or more in range from a few millimeters to 20cm or more in diameter diameter

Smooth, lobulated surfaceSmooth, lobulated surface

Solid portion Solid portion granular, trabeculatedgranular, trabeculated Yelow or gray-yellowYelow or gray-yellow

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

““Coffee bean” groovCoffee bean” grooved nucleied nuclei

Call-Exner bodiesCall-Exner bodies Small clusters or roSmall clusters or ro

settes around a censettes around a central cavitytral cavity

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

- Diagnosis -- Diagnosis -

Of the rare prepubertal patientsOf the rare prepubertal patients 75% are associated with sexual pseudoprecocity75% are associated with sexual pseudoprecocity because of the estrogen secretionbecause of the estrogen secretion

For women of reproductive age For women of reproductive age

menstrual irregulartities or secondary amenorrhea menstrual irregulartities or secondary amenorrhea cystic hyperplasia of the endometriumcystic hyperplasia of the endometrium

For postmenopausal women For postmenopausal women abnormal uterine bleeding abnormal uterine bleeding

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

Endometrial cancer in 5% Endometrial cancer in 5%

Endometrial hyperplasia in 25-50%Endometrial hyperplasia in 25-50%

Ascites is present in about 10%Ascites is present in about 10%

Hemorrhagic Hemorrhagic : occasionally rupture and produce a : occasionally rupture and produce a hemoperitoneumhemoperitoneum

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

Usually stage I at diagnosis Usually stage I at diagnosis but may recur 5-30 years after initial diagnosisbut may recur 5-30 years after initial diagnosis

Hematogenously spreadHematogenously spread Lungs, liver, brain metastasis years after initial diagnoLungs, liver, brain metastasis years after initial diagno

sissis

Recur -> progress rapidlyRecur -> progress rapidly

Inhibin : useful markerInhibin : useful marker

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

- Treatment -- Treatment -

The treatment depends on the age of the patient The treatment depends on the age of the patient and the extent of disease and the extent of disease

For most patients, surgery alone is sufficient priFor most patients, surgery alone is sufficient primary therapy mary therapy

Radiation and chemotherapy Radiation and chemotherapy recurrent or metastatic disease recurrent or metastatic disease

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

SurgerySurgery

A unilateral salpingo-oophorectomy A unilateral salpingo-oophorectomy • stage Ia tumors in children or in women of reprodustage Ia tumors in children or in women of reprodu

ctive age ctive age • bilateral in only about 2% of patientsbilateral in only about 2% of patients

If a granulosa-cell tumor is identified by frozen If a granulosa-cell tumor is identified by frozen section section • a staging operation is performeda staging operation is performed• assessment of the contralateral ovary - biopsy assessment of the contralateral ovary - biopsy

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

For premenopausal patients in whom the uteruFor premenopausal patients in whom the uterus is left in situs is left in situ• Endometrial biopsys should be perfromedEndometrial biopsys should be perfromed• the possibiltiy of coexistent adenocarcinoma of the the possibiltiy of coexistent adenocarcinoma of the

endometrium endometrium

Radiation Radiation No evidence to support the use of adjuvant radNo evidence to support the use of adjuvant rad

iation therapy for granulosa-cell tumors iation therapy for granulosa-cell tumors

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

Chemotherapy Chemotherapy

No evidence that adjuvant chemotherapy will pNo evidence that adjuvant chemotherapy will prevent recurrence of diseaserevent recurrence of disease

Metastatic lesions and recurrences have been Metastatic lesions and recurrences have been treated treated

The most effective regimen : BEPThe most effective regimen : BEP

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Granulosa-stromal cell tumorGranulosa-stromal cell tumor

- Prognosis -- Prognosis -

Prolonged natural history, Prolonged natural history, tendency toward late relapsetendency toward late relapse

Survival rateSurvival rate 10 YSR ; 90 % 10 YSR ; 90 % 20 YSR ; 75 % 20 YSR ; 75 %

The DNA ploidy -> correlated with survival The DNA ploidy -> correlated with survival Residual-negative DNA diploid tumors had a 10-year pResidual-negative DNA diploid tumors had a 10-year p

rogression-free survival of 96 % rogression-free survival of 96 %

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Sertoli-Leydig TumorsSertoli-Leydig Tumors

Extremely rare : less than 0.2% of ovarian Extremely rare : less than 0.2% of ovarian cancercancer

Most frequently in the third and fourth decades : Most frequently in the third and fourth decades : 75% in younger than 40years75% in younger than 40years

Low grade malignanciesLow grade malignancies

Androgen : clinical virilization in 70%-85%Androgen : clinical virilization in 70%-85% Oligomenorrhea, amenorrhea, breast atrophy, acne, hiOligomenorrhea, amenorrhea, breast atrophy, acne, hi

rsutism, clitoromegaly, deepening of the voice, recedinrsutism, clitoromegaly, deepening of the voice, receding hairline g hairline

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Sertoli-Leydig TumorsSertoli-Leydig Tumors

TreatmentTreatment In reproductive years In reproductive years

• Unilateral salpingo-oophorectomy and evaluation of the contraUnilateral salpingo-oophorectomy and evaluation of the contralateral ovarylateral ovary

• Low-grade lesion are only rarely bilateral (<1%)Low-grade lesion are only rarely bilateral (<1%) Older patientsOlder patients

• TAH c BSOTAH c BSO

PrognosisPrognosis The 5-year survival rate : 70-90%The 5-year survival rate : 70-90% Recurrences : uncommonRecurrences : uncommon

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Fallopian tube cancerFallopian tube cancer

0.3% of all female genital tract0.3% of all female genital tract

Similar to ovarian cancerSimilar to ovarian cancer The evaluation and treatment are the sameThe evaluation and treatment are the same

Frequently involved secondarily from other primarFrequently involved secondarily from other primary sitesy sites ovaries, endometrium, GI tract, or breast ovaries, endometrium, GI tract, or breast

Most frequently in the fifth and sixth decade Most frequently in the fifth and sixth decade mean age : 55-60 years mean age : 55-60 years

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Fallopian tube cancerFallopian tube cancer

- Symptoms and Signs -- Symptoms and Signs -

Classic triadClassic triad① ① a prominent watery vaginal discharge a prominent watery vaginal discharge

② ② pelvic pain pelvic pain

③ ③ a pelvic mass a pelvic mass

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Fallopian tube cancerFallopian tube cancer

Vaginal discharge or bleeding Vaginal discharge or bleeding The most common symptom (more than 50%) The most common symptom (more than 50%) For perimenopausal and postmenopausal women with For perimenopausal and postmenopausal women with

an unusual, unexplained,or persistent vaginal dischargan unusual, unexplained,or persistent vaginal dischargee

-> the clinician should be concerned about the -> the clinician should be concerned about the possibility of an occult tubal cancer possibility of an occult tubal cancer Often found incidentally in asymptomatic women at thOften found incidentally in asymptomatic women at th

e time of TAH and BSOe time of TAH and BSO

Pelvic mass : about 60%Pelvic mass : about 60%

Ascites : advanced disease Ascites : advanced disease

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Fallopian tube cancerFallopian tube cancer

- Spread pattern -- Spread pattern -

The same manner as epithelial ovarian malignanThe same manner as epithelial ovarian malignancies cies by the transcoelomic exfoliation of cells by the transcoelomic exfoliation of cells -> implant throughout the peritoneal cavity -> implant throughout the peritoneal cavity

Permeated with lymphatic channels Permeated with lymphatic channels spread to the para-aortic and pelvic lymph nodes is cospread to the para-aortic and pelvic lymph nodes is co

mmon(33%) mmon(33%)

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Fallopian tube cancerFallopian tube cancer

- Staging -- Staging -

Based on the surgical findings at laparotoBased on the surgical findings at laparotomymy

stage I : 20-25% stage I : 20-25% stage II : 20-25% stage II : 20-25% stage III : 40-45% stage III : 40-45% stage IV : 5-10% stage IV : 5-10%

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Fallopian tube cancerFallopian tube cancer

- Treatment -- Treatment - Similar to epithelial ovarian cancer Similar to epithelial ovarian cancer

Exploratory laparotomy is necessary Exploratory laparotomy is necessary to remove the primary tumor (TAH c BSO) to remove the primary tumor (TAH c BSO) to stage the disease (No gross tumor spread)to stage the disease (No gross tumor spread) to resect metastases (as much as possible)to resect metastases (as much as possible)

the most frequently employed treatment the most frequently employed treatment combination chemotherapy (PC or PAC) combination chemotherapy (PC or PAC)

radiation also used in selected cases radiation also used in selected cases

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Fallopian tube cancerFallopian tube cancer

- Prognosis -- Prognosis -

Overall 5-year survival : about 40% Overall 5-year survival : about 40% higher than for patients with ovarian cancer higher than for patients with ovarian cancer higher proportion of early-stage disease higher proportion of early-stage disease

5-year survival rate5-year survival rate stage I - 65% stage I - 65% stage II - 50-60% stage II - 50-60% stage III and IV - 10-20% stage III and IV - 10-20%

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Tubal SarcomasTubal Sarcomas

Malignant mixed mesodermal tumorsMalignant mixed mesodermal tumors

In the sixth decadeIn the sixth decade

Advanced at the time of diagnosisAdvanced at the time of diagnosis

Platinum based combination chemotherapy Platinum based combination chemotherapy (if all gross disease can be resected)(if all gross disease can be resected)

Survival is generally poorSurvival is generally poor

Most patients die of their disease within 2 yearsMost patients die of their disease within 2 years