Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미 Nonepithelial Ovarian Cancers Compared with epithelial ovarian cancers, other malignant tumors of the ovary.
Download ReportTranscript Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미 Nonepithelial Ovarian Cancers Compared with epithelial ovarian cancers, other malignant tumors of the ovary.
Novak 33. Ovarian ca Nonepithelial Ovarian Cancers 부산백병원 산부인과 R2 박영미 Nonepithelial Ovarian Cancers Compared with epithelial ovarian cancers, other malignant tumors of the ovary are uncommon about 10% of all ovarian cancers 1. malinancies of germ cell origin, sex cord-stromal cell origin, 2. metastatic carcinoma to ovary 3. extremely rare ovarian cancers (sarcoma, lipoid cell tumors) Germ-Cell Malignancies Germ-Cell Malignancies Germ-Cell Malignancies ◆ Serum tumor markers in malignant germ cell tumors : can be clinically useful in the diagnosis of a pelvic mass and in monitoring course of patient after surgery α-fetoprotein(AFP), human chorionic gonadotropin(hCG) : secreted by germ cell malignancy Placental alkaline phosphatase (PLAP), lactate dehydrogenase(LDH) : produced by dysgerminoma Germ-Cell Malignancies ◆ Symptoms Germ-cell malignancies grow rapidly, in contrast to the relatively slow growing epithelial ovarian tumors : often are characterized by subacute pelvic pain related to capsular distension, hemorrhage, or necrosis : may produce pressure symptoms on the bladder or rectum Germ-Cell Malignancies In menarchal patients, menstrual irregularities may also occur Some young patients may misinterpret the early symptoms of a neoplasm as pregnancy --> This can lead to a delay in the diagnosis Acute symptoms associated with torsion or rupture of the adnexa In more advanced cases, ascites and abdominal distension may develop Germ-Cell Malignancies ◆ Diagnosis Adnexal masses will usually require surgical exploration 2 cm or larger in premenarchal patient 8 cm or larger in other premennopausal patient Predominantly cystic lesions up to 8cm in diameters in postmenarcheal patients : may be observed or given oral contraceptives for two menstrual cycles Germ-Cell Malignancies For young patient Blood test - serum hCG and AFP titers, CBC, LFT Chest x-ray - evaluation for metastasis to the lung or mediastinum Karyotype - preoperatively for all premenarcheal girl because of the propensity of these tumors to arise in dysgenetic gonads CT or MRI - may document retroperitoneal lymphadenopathy or liver metastases but, such expensive and time- consuming evaluation is unnecessary because the patients require surgical exploration Dysgerminoma ◆ Clinical Characteristics The most common malignant germ-cell tumor (30-40%) 1-3% of all ovarian cancer 5-10% of ovarian cancers in patients younger than 20 years of age * 5% : before the age of 10 years, * 75% : between the ages of 10 and 30 years * rarely occur after 50 years of age Dysgerminoma 20-30% of ovarian malignancies associated with pregnancy are dysgerminomas Found in both sexes and may arise in gonadal or extragonadal sites Size varies widely, but usually 5-15cm in diameter Capsule is slightly bosselated, the cut surface consistency is spongy, the color is gray-brown Dysgerminoma The histologic characteristics The large round, ovoid, or polygonal cells abundant, clear, very pale staining cytoplasm, large and irregular nuclei, and prominent nucleoli Dysgerminoma Approximately 5% of dysgerminomas are discovered in phenotypic females with abnormal gonads. pure gonadal dysgenesis (46XY, bilateral streak gonads), mixed gonadal dysgenesis (45X/46XY, unilateral streak gonad, contralateral testis), androgen insensitivity syndrome (46XY, testicular feminization) ∴ the karyotype should be determined in premenarcheal patients with a pelvic mass Dysgerminoma About 75% of dysgerminomas are stage I at diagnosis : 85-90 % are confined to one ovary : 10-15% are bilateral - - Dysgerminoama is the only germ-cell malignancy that has this significant rate of bilaterality Other germ-cell tumor are rarely bilateral Contralateral ovary has been preserved : diseases can develop in 5-10% of the retained gonads over next 2 years Dysgerminoma In the 25% of patients who present with metastatic disease the tumor most commonly spreads via lymphatic system Metastases to the lungs, liver, brain : with long standing or recurrent disease Metastasis to the mediastinum and supraclavicular lymph nodes : a late manifestation of disease Dysgerminoma ◆ Treatment The treatment of early dysgerminoma : primarily surgical, including resection of the primary lesion and proper surgical staging Chemotherapy or radiation is administered to patients with metastatic disease - - Special consideration must be given to the preservation of fertility because the disease principally affects girls and young women Dysgerminoma Surgery Minimum operation : unilateral oophorectomy If there is a desire to preserve fertility, even in the presence of metastatic disease : contralateral ovary, fallopian tube, and uterus should be left in situ : because of the sensitivity of the tumor to chemotherapy If fertility need not be preserved : TAH and BSO with advanced disease Dysgerminoma Karyotype analysis reveals a Y chromosome --> both ovaries should be removed Dysgerminoma is the only germ-cell tumor that tends to be bilateral --> bisection of the contralateral ovary and excisional biopsy of any suspicious lesion If a small contralateral tumor is found --> resect it and preserve some normal ovay Dysgerminoma Radiation Dysgerminoma are very sensitive to radiation therapy Doses of 2500-3500cGy may be curative Loss of fertility is a problem • radiation should rarely be used as first-line treatment Dysgerminoma Chemotherapy Metastatic dysgerminomas with systemic chemotherapy • the treatment of choice • preservation of fertility The most frequently used regimens • BEP (bleomycin, etoposide, cisplatin) • VBP (vinblastine, bleomycin, cisplatin) • VAC (vincristine, actinomycin, cyclophosphamide) Dysgerminoma Cysplatin-based combination chemoTx • Advanced stage, incompletely resected dysgerminoma have an excellent prognosis • The best regimen : Four cycles of BEP Macroscopic disease has all been resected at the primary operation -> No need to perform a second-look laparotomy Extensive macorscopic residual disease at the start of chemotherapy -> a second-look operation could be used • effective second-line therapy is available • the earlier persistent disease is identified, the better the prognosis Dysgerminoma Dysgerminoma ◆ Recurrent Disease About 75% of recurrences occur within the first year after initial treatment most common site : peritoneal cavity, retroperitoneal LN Patients with recurrent disease who have had no therapy other than surgery -> should be treated with chemotherapy Dysgerminoma If prior chemotharapy with BEP regimen POMB-ACE may used • Vincristine, bleomycin, cisplatin, etoposide, actinomycin D, cyclophosphamide The use of high-dose chemotherapy • Carboplatin, etoposide Radiation therapy is effective for this disease ; major disadvantage is loss of fertility Dysgerminoma ◆ Pregnancy Dysgerminomas tend to occur in young patient -> may coexist with pregnancy Stage Ia More advanced diseases the tumor can be removed intact & the pregnancy continued continuation of the pregnancy depend on gestational age Chemotherapy in 2nd & 3rd trimester in the same dosages as given for the nonpregnant patients without apparent detriment to the fetus Dysgerminoma ◆ Prognosis Stage Ia (unilateral encapsulated dysgerminoma) -> unilateral oophorectomy alone : 5yr disease-free survival rate of greater than 95% Higher tendency to recurrence lesions larger than 10-15 cm in diameter age younger than 20 years a microscopic pattern that includes numerous mitoses, anaplasia, medullary pattern Dysgerminoma In the past, Surgery for advanced disease followed by pelvic and abdominal radiation resulted in a 5-year survival rate of 63-83%, Now With the use of VBP or BEP combination chemotherapy cure rates of 85-90% for this same group Immature teratomas Fewer than 1% of all ovarian cancer 2nd most common germ-cell malignancy 10-20% of all ovarian malignancy in younger than 20 years ago of age 30% of deaths from ovarian cancer in younger than 20 years ago of age About 50% of pure immature teratoma in women between 10 and 20 years Rarely occur postmenopausal women Immature teratomas - Pathology – - Neural tissues : demonstrate most clearly the importance of the ability to mature Immature teratomas are classified : according to a grading system based on the degree of differentiation and the quantity of immature neural tissue Grade 1 tumor : <1 LPF contains immature neural elements Grade 2 tumor : 1-3 LPFs with immature elements Grade 3 tumor : >3 LPFs with these elements Immature teratomas The prognosis can be correlated with the grade of these immature neural elements With a higher grade, there is a poorer prognosis Malignant change in benign cystic teratomas occuring in 1-2% of cases usually after the 40 years of age Immature teratomas - Diagnosis Some of these lesions will contain calcification similar to mature teratomas Calcification can be detected by an x-ray of the abdomen or by ultrasonography Tumor markers are negative unless a mixed germcell tumor is present Immature teratomas - Treatment Surgery For premenopausal patient, confined to a single ovary : unilateral ooporectomy and surgical staging For postmenopausal patients : TAH and BSO Contralateral involvement is rare and routine resection or wedge biopsy of the contralateral ovary is unnecessary Immature teratomas Chemotharapy Stage Ia, grade 1 : an excellent prognosis : no adjuvant therapy is required Stage Ia, grade 2 or 3 : adjuvant chemotherapy should be used Ascites : Chemotherapy is also indicated regardless of tumor grade Immature teratomas Regimen : VAC (most frequently used in the past) : BEP, VBP (the newer approach) • the BEP regimen is superior to the VAC regimen in the treatment of completely resected nondysgerminomatous germ cells tumors of the ovary The switch from VBP to BEP • replacement of vinblastine with etoposide • a better therapeutic index, especially less neurologic and gastrointestinal toxicity Immature teratomas Radiation therapy Generally not used in the primary treatment No evidence that the combination of chemotherapy and radiation has a higher rate of disease control than chemotherapy alone For patients with localized persistent disease after chemotherapy Immature teratomas - Second-Look Laparotomy The need for second-look operation has been questioned It seems not to be justified in patient who have received chemotherapy in an adjuvant setting, because chemotherapy in these patients is so effective Sampling of any peritoneal lesions and the retroperitoneal lymph nodes Only mature elements : chemoTx should be discontinued Persistent immature elements : alternative chemoTx Immature teratomas - Prognosis The most important prognostic feature : the grade of the lesion the stage of disease and the extent of tumor at the initiation of treatment -> have an impact on the curability the 5-year survival rate all stage : 70-80% surgical stage I : 90-95 % The 5yr survival rates for all stages with grade 1, 2, 3 : 82%, 62%, 30% Endodermal Sinus Tumor Yolk sac carcinoma 3rd most frequent malignant germ-cell tumor Median age ; 16-18 year Abdominal or pelvic pain The most frequent initial symptom about 75% Asymptomatic pelvic mass In 10% Endodermal Sinus Tumor - Pathology The gross : soft grayish-brown Cystic areas : degeneration of the rapidly growing lesions The capsule is intact Unilateral in 100% Biopsy of the opposite ovary in such young patients is contraindicated Endodermal Sinus Tumor Schill-Duval body Microscopically, the characteristic feature The cystic space is lined with a layer of flattened or irregular endothelium into which projects a glomerulus-like tuft with a central vascular core Endodermal Sinus Tumor Most EST secrete AFP There is a good correlation between the extent of disease and the level of AFP AFP is useful in monitoring the patient's response to treatment Endodermal Sinus Tumor - Treatment Surgery Unilateral salpingo-oophorectomy and a frozen section for diagnosis Any gross metastases should be removed Surgical staging is not indicated • All patients need chemotherapy Endodermal Sinus Tumor The tumors tend to be solid and large • In size from 7 to 28 cm (median 15 cm) Bilaterality is not seen Most patients have early stage disease • Stage I : 71% • Stage II : 6% • Stage III : 23% Endodermal Sinus Tumor Chemotherapy All patients with EST are treated with either adjuvant or therapeutic chemotherapy VBP regimen • more effective regimen in the treatment of measurable of incompletely resected tumor POMB-ACE regimen • Primary therapy for patients with liver or brain metastases • Moderately myelosuppressive • the intervals between each course can be kept to a maximum of 14days (usually 9 to 11 days) Endodermal Sinus Tumor Cisplatin-containing combination chemotherapy, BEP or POMB-ACE • primary chemotherapy for EST • 3 cycles : stage I & completely resected disease • 2 further cycles after negative tumor marker status : macroscopic residual disease before chemotherapy Endodermal Sinus Tumor - Second-Look Laparotomy The value of a second-look operation has yet to be established in patients with EST It seems reasonable to omit the operation Pure low stage lesions AFP values return to normal Remain normal for the balance of their treatment Embryonal Carcinoma Extremely rare tumor Distinguished from a choriocarcinoma The patients are very young By the absence of syncytiotrophoblastic and cytotrophoblastic cells Between 4 and 28 years (median 14yr) Estrogen secretion precocious pseudopuberty Irregular bleeding Embryonal Carcinoma The primary lesions tend to be large About two-thirds are confined to one ovary at the time of diagnosis The treatment of embryonal carcinoma is the same as for the EST Unilateral oophorectomy followed by combination chemotherapy with BEP Choriocarcinoma of the Ovary Extremely rare tumor The same appearance as gestational choriocarcinoma metastatic to the ovaries Most patients are younger than 20 years High hCG Isosexual precocity in about 50% of patients before menarche Choriocarcinoma of the Ovary MAC regimen : complete responses have been reported Methotrexate Actinomycin D Cyclophosphamide The prognosis has been poor Most patients having metastases to organ parenchyma at the time of diagnosis Polyembryoma Extremely rare tumor Composed of embryoid bodies Very young & premenarcheal girls Pseudopuberty Elevated AFP & hCG VAC regimen : effective Mixed Germ Cell Tumors The most common component of a mixed malignancy The most frequent combination Dysgerminoma in 80% EST in 70% Immature teratoma in 53% Choriocarcinoma in 20% Embryonal carcinoma in 16% Dysgerminoma and EST Combination chemotherapy BEP Mixed Germ Cell Tumors Second look laparotomy Macroscopic desease was present at initiation of chemotherapy The most important prognostic features The size of the primary tumor • Stage IA, samller than 10cm : survival is 100% The relative size of most malignant component • Less than one-third EST, choriocarcinoma, grade 3 immature teratoma : excellent prognosis Sex Cord-Stromal Tumors Sex Cord-Stromal Tumors 5-8 % of all ovarian malignancies derived from the sex cords and the ovarian stroma or mesenchyme Granulosa-stromal cell tumor - granulosa cell tumor low-grade malignancy secrete estrogen seen in womon of all ages bilateral in only 2% of patients Granulosa-stromal cell tumor - Pathology range from a few millimeters to 20cm or more in diameter Smooth, lobulated surface Solid portion granular, trabeculated Yelow or gray-yellow Granulosa-stromal cell tumor “Coffee bean” grooved nuclei Call-Exner bodies Small clusters or rosettes around a central cavity Granulosa-stromal cell tumor - Diagnosis Of the rare prepubertal patients For women of reproductive age 75% are associated with sexual pseudoprecocity because of the estrogen secretion menstrual irregulartities or secondary amenorrhea cystic hyperplasia of the endometrium For postmenopausal women abnormal uterine bleeding Granulosa-stromal cell tumor Endometrial cancer in 5% Endometrial hyperplasia in 25-50% Ascites is present in about 10% Hemorrhagic : occasionally rupture and produce a hemoperitoneum Granulosa-stromal cell tumor Usually stage I at diagnosis but may recur 5-30 years after initial diagnosis Hematogenously spread Lungs, liver, brain metastasis years after initial diagnosis Recur -> progress rapidly Inhibin : useful marker Granulosa-stromal cell tumor - Treatment The treatment depends on the age of the patient and the extent of disease For most patients, surgery alone is sufficient primary therapy Radiation and chemotherapy recurrent or metastatic disease Granulosa-stromal cell tumor Surgery A unilateral salpingo-oophorectomy • stage Ia tumors in children or in women of reproductive age • bilateral in only about 2% of patients If a granulosa-cell tumor is identified by frozen section • a staging operation is performed • assessment of the contralateral ovary - biopsy Granulosa-stromal cell tumor For premenopausal patients in whom the uterus is left in situ • Endometrial biopsys should be perfromed • the possibiltiy of coexistent adenocarcinoma of the endometrium Radiation No evidence to support the use of adjuvant radiation therapy for granulosa-cell tumors Granulosa-stromal cell tumor Chemotherapy No evidence that adjuvant chemotherapy will prevent recurrence of disease Metastatic lesions and recurrences have been treated The most effective regimen : BEP Granulosa-stromal cell tumor - Prognosis Prolonged natural history, tendency toward late relapse Survival rate 10 YSR ; 90 % 20 YSR ; 75 % The DNA ploidy -> correlated with survival Residual-negative DNA diploid tumors had a 10year progression-free survival of 96 % Sertoli-Leydig Tumors Extremely rare : less than 0.2% of ovarian cancer Most frequently in the third and fourth decades : 75% in younger than 40years Low grade malignancies Androgen : clinical virilization in 70%-85% Oligomenorrhea, amenorrhea, breast atrophy, acne, hirsutism, clitoromegaly, deepening of the voice, receding hairline Sertoli-Leydig Tumors Treatment In reproductive years • Unilateral salpingo-oophorectomy and evaluation of the contralateral ovary • Low-grade lesion are only rarely bilateral (<1%) Older patients • TAH c BSO Prognosis The 5-year survival rate : 70-90% Recurrences : uncommon Fallopian tube cancer 0.3% of all female genital tract Similar to ovarian cancer Frequently involved secondarily from other primary sites The evaluation and treatment are the same ovaries, endometrium, GI tract, or breast Most frequently in the fifth and sixth decade mean age : 55-60 years Fallopian tube cancer - Symptoms and Signs Classic triad ① a prominent watery vaginal discharge ② pelvic pain ③ a pelvic mass Fallopian tube cancer Vaginal discharge or bleeding The most common symptom (more than 50%) For perimenopausal and postmenopausal women with an unusual, unexplained,or persistent vaginal discharge -> the clinician should be concerned about the possibility of an occult tubal cancer Often found incidentally in asymptomatic women at the time of TAH and BSO Pelvic mass : about 60% Ascites : advanced disease Fallopian tube cancer - Spread pattern The same manner as epithelial ovarian malignancies by the transcoelomic exfoliation of cells -> implant throughout the peritoneal cavity Permeated with lymphatic channels spread to the para-aortic and pelvic lymph nodes is common(33%) Fallopian tube cancer - Staging Based on the surgical findings at laparotomy stage stage stage stage I : 20-25% II : 20-25% III : 40-45% IV : 5-10% Fallopian tube cancer - Treatment Similar to epithelial ovarian cancer Exploratory laparotomy is necessary the most frequently employed treatment to remove the primary tumor (TAH c BSO) to stage the disease (No gross tumor spread) to resect metastases (as much as possible) combination chemotherapy (PC or PAC) radiation also used in selected cases Fallopian tube cancer - Prognosis Overall 5-year survival : about 40% higher than for patients with ovarian cancer higher proportion of early-stage disease 5-year survival rate stage I - 65% stage II - 50-60% stage III and IV - 10-20% Tubal Sarcomas Malignant mixed mesodermal tumors In the sixth decade Advanced at the time of diagnosis Platinum based combination chemotherapy (if all gross disease can be resected) Survival is generally poor Most patients die of their disease within 2 years