Gynonco Flashcards
1st line chemo for advanced ovarian cancer
6 cycles of Taxol+ carboplatin
Ovarian cystectomy revealed borderline serous ovarian tumor
Limited staging, USO
Granulosa cell tumor immunohistochemical marker:
immunostaining for inhibin antibody, eosinophilic call-Exner bodies
Beta-unit similarity btw — and B-hcg : the same amino acids consequences
LH
Cannonball appearance in the lungs:
Mets
Phantom Bhcg :
Due to heterophilic Ab
To dx: do urine pregnancy test
Do not give NSAIDS and carboxyl compound containing products.” Like penicillin” along with chemotherapy that toxic to nephro
Warn
Medical management of fibroids:
selective progesterone receptor modulators
like ulipristal acetate (UPA)
Pedunculated UFs localized in the submucosa, extending inside the uterine cavity, are classified as type
0
submucosal UFs that have ±50% of intramural location considered types …,…
1 and 2
Uterine Fibroids are completely located intramural with contact to the endometrium considered type:
Type 3
UFs are intramural lying entirely in the myometrium considered type
type 4
subserosal UFs with ±50% of intramural location considered types
Types 5–6
UTERINE FIBROIDS THAT attached to the serosa by a stalk (pedunculated) CONSIDERED TYPE…
7
all other UFs not related to the myometrium such as cervical or parasitic lesions considered type
8
Increased LDH in
Dysgerminoma
Increased A-FP in which ovarian Tumor type
Endodermal sinus Tumor
Dysgerminoma mode of transmission
Lymphatic
Dysgerminoma percentage of being bilateral
15 %
Indications of cone bx:
- Discrepancy btw pap and Colpo
- Diagnostic conization is indicated in the following situations:
Finding epithelial cell abnormalities, in particular high-grade squamous intraepithelial lesions (HSIL) or low-grade squamous intraepithelial lesions (LSIL) in the absence of gross or colposcopic lesions of the cervix
Unsatisfactory colposcopy, defined as the examiner’s inability to view the entire transformation zone, including the squamocolumnar junction, in women with epithelial cell abnormalities
Uncertainty regarding the presence or absence of microinvasion or invasion following the diagnosis of CIN by directed biopsy
Finding CIN or microinvasive cancer during endocervical curettage
Cytologic or histologic evidence of premalignant or malignant glandular epithelium
Cytologic diagnosis inconsistent with histologic diagnosis based on directed biopsy findings - Therapeutic conization
-Therapeutic conization is currently the preferred modality to treat CIN grades 2 and 3. All described approaches (ie, cold-knife, laser, LEEP) are equally effective, as found by Mitchell and colleagues.
Simple hysterectomy only for which stage of Cervical ca
Stage 1A1
serum glycoprotein CA-125 concentration (normal range 0–35 kU/L) is elevated in 80% of women with ovarian cancer. However, the levels can be within the normal range in 50% of women with stage I disease. What malignancies can be high with?
epithelial ovarian, colon, or breast cancer.
-
USS and measurement of serum levels of CA-125 should be performed every 4 months. If there is no change in the size of the cyst or the cyst has resolved after 1 year of follow-up, then the patient can be discharged from follow-up.
In postmenopausal Women at intermediate risk of malignancy (RMI <200) with Simple, unilateral, unilocular ovarian cysts, management ?
can be suitable for laparoscopic surgery. Laparoscopic management of ovarian cysts in post-menopausal women should involve oophorectomy (usually bilateral), rather than cystectomy.
In postmenopausal Women at high risk of malignancy (usually RMI >200 or clinical suspicion) presenting with adnexal mass, mangament ?
need to be managed by a gynae- cological oncologist in a cancer centre. The aim of surgery in these cases is to confirm the diagnosis, to assess the extent of the disease, and to attempt optimal debulking. The laparotomy should be performed through a midline incision and include: collection of peritoneal fluid for cytology, bilateral salpingo-oophorectomy and hysterectomy, omentectomy, appendicectomy, biopsies from any suspicious peritoneal surfaces, and para-aortic lymph node sampling.
Endometrial hyperplasia percentage to convert to endometrial cancer based on WHO classification
Simple without atypia 1%, with 8-10%
Complex without atypia 3%, with atypia 29-30%
Atypical polyploid adenomyosis associated with
Uterine adenocarcinoma
Occasionally, the plateauing or increasing hCG levels are a result of a false-positive laboratory test result caused by heterophilic antibodies cross-reacting with the hCG test. Such false-positive test results, also known as “___________,”
phantom hCG
Mode of metastasis of ovarian cancer:
Cell exfoliation
Sex cord–stromal tumors accounts for approximately -% of ovarian neoplasms
Sex cord–stromal tumors accounts for approximately 6% ( 3 to 5% -William-) of ovarian neoplasms
characteristic microscopic pattern of Granulosa cell tumors
Call-Exner bodies, eosinophilic bodies surrounded by granulosa cells.
granulosa cell tumor clinical presentation:
Approximately 5% occur before puberty and they can be one cause of precocious puberty.
increased levels of blood estrogens, uterine bleeding, and occasionally endometrial carcinoma. It is estimated that approximately 5% of the granulosa cell tumors in adults are associated with endometrial carcinoma. In menstruating women, the functional granulosa cell tumor can produce abnormal menstrual patterns, menorrhagia, and even amenorrhea.
Krukenberg tumor most characteristic pathological feature
characterized by mucin-laden, signet-ring cells within ovarian stroma.
A 45-year-old woman with history of vulval itching and soreness for past two years attends the gynaecology clinic. She is a smoker. She gives a history of using high potency steroid ointment previously with no symptom relief. A biopsy in the clinic reports vulval intraepithelial neoplasia (VIN) 3. You counsel her for excision of the lesion. What percentage of VIN ultimately have unrecognised invasion detected on excision?
A. 5%
B. 10%
C. 15%
D. 20%
E. 25%
D. 20%
Approximately … percent of inherited ovarian cancers result from germline mutations in the BRCA I, BRCA.2, or other homologous recombination deficiency genes.
Approximately 75 percent of inherited ovarian cancers result from germline mutations in the BRCA I, BRCA.2, or other homologous recombination deficiency genes.
The BRCA I gene is located on chromosome 17 q21. Patients with a proven mutation have a dramatically elevated risk of developing ovarian cancer (-%). BRCA2 is located on chromosome 13q12 and in general is less likely to lead to ovarian cancer (-%). The estimated lifetime risk of breast cancer with a BRCA I is ….. % and BRCA 2 mutation is —- %
The BRCA I gene is located on chromosome 17 q21. Patients with a proven mutation have a dramatically elevated risk of developing ovarian cancer (39 to 46%). BRCA2 is located on chromosome 13q12 and in general is less likely to lead to ovarian cancer (10 to 27%). The estimated lifetime risk of breast cancer with a BRCA I (65%) and BRCA 2 mutation is 70% (Kuchenbaecker,2017) وفي رواية ( btw 45 to 85 % )
In low-risk patients who are not BRCA. carriers, risk-reducing salpingectomy also is now considered in those undergoing hysterectomy or permanent sterilization. Ovarian cancer risk is reduced up to –%
In low-risk patients who are not BRCA. carriers, risk-reducing salpingectomy also is now considered in those undergoing hys-terectomy or permanent sterilization. Ovarian cancer risk is reduced up to 65%
In BRCA carriers, BSO procedure is approximately –% effective in preventing epithelial ovarian cancer (Kauff, 2002; Rebbeck, 2002). Prophylactic BSO also reduces the risk of developing breast cancer by -% (Rebbeck, 2002). Predictably, the protective effect is strongest among premenopausal women (Kramer, 2005). In women with HNPCC, the ovarian cancer risk reduction approaches -%
In BRCA carriers, the procedure is approximately 90-percent effective in preventing epithelial ovarian cancer (Kauff, 2002; Rebbeck, 2002). Prophylactic BSO also reduces the risk of developing breast cancer by 50 % (Rebbeck, 2002). Predictably, the protective effect is strongest among premenopausal women (Kramer, 2005). In women with HNPCC, the ovarian cancer risk reduction approaches 100 %
Endometrial cancer incidence is
3% in general population or 1/42.
- Ovarian cancer incidence is
1/72 or 1.5% in general population.
Pseudo-pseudo Meigs’ syndrome (PPMS) or Tjalma syndrome
rare manifestation of patients with systemic lupus erythematosus (SLE), defined by the presence of ascites, pleural effusions and an elevated CA-125 level.
psammoma bodies can be seen in which type of gyne tumors
- serous cystadenocarcinoma of the ovary
Management Abnormal Pap Smear
IF Cytology negative, HPV+
- occur in less than 10 percent of screened patients . • Cotesting is repeated in 12m. ( risk of high-grade lesion is low, and most HPV infections will resolve during this time)
• Colposcopy is recommended for persistently positive HPV DNA test results.
IN ASCUS — WHAT IS THE risk OF CIN 2/3
5-10%, cancer 1-2/1000.
Management of ASCUS If repeated pap abnormal
or if ASCUS, HPV positive :
colpo
• Reflex HPV testing >25 y/o (acceptable 21-24, recommended if HIV+)
Management of ASCUS , HPV negative:
cotest 3 years or cytology alone after one year if <25.
Management of ASCUS Without HPV testing
— repeat cytology 1y (preferred age 21-24)
in LSIL- what is the risk of CIN2/3
15-30%
management of LSIL, w.out HPV tesing or HPV positive:
COLPO
Reflex testing is not indicated in reproductive age women as 75-85% will be positive. Can consider reflex testing in postmenopausal women without HPV test.
management of LSIL, HPV negative:
repeat cotest 1y preferred, colpo acceptable
Age 21-24 w/LSIL : cytology follow up preferred.
HIV: colpo (ACOG)
Management of Abnormal Pap Smear
if ASC-H:
Colpo — if inadequate, diagnostic excisional procedure indicated.
if ASC-H: the risk of HSIL
25%
Management of Abnormal Pap Smear
in HSIL:
• Colpo- immediate LEEP also an option “see- and- LEEP approach.”
• Colpo may miss high grade lesion and the most HSIL cytologies eventually result in excision for diagnosis or tx.
• Inadequate colpo for excision.
if pap smear showed HSIL: what is the risk of CIN2/3 and invasive SCC?
70% CIN2/3, 1-2% invasive SCC
Management of Abnormal Pap Smear
if AGC, AGC favor neoplasia, AIS
• Colpo, endocervical sampling • Endometrial sampling in patients 35 years and older or in younger women with RF.
• Atypical endometrial cells: initial endometrial and endocervical sampling acceptable with colpo if negative.
• Diagnostic excision is indicated following AGC favor neoplasia and AIS pap results if initial colpo evaluation does not result in a cancer diagnosis
pap smear showed Unsatisfactory Pap tests, next step?
repeated in 2 to 4 months.
• If atrophy or a specific infection is present, treatment before repeat cytology may be helpful.
• If the result is unsatisfactory again, colposcopy is recommended as this persistent result confers increased CIN risk
Colposcopy is recommended for pts with:
- ASC-H cytology, regardless of HPV
- HPV18+ NILM ( Negative for intraepithelial lesion or malignancy ) and HPV16+ NILM
- After 2 consecutive unsat screening tests
Incidence of Cervical Cancer in all races + (Asian?)
7.3 (Asian 6.4)
2.3
It is the second most common cancer in women worldwide, and the third most common cause of female cancer mortality in developing countries
Cervical cancer
(4th world wide among all malignancies in women per WHO 2019)
Types of cervical cancer include
squamous cell carcinoma (most common), invasive adenocarcinoma, small cell neuroendocrine carcinoma, and other rare histologic types.
Evaluation of cervical cancer
- Early stage disease is usually asymptomatic and detected by screening with cervical smear.
- Symptoms, if present, are usually vaginal bleeding or blood-stained vaginal discharge.
- Diagnosis is usually made using colposcopically directed cervical biopsy.
- Imaging should be done for clinical staging and risk assessment (Strong recommendation).
Management For early invasive cervical cancer (small tumors ≤ 4 cm confined to cervix) initial treatment is
surgery or radiation (Strong recommendation).
Approximately … percent of all breast cancers are due to mutations in the BRCA2 gene
Approximately two percent of all breast cancers are due to mutations in the BRCA2 gene
HPV 16 commonly associated with which type of cancer
Squamous cell carcinoma
HPV 18 commonly associated with which type of cancer
Adenocarcinoma and Neuroendocrine tumors
HPV 6 and 11 can cause
Benign genital warts
If Atypical glandular cell found in Pap smear the risk of CIN 2&3
10%
In Pt with low risk HPV (presented with genital warts) because the risk of getting high risk HPV the follow-up plan ?
Yearly Pap test screening for 2-3 years if negative then for it will be back every 3 years
(?American association)
vulval adenocarcinoma prevalence
rare histological diagnosis found in less than 10% of vulval cancers.
the most common vulvar malignancy
1st Squamous cell carcinoma (accounts for 4%-5% of all gynecologic malignancies)
And account approximately 90 percent of vulvar carcinoma
2nd most common is Malignant melanoma
Vulvar squamous cell carcinoma (VSCC) is often categorized by
the presence or absence of human papillomavirus (HPV) in the tumor.
Diseases associated with HPV-negative VSCC ( vulvar squamous cell carcinoma)
Dermatological diseases involving chronic inflammation (such as lichen sclerosis and lichen simplex chronicus)
risk factor for HPV-associated VSCC.
Smoking
Vulvar cancer prevalence
1.1% of all female cancers and 3.6% of all gynecological cancers
Schiller duval bodies
Endodermal sinus tumor
When do you Stop cervical cancer screening?
after age 65 years if there is consecutive normal testing for prior 10 years, or after hysterectomy for benign condition with removal of the cervix (Strong recommendation).
What are the Three major categories of malignant ovarian tumors.
1) Epithelial ovarian cancers account for 90 to 95 percent of malignant ovarian tumors
2) Germ cell 2-3%
3) sex cord-stromal ovarian tumors account for 6%
the most common subtype of all germ cell tumors accounts for 95 percent of
The mature cystic teratoma, also called dermoid cyst
Malignant germ cell tumors
dysgerminoma, yolk sac tumor, endodermal sinus tumor, polyembryoma, embryonal ,immature teratoma, choriocarcinoma,mixed.
Three clinical features distinguish malignant germ cell tumors from epithelial ovarian cancers. Which are ..?
First. individuals typically are younger, usually in their teens or early 20s. Most have stage I disease at diagnosis. Last, prognosis is excellent-even for those with advanced disease–due to exquisite tumor chemosensitivity. Fertility-sparing surgery is the primary treatment for women seeking future pregnancy, although most will require postoperative chemotherapy.
2nd line of endometrioid tumors and positive estrogen receptor status
Systemic hormonal: Tamoxifen or a combination of tamoxifen and progestin (used for patients who wish to preserve fertility and for patients with advanced or recurrent disease in a palliative setting)
(Letrozole can be given as well
Systematic Review (Weelden,2019)
Modified WHO Classification of Ovarian Germ Cell Tumors
Dysgerminoma
Yolk sac tumor (former endodermal sinus tumor)
Embryonal carcinoma
Nongestational choriocarcinoma
Mature teratoma Solid Cystic (dermoid cyst)
Immature teratoma
Mixed germ cell tumor
Monodermal teratoma and highly specialized types arising from a mature cystic teratoma which includes
Thyroid turners (struma ovarii: benign or malignant)
Carcinoids
Neuroectodermal tumors
Carcinomas (squamous cell or adeno-)
Sebaceous tumors
the most common ovarian malignancy detected during pregnancy.
Dysgerminoma
the most common ovarian malignancy detected during pregnancy.
Dysgerminoma
(This is believed to be an age-related coincidence, however, and not due to gestation)
Five percent of ******* are discovered in phenotypic females with karyotypically abnormal gonads, specifically, with a normal or abnormal Y chromosome (Morimura, 1998). Commonly, this group includes those with Turner syndrome mosaicism (45,X/46,XY) and with Swyer syndrome (46,XY, pure gonadal dysgenesis)
dysgerminomas
(The dysgenetic gonads of these individuals often contain gonadoblastomas, which are benign germ cell neoplasms. These tumors may regress or alternatively may undergo malignant transformation, most commonly to dysgerminoma. Because approximately 40 percent of gonadoblastomas in these individuals undergo malignant transformation, both ovaries are removed)
the only germ cell malignancy with a significant rate of bilateral ovarian involvement-15 to 20 percent.
Dysgerminomas
characterized microscopically by a relatively monot~ nous proliferation of large, rounded, polyhedral dear eel Is that are rich in cytoplasmic glycogen. These contain uniform central rounded or squar~ged nuclei with one or a few prominent nucleoli.
Dysgerminoma
Dysgerminoma tumor cells closely resemble the primordial germ cell of the embryo and are histologically identical to **** of the testis.
seminoma
The standard treatment of dysgerminoma
usually involves fertility-sparing surgery with unilateral salpingo-oophorcctomy (USO). In some extenuating circumstances, ovarian cystectomy may be considered (Vicus, 2010). Surgical staging is generally extrapolated from epithelial ovarian cancer, but lymphadenectomy is particularly important (Chap. 35). Of the malignant germ cell tumors, dysgerminoma has the highest rate of nodal metastases, approximately 25 to 30 percent (Kumar, 2008). Although staging deviations do not adversely affect survival, comprehensive staging allows a safe observation strategy for stage IA tumors (Billmire, 2004; Palenzuela, 2008). Preservation of the contralateral ovary leads to “recurrent” dysgerminoma in 5 to 10 percent of retained gonads during the next 2 years.
Dysgerminomas have the best prognosis of all malignant ovarian germ cell tumor variants. Two thirds are stage I at diagnosis, and the 5-year disease-specific survival rate approximates
99 %
Even those with advanced disease have high survival rates following chemotherapy. For example, those with stage II-IV disease have a greater than 98-percent survival rate with platinum-based agents (Chan, 2008). a result carboplatin may be preferable to cisplatin in these patients due to equivalent outcomes with reduced long-term toxicity (Shah, 2018; Skalleberg, 2017).
Yolk sac tumors (previously called endodermal sinus rumors) account for ** percent of all malignant ovarian germ cell tumors
10 to 20
the most common gynecologic malignancy
endometrial cancer
Risk factors of endometrial cancer
obesity and advancing age.
excess-estrogen environment (type I endometrial cancer)
Polycystic ovarian syndrome Long-term, high-dose unopposed menopausal estrogens Early age of menarche Late age of natural menopause Infertility Nulliparity Menstrual irregularities North America or northern Europe residence Higher education or income level White race Older age Tamoxifen, hereditry (lynch syndrome), high cumulative doses DM, CHTN, or gallbladder disease Lower risk with Long-term COC use Cigarette smoking
The cornerstone of treatment of endometrial cancer
hysterectomy with bilateral salpingo-oophorectomy (BSO) and surgical staging that includes lymph node assessment for most women. Of affected women, 67 percent will have stage I disease that is potentially curable by surgery alone, although high-risk stage I patients often receive adjuvant therapy (Siegd, 2019).
the sixth leading cause of cancer deaths among women
Endometrial cancer
Endometrial adenocarcinomas are categorized as
type I or type II based on histology.
Type I, that is, endometrioid type, makes up 80 to 90 percent of all cases (Felix, 2010).
The other 10 to 20 percent are type II cancers, namely, the non-endometrioid histologic types that include serous and clear cell adenocarcinomas and carcinosarcoma.
The lifetime risk of developing endometrial cancer
3-percent (1:32)
If EC invades the Bowel stroma not mucosa what stage
IIIB
the most common extracolonic manifestation of Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC])
Endometrial cancer
Of all endometrial cancer cases, 2.3 percent are attributable to Lynch syndrome, and these cases develop more than 10 years earlier than sporadic endometrial cancer (Resnick, 2009).
Lynch syndrome (hereditary nonpolyposis colorectal cancer [HNPCC]) mode of Inheritance
This autosomal-dominant syndrome results primarily from mutations in the mismatch repair genes MLH1, MSH2, MSH6, and PMS2
Gene mutation prevents repair of base mismatches, which are commonly produced during DNA replication. Inactivity of this DNA repair system leads to mutations that can promote carcinogenesis. Mutation carriers have a risk of developing endometrial cancer that ranges from 40 to 60 percent. Among affected women, endometrial cancer often develops at a young age, and the risk for this cancer actually exceeds that for colorectal cancer
Tamoxifen causes a – to – fold higher risk of developing endometrial cancer by its modest “unopposed” estrogenic effect on the endometrium
Tamoxifen causes a two-to three fold higher risk of developing endometrial cancer by its modest “unopposed” estrogenic effect on the endometrium.
(cancer rates rise linearly with the duration and cumulative dose of tamoxifen therapy)
Accordingly, women taking tamoxifen are counseled regarding this endometrial risk and should report vaginal spotting, bleeding, or discharge. That said, unless a tamoxifen-treated patient has such symptoms, routine endometrial surveillance does not improve early detection rates (American College of Obstetricians and Gynecologists, 2019c}.
combination oral contraceptive (COC) use for at least 1 year confers as much as a — to – percent reduced endometrial cancer risk. Risk reduction extends for 10 to 20 years.
combination oral contraceptive (COC) use for at least 1 year confers as much as a 30-to 50-percent reduced endometrial cancer risk. Risk reduction extends for 10 to 20 years.
Endometrial hyperplasia is defined as
endometrial thickening with proliferation of irregularly sized and shaped glands and an increased gland-to-stroma ratio.
(In the absence of such thickening, lesions are best designated as disorderly proliferative mdometrium or focal glandular crowding)
The classification system of endometrial hyperplasia used by the World Health Organization {WHO) and International Society of Gynecological Pathologists designates two different types with varying malignant potential
1) Hyperplasia without atypia is characterized by exaggerated endometrial gland proliferation and an increased gland-to-stroma ratio compared with normal proliferative endometrium, but without significant cytologic atypia.
2) Atypical endometrial hyperplasias are clearly associated with the subsequent development of adenocarcinoma
Although endometrial hyperplasias are formally classified in these two different groups, they tend to be morphologically heterogeneous, Endometrial intraepithelial neoplasia (EIN) is a term introduced to more accurately distinguish the two very different clinical categories of hyperplasia.
Endometrial intraepithelial neoplasia (EIN) is a term introduced to more accurately distinguish the two very different clinical categories of hyperplasia. These are:
(1) nonnal polyclonal endometrium diffusely responding to an abnormal hormonal environment and
(2) intrinsically proliferative monoclonal lesions that arise focally and confer an devated risk of adenocarcinoma
The ElN classification system is a more accurate and reproducible way to predict progression to cancer and is recognized by the American College of Obstetricians and Gynecologisu and Society of Gynecologic Oncology (2017a). However, it is not been universally implemented
Pipelle office endometrial biopsy (EMB) indications:
The American College of Obstetricians and Gynecologists (2016) recommends such a sample for women older than 45 years with AUB. EMB is also considered for those younger than 45 with chronic excess estrogen exposure (exogenous or endogenous), failed medical management, and persistent AUB.
All patients older than 35 years with AGC cervical cytology should undergo endometrial biopsy. Endometrial biopsy also is recommended for women of any age with AGC cytology and risk factors for endometrial cancer (eg, abnormal
bleeding, obesity, anovulation) or cytologic diagnosis of AGC, favor endometrial origin.
Cut-off point for endometrial thickness that mandate endometrial sample in symptomatic postmenopausal women
For these women, endometrial stripe thickness measurements less or equal to 4 mm and associated with bleeding that is a.attributed to endomcttial atrophy (Amerian College of Obstmicians and Gynecologim, 2018b). Postmcnopausal women with a thicker endometrium warrant biopsy. Sonography may also identify abnormal echostructural changes in the endometrium. Cystic endometrial changes suggest polyps, homogeneously thickened endometrium may indicate hyperplasia, and a heterogeneous structural pattern is suspicious for malignancy. However, these sonographic findings show great overlap and cannot be used alone.
Cut-off point for endometrial thickness that mandate endometrial sample in asymptomatic postmenopausal women
Endometrial thickness >4 mm may be identified in postmenopausal women undergoing sonographic evaluation for reasons unrelated to postmenopausal bleeding. The positive predictive value of an •abnormal” endometrial thickness in asymptomatic women would be expected to be low, because the disease prevalence in asymptomatic patients is low. It is therefore reasonable to use a higher threshold value for these patients. The Society of Obstetrics and Gynecology of Canada suggests 11 mm as the threshold in asymptomatic women (Wolfman, 2010).
yolk sac tumor pathognomic histopathology feature
Schiller-Duval body (This structure consists of a central caplllary surrounded by tumor cells, present within a cystic space that may be lined by flat to cuboidal tumor cells)
Features of yolk sac tumor age of population:
One third of individuals are premenarchal at the time of initial presentation. Involvement of both gonads is rare, and the other ovaty is usually involved with metastatic disease only when other metastases are found in the peritoneal cavity.
In immature teratoma, survival is predicted most accurately by stage and by histologic grade of the tumor. How to counsel the patient ?
almost three quarters of immature teratomas are stage I at diagnosis and have a 5~year survival rate of 98 percent (Chan, 2008). Those with stage IA grade 1 immature teratomas have an excellent prognosis and do not require adjuvant chemotherapy (Bona,1994; Marina, 1999). Patients with stage II-IV disease have a 5-year survival rate ranging from 73 to 88 percent (Chan, 2008).
the standard care of management for immature teratoma and other malignant germ cell tumors in reproductive-aged women
Unilateral salpingo-oophorectomy
The most frequent site of dissemination of immature teratoma is
the peritoneum and much less commonly the retroperitoneal lymph nodes.
The most common Malignant Transformation variant of Mature Cystic Teratomas
Squamous cell carcinoma is most common and is found in approximately 1 percent of mature cystic teratomas typically develop in postmenopausal women
Steps of surgical staging of ovarian cancer:
- vertical abdominal incision is still traditionally recommended if an advanced ovarian malignancy is suspected.
- If present, ascites is evacuated and sent for cytologic evaluation. Otherwise, washings of the pelvis and paracolic gutters are collected for analysis prior to manipulation of the intraperitoneal contents.
- The entire peritoneal cavity is systematically inspected. The ovaries are assessed for size, tumor involvement, capsular rupture, external excrescences, and adherence to surrounding structures.
- Fertility-sparing USO is performed in all reproductive-aged women diagnosed with malignant ovarian germ cell tumors, as this conservative approach in general does not adversely affect survival
who has completed childbearing and would derive little benefit from retaining an ovary, hysterectomy with bilateral salpingo-oophorectomy (BSO) is appropriate - lymphadenectomy is most important for dysge.rminomas, whereas staging peritoneal and omental biopsies are particularly valuable for yolk sac tumors and immature teratomas
- Cytoreductive surgery is recommended for advanced-stage nondysgenninomatous malignant ovaiian germ cell tumors if it can be accomplished with minimal residual disease (Ovarian dysgerminomas are so chemosensitive they do not generally require aggressive attempts at debulking)
Chemotherapy standard regimen for malignant germ cell ovarian tumors
The standard regimen is a 5-day course of bleomycin, etoposide, and cisplatin (BEP) given every 3 weeks (Gershenson, 1990; Williams, 1987). Modified 3-day BEP combinations also are safe and effective (Chen, 2014; Dimopoulos, 2004). Carboplatin and etoposide, given in three cycles, has shown promise as an alternative for selected patients (Williams, 2004). For women with incompletely resected disease, at least four courses ofBEP are usually recommended (Morgan, 2016).
the preferred treatment for recurrent ovarian germ cell tumors in women initially managed with surgery alone.
At least four courses of BEP chemotherapy, Patients who achieved a sustained clinical remission of greater than 6 months after completing BEP or another platinum-based chemotherapy regimen may be treated again with BEP. Because their tumors are generally more responsive, these “platinum-sensitive” patients have a much better prognosis.
However, women who do not achieve remission with BEP chemotherapy or relapse within a few months (fewer than 6) are considered “platinum-resistant,” and treatment options are limited. Chemorefractory cases with dysgerminoma or immature teratoma appear to have a better outcome than other subtypes, and surgical salvage aimed at achieving no residual disease may benefit some patients (Li, 2007). Other palliative options for this group include vincristine, dactinomycin, and cyclophosphamide (VAC) or paclitaxel (Morgan, 2016).
Mature cystic teratomas (dermoid cysts) make up —- of tumors resected during pregnancy
Mature cystic teratomas (dermoid cysts) make up one third of tumors resected during pregnancy
Management of germ cells tumor in pregnancy
Surgical staging as non pregnant
for patients with nondysgerminomatous tumors (mainly yolk sac tumors and immature teratomas) and those with incompletely resected disease, chemotherapy during pregnancy is strongly considered.
Age of population of sex cord stromal ovarian tumors
ovarian SCST s typically affect women of all ages. This range contains a unique bimodal distribution that reflects inherent tumor heterogeneity. For example, juvenile granulosa cell tumors, Sertoli-Leydig cell tumors, and sclerosing stromal tumors are found predominantly in prepubertal girls and women within the first three decades of life (Schneider, 2005). Adult granulosa cell tumors commonly develop in older women, at an average age in the mid-50s (van Meurs, 2013).
Genetic etiology behind SCST (sex cord stromal ovarian tumors)
The etiology of SCSTs is largely unknown. However, a single, recurrent FOXL2 gene mutation is present in vinually all adult-type granulosa cell tumors (Schrader, 2009; Shah, 2009). Also, women with a germline DICER1 mutation are predisposed to developing SCSTs (Heravi-Moussavi, 2012)
ovarian SCSTs develop in association with several defined hereditary disorders at a frequency that exceeds mere chance. These include
Ollier disease, which is characterized by multiple benign but disfiguring cartilaginous neoplasms, and Peutz-Jeghers syndrome, characterized by intestinal hamartomatous polyps (Stevens, 2005).
serum testosterone levels> ISO ng/dL or dehydroepiandrosterone sulfate (DHEAS) levels >8000 µg/L strongly suggest the possibility of
an androgen-secreting tumor
Modified WHO Classification of Ovarian Sex Cord-Stromal Tumors
*Pure stromal tumors: Fibroma/fibrosarcoma Thecoma Sclerosing stromal tumor Leydig cell tumor Steroid cell tumor
*Pure sex cord tumors: Granulosa cell tumor Adult type Juvenile type Sertoli cell tumor Sex cord tumor with annular tubules
*Mixed sex cord-stromal tumors: Sertoli-Leydig cell tumors Sex cord-stromal turners, NOS
Embryonic origin of granulosa and Sertoli cells
develop from the sex cords and thus from the the coelomic epithelium ( misoderm)
thoca cells, Lcydig cells, and 6broblasts are derived from .
the mesechyme
Seventy percent of ovar· ian SCSTs are
granulosa cell tumors
the most definitive treatment of endometrial hyperplasia
Hysterectomy
Management of Premenopausal women with nonatypical endometrial hyperplasia
a 3-to 6-month course of low-dose progestin therapy. Cyclic medroxyprogesterone acetate (MPA) (Provera) given orally for 12 to 14 days each month at a dose of 10 to 20 mg daily is commonly used. Continuous daily dosing with MPA 10 mg is suitable and may be more effective than cyclic administration in reversing hyperplastic changes. Another frequently used option is COC pills for those without contraindications. The levonorgestrel-releasing IUD also is effective (Gallos, 2010; 0rbo, 2014; Scarselli, 2011).
Managment of Postmenopausal women with nonatypical endometrial hyperplasia
low-dose oral cyclic MPA or a continuous 10-mg daily regimen, Importantly, in older women, providers should be confident that the sample obtained is adequate to exclude cytologic atypia. D & C may be indicated at times, especially if the tissue from Pipelle sampling is scant or if recurrent bleeding is noted. Affected postmenopausal patients who have a contraindication to progestin therapy or who cannot tolerate the therapy can be expectantly managed. Complex hyperplasia without atypia is usually treated chronically with progestins. Office endometrial biopsy is recommended every 3 to 6 months until lesion resolution is achieved.
In cases of endometrial hyperplasia without atypia, the risk of progression to endometrial cancer is
only 1 to 3 percent. The overall clinical and pathologic regression rates to progestin therapy range from 70 to 80 percent for nonatypical endometrial hyperplasia (Rattanachaiyanont, 2005; Reed, 2009).
Patients on progestins with persistent endometrial hyperplasia without atypia on repeated biopsy may be switched to
higher-dose regimen such as MPA 40 to 100 mg orally daily. Also, megestrol acetate (Megace), 160 mg daily or 80 mg twice daily, is suitable. It can be increased even up to 160 mg twice daily if no regression is initially achieved. Again, a clinician must confirm that hormonal ablation has occurred by resampling the endometrium after a suitable therapeutic interval, usually 3 to 6 months. Hysterectomy may also be considered for lesions that are refractory to medical management.