• 1.
  

  a) T b) T c) F d) T e) T

The incidence of adnexal masses in pregnancy vary from 0.15% to 5.7%; clinically significant masses range from 1 in 25 to 1 in 8000 pregnancies. Most of these masses are innocuous and spontaneously resolve during pregnancy. A higher trend in reporting is possibly explained by the increasing use of ultrasound as a routine antenatal evaluation and delay of childbearing to an older age. The variation in incidence accounts for differences in detection and management protocols and includes borderline neoplasms. A functional ovarian cyst is the most common benign cyst seen in pregnancy occurring in approximately 75% of patients. Mature teratomas are the most common persistent ovarian cyst (40%) in pregnancy. Approximately 50% of OCs in pregnancy are epithelial in origin. Germ cell and stromal tumours account for 30% and the remaining 20% consist of rare tumour entities e.g. sarcomas and secondary metastases to the ovary. Thus, epithelial ovarian cancer (EOC) is more commonly reported in pregnant patients than germ cell tumours, contrary to the distribution seen in non-pregnant patients of the same age group. The resolution rate of adnexal masses in the second trimester of pregnancy is 60–70%. Persisting masses have the potential to cause complications in 10–30% pregnancies. Size and morphology criterion on ultrasound decide between which masses are for intervention and which can be kept under surveillance.

• 2.
  

  a) F b) F c) F d) T e) T

Most adnexal masses are incidentally detected on routine first trimester ultrasound. Pain, obstruction of labour and hemodynamic instability are uncommon acute presentations necessitating urgent intervention. The sensitivity of detecting ovarian cysts on clinical examination in pregnancy is between 15–50%. Clinical assessment is subject to inter-observer variation and is often masked by pregnancy induced pelvic changes. Moreover, routine internal pelvic examination during the first trimester of pregnancy has fallen into disfavor in view of the risk of introducing infection. A persistent 5cm ovarian cyst on USS should prompt investigation during pregnancy. Other features on ultrasound indicating a malignant potential are solid areas, papillary projections and ascites on ultrasound in addition to the size criterion. Colour Doppler in pregnancy may be less informative. For those masses which the IOTA rules yielded an inconclusive result, subjective assessment of ultrasonic findings by an experienced ultrasound examiner was the most accurate predictor of malignancy. MRI is a useful adjunct when sonography is inconclusive or insufficient to guide management of an adnexal mass.

• 3.
  

  a) F b) T c) F d) F e) T

Scheduling surgery between 16–20 weeks allows for spontaneous resolution of masses, exclusion of a fetal congenital anomaly, reduced risk of preterm labour and better uterine visualization with advanced gestational age. However surgery should not be delayed beyond 23 weeks in view of poorer outcomes due to delay in treatment in case of a malignancy or risk of complications in cases of benign masses. A laparoscopic approach is associated with a rapid return to post-operative bowel function, decreased post-operative incisional pain and narcotic use, lower morbidity from atelectesis and thromboembolic events, lower need for uterine traction leading to less irritability and faster post-operative ambulation and return to regular activity. There is level 2 evidence available supporting the use of laparoscopy in pregnancy over laparotomy. Poorer fetal outcomes are associated beyond 23 weeks of gestation. The overall outcome depends upon size of the tumor, risk of malignancy and the period of gestation. Surgical intervention has shown not to have an adverse impact on overall obstetric outcome. Some authors report an increase in hysterectomy, rates of caesarian delivery, blood transfusion, prolonged hospitalization for these women, but no effect in neonatal outcome. Hypotension is associated with a laparoscopic approach in pregnancy due to increased intra-abdominal pressure and inferior vena cava compression. Alteration in fetal vital parameters, hypercarbia, CO2 embolism, increase in carbon monoxide in fetal blood and inadvertent uterine injury due to trocar placement are other complications which may occur. Micro-papillary and serous histopathological subtypes have a worse prognosis, indicating contralateral foci of invasive carcinoma, lymphatic spread and extra-pelvic disease. A full surgical re-staging is warranted in these patients. In a French multi-centre study, 21% of mucinous BOTs exhibited intraepithelial carcinoma or micro-invasion and 47% of serous BOTs exhibited micro-papillary features, noninvasive implants or micro-invasion. Re-staging surgery performed in 52% patients resulted in upstaging in 24% of cases. Recurrence rate with serous BOT with micro-papillary features or peritoneal implants was 7.5%.

• 4.
  

  a) F b) T c) F d) F e) F

Ideally the delivery should be planned 3–4 weeks after the last chemotherapy cycle to avoid fetal neutropenia due to transient aplasia. Most cytotoxic agents cross the placental barrier. Isolated case reports, with no adverse perinatal outcome encourage its use, however keeping in mind the theoretical risk of teratogenicity most authors recommend use after 20 weeks of gestation. CNS and neural tube defects are seen primarily between the 2 ^nd to 8 ^th weeks of gestation. Ophthalmic, genito-urinary and haematologic complications occur during week 8 to week 12 of pregnancy. 10–20 % of patients receiving chemotherapy in pregnancy develop major congenital malformations. These occur in 17% of patients with single agent regimens and 25 % with multi-agent regimens in the first trimester. Doll et al. described a teratogenic risk of only 1.3% for the combination of carboplatin in the second and third trimester in contrast to an elevated risk up to 25% in the first trimester Fetal echo is recommended at 20-22 weeks of gestation to rule out cardiac malformations. Ventriculomegaly, micro-ophthalmia and cerebral atrophy are reported fetal risks associated with platin-based chemotherapy.

• 5.
  

  a) T b) T c) T d) T e) F

White blood cell count and alkaline phosphatase are both elevated in pregnancy. Many specific tumor markers are also impacted by pregnancy, and therefore are either not useful or are not as predictive as in the non-pregnant population. Ovarian cancer antigen 125 (CA-125) concentrations have been shown to be elevated in the first trimester with wide variation between weeks 5 and 8, normalize during the second and third trimesters, rise again immediately after delivery, also with wide fluctuations, with generally do not return to baseline until 10 weeks postpartum. More recently, the concentration of the biomarker human epididymis protein 4 (HE4), was found to be lower in pregnant women when compared with non-pregnant or pre-menopausal women. Other markers whose levels and thus clinical utility may be altered by pregnancy include human chorionic gonadotropin (HCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH), whereas carcinoembryonic antigen (CEA) and CA 19-9 are not affected by pregnancy.

• 6.
  

  a) T b) T c) F d) F e) F

For any imaging modality, the principle of using it only when clinically indicated, for the shortest amount of time and with the lowest level of energy compatible with an accurate diagnosis should be employed. This will limit any potential fetal effects. Ionizing radiation can theoretically result in three harmful fetal effects: cell death (and related teratogenic consequences), carcinogenesis, and genetic effects or mutations in germ cells. However, these effects are unlikely after exposure to the low radiologic doses associated with current diagnostic imaging procedures. The rad or gray (Gy) signify the dose, or the amount of energy deposited per kilogram of tissue, with 1 Gy equal to 100 rad. The rem and Sv represent the relative effective dose, or the amount of energy deposited per kilogram of tissue normalized for biologic effectiveness, with 1 Sv equal to 100 rem. The generally accepted safe range of radiation during pregnancy is less than 5 rad. This threshold is lower than the lowest dose believed to have biological fetal consequences and has not been associated with adverse fetal effects, including an increase in fetal anomalies or pregnancy loss. MRI is also a safe imaging modality in pregnancy because it utilizes magnets that alter the energy state of hydrogen protons and is not associated with known adverse fetal effects. However, the safety of gadolinium, a paramagnetic contrast agent, has not been confirmed. Studies of its effects on human fetal development are lacking, but animal studies have demonstrated increased rates of spontaneous abortion, skeletal abnormalities and visceral abnormalities when given at 2–7 times the recommended human dose. Neonatal hypothyroidism has been reported when some iodinated agents are used after 12 weeks of pregnancy, when the fetal thyroid becomes functional and can concentrate iodine. For this reason, radiopaque contrast agents should generally be avoided unless they are essential for diagnosis.

• 7.
  

  a) F b) F c) T d) F e) T

The time between conception and approximately 10 days post-conception is called the “all-or-none” period, meaning that if there is exposure to a chemotherapeutic agent or any other noxious insult but the embryo survives, there will likely be no adverse effects. From 10 days post-conception to 8 weeks’ gestation, the main period of organogenesis, exposure to chemotherapeutic agents can result in major congenital malformations; up to 16% of fetuses exposed to chemotherapy during the first trimester are born with a congenital malformation. Combination chemotherapy was associated with an increase in adverse outcomes (25%) when compared to single-agent therapy. Exposure to chemotherapy in the second and third trimesters is considered relatively safe because most organs have formed, however, certain systems remain vulnerable (for example the central nervous system and the hematologic system). Complications that have been reported after prenatal exposure in the second and third trimesters include preterm delivery, fetal growth restriction and intra-uterine fetal demise. Fortunately, available clinical data suggest that most fetuses exposed to chemotherapy starting in the second trimester do not experience significant long-term complications. Biologic agents such as monoclonal antibodies are large molecules that require active transport via the placenta to reach the fetus and it has been shown that this does not take place prior till the 14 ^th week of gestation. This suggests that exposure to monoclonal antibodies during the first trimester is unlikely to have an adverse effect, whereas second and third trimester exposure may be harmful. Small molecule agents, such as tyrosine kinase inhibitors, can cross the placenta throughout pregnancy and should be avoided in the first trimester, similar to standard chemotherapy.

• 8.
  

  a) T b) F c) F d) T e) T

Breast cancer in pregnancy is most often axillary lymph node-positive and presents with a larger primary tumor size than outside of pregnancy. Histologically, the tumors are often poorly differentiated, are more frequently estrogen and progesterone receptor negative, and approximately 30% are HER2/neu-positive. Approximately 65–90% of pregnant patients are diagnosed with stage II or III breast cancer compared to 45–65% of non-pregnant patients, with more non-pregnant women being diagnosed with stage I disease. With a finding of CIN2-3, colposcopy should be performed every trimester and additional biopsies performed if progression to malignancy is suspected. Although these lesions rarely progress, postpartum follow-up is necessary because approximately 50% of high-grade lesions will persist. The routine use of ultrasound during pregnancy has made the diagnosis of adnexal masses a common occurrence, with an estimated incidence of 1 in 600 to 1,500 pregnancies. Fortunately, most are benign; only 1–3% are found to be malignant and most are diagnosed in early stages. Unfortunately, pregnancy seems to be adversely affected by leukemia with increased rates of preterm delivery, growth restriction, intrauterine fetal demise, and spontaneous abortion. Additionally, the hematologic changes seen with acute leukemia may compound the normal physiologic changes seen in pregnancy leading to an increased risk of thrombosis, bleeding, and disseminated intravascular coagulation. Melanoma more commonly metastasizes to the placenta than other cancers, so placental pathology examination to evaluate for metastatic disease is necessary. Unfortunately, fetal metastases have also been reported.

• 9.
  

  a) T b) F c) F d) T e) T

It is essential that the counsellor should be honest to provide information about the illness. He or she should not adopt a defensive attitude to address the patient’s concerns. Having family members with the patient will give her strength to cope with the situation. The counsellor should show empathy rather than sympathy which will create more emotion. Fear, anxiety, sadness, and despair are common reactions during breaking bad news. The presence of a psychotherapist would allay some of these emotional reactions. Final decisions regarding management should be taken with the consent of the patient.

• 10.
  

  a) T b) T c) T d) T e) F

Many studies have shown psychological distress is more common during the postpartum period. Having malignancy, itself, is not an indication to perform Caesarean section. The risk of thromboembolism and postpartum haemorrhage is more common during the postpartum period.

• 11.
  

  a) F b) T c) T d) T e) F

Management of vulva cancer should not be delayed in pregnancy due to the detrimental effect on prognosis. As in the non-pregnant state, any suspicious lesion, presenting in all trimesters should be biopsied to obtain a histological diagnosis prior to offering treatment. MRI is the preferred imaging tool in pregnancy. In general, chemotherapeutic agents when used in the 2 ^nd and 3 ^rd trimester has not shown to cause structural abnormalities in fetus or developmental problems in childhood. Vaginal delivery is possible following vulval surgery providing that the wound has healed or when the tumour is too large leading to increased risk of hemorrhage during vaginal birth. Caesarean section is only indicated for obstetric reasons and should be considered in women who have vulval scarring, or following plastic reconstruction surgery.

• 12.
  

  a) F b) F c) F d) T e) F

Squamous cell carcinoma is more common than adenocarcinoma. The incidence of lower genital tract cancer is increasing. Vaginal clear cell cancer is associated with exposure to diethylstilbestrol in utero and is very rare. Vulval melanoma is no more nor less common in or out of pregnancy.

• 13.
  

  a) F b) T c) F d) F e) T

Sentinel node biopsy using 99mTC only (no blue dye) has been reported in one case report with no harm cause to fetus. 95% of cases had bilateral inguinal femoral node dissection and this is mainly performed in the post-partum period. The lower 1/3 of vagina drains into the inguinal lymph nodes; therefore, inguinal-femoral lymphadenectomy is performed in cancer involving the lower 1/3 of vagina. The majority of vulvectomy is performed during the post-partum period (59.3%). The second most common timing for surgical treatment is in the 2 ^nd trimester and only one case was performed in the 1 ^st trimester.

• 14.
  

  a) F b) F c) T d) F e) F

Chemotherapy can be used in pregnancy for breast cancer except prior to 14 weeks due to the risk of teratogenesis. This can include Taxanes. Whilst most drugs have reduced concentrations due to altered pharmacokinetics (principally increased clearance) no changes to drug dose are required. The pharmacodynamics of most drugs are not intrinsically altered in pregnancy.

• 15.
  

  a) F b) F c) F d) T e) F

Whilst radiation is best avoided it is important to do the most appropriate diagnostic test to gain a diagnosis promptly. Shielding of the abdomen can significantly reduce the amount of radiation exposure but there will always be some scatter. Both breasts should be imaged as bilateral cancer may be missed. Mammography is one of the first investigations of choice as part of an assessment of a breast lump in or out of pregnancy.

• 16.
  

  a) F b) T c) F d) F e) F

Termination of pregnancy can be considered or opted for by a woman with concurrent breast cancer but it is not indicated or specifically necessary as it has no effect on survival and use of chemotherapy outside the first trimester. The need for anti-oestrogen adjuvant therapy is dependent upon E2 receptor status – cancers in pregnancy tend to be E2 receptor negative.

• 17.
  

  a) F b) T c) F d) T e) F

Surgery for breast cancer in pregnancy should follow the same guidelines as for non-pregnant patients and be individually tailored. Anesthetic exposure is not a major concern nor the ability to reconstruct – the breast changes considerably and this just needs to be borne in mind.

• 18.
  

  a) F b) T c) F d) F e) T

Laparoscopic PLND in pregnancy is indicated after the first trimester and before 22 weeks of gestation. This patient has a diagnosis of stage IIB cervical cancer. The gold standard treatment outside of pregnancy is chemo/radiotherapy. Considering her POH, a careful discussion should be offered regarding pros/cons on pregnancy preserving management. Trachelectomy should not be offered in pregnancy preserving treatment of stage IIB cervical cancer. Chemotherapy could be offered in pregnancy preserving treatment and the surgical lymph node assessment is not mandatory before starting therapy. TOP is legal in the UK before 24 weeks. Once the uterus is empty the standard treatment should be started as soon as possible.

• 19.
  

  a) F b) F c) T d) F e) T

Melanoma is the most common malignancy detected in pregnancy followed by breast and cervical cancer. Stage 1B1 can be treated conservatively until fetal viability is achieved and treated after delivery as in non-pregnant women. Indeed a careful discussion is mandatory.

Vaginal delivery should be avoided in view of the risk of developing metastasis in the episiotomy site and haemorrhage. Classical incision is preferred in order to avoid tumour dissemination. In micro invasive tumors (Stages 1A1/1A2), pregnancy preserving treatment can be offered and the management of tumor is the same as in non-pregnant women. Fetal viability, stage of disease and future fertility desire are the most important aspects to be considered in the management of cervical cancer in pregnancy.

• 20.
  

  a) F b) T c) F d) F e) T

All cervical lesions noted in pregnancy should be biopsied. Punch biopsy is considered safe in pregnancy, however it should be deferred until after the first trimester. In view of the fact that the lady is 18 weeks pregnant the punch biopsy is indicated without any delay. Cone biopsy is considered safe in pregnancy, however without a biopsy there is no indication for performing that procedure. Imaging assessment should be started once the histology is positive for cancer.

• 21.
  

  a) T b) T c) F d) T e) T

A young patient presenting with cervical cancer in pregnancy presents a complex problem. Once the diagnosis of cancer is confirmed, the gestational age and stage of the disease must be determined. If the patient’s gestation is in the first trimester, most authorities would recommend termination of pregnancy followed by definitive treatment according to the stage. However, because of the complex social and psychological issues involved, a multidisciplinary approach involving the obstetrician and the gynecologic oncologist is important. Also the patient’s wishes on the outcome of the pregnancy must be taken into consideration. The mode of delivery is irrelevant in advanced stages of pregnancy, as it is always by a Caesarean section.

• 22.
  

  a) F b) F c) F d) T e) T

The biggest fear of using any chemotherapy is the potential teratogenic effects of these agents and the risk of miscarriage. The teratogenicity of any drug depends on the timing of exposure, the dose, and the degree to which the drug crosses the placenta. The most vulnerable period appears to be the period of organogenesis, weeks 2–8 after conception. First trimester use of chemotherapy may result in spontaneous abortion, fetal death and fetal malformations. When the drugs are given in the second and third trimester, there is increased risk of intrauterine growth restriction and low birth weight. The pharmacokinetics of drugs in pregnancy is poorly understood. Trans-placental passage of drugs and their metabolism in pregnant patients is still under investigation and it varies according to individual drug. In early stage disease where the tumour is small, use of NACT may allow fertility preserving procedures like trachelectomy instead of hysterectomy.

• 23.
  

  a) T b) F c) F d) F e) T

The incidence of CIN complicating pregnancy is 2000–8000 per 100,000 pregnancies. A number of studies have demonstrated high rates of regression of CIN during pregnancy. Paraskevaidis et al. reported postpartum regression in 48.1% of women with an antenatal impression of CIN2/3. The UK NHSCSP recommend that women with suspected CIN3 in whom colposcopy has excluded invasive disease, should have treatment deferred until at least 12 weeks post-delivery. Cervical smears taken during pregnancy can be difficult to interpret due to pregnancy-related changes and can cause minor vaginal bleeding. Consequently, the NHSCSP advocate that routine screening should not be performed during pregnancy. The management of VIN during pregnancy is the same as for non-gravid women. If a suspicious vulval lesion is noted during pregnancy, it should be biopsied.

• 24.
  

  a) F b) T c) T d) F e) F

There is currently no evidence, which suggests that colposcopy results in preterm delivery or miscarriage. Colposcopy during pregnancy is indicated if: (i) CIN is confirmed histologically but the woman conceives prior to definitive treatment, (ii) abnormal cytology is detected on an opportunistic smear taken during pregnancy, (iii) abnormal cytology is detected but the woman becomes pregnant while awaiting referral to colposcopy, (iv) the woman has previously been treated for CGIN or CIN2/3 with involved or uncertain margin status. Colposcopy during pregnancy requires a high degree of skill to discriminate between changes attributable to pregnancy and pathological lesions and therefore should only be undertaken by experienced colposcopists.

• 25.
  

  a) T b) T c) F d) T e) T

HPV vaccination in pregnancy is not associated with any adverse pregnancy outcomes. Kyrgiou et al. & Arbyn et al. found that cold-knife and laser conisation were associated with an increased risk of preterm birth. Conversely, ablative techniques such as laser vaporisation were not associated with adverse obstetric outcomes. More recently, it has emerged that the risk of serious adverse pregnancy outcomes are increased with multiple conisations. Ortoft et al. noted a 2.8-fold increase in perinatal death after a single conisation and a 10-fold increase in preterm delivery after two conisations. Most studies on adverse pregnancy outcomes after treatment for CIN are small case-control studies.

• 26.
  

  a) F b) F c) T d) T e) T

The UK NHSCSP advise that excisional biopsy should only be performed in pregnancy in order to exclude invasive cancer. If invasive cancer has been excluded at the time of colposcopic examination, definitive treatment should be deferred until at least 12 weeks following delivery. Where invasive disease is suspected during pregnancy, conventional punch biopsies may not be adequate as they cannot safely confirm or exclude micro-invasion, and may fail to give a representative sample. Women with suspected CIN2/3, should be reviewed at 3-monthly intervals during pregnancy, with a final assessment 3–4 months following delivery. The cervix is more vascular during pregnancy secondary to physiological changes and thus haemorrhage is more likely if biopsies are taken.

• 27.
  

  a) T b) F c) T d) T e) T

Deterministic effects by definition have a cause and effect relationship and also mean that once a threshold dose has been exceeded the severity of the effect will increase in a linear fashion with increasing dose. Stochastic effects are radiation effects that occur by chance, for example, induction of cancer, and the risk increases in a linear quadratic relationship with dose. The threshold dose is 0.1Gy. This refers to the radiation dose below which fetal effects are unlikely to be harmful.

• 28.
  

  a) T b) T c) F d) F e) T

There has been evidence with appropriate shielding and radiation techniques supra-diaphragmatic radiotherapy to the breast, lymphoma and naso-pharyngeal cancer can be given. Pelvic radiotherapy is not appropriate in pregnancy. There have been some reports of patients receiving neo-adjuvant chemotherapy and delaying pelvic radiotherapy until the post-partum period.

• 29.
  

  a) T b) F c) T d) T e) F

SCC levels are elevated in between 57–70% of women with a primary squamous cell carcinoma of the cervix, but are also increased in women with squamous cell carcinomas of other origins. It is thought that SCC is a marker for cellular differentiation for squamous cells. Values of SCC are high in the umbilical cord, and even higher in the amniotic fluid with the fetus being the producer of this marker and it is therefore labelled as an onco-fetal antigen. HE4 is a sensitive and specific tumour marker for ovarian cancer and is less frequently elevated in benign conditions (compared to CA 125). In pregnant women, HE4 values were found to be significantly lower than in non-pregnant pre-menopausal women. CA 125 is used for monitoring non-mucinous epithelial ovarian cancer. The high concentration of CA 125 in decidual cells, amniotic fluid and amnion cells and low levels in umbilical cord blood suggest that the fetus itself does not produce CA 125. Due to it large molecular weight is does not transfer across the basal membrane and disruption of this membrane can cause higher maternal plasma levels. In the first trimester this is caused by trophoblastic invasion in the decidua and in the third trimester and puerperium from detachment of the placenta. CA 15-3 is an immunoassay for detection of the mucin (MUC)-1 antigen. This membrane-bound mucin is overexpressed in breast cancer cells and elevated levels can be found in the serum of >70% of patients with advanced breast cancer. It is however also present in trophoblastic tissue. For that reason, MUC-1 increases during pregnancy and especially during the third trimester. AMH is a serum marker for granulosa cell tumours but is not elevated during pregnancy. These levels during pregnancy are the same as for women in the follicular phase and tend to decrease with progression of pregnancy.

• 30.
  

  a) T b) F c) F d) T e) T

Ionizing imaging techniques expose the fetus to potentially harmful radiation. The cumulative fetal radiation exposure should kept below 100 mGy to prevent adverse fetal outcome. Below this threshold the increased risk of malformation and childhood cancer is approximately 1% higher compared to the non-exposed pregnant population. The expected mode of delivery should does not influence the imaging technique best suitable for diagnosis and staging in pregnant women with cancer. Unless there is an acute life-threatening situation, there is no rush in imaging pregnant patients although unreasonable delay should be avoided. It is strongly advised to have a multidisciplinary tumour board meeting to discuss further diagnostic imaging management and, if necessary, ask for a second opinion in order to avoid suboptimal imaging strategies and accumulation of fetal radiation exposure above the preferred 100 mGy threshold further along in pregnancy. Pregnancy related changes to the body might disadvantage certain imaging techniques. Metastatic disease influences maternal outcome and may change treatment interventions, so it is important to assess. During pregnancy, some of the staging techniques increase fetal radiation and are therefore only justified when the mother benefits from it. It is therefore important to calculate the risk of metastatic disease and based on this risk assessment decide whether or not staging is appropriate.