A 62-year-old woman presents with post-menopausal bleeding. Staging laparotomy, hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and lymph-node dissection reveal uterine carcino-sarcoma. The tumour invades the myometrium, but is confined to the uterus. Which of the following treatments is/are considered appropriate adjuvant treatment(s)?

• a)

  Observation with no further treatment.

• b)

  Whole abdominal radiation plus concurrent cisplatin chemotherapy.

• c)

  Ifosfamide plus cisplatin chemotherapy.

• d)

  Intra-vaginal brachytherapy. e) Combined brachytherapy and external beam irradiation

A 47-year-old woman undergoes myomectomy to remove a large uterine fibroid. Histologic review shows high-grade uterine leiomyosarcoma with over 50 mitoses per 10 high power field. She returns for hysterectomy and bilateral salpingo-oophorectomy. Residual leiomyosarcoma is found in the uterus, but has not extended to the uterine serosa or ovaries. Post-resection imaging by computed tomography scan shows no evidence of persistent or metastatic disease. Which of the following adjuvant intervention(s) has/have been shown to improve overall survival in this situation?

• a)

  Doxorubicin-based chemotherapy.

• b)

  Gemcitabine-docetaxel chemotherapy.

• c)

  Whole pelvic radiation.

• d)

  Intra-vaginal brachytherapy.

• e)

  Combined radiation and doxorubicin-based chemotherapy.

A 66-year old woman with a history of myocardial infarction and medically controlled congestive heart failure undergoes hysterectomy for post-menopausal bleeding. Pathology shows high-grade leiomyosarcoma. Post-resection imaging shows multiple bilateral lung metastases ranging up to 6 cm in size. Her resting cardiac ejection fraction is 45%. Which of the following is reasonable first-line treatment?

• a)

  Liposomal doxorubicin plus ifosfamide.

• b)

  Fixed-dose rate gemcitabine plus docetaxel.

• c)

  Cisplatin only

• d)

  Tamoxifen only

• e)

  Anastrozol only

A new International Federation of Gynecology and Obstetrics (FIGO) classification and staging system has been specifically designed for uterine sarcomas in an attempt to reflect their different biological behaviours. The following statement(s) is/are true about this staging system:

• a)

  Stage I leiomyosarcomas are subdivided according to lymph-node status.

• b)

  Stage I leiomyosarcomas are subdivided according to myometrial invasion.

• c)

  Stage I low-grade endometrial stromal sarcomas are subdivided according to lymph-node status.

• d)

  Subdivision of stage I adenosarcomas takes into account the presence of sarcomatous overgrowth.

• e)

  Carcinosarcomas are staged as endometrial carcinomas.

The following statement(s) is/are true about the relevance of lymph-node status in uterine sarcomas:

• a)

  Positive lymph nodes have an independent prognostic relevance for uterine leiomyosarcoma.

• b)

  Lymphadenectomy is of prognostic significance in women with endometrial stromal sarcoma.

• c)

  Lymphadenectomy significantly improves the clinical outcome of women with endometrial stromal sarcoma.

• d)

  Data from meta-analysis showed that positives lymph nodes have no prognostic relevance for uterine carcinosarcomas.

• e)

  Positive lymph nodes could have a different effect on the risk of recurrence in women with homologous or heterologous uterine carcinosarcoma.

The following statement(s) is/are true about the relevance of biological variables in uterine sarcomas:

• a)

  Progesterone receptor expression may have a prognostic relevance for leiomyosarcoma.

• b)

  p16 and p53 overexpression are similar in uterine leiomyosarcomas and leiomyomas.

• c)

  Biomarkers for cell proliferation and apoptosis have no prognostic relevance for leiomyosarcoma.

• d)

  Progesterone receptors are rarely expressed in low-grade endometrial stromal sarcomas.

• e)

  Serum CA125 assay seem to have a prognostic relevance for women with leiomyosarcoma.

The following statement(s) is/are true about the prognosis of women with low-grade endometrial stromal sarcoma and uterine adenosarcoma:

• a)

  The prognosis of women with stage I low-grade endometrial stromal sarcoma is significantly better than that of women with stage I leiomyosarcoma.

• b)

  Tumour size has no prognostic relevance for women with stage I low-grade endometrial stromal sarcoma.

• c)

  Oestrogen replacement therapy is detrimental for women who have previously had hysterectomies for low-grade endometrial stromal sarcoma.

• d)

  The prognosis of uterine adenosarcoma is poor, and 5-year survival is less than 20%.

• e)

  No pathological features have been detected to correlate with the prognosis of women with uterine adenosarcoma.

The following statement(s) regarding leiomyosarcoma is/are true:

• a)

  Most studies have shown that stage is the most significant prognostic factor.

• b)

  The staging system by the American Joint Committee on Cancer provides a better prognostic estimation than the one by the International Federation of Gynecology and Obstetrics.

• c)

  Most studies have shown that tumour size over 5 cm is a strong independent prognostic indicator.

• d)

  Lymphadenectomy is not necessary if evidence of extra-uterine diseases is lacking.

• e)

  Leiomyosarcoma should be staged as IIIb when a preoperative CT scan shows two liver parenchymal lesions proven to be leiomyosarcoma by guided biopsy.

The following statement(s) regarding endometrial stromal sarcoma (ESS) is/are true:

• a)

  Poorly differentiated or undifferentiated ESS has infiltrative myometrial invasion.

• b)

  ESS (low-grade) has an indolent course and less than 10% of women will have recurrence.

• c)

  Cervical involvement is not a prognostic indicator for both ESS (low grade) and undifferentiated endometrial sarcoma.

• d)

  Some studies have shown that women with ESS (low grade) with lymph-node metastasis have a good 5-year survival rate.

• e)

  Ovarian-sparing surgery is safe in young women with early stage disease.

The following statement(s) regarding adenosarcoma is/are true:

• a)

  Most studies have shown that adenosarcoma with a heterologous component has a worse outcome.

• b)

  Adenosarcoma of the endocervix limited to the cervix clinically is staged as stage I even if ovarian metastasis is proven histologically.

• c)

  Routine lymphadenectomy has no role, as the incidence of lymph-node metastasis is low.

• d)

  Adenosarcoma with sarcomatous overgrowth (ASSO) is defined as having sarcomatous component over 50% of the whole tumour volume.

• e)

  ASSO has a better clinical course than carcinosarcoma.

The following statement(s) is/are true about the surgical treatment of early stage uterine carcinosarcoma that is confined to the uterus:

• a)

  The incidence of lymph-node metastasis is negligible.

• b)

  Ovarian tissues can be preserved in premenopausal women.

• c)

  Peritoneal staging procedures, including washing cytology, peritoneal biopsies, and omentectomy, is not required.

• d)

  Pelvic and para-aortic lymph-node dissection is recommended.

• e)

  The survival benefit of lymph-node dissection is well known.

The following statement(s) is/are true about the surgical treatment of uterine leiomyosarcoma:

• a)

  Peritoneal staging procedures, including washing cytology, peritoneal biopsies, and omentectomy, is recommended in early stage disease.

• b)

  Bilateral salpingo-oophorectomy is mandatory even in premenopausal women.

• c)

  If extra-uterine disease is encountered during surgery, complete debulking is recommended.

• d)

  Pelvic and para-aortic lymph-node dissection is recommended even in early stage disease.

• e)

  Isolated recurrent disease of the lung is a contraindication to surgical treatment.

The following statement(s) is/are true about the surgical treatment of low-grade endometrial stromal sarcoma:

• a)

  Bilateral salpingo-oophorectomy is mandatory even in premenopausal women with early stage disease.

• b)

  If extra-uterine disease is encountered during surgery, aggressive surgery to achieve complete cytoreduction is of less importance.

• c)

  Pelvic and para-aortic lymph-node dissection is recommended even in early stage disease.

• d)

  Lymph-node dissection is associated with prolonged survival in advanced-stage disease.

• e)

  Prolonged survival and cure are common after surgical resection of recurrent disease.

The following features are commonly found in low-grade endometrial stromal sarcoma:

• a)

  Infiltrative borders.

• b)

  Marked cytological atypia.

• c)

  Lympho-vascular permeation.

• d)

  Positivity for CD10.

• e)

  Positivity for progestogen receptors.

Co-existing epithelial and stromal components may be found in the following:

• a)

  Adenosarcoma.

• b)

  Carcinosarcoma.

• c)

  Uterine tumour resembling ovarian sex-cord stromal tumour.

• d)

  Atypical polypoid adenomyoma.

• e)

  Adenofibroma.

The following statement(s) is/are true about Müllerian adenofibroma and adenosarcoma:

• a)

  The adenofibroma is the precursor lesion of adenosarcoma.

• b)

  Adenofibromas are more common than adenosarcomas.

• c)

  Adenosarcomas show a mixture of apparently benign glandular epithelium and low-grade sarcoma, usually of endometrial stromal type.

• d)

  A biphasic tumour with hypercellularity and atypia, which appears condensed around the glands, is diagnosed as an adenosarcoma in the absence of mitotic figures.

• e)

  Myometrial invasion and sarcomatous overgrowth are the only morphologic features of adenosarcomas associated with an increased risk of recurrence.

The following statement(s) is/are true about carcinosarcomas (malignant Müllerian mixed tumours):

• a)

  Microscopically, carcinosarcomas are composed of malignant epithelial and mesenchymal elements that merge with one another.

• b)

  In carcinosarcomas, tumour progression follows a true epithelial-mesenchymal transition.

• c)

  The most common epithelial component is an FIGO grade 1 endometrioid adenocarcinoma, and the most frequent mesenchymal component is of low-grade endometrial stromal type.

• d)

  The overall 5-year survival for carcinosarcomas is around 30% and for stage I tumours about 50%.

• e)

  The presence of heterologous elements is a statistically significant poor prognostic factor in women diagnosed with stage I carcinosarcomas.

Regarding carcinosarcoma development:

• a)

  Epithelial cells trans-differentiate to malignant mesenchymal cells by progressive loss of E-cadherin expression

• b)

  Epithelial cells trans-differentiate to malignant mesenchymal cells by progressive loss of N-cadherin expression

• c)

  Epithelial cells trans-differentiate to malignant mesenchymal cells and gain cadherin-11 expression

• d)

  Epithelial cells trans-differentiate to malignant mesenchymal cells and gain vimentin expression

• e)

  Epithelial cells trans-differentiate to malignant mesenchymal cells and lose fibronectin expression

Regarding the epithelial and sarcomatous component of carcinosarcoma the following is/are true:

• a)

  The carcinomatous component is serous in one third of cases

• b)

  The carcinomatous component is endometrioid in one third of cases

• c)

  The carcinomatous component is clear cell in one third of cases

• d)

  The carcinomatous component is poorly differentiated in over half of cases

• e)

  The sarcomatous components are homologous in half of cases

Which of the following favour a diagnosis of atypical polypoid adenomyoma?

• a)

  An endocervical polyp from a middle-age nulliparous woman.

• b)

  A biphasic tumour composed of high-grade and irregular endometrial glands separated by elongated bundles of smooth-muscle tissue.

• c)

  Fragments of normal background endometrium found in curettings or biopsy.

• d)

  The margin between the lesion and the underlying myometrium being usually rounded and well circumscribed.

• e)

  Squamous morules (metaplasia) obliterating the glandular lumens in 90% of cases.

Histologic diagnosis of uterine leiomyosarcomas requires the finding of:

• a)

  Diffuse atypia and infarct-type necrosis.

• b)

  Diffuse atypia, greater than 10 MFs/10 HPFs and tumour cell necrosis.

• c)

  Infiltrative border and hypercellularity.

• d)

  Vascular invasion and epithelioid morphology.

• e)

  Myxoid differentiation.

The histologic uncertainty for a pathologist to make a diagnosis of smooth-muscle tumour of uncertain malignant potential (STUMP) include(s):

• a)

  Necrosis of an uncertain type.

• b)

  Whether the tumour cells are spindle or epithelioid.

• c)

  Uncertainty if the cellularity is sufficiently high.

• d)

  Uncertainty if the mitotic count is correct.

• e)

  Uncertainty if the tumour is of smooth-muscle or endometrial stromal differentiation.

The following is associated with a more aggressive behaviour in leiomyosarcomas:

• a)

  Myxoid differentiation.

• b)

  Epithelioid differentiation.

• c)

  Sex-cord differentiation.

• d)

  Presence of lipoblasts.

• e)

  Large size.

According to the new FIGO staging published in 2009:

• a)

  Tumour size of greater than 5 cm and tumour limited to the uterus is stage IA for carcinosarcoma.

• b)

  Tumour extending to the adnexa is stage IIA for endometrial stromal sarcoma

• c)

  Tumour invading abdominal tissue in more than one site is stage IIIB for leiomyosarcoma.

• d)

  Tumour extending to the bladder or rectum is IVA for endometrial stromal sarcoma, leiomyosarcoma (LMS) or carcinosarcoma.

• e)

  Extrauterine involvement of pelvic tissue for carcinosarcoma is stage IIB.

Which are the following is/are true:

• a)

  The histopathologic diagnosis of uterine LMS has to meet at least two microscopic criteria of: severe nuclear atypia, significant mitotic count >10 per 10 high-power-fields and coagulative tumour cell necrosis.

• b)

  Uterine LMS almost always has epithelial growth factor receptor 1 and 2 (ERRBB1/EGFR) and ERBB2 expression.

• c)

  The old classification of high-grade endometrial stromal sarcoma has been replaced by undifferentiated endometrial sarcoma due to its exhibition of extensive myometrial invasion, severe nuclear pleomorphism, high mitotic activity, tumour cell necrosis, or both, and lack of smooth muscle or endometrial stromal differentiation.

• d)

  The histogenesis of carcinosarcoma remains unclear, but recent immunohistochemical and molecular genetic studies have attributed carcinosarcoma to a metaplastic carcinoma.

• e)

  Uterine sarcoma represents 8% of primary uterine malignancies according to the most recent analysis of the Surveillance, Epidemiology and End Results database, which reflects a rather stable incidence of uterine sarcoma in the USA.

Which of the following statements about imaging diagnoses is/are true?

• a)

  Transvaginal pulsed and colour Doppler ultrasonography are based mainly on the evaluation of blood flow impedance of the uterine, myometrial, endometrial vessels, or all three. Malignant tumours are usually associated with decreased blood flow impedance.

• b)

  Diffusion weighted imaging reveals tissue characteristics on the basis of the diffusion motion of water molecules (Brownian motion). Apparent diffusion coefficient values can be calculated reflecting the influence by nuclear-to-cytoplasm ratio and cellular density in solid tissues. Malignant tumours are usually associated with increased apparent diffusion coefficient values.

• c)

  Uterine sarcoma often manifests as a large infiltrating myometrial mass of heterogeneous hypo-intensity on T1-weighted image and intermediate to high signal intensity on T2-weighted images

• d)

  It has been shown that positron emission tomography leads to improvement of overall survival compared with historical controls.

• e)

  Positron emission tomography and CT have been shown to be effective in detecting early extra-pelvic recurrence in the post-therapy surveillance of uterine sarcoma.

Regarding studies on chemotherapeutic agents the following has/have been shown to be beneficial in the treatment of leiomyosarcoma:

• a)

  Cisplatin

• b)

  Etoposide

• c)

  Topotecan

• d)

  Thalidomide

• e)

  Trimetrexate

Regarding prognostic markers for uterine leiomyosarcoma the following has/have been shown to be clinically useful:

• a)

  DNA ploidy and S-phase fraction (SPF)

• b)

  Vascular endothelial-growth factor ( VEGF)

• c)

  Oestrogen receptor positivity

• d)

  Progesterone receptor positivity

• e)

  p53 expression

Regarding prognostic markers for carcinosarcoma the following has/have been shown to be clinically useful:

• a)

  P53 expression

• b)

  DNA-ploidy and S-phase fraction (SPF)

• c)

  Ki-67 expression

• d)

  mdm-2 expression

• e)

  bcl-2 expression

The following is/are recognized immune-histochemical features of carcinosarscoma

• a)

  Serous components should express p53

• b)

  Serous components should express epithelial membrane antigen

• c)

  Rhabdomyoblastic elements should express CD34

• d)

  The sarcomatous homologous component expresses CD10

• e)

  The sarcomatous homologous component expresses CD34.