2007, Vol 5, No 2
Principles of histopathological diagnosis of uterine sarcomas
GIN ONKOL 2007, 5 (2), p. 54-60
ABSTRACT

Based on their histogenesis, uterine sarcomas may be subdivided into three main groups: 1) tumours originating in endometrial stroma, 2) tumours originating in uterine smooth muscle and 3) mixed tumours presenting both epithelial and mesenchymal components (mixed müllerian malignant tumours). Histological classification of uterine mesenchymal neoplasms underwent several modifications. Currently in force is the WHO classification issued in 2003. As regards histological maturity, they may be subdivided into benign tumours, tumours with undetermined malignant potential and malignant tumours. On the clinical grounds, the key issue is to determine the histological type and degree of maturity of mesenchymal tumour of corpus uteri. Endometrial tumours of muscular and stromal origin, presenting a typical morphological pattern, do not pose diagnostic problems and determination of their histopathology is usually possible based on routine hematoxylin-eosin staining. However, there are cases with an ambiguous appearance on microscopic studies, which require implementation of additional techniques in order to determine precisely their histogenesis and degree of maturity. The most common type of uterine sarcoma is leiomyosarcoma. In patients with this tumour type, the 5-year survival rate is 25-75% and the risk of metastases is estimated at 45-73%. Patients with tumours initially limited to the uterus may take an aggressive clinical course. Three key microscopic criteria enable the diagnosis of a leiomyosarcoma: coagulation necrosis, mitotic activity, and nuclear atypia. In the most common spindle-cell tumours of muscular origin, over 10 mitotic figures per 10 high power fields (HPFs) is considered a sign of malignancy, while in the rare myxoid muscular tumour, the borderline value is 3 mitotic figures per 10 HPFs. Endometrial stromal sarcomas of the corpus uteri are rare, making up for about 10% of uterine sarcomas and 0.2% of all malignant tumours with this location. Low-grade endometrial stromal sarcoma is a malignant tumour composed of cells similar to endometrial stromal cells. Usually it develops in middle-aged women. A characteristic feature is infiltrating growth pattern, with invasion of muscular layer of corpus uteri and of lymphatic vessels’ lumen. A typical finding are finger-like excrescences of tumour tissue within vascular spaces. Sarcoma cells usually present mild nuclear polymorphism and less than 10 mitotic figures per 10 HPFs. Noteworthy is, that the number of mitotic figures is not a criterion of differentiation of both above mentioned types of uterine stromal sarcoma. Non-differentiated endometrial sarcoma usually develops in elderly women, the mean age at presentation being 61. The tumour diffusely infiltrates the wall of corpus uteri, leading to widespread destruction and necrosis. Microscopic appearance is characterized by pleomorphic cells, from round and spindle-like to bizarre cells. Visible are numerous mitotic figures, from 10 to 40-50 per 10 HPFs. To conclude it should be emphasized that uterine corpus sarcomas presenting an atypical or mixed microscopic appearance, require confirmation of diagnosis by immunohistochemical staining. Three antibodies – h-caldesmon, desmin and CD10 – constitute the basic diagnostic panel.

Keywords: uterine sarcoma, leiomyosarcoma, endometrial uterine sarcoma, CD10, h-caldesmon
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Surgical treatment of ovarian cancer
GIN ONKOL 2007, 5 (2), p. 61-74
ABSTRACT

The paper presents current algorithms of surgical treatment of patients with ovarian cancer. At early clinical stages (FIGO stage I and II), the basic principle of surgical treatment is radical excision of malignant lesions within the pelvis and meticulous search for metastatic foci of tumour within the mid-abdomen and epigastrium. Therefore, mandatory procedures include omentectomy, multiple sampling of peritoneum (including diaphragmatic lining) and periaortal lymph nodes. In late-stage disease (FIGO stages III and IV), the main task is to remove all metastatic foci, both within the abdominal cavity and retroperitoneal space. In late-stage cases, surgery requires great expertise of both surgical, anesthetic and physiotherapy teams. Required are also precise surgical instruments, including argon bipolar coagulation, a reliable diathermy unit and a kit of self-retaining retractors. Extensive cytoreductive procedures are burdened by an elevated complication rate, therefore in selected cases preoperative (neoadjuvant) chemotherapy is used.

Keywords: chemotherapy, ovarian cancer, cytoreductive surgery, second-look surgery, secondary debulking surgery
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Determination of diagnostic value of selected immunohistochemical tests in patients with uterine corpus sarcoma and their therapeutic and prognostic usefulness
GIN ONKOL 2007, 5 (2), p. 75-86
ABSTRACT

Uterine sarcomas represent a rare and heterogenous group of tumours, sometimes demonstrating multidirectional differentiation. Histological type of the sarcoma influences the choice of therapeutic modality. Aim of paper: Determination of diagnostic value of selected immunohistochemical studies (MIB1, caldesmon, desmin, SMA, SrMa, CKAE1/3) in the definition of histological type of tumour. Assessment of expression of the protein c-kit (CD117) MIB1 and inhibin and their prognostic role. Material and method: Study material consisted of a group of patients with uterine sarcoma, treated at the Center of Oncology in Warsaw, Poland, since 1999 thru 2006, from whom surgical specimens and paraffin blocks were obtained. Of 120 eligible patients, complete clinical data and specimens suitable for foreseen studies were available in 66 cases and this group became the subject of further analyses. Immunohistochemical (IHC) tests were performed using a panel of antibodies (SMA, SrMa, desmin, h-caldesmon, CD10, CKAE, MIB1, inhibin and CD117). Diagnostic value of IHC studies was assessed by descriptive statistical tests. Original histopathological findings were confronted with the results of validated IHC tests. Survival was assessed based on Kaplan-Meier curves and follow-up time – by an inverse Kaplan-Meier curve. Prognostic factors were analysed by the Cox method. Threshold of statistical significance has been set at p=0.05. Results: Original microscopic findings have had to be modified as to histological type of sarcoma in about 1/3 of the cases. Histological diagnosis was an independent prognostic factor, influencing both overall survival rate and time to tumour recurrence. Prognostic factors influencing recurrence-free survival were: invasion of perivascular lymph space (lymph space invasion – LSI), proliferative index (MB1) and severity of tumour cell necrosis. Conclusions: Application of a panel of suitable IHC tests contributes to a more precise determination of tumour type, assisting in an optimal choice of adjuvant treatment modality and thus in improvement of the patients' prognosis.

Keywords: corpus uteri sarcoma, diagnosis, markers, immunohistochemistry, treatment
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Correlation between alterations in GFR and coagulation parameters in urine of patients with stage IIB-IIIB uterine cervix cancer treated by radiochemotherapy
GIN ONKOL 2007, 5 (2), p. 87-101
ABSTRACT

Introduction: Radio- and chemotherapy increase the risk of disorders in the hemostasis system. Pathologic activation of coagulation and fibrinolysis may lead to formation of clots in microcirculation of many organs and subsequently to their dysfunction. Presence of serum coagulation proteins in urine may indicate renal dysfunction. Aim of paper: 1) Evaluation of correlation between hemostatic parameters in urine of patients with stage IIB-IIIB cervical cancer and results of dynamic scintigraphy. 2) Assessment of influence of prophylactic administration of low-molecular-weight heparins (LMWH) on renal function in this patient population. Material and method: The study was randomized. Treatment protocol included radiotherapy (46-65 Gy administered by the box technique) and cisplatin (40 mg/m2 q7d) in patients with normal serum creatinine level. Renal function was assessed by dynamic scintigraphy and glomerular filtration rate (GFR) was determined. Parameters of serum hemostatic system assessed included: D-dimers, PAP, PAI-1, tPA, F1+2 and TAT. Patients were subdivided into 2 groups: a study group – with reduced GFR and a control – with normal GFR. Half of the patients in the study group received 2850 I.U. aXa or 0.3 mL nadroparin during and 6 weeks after chemotherapy (randomization list). Results: Reduction of GFR in the control group (median -9.7%) and in the study group without nadroparin (median -9.9%) were noticed. In the study group receiving nadroparin, an increase of GFR (median 22.3%) was seen. Significant differences were noticed between alterations of GFR in the control and study groups receiving nadroparin and between study groups with and without nadroparin (p=0.0001). Assessment of parameters of hemostatic system in urine revealed activation of fibrinolysis in patients receiving nadroparin and its further inhibition in the group without nadroparin. Conclusions: 1) Alterations in GFR values correlate with changes in hemostasis parameters assessed in urine. An increase of GFR is associated with alterations consistent with inhibition of coagulation and activation of fibrinolysis. Inhibition of fibrinolysis and continuous activation of coagulation results in reduction of GFR values. 2) Prophylactic administration of LMWH enhance activation of fibrinolysis, resulting in an improvement of GFR values in this patient population.

Keywords: cervical cancer, radiochemotherapy, renal failure, hemostatic parameters in urine, glomerular filtration rate (GFR)
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Analysis of prognostic value of CA 125 relating to effectiveness of surgery and symptom-free survival in patients with FIGO stage III ovarian cancer
GIN ONKOL 2007, 5 (2), p. 102-110
ABSTRACT

Aim of paper: The aim of paper was to assess the prognostic value of preoperative CA 125 level in patients with late-stage ovarian cancer, particularly in correlation with optimal cytoreduction rate and duration of symptom-free survival. Material and methods: Retrospective analysis included 76 patients with FIGO stage III ovarian cancer. Using the uni- and multivariate models, prognostic value of the following parameters was assessed: preoperative CA 125 level, clinical stage, histological type and grade of maturity in correlation with quality of cytoreduction and symptom-free survival. Results: Baseline CA 125 serum level in the entire study population ranged from 35 to 9740 IU (median: 1117 IU). Optimal cytoreduction rate for the entire population was: 73.7% for CA 125 level below 288 IU, 47.4% for CA 125 level 288-1118 IU, 26.3% for CA 125 level 1119-2880 IU and 15.8% for CA 125 above 2880 IU (p=0.019; χ2). In the logistic-regression model, only CA 125 level had a significant influence on quality of cytoreduction. Analysis of correlation of other prognostic factors on symptom-free survival revealed, that only CA 125 and histological maturity grade correlated significantly with survival. Conclusions: Preoperative serum CA 125 level is significantly correlated with optimal cytoreduction rate achieved, as well as with risk of death and symptom-free survival.

Keywords: CA 125 level, advanced ovarian cancer, CA 125 prognostic value, cytoreductive surgery in ovarian cancer, CA 125 follow-up
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