Malignant bone neoplasms contribute to about 7% of paediatric cancer. Within the last 20 years much has changed in cancer treatment. Neoadjuvant chemotherapy, as the first phase of comprehensive treatment, results in regression of the tumour and makes limb salvage surgery possible. An exact analysis of 36 patients with osteosarcoma of different localisation, treated at the National Research Institute of Mother and Child between 1991 and 1996 was carried out. Treatment was started with pre-operative adjuvant chemotherapy with ADM and CDDP, administrated during 6 weeks. The regimen and the length of administration depended on stage of disease and tumour reaction to chemotherapy. Amputations or limb salvage surgery was conducted as a second phase of therapy. Postoperative chemotherapy was given for 6 months. Tumour reaction to chemotherapy was described according to the Huvos scale - percentage map of necrosis and regression areas in the neoplastic tissue. The analysis shows good results after chemotherapy with ADM and CDDP.

Between April 1994 and December 1999, 34 children aged from 5 to 20 years (23 females and 11 males) suffering from osteosarcoma, were treated according to the SFOP-94 protocol. The primary preoperative chemotherapy consists of adriamycin and high-dose methotrexate administration. There were 28 patients with non-metastatic tumours of the extremities and 6 children presented disseminated disease with pulmonary metastases. The primary localization included femur - 20 patients, tibia - 9 patients and humerus - 5 patients. In 26 patients limb-salvage surgery was applied. The programme of chemotherapy was changed in 4 children because of toxicity of methotrexate (1 patient) and progression of disease (3 patients). 26 out of 34 (76,5 %) children are alive including 24 out of 28 patients with localized disease. EFS calculated according to Kaplan-Meier analysis was 60 % at 67 months.

Therapeutic approach in osteogenic sarcoma until 1982 was connected mainly with surgery. Introduction of chemotherapy to the therapeutic protocols of osteogenic sarcoma improved the 5 years survival of patients with osteogenic sarcoma from 20% to 60-70%. The approach to surgical treatment was also changed. The principle of this treatment is usually to perform an operation to spare the limb with an intraoperative frozen section examination of bone marrow. In our Institute during the last 14 years about 300 cases were diagnosed, out of which about 200 were treated surgically, among these about 50% underwent treatment by salvage operations. Only in 7 cases local recurrences of disease were confirmed. Five of these cases were tumours of distal metaphysis of the femur, one case of proximal metaphysis of the tibia and one case of proximal metaphysis of the humeral bone. The sex range M/F was: 5/2, the average age of onset about 14 years. Various factors playing a role in therapeutic adversities were analysed. Among these were: radical surgery, grade of differentiation of the tumour, histological subtype, soft tissue infiltration, reaction to preoperative therapy and the type of chemotherapy. The conducted analysis indicates the role played by sparing surgery in adversities in therapy (3 cases). Attention was also given to the distinct tendency of osteogenic sarcoma to produce vascular embolism which is a source of haematogenously spreading metastases. In 7 cases vascular tumour embolism caused the appaerance of metastatic focuses adjacent to the primary tumour. A certain role in therapeutic adverities is played by the lack of response to preoperative chemotherapy (4/7 cases). The influence of other factors needs further investigation.

The material comprises 195 cases of osteogenic sarcoma in children and adolescents. The tumours were grouped in accordance with two classifications; gradual classification which incorporates three levels of morphological maturation of sarcoma and structural classification which distinguishes conventional and nonconventional types of sarcoma. In every case histological mapping of the tumour was performed with the aim to establish the percentage of necrosis and postnecrotic resorbtion of the tumorous mass after the initial chemotherapy. The purpose of this study was to establish the correlation of the tumour necrosis with both histopathological classifications. The main conclusion was, that the gradual classification is more accurate for the changes occurring in the tumour tissue after chemotherapy.

The histopathological features of the primary site and 102 pulmonal metastases were compared in the material from 40 malignancies in children and adolescents. All patients were treated by chemotherapy. Among the malignancies 30 were osteogenic sarcomas. A great histological variability in the multiple metastases removed at one surgical procedure and also in the metastases removed in the subsequent surgeries, were found. Summing up, the whole investigation; in 61.8% of metastatic focusses no difference was found in the histopathological patterns seen at the primary site and pulmonary metastases, in 17.6% total regression was observed, in 13.8% dedifferentiation and in 6.8% maturation of the tumours tissue were observed.

The performed analysis concerned the results of the histopathological examination of 169 cases of osteogenic sarcomas with reference to diagnostic difficulties. It was found that the most difficult cases belong to the extreme groups of the classification i.e. were high or very low differentiated osteogenic sarcomas. The most difficult diagnostically cases according to the structural classification concern analogically the extreme group of cases of the non-conventional histology. However, the dominant number of the diagnosed cases did not belong to the extreme groups of classification.

The histopathology of 224 tumours of neuroblastic origin was analysed in relation to the age of patients. Maturing neuroblastomas (NBS) dominated in infants, where as in the most numerous group of children 1-5 years of age, prevalence of neuroblastomas without any signs of maturation was noted. In children over 5 years of age a high incidence of tumours with evident maturation was noted (ganglioneuroblastomas and ganglioneuromas). The prevalence of maturing neuroblastomas in infants correlate well with an advantageous clinical course of neuroblastomas at this age.

In this paper the role local surgical and radiological control in the treatment of soft tissue sarcomas in children was analyzed. All children were treated according to CWS-91 and SIOP-IV protocols. Eighty three children with RMS A + E, EES/PNET, SS, UDS were included in the analysis. The primary surgery consisted of R0 (5%), R1 (18%) or R2 (16%) resection. In majority of cases (61%) primary surgical intervention was limited to diagnostic biopsy. Conventional or hyperfractionated radiotherapy was performed in 42.8%, 73.8% and 75% of children with disease stage II, III and IV, respectively. Delayed surgery was performed in 20 out of 53 (37.7%) children with stage III of the disease. In 5 patients without primary focus (urinary bladder in 3 and prostate in 2 cases) removed, progression of the disease occurred. In 5 children (stage IV) with progression of the disease no secondary surgery was performed. In 4 of them the primary tumor exceeded 10 cm in diameter. No delayed surgery was performed in 69% of relapsed children with stage III of the disease. Planned radiation therapy was not performed in 15.9% of cases. Primary local surgical control of primary tumor is of great importance for remission duration. In children who underwent delayed surgery the estimated EFS was of 0.7, in comparison with 0.5 EFS of those without secondary surgical treatment.

Between December 1989 and April 1998 twenty eight children aged from 5 to 20 years (18 female and 10 male) suffering from osteosarcoma were treated according to the OS-SFOP-94 protocol. Twenty four patients presented with localized tumor of extremities and four with pulmonary metastases. The majority of primary tumors exceeded 150 ml of volume. The primary preoperative chemotherapy consisted of adriamycin (70 mg/m2 every four weeks) and high-dose methotrexate (12 g/m2 every week). In 20 patients limb-salvage surgery was applied, in three children--amputation and in one child tibia resection with genu arthrodesis was applied. Five of 28 patients died, one because of treatment related infection, 2 non-responders with metastatic osteosarcoma due to progressive disease, and one because of local relapse with pulmonary metastasis non-responding to therapy, one because of treatment refusal. Twenty one from 25 children are alive from 5 to 51 months. Event frae survival of children with localized disease calculated according to Kaplan-Meier analysis was 64.17% in the 51st month. The main cause of failure in the treatment of osteosarcoma in children is primary and secondary progression of disease. The toleration and results of treatment for osteosarcoma in children according to the OS-SFOP-94 is satisfactory.

The paper presents the review of prognostic factors which were investigated from the first interests of neuroblastoma, as a model for cancer biology in pediatric oncology. The authors on the basis of other authors experiences and on the own observations, as well stress the importance of basic sciences from the field of molecular biology, cytogenetics and biochemistry, leading to better understanding of the nature of neuroblastoma and to introduction of rational treatment. The stratification of neuroblastoma patients according to the known prognostic variables influenced favourably treatment results.

OBJECTIVE This study was conducted to detect the expression of laminin (LN) and laminin receptor (LN-R) in the specimens of hydatidiform mole (HM), invasive mole (IM) and choriocarcinoma(CC), respectively. METHODS The immunohistological staining method was used. RESULTS It was found that the level of the laminin expression was higher in the specimens of choriocarcinoma at more advanced stage. CONCLUSION The results suggest that there may be relations between the invasion and metastasis of choriocacinoma cell and the malignant degree of this disease, chemotherapy has some effect on the expression of LN and LN-R in gestational trophablastic tumor (GTT), and that LN and LN-R may be of potential value in GTT treatment. However, referring whether LN and LN-R could be used as clinical prognosticators, further studies will be needed.

Gestational trophoblastic disease refers to a spectrum of proliferative disorders of the placental trophoblast, with a wide range of histologic appearances and clinical behaviors. This review discusses the more recent developments in the diagnosis of these entities. Changes in criteria for the histologic diagnosis of these lesions due to earlier clinical diagnosis are reviewed, and the ability to make more accurate diagnoses due to the introduction of newer antibodies such as p57 is highlighted. A discussion of epithelioid trophoblastic tumor, a newly introduced tumor subtype, with its differential diagnosis from placental-site trophoblastic tumor and squamous cell carcinoma is also presented. Last, a brief discussion on the role of genetic studies and the future direction of research in elucidating the nature of this intriguing group of lesions is presented.

Gestational trophoblastic disease (GTD) is a heterogeneous group of diseases. This used to include partial and complete hydatidiform moles, invasive mole, choriocarcinoma and placental site trophoblastic tumour. In recent years, new entities, including epithelioid trophoblastic tumour, have been added to this family. Non-neoplastic and neoplastic lesions derived from implantation site and chorion intermediate trophoblast have been gaining attention in the literature. New markers for trophoblasts have been identified facilitating histological diagnosis in cases with unusual clinical or pathological features. It is worth noting that histological distinction between hydropic abortion and partial mole and between complete and partial moles, especially at early gestational age, may be difficult. It may not be possible to predict progress of the heterogeneous group of GTD from histopathological features, except probably in placental site trophoblastic tumour. Alternative biological markers may be explored for better patient management.

OBJECTIVE This study was done to determine whether the expressions of p53, PCNA, and Ki-67 could differentiate spontaneous abortions with hydropic changes from gestational trophoblastic diseases. MATERIALS AND METHODS Twenty partial hydatidiform moles, 21 complete hydatidiform moles, nine invasive hydatidiform moles, three choriocarcinomas and 19 first trimester hydropic spontaneous abortions were evaluated by means of immunohistochemical methods with antibodies to p53, PCNA, and Ki-67 in this study. RESULTS The Ki-67, PCNA, and p53 immunoreactivity was significantly higher in the gestational trophoblastic disease group than in the spontaneous abortion group with hydropic changes. None of the three parameters provided reliable discrimination among gestational trophoblastic disease subgroups. CONCLUSION Our findings suggest that expressions of Ki-67, proliferating cell nuclear antigen and p53 can be used to differentiate between spontaneous abortion with hydropic changes and gestational trophoblastic disease when all three markers are used together.

Human trophoblast in normal implantation and placentation appears to undergo two different pathways of differentiation resulting in the development of villous and extravillous trophoblast. Cytotrophoblast (CT) differentiates abruptly into syncytiotrophoblast (ST) on the villous surface as compared with the spectrum of differentiation exhibited by extravillous trophoblast where CT differentiates into intermediate trophoblast (IT) and then into multinucleated intermediate trophoblastic cells (MITC). The various types of gestational trophoblastic lesions can be defined and related to discrete pathologic aberrations occurring at different stages of trophoblastic differentiation. The rapid advance in the discovery of new trophoblastic markers has facilitated the molecular dissection of the lineage and differentiation stages of trophoblast and related these to various trophoblastic lesions. Furthermore, antibodies against these markers, especially those that are able to recognize formalin-resistant epitopes, have considerable value in the study and differential diagnosis of different types of gestational trophoblastic disease.

Gestational trophoblastic disease (GTD) forms a heterogeneous group of interrelated lesions which are characterized by an abnormal proliferation of the different types of trophoblastic epithelium. Complete hydatidiform moles represent a noninvasive placental disease that is characterized by hydropic swelling of the chorionic villi with marked trophoblastic proliferation. The partial mole contains two populations of villi: one of normal size, the other hydropic with less marked trophoblastic hyperplasia. The risk of developing persistent GTD is very low. Choriocarcinomas represent an avillous invasive proliferation of trophoblastic cells surrounded by necroses and hemorrhages displaying a dimorphic pattern with early vascular invasion and hematogeneous metastatic spread. Placental site trophoblastic tumor (PSTT) resembles the rarest form of GTD. In its cellular composition, PSTT preferentially contains intermediate trophoblastic cells with typically positive hPL-immunostaining. Mostly, PSTT's are benign tumors, but malignant cases are well known. Miscelleanous forms of GTD include the exaggerated placental site and the placental site nodule or plaque. Both lesions are proliferations of the intermediate trophoblast. Staging of GTD should only be applied in cases of persistent disease. All different staging systems, including the revised FIGO system, the classification of the National Institute of Health (NIH), the WHO scoring system and the currently adopted TNM-system are able to define high risk patients.

Although considerable progress has been made in the understanding of the biology of gestational trophoblastic tumors, future generations will undoubtedly classify our current knowledge base as basic. It is our hope that by more precisely defining the genetic basis for these diverse lesions, we may be able to develop better diagnostic, surveillance, and treatment modalities for affected patients.