Clinical presentation and therapeutic actions
A one year-old boy with Rb suspection was referred to the Department of Pediatrics, University of Debrecen. Given the bilateral, large primary extent of the tumor not suitable for local therapy systemic chemotherapy was immediately introduced. Two cyclophosphamide/vincristine block, advised for infant neuroblastoma was applied with partial response. Thus therapy was continued with three more intensive carboplatin/etoposide/vincristine block, but without further tumor regression, so three additional VEC (vincristine/etoposide/cyclophosphamide) was introduced that resulted in significant tumor regression making possible local therapy. Until the local intervention two additional VEC was applied with decreased (60%) dose in view of the patient tolerance. Then a local brachytherapy (Ruthenium-106 applicator) was applied on the right side, and cryotherapy on the left side. Five months later a progression was observed on the right side that extend the local control borders. As a bridge therapy VEC with cisplatin, then 50 Gy external radiotherapy was applied for both sides. However, progression was occured five months later, so enucleation was necessary on the right, and then unfortunately on the left side three months apart (Sample 1 – S1 and 2 - S2). Telemetric radiotherapy followed enucleation on both sides in 50 Gy doses. The proband, at the age of 10 years presented osteosarcoma of the left orbita that was surgically resected (S3). EURAMOS1 and than EURO EWING99-VIDE protocol was used for chemotherapy. One year later osteosarcoma presented on the left tibia as well and was resected 17 cm of the its proximal region (S4). Resected tibial bone was irradiated using 100 Gy and EURAMOS1/COSS chemotherapy was applied. At the age of 12 years, left femur and multiple pulmonary metastases were diagnosed. Up to the upper third, the left femur was amputated and osteosarcoma was proved by histological examination (S5). According to the bad general condition of the child, pulmonary tumor was sentenced as inoperable. Three months later the proband died due to breathing complications. Progressive metastases of both sides of the lungs were demonstrated as cause of death during autopsy. Postmortem sampling from the pulmonary metastases (S6) and from the intact skin (sample S7, for non-tumor control purposes) was done. Samples provided for the comparative study and related histological diagnoses are summarized in Table 1 .