Background

Cryosurgery is a well established modality in the treatment of benign aggressive and low grade malignant tumours. In this setting it allows for intra-lesional resection and preservation of function without compromising oncological outcome. Here we present the outcome of 87 patients treated with cryosurgery for low-grade chondrosarcoma of bone.

Between December 1995 and March 2003, 38 adult patients with intermediate or high-grade liposarcoma in a limb were treated by limb-sparing surgery and post-operative radiotherapy. The ten-year local recurrence-free survival was 83%, the ten-year metastasis-free survival 61%, the ten-year disease-free survival 51% and the ten-year overall survival 67%. Analysis of failure and success showed no association with the age of the patients, gender, the location of the primary tumour, the type of liposarcoma and the quality of resection.

Our results indicate that liposarcoma may recur even ten years after the end of definitive therapy and may spread to unexpected sites as for soft-tissue sarcoma.

Introduction: Chromosomal analysis is becoming increasingly useful in the diagnosis and management of bone and soft-tissue sarcomas. The identification of chromosomal aberrations such as translations, deletions, additions of a part or whole chromosome, and other markers are associated with specific tumor subtypes.

Material and Methods: Between 1998 and 2000, 78 bone and soft-tissue tumors were analyzed. Cytogenetic analysis was carried on a short-term cultured tissues by G-banding FISH and SKY procedures, as needed. Histopathological diagnoses included osteosarcoma – 16, Ewing’s sarcoma – 13, synovial sarcoma – 4, rhabdomyosarcoma – 4 (alveolar – 3, embryonal – 1), liposarcoma – 3, extra-abdominal fibromatosis – 3, alveolar soft part sarcoma – 12, and other soft-tissue sarcoma – 12. Other diagnoses included 8 hematological malignancies and 13 benign tumors.

Results: Eight of the 16 osteosarcomas studies demonstrated complex hyperploid karyotypes compatible with the diagnosis of high-grade osteosarcoma. In most Ewing’s sarcoma, including three cases with a typical t(11;22) translocation, other chromosomal abnormalities such as trisomies of chromosomes 5,6,8, and 14 were observed. Three of the four synovial sarcomas had the typical t(X;18)(p11.2;q11.2) translocation. One of the synovial sarcomas was initially diagnosed on a histopathological basis as Ewing’s sarcoma but the cytogenetic analysis showed a complex X;18 translocation and led to change in diagnosis and related treatment. Only one of the alveolar rhabdomyosarcomas demonstrated the typical t(2;13)(q35;q14) translocation, while hypertetraploid set with double minutes (dmin) was detected in the other two cases. By using SKY, chromosome 1 was determined as the origin of one of the dmins, suggesting that PAX7 amplification could be involved in the pathogenesis of this tumor.

Conclusions: Cytogenetic analysis of bone and soft-tissue tumors are of important clinical value for accurate diagnosis of tumor type. It can also provide information suggesting the pathogenesis of these tumors.

Introduction: Modern cancer treatment has substantially increased the survival of patients with various malignancies. One of the late sequelae of a successful treatment is the development of a second malignant tumor. However, in many cases of second primary cancers, exposure to chemotherapy or radiation therapy is not evident, and it should be postulated that the putative mechanism for the development of the second cancer is different.

Material and Methods: Retrospective search of data files of 610 patients with soft-tissue or bone sarcomas that were treated by the authors from January 1995 through December 1999 were performed.

Results: Out of 375 patients with soft-tissue sarcoma (STS), 28 (7.5%) developed other malignant neoplasm either before or after its diagnosis. The second tumor types included mainly STS and renal cell carcinoma. The time interval between the diagnosis of STS and the second malignancy was o to 21 years. Three patients developed a third primary tumor within 0–3 years after the diagnosis of the second tumor. The median overall survival was > 78 months.

Conclusions: The phenomenon of two or three primary neoplasms in patients in whom one of the tumors was STS occurs in a rate of 7.5% – a significantly higher rate than the occurrence of STS among the general cancer population (1%). Most cases are detected incidentally. The clinical implications are the need to search for an occult second primary in patients with STS as an integral part of their follow-up. It is especially true in patients with primary MFH who show increased risk for developing a renal cell carcinoma.

Introduction: Soft-tissue sarcomas (STS) in children and young adults are rare. This is a heterogeneous group of tumors, which is traditionally divided to rhabdomyo-sarcomas and non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS). These tumors are further classified to high- and low-grade tumors.

Material and Methods: Between 1988 and 1999, the authors treated 50 patients (25 males, 25 females) under the age of 20 who were diagnosed with a soft-tissue sarcoma.

Histopathological Diagnoses: rhabdomyosarcoma – 11, synovial sarcoma – 6, other high-grade STS (extraskeletal Ewing’s sarcoma, epitheloid sarcoma, neurofibrosarcoma, hemangiopericytoma, fibrosarcoma, and unclassified sarcoma) – 17. Seven patients were diagnosed with low-grade STS and 9 patients with an aggressive desmoid tumor.

Anatomic Location: Lower extremities – 30, upper extremities – 9, shoulder girdle – 2, trunk – 4, pelvic girdle – 5.

Preoperative Treatment: Thirty patients received neo-adjuvant chemotherapy, four patients underwent isolated limb perfusion with TNF and melphalan, and one patient received preoperative radiation therapy. Surgery: Forty-seven underwent limb-sparing resections and 3 underwent primary amputation. Wide margins were achieved in 37 patients and marginal margins in 10. Intralesional resection was performed in 3 patients.

Postoperative Treatment: Thirty-seven patients received adjuvant chemotherapy and 34 received radiation therapy.

Oncological Status: At the most recent follow-up, 24 patients of the 37 patients with high-grade STS have no evidence of disease, three are alive with disease, and seven are dead. Fourteen of the 16 patients with low-grade tumors have no evidence of disease and 2 are alive with disease. There were 4 secondary amputations due to local tumor recurrence.

Conclusions: Management of soft-tissue sarcomas in children and young adults requires the judgmental use of pre- and postoperative treatment modalities. Local tumor control can be achieved in the majority of the patients. A longer follow-up is required to determine the overall survival of these patients.

Introduction: Telomerase is a ribonucleoprotein that adds TTA GGG nucleotide repeated into the ends of eukaryotic chromosomes to maintain their integrity. Most of the normal somatic cells do not express telomerase while telomerase is expressed in the vast majority of malignant tumor cells. Contradictory and limited data have been reported concerning the telomerase expression in soft-tissue sarcomas. The current study evaluates telomerase expression in a single histologic type of a high-grade soft-tissue sarcoma.

Materials and Methods: A non-radioactive in situ hybridization (ISH) method was used to study the expression of the RNA component of human telomerase in 55 paraffin embedded archives tissue samples of patients who were diagnosed with synovial sarcoma, the diagnosis of which was based on morphologic, immunohistochemical, and cytogenetic characteristics. The intensity and distribution of telomerase RNA was scored by two different investigators. Intensity was graded as weak, moderate, or intensive. These parameters were further correlated to the oncologic status of the patient.

Results: The majority of the investigated specimens demonstrated moderate to intensive telomerase RNA intensity with a diffuse distribution throughout the specimen. A positive correlation was found between telomerase intensity and progression of the underlying disease.

Conclusions: Results of the current series suggest that upregulating of telomerase expression may play a role in the pathogenesis and biological activity of synovial sarcoma. This upregulation as detected by ISH assay may be a useful prognostic tool in the evaluation of these patients.

Background: The c-ebB-2 gene and its products (also designated HER-2 and c-neu) encode for a 185-kd transmembrane glycoprotein with intracellular tyrosine kinase activity. C-erbB-2 belongs to the epidermal growth factor receptor family, of which there are four known members, and has molecular homology to the epidermal growth factor receptor. It seems that this family is critical in control of growth, differentiation, and mobility of many normal and transformed epithelial cell types.

Materials and Methods: We have looked for over expression of c-erbB-2 gene product in 230 cases of soft tissue sarcoma, in order to establish a possible new prognostic marker, and a potentially new treatment option.

Results: In all the cases, irrespective of the sarcoma histological type, the immunostaining for erbB-2 was negative.

Conclusions: Applications of erbB-2 for prognostication as well as the option of receptor targeting by trastuzumab monoclonal antibodies were aborted.

Background: We have recently observed that many of our sarcoma patients presented also with thyroid disorders. Literature data are almost unavailable on this topic.

Materials and Methods: Retrospective analysis of files of patients with sarcoma and clinically overt thyroid disorders.

Results: Out of 375 patients with soft tissue sarcomas (STS) and 235 with bone sarcoma (BS) including small blue round cell tumors (SBRC), 28 patients (4.6%) had an associated significant thyroid disorder. The types of sarcoma were mainly liposarcoma followed by malignant fibrous histiocytoma, leiomyosarcoma and bone sarcoma. The primary sites were mainly limb and trunk. The interval between the diagnosis of the thyroid disorder and the sarcoma varied between {−14} years (thyroid first) and {+16.5} years (thyroid later) with a median of {−0.2} years. Thyroid disorders included goiter, thyroiditis and carcinoma.

Conclusions: There are basic-science and clinical evidences to a possible common pathway that leads to the association between overt thyroid disorders and sarcomas of bone or soft tissues. Oncogene erbA activity is related to thyroid receptors to T3 and to development of sarcoma. Cross talk of the sarcoma oncogene and the erbA might contribute to the development of sarcoma. The thyroid hormone receptor and the highly related viral oncoprotein v-erbA are found exclusively in the nucleus as stable constituents of chromatin. It has been shown that v-erbA can block the spontaneous differentiation in erythroid cells transformed by various retroviral oncogenes. V-erbA can alter the spectrum of neoplasia induced by the v-src oncogene, which causes predominantly sarcomas and erythroblastosis in chicks. The erbA can cooperate with other oncogenes such as v-erbB or with v-fms, v-ras, and c-kit. Cooperation with v-myc may play a role in the development of rhabdomyosarcoma especially in thyroid hormone deficiency state. The possible clinical implications are the need to screen patients with sarcoma to thyroid disorders, and patients with thyroid disorders for malignant diseases.

Background: The surgical treatment of extensive diffuse Pigmented Villonodular Synovitis (PVNS) of large joints alone, is unsatisfactory, with high rates of local recurrence. Postsynovectomy adjuvant treatment with external beam radiation therapy or intraarticular injection of Yttrium90 (Y90) yielded better results.

Aims: Experience with 10 cases treated with debulking surgery followed by intraarticular injection of Y90 is reported.

Methods: Between January 1989 and June 1998, 10 patients (8 males and 2 females aged 15049 years) with extensive diffuse PVNS were treated. In 6 patients the knee joint, in 3 patients the ankle joint, and in 1 patient the hip joint were involved. The 10 patients underwent 15 operations, 1 patient had 3 surgical procedures, and 3 patients underwent 2 surgeries (interval between re-operations for local recurrence were 2–4 years). All patients had an intraarticular injection of 15–25 mCi of Y90, 6–8 weeks after the last surgery.

Results: Follow up time was 2.5–12 years (mean 6 years). All patients were followed by repeated computerized tomography (CT) scans, magnetic resonance imaging (MRI), plain X-ray films and bone scans semi-annually. In 9 patients no evidence of disease and no progression of bone or articular destruction have been noted. In 1 patient stabilization of disease was achieved with no further evidence of bony or articular damage. No complications were noticed after surgery, nor after the intraarticular Y90 injection.

Conclusions: A combination of debulking surgery with intraarticular injection of Y90 for extensive diffuse PVNS of major joints is a reliable way of treatment with good results.