Chordomas are rare neoplasms originating from notochordal remnants. They usually affect the midline and the standard treatment consists of surgery and radiotherapy. The present study investigates the expression of survivin, DR4 and DR5 to evaluate potential molecular targets for future therapy-strategies.

The study-group included 33 chordomas obtained from 21 male and 9 female patients. At time of diagnosis the patients’ age ranged from 24 to 80 years (51.9 ys.). Tumours were located on the scull-base, in the sacral/coccygeal area and the column in 13, 10, and 7 cases, respectively. Tumour-volume, known in 16 cases, ranged from 3.6 to 668.2 cm3 (mean size 130.7cm3). Immunohistochemistry was performed with antibodies against survivin, DR4, DR5. The staining pattern (cytoplasmic and/or nuclear), percentage of positive tumour-cells and staining-intensity were evaluated.

Histologically the tumours were classified as classic, chondroid and dedifferentiated chordomas in 27, 2 and 1 case, respectively. Survivin expression was obtained in 87.5% of the cases. The staining pattern was cytoplasmic in all cases and an additional nuclear staining was detected in two. Staining-intensity was predominantly weak. In 87.9% of cases DR4 staining was investigated in more than 10% of the tumour-cells. The immunoreaction was cytoplasmic (87.9%) and a nuclear staining was additionally detected in two cases. The staining-intensity was predominantly weak. In 81.8% of the chordomas DR5 staining was obtained in more than 10% of the tumour-cells. The staining pattern was cytoplasmic (84.4%) and in one case cytoplasmic and nuclear. The staining-intensity was predominantly moderate.

We hypothesise, based on the availability of new chemo- or immunotherapeutic agents like Mapatumumab (agonistic human monoclonal antibody to DR4, tested in solid tumours) and YM155 (new small-molecular inhibitor of survivin, tested in solid tumours and lymphoma), that survivin, DR4 and DR5 may act as potential molecular targets in future therapy of chordomas.

Epitheloid haemangioendothelioma is a rare tumour of vascular origin. It is characterised by the appearance of epitheloid endothelial cells and occurs typically in soft-tissue, skin, and liver. Less frequently it is found in bone. The tumour is more often located in the long bones of the lower extremities, and the pelvis than in the upper extremities, vertebral column, and flat bones. The lesion nearly affects all age groups and there is a male predilection.

Case 1: A 71-year old woman had pain in the area of her right hip after a downfall. X-ray showed a lucency of the cortical substance of the right femur. Scintigraphy showed a cortical lesion, oedema of the bone-marrow and an involvement of soft-tissue. Carcinoembryonic antigen, CD 31, and CD 8 were positive. An open biopsy verified an epitheloid haemangioendothelioma. Staging was negative. A wide resection of the proximal femur and reconstruction with a tumour-prosthesis were performed. Four months later the patient had osteolytic metastases of os ilium, os pubis, acetabulum and in the fifth lumbar vertebra. The patient died 8 months after the wide resection of the tumour because of myocardial infarction.

Case 2: An epitheloid haemangioendothelioma of the liver was diagnosed in a 21-year old male patient. Twelve years after the primary tumour the patient had osteolyses of the first cervical vertebra, manubrium sterni, and ribs. An open biopsy verified the metastatic spread. Local radiotherapy was performed. Furthermore the patient developed a destruction of processus spinosus and a pathologic fracture of first thoracic vertebra. The patient died of metastatic disease 2 years later or 14 years after the initial diagnosis.

Epitheloid haemangioendothelioma of bone is a rare tumour and the diagnosis is quite difficult. Metastatic rate is about 20–30% and mortality about 10–20%. As presented in our cases bone involvement could either be attributed to primary haemangioendotheliomas of bone or to metastases of non-osseous forms. As in our cases it has been reported, that predicting prognosis is difcult, however nuclear atypia, mitotic activity, spindling of cells, and necrosis have been reported as negative prognostic factors.