|Year : 2007 | Volume
| Issue : 2 | Page : 79-81
Solitary hemorrhagic intra-cerebral metastatic osteosarcoma
Purav Patel1, T Raja2, S Annapurneswari3, M Balamurugan4
1 Registrar neurosurgery, Apollo Speciality Hospital, Chennai, India
2 Medical oncologist, Apollo Speciality Hospital, Chennai, India
3 Pathologist, Apollo Speciality Hospital, Chennai, India
4 Neurosurgeon, Apollo Speciality Hospital, Chennai, India
Department of Neurosurgery, Apollo Speciality Hospital, 320- Anna Salai, Chennai - 600 035
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Osteosarcoma is the most common type of bone malignancy. The primary mode of metastasis is hematogenous. Lung metastasis is common. Isolated hemorrhagic intra-cerebral metastasis has not been reported earlier. This case report is of an 11-year-old boy with proximal tibial osteosarcoma who presented with right focal seizures secondary to a hemorrhagic solitary deposit in the left posterior frontal region. Histopathology confirmed this to be a metastasis from an osteosarcoma.
Keywords: Hemorrhagic cerebral metastasis, osteosarcoma
|How to cite this article:|
Patel P, Raja T, Annapurneswari S, Balamurugan M. Solitary hemorrhagic intra-cerebral metastatic osteosarcoma. J Pediatr Neurosci 2007;2:79-81
| Case Report|| |
Evaluation of an 11-year-old boy with history of pain and swelling over the medial aspect of the right knee revealed a bony growth. Biopsy revealed an osteogenic sarcoma. There was no history of fever, cough, breathing difficulty or weakness of limbs. There was no focal neurological deficit. Histopathology revealed trabeculae of bone with an infiltrating neoplasm; numerous calcified osteoids surrounded by oval-to-fusiform cells with hyperchromatic nuclei and increased mitotic figures [Figure - 1]. Findings were consistent with high-grade osteogenic sarcoma.
Neo-adjuvant chemotherapy followed by wide resection of the primary tumor was planned. Three cycles of chemotherapy were given at 20 days' intervals with Inj. Cisplatin 50 mg i.v. (D1, D2) and Inj. Adriamycin 25 mg i.v. (D1, D2, D3). Routine blood parameters and X ray chest were normal.
Tumor excision and Custom Mega Prosthesis insertion was completed 4 weeks after the biopsy. Histopathology revealed tumor cells in sheets and diffuse pattern with cystic changes. Cells had pleomorphic, hyperchromatic nuclei with deposition of tumor osteoid in a lacelike pattern. Numerous giant cells and multinucleated osteoblast-like giant cells were present. Tumor necrosis was only 5-10%. As the tumor necrosis was low, fourth and fifth chemotherapy cycles were given with Inj. Methotrexate 9 gm in normal saline (D1), Inj. Leukovorin 15 mg i.v. 6-hourly (D2, D3).
As the patient had persistent pain, CAT scan of the right leg was done and this revealed a recurrent tumor adjacent to the anterior cortex of the right tibia (3.5 cm × 4 cm). In January 2004 an above-knee amputation (2 months after initial excision) with biopsy of the skin and subcutaneous tissue of the right leg was done [Figure - 2]. Histopathology revealed malignant tissue with highly cellular oval cells with pleomorphic cells; increased mitosis. Osteoid production and scattered giant cells were present, suggestive of recurrent tumor . Sixth chemotherapy cycle was given with Methotrexate and Leukovorin.
Three days following chemotherapy, the patient developed right focal seizures with transient dysphasia and fever. CT scan brain (plain) revealed right frontal solitary intra-parenchymal hyperdense lesion measuring 4 cm × 3 cm × 4 cm, with peri-lesional edema and mass effect [Figure - 3]. Skeletal and lung survey did not reveal any other lesions.
Total excision of the tumor was achieved. The overlying cortex was xanthochromic with evidence of intra-tumoral bleed. Histopathology revealed hemorrhage and foci of necrosis with solid and cystic areas. Tumor cells were oval to fusiform with enlarged hyperchromatic, pleomorphic nuclei with increased mitosis. Osteoid seams and giant cells were seen among the tumor cells, consistent with hemorrhagic osteosarcoma metastasis [Figure - 4]. Postoperative period was uneventful. The patient has presently completed radiotherapy to the tumor bed (60 Gy in 30 fractions, 6 MV photons with 4-field wedge technique).
| Discussion|| |
Osteogenic sarcoma is the most common type of bone malignancy. ,,,,, The distinguishing characteristic is the production of osteoid or immature bone directly from malignant spindle cell stroma. Common sites include distal femur or proximal tibia (50-60%), followed by humerus. Seventy-five percent of cases involve tubular long bones. Classic osteosarcoma is metaphyseal in origin; only 9% are diaphyseal. ,
Osteosarcoma can be divided into several subtypes depending on clinical, radiological and microscopic features - 50%-osteoblastic, 25%-fibroblastic and 25%-chondroblastic. There is no correlation between the prognosis and pathology. 
Most common prognostic factor in osteosarcoma is metastasis at presentation. Primary mode of metastasis is hematogenous.  This usually occurs within 18-24 months of the primary disease.  Eighty percent of all patients with diagnosis of osteosarcoma already have pulmonary metastatic lesion even if they are not obvious on X rays. Less commonly involved and generally seen either pre-terminally or at postmortem are the heart and visceral abdominal structures and rarely the brain. 
Preoperative neo-adjuvant chemotherapy, however, also provides an important prognostic factor in osteosarcoma because a greater degree of drug-induced tumor necrosis is associated with a significantly higher survival rate. Necrosis of 90% of the tumor mass is considered as a good therapy response.  Moreover, chemotherapy treats potential metastasis. After adjuvant chemotherapy, fewer lung metastases have been observed, and the metastases appear later than in the pre-chemotherapy era.
Nonpulmonary metastases are becoming more common among patients currently treated for osteosarcoma.  Brain metastasis is uncommon in osteosarcoma, but this may be changing with prolonged patient survival in the modern chemotherapy era. ,,,,
In this case the tumor necrosis was only 5-10%, after the first three cycles of chemotherapy. While there are reports describing hemorrhage in a chondroblastic osteosarcoma of the skull,  reports are not available of intra-tumoral hemorrhage in osteogenic sarcoma. The commonest intra-cerebral hemorrhagic metastasis is malignant melanoma.
Since the advent of multimodal therapy, including advances in surgical systems, imaging modalities, multi-agent chemotherapy regimens and surgical treatment, survival among patients with osteosarcoma in general and among those with aggressive tumors has improved from 20 to 60-70%. ,,, Consequently, the pattern of relapse is also changing. ,,
| Conclusions|| |
Brain metastasis is uncommon in osteosarcoma. Hemorrhage in a metastasis is even rarer. Recent reports suggest that consequent to prolonged survival, systemic metastasis in osteogenic sarcoma may be increasing. ,,,,
| Acknowledgments|| |
We thank Dr. K. Ganapathy, Senior Consultant Neurosurgeon, Apollo Hospitals, Chennai, for reviewing the article and providing useful suggestions.
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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4]