Neurol Med Chir (Tokyo) 50, 407¿409, 2010 Synchronous Multifocal Osteosarcoma Involving the Skull Presenting With Intracranial Hemorrhage —Case Report— Hikari SATO, Nakamasa HAYASHI, Hiromichi YAMAMOTO, Shoichi NAGAI, Kazuo OHMORI*, Masahiko KANAMORI*, and Shunro ENDO Departments of Neurosurgery and *Orthopedics, Faculty of Medicine, University of Toyama, Toyama Abstract A 40-year-old man presented with a rare case of synchronous multifocal osteosarcoma involving the skull associated with intracerebral hemorrhage, manifesting as sudden headache and left homonymous hemianopia. Computed tomography revealed a skull tumor in the right occipital bone and intracerebral hemorrhage in the right occipital lobe. Gross total resection of the skull tumor with hematoma was performed. The histological diagnosis was osteosarcoma. The tumor cells had invaded into the surrounding brain parenchyma, resulting in intracerebral hemorrhage. Key words: brain invasion, intracerebral hemorrhage, multifocal osteosarcoma, skull tumor intracranial hemorrhage, Introduction Osteosarcoma is the most common primary malignant neoplasm of bone and can occur anywhere in the body, but is most commonly found in the long bones, especially around the knee. Synchronous multifocal osteosarcoma, a rare variant of osteosarcoma, is described as the simultaneous appearance of two or more tumors at any site in the peripheral or axial skeleton.7,8,10,11,14,15,18,22,25) We present a case of synchronous multifocal osteosarcoma involving the skull presenting with intracerebral hemorrhage. Case Report A 40-year-old man presented with a 4-month history of low back pain. Vertebral magnetic resonance imaging demonstrated multiple extradural lesions compressing the spinal cord. Gallium systemic bone scintigraphy revealed multiple regions of hyperaccumulation in the skeleton including the skull (Fig. 1A). Computed tomography (CT) of the chest and abdomen found no abnormalities. Biopsy of the dominant lesion in the left femur was performed and revealed a lesion consistent with an osteoblastic osteosarcoma. The diagnosis was type II synchronous multifocal osteosarcoma. The patient was treated with 2 cycles of chemotherapy with methotrexate, adriamycin, and cisplatin in the Department of Orthopedics in our hospital. Four months later, the patient complained of sudden headache and left homonymous hemianopia. Head CT revealed a Received August 21, 2009; Accepted Fig. 1 A: Gallium systemic bone scintigrams revealing multiple regions of hyperaccumulation in the skeleton including the skull. B: Computed tomography scan showing a skull tumor in the right occipital bone and intracerebral hemorrhage in the right occipital lobe. tumor of the skull in the right occipital bone and intracerebral hemorrhage in the right occipital lobe (Fig. 1B). Cerebral digital subtraction angiography revealed no vascular abnormalities such as arteriovenous malformation or cerebral aneurysm. The patient underwent a right occipital craniotomy under general anesthesia in the prone position. A horseshoeshaped skin incision was created in the occipital region. September 29, 2009 407 H. Sato et al. 408 Fig. 2 Photomicrograph of the brain tissue surrounding the tumor showing large tumor cells with eosinophilic cytoplasm, ill-defined contours, and prominent nucleoli have invaded the surrounding brain parenchyma with intracerebral hemorrhage. Hematoxylin and eosin stain, original magnification ×40. Protuberance of the occipital bone was recognized, and osteoclastic craniectomy was performed around this lesion. The lesion had penetrated through the dura mater and into the brain tissue. The dura mater around the tumor was circumferentially cut, and the tumor was removed with the surrounding brain tissue and hematoma. The tumor was about 6 × 6 × 4 cm in size with a smooth surface. Histological examination revealed tumor cells with eosinophilic cytoplasm, ill-defined contours, and prominent nucleoli had invaded the surrounding brain parenchyma with intracerebral hemorrhage consistent with an osteoblastic osteosarcoma of the skull (Fig. 2). Postoperatively, the patient's headache disappeared, but left homonymous hemianopia persisted and was unchanged. Two weeks after the craniotomy, he underwent laminectomy of the lumbosacral spine (L5–S1) for relief of pain of the lower extremities. Thereafter, he was treated conservatively and died approximately 14 months after the diagnosis of synchronous multifocal osteosarcoma. Autopsy was not performed. Discussion Primary osteosarcoma of the skull is rare.4,5,12,23) The most common complaint associated with this type of tumor is a growing protuberance on the head that may or may not be tender.5) The cranial vault is affected more often than the base of the skull.20) Previously reported cases include three of primary osteosarcoma involving the skull combined with intracranial hemorrhage.1,23,26) One case of primary osteosarcoma of the temporal skull base was combined with subdural hematoma.23) The tumor was firm and rigidly adherent to the dura in the middle cranial fossa. The extradural tumor was totally excised but the subdural hematoma could not be completely removed because of tight adhesion to the brain. Histological examination showed that tumor cells were present in the subdural hematoma. The tumor recurred after initial surgical intervention and chemotherapy, and the patient died 15 months after diagnosis. Another case of primary osteosarcoma of the tem- poral fossa was treated by radical excision of a tumor of the skull base.1) Histological examination found no evident parenchymal invasion. The patient was alive and without evidence of disease 8 months after presentation but died shortly thereafter of complications related to adjuvant therapy. A case of intracranial osteosarcoma occurred at the site of previous radiosurgery.21) Cerebral hemorrhage occurred in the peritumoral region. The tumor and surrounding hematoma were completely excised. Parenchymal invasion was not present. The patient underwent adjuvant combination chemotherapy consisting of highdose methotrexate, doxorubicin, and cisplatinum, and was alive without evidence of disease 12 months after diagnosis. Synchronous multifocal osteosarcoma is a rare condition, with a reported incidence of 1 to 3%.7,11) Multifocal osteosarcoma may be an unusual form of osteosarcoma with rapid metastasis, regardless of the presence of pulmonary metastases, and usually presents as one dominant lesion and multiple small lesions.8,10,18) Metastasis via the vertebral venous plexus system may be a plausible mechanism of bone-to-bone metastasis without evidence of pulmonary metastasis.7,9,15) Multifocal osteosarcoma can be classified according to histology, patient age, and time at presentation of multiple osseous lesions.2) Type I patients are less than 18 years of age, with multiple histologically anaplastic osseous lesions appearing within 5 months of the initial presentation. Type II patients are older than 18 years of age, and present with multiple osseous lesions that are histologically well differentiated. Type IIIA and IIIB represent categories of metastatic disease, with patients presenting with secondary lesions 5 months or more after the initial presentation. Synchronous multifocal osteosarcoma involving the skull is relatively rare.6,10,13,15–19,22,24,25) A study of skeletal distribution of secondary foci of multifocal osteosarcoma found 5 of 175 secondary lesions (3%) involved the skull in 29 cases of multifocal osteosarcoma.10) The present case was synchronous multifocal osteosarcoma involving the calvarium and manifesting as intracerebral hemorrhage. Histological examination revealed tumor cells present in the surrounding brain tissue. Brain metastases have been reported in 5.7% of patients with a diagnosis of osteosarcoma with lung metastasis.3) The clinical presentation in such cases tends to be acute and catastrophic, necessitates emergency management, and is associated with major morbidity. Since the present patient had no evidence of lung metastasis, we speculated that the skull tumor had invaded the surrounding brain tissue through the dura mater. The prognosis for patients with synchronous multifocal osteosarcoma is very poor.7,10,14,15,18) The mean survival of type I patients is 6 months, and that of type II patients is between 5 months and 4 years.2,8,15) Pulmonary metastases are considered to be one of the major factors affecting the prognosis of unifocal osteosarcoma and multifocal osteosarcoma.22) The present patient died 14 months after the diagnosis of type II synchronous multifocal osteosarcoma, despite surgical intervention and chemotherapy. 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Gan No Rinsho 28: 1735–1739, 1982 (Jpn) Address reprint requests to: Nakamasa Hayashi, M.D., Department of Neurosurgery, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama 930–0194, Japan. e-mail: nakamasa@iwa.att.ne.jp