Skull osteosarcoma: illustrated review

Acta Neurochir (Wien) (2004) 146: 1235–1239 DOI 10.1007/s00701-004-0376-3

Review Article Skull osteosarcoma: illustrated review L. Mascarenhas1 , A. Peteiro2 , C. A. Ribeiro3 , Z. Magalha˜es4 , H. Roma˜o1 , F. Magalha˜es2 , A. M. Reis4 , J. Resende Pereira4 , M. Honavar2, M. Resende1 , and A. Rocha Vaz1 1

Neurosurgery Service, Pedro Hispano Hospital, Matosinhos, Portugal Anatomic Pathology Service, Pedro Hispano Hospital, Matosinhos, Portugal 3 Radiology Service, Pedro Hispano Hospital, Matosinhos, Portugal 4 Neuroradiology Service, Pedro Hispano Hospital, Matosinhos, Portugal 2

Received November 28, 2003; accepted July 20, 2004; published online September 3, 2004 # Springer-Verlag 2004

Summary

Classification

A case of conventional intramedullary osteosarcoma (epithelioid subtype) with 10 years of evolution and another of high grade surface osteosarcoma of the chondroblastic type, both in the skull, gave rise to several diagnostic and therapeutic difficulties. Key points concerning the definition, classification, imaging, clinical series data and treatment options available for skull osteosarcoma are highlighted.

The two basic components of osteosarcoma are the sarcomatous tumor cells and the matrix [1, 3]. Depending on whether the predominant element of the matrix is osteoid, cartilage or fibrous tissue, osteosarcomas can be classified as osteoblastic, chondroblastic or fibroblastic respectively. The appearance of the cells is variable and also allows categorization of the tumor into several subtypes. In small cell osteosarcoma there is a preponderance of round cells with scarce cytoplasm, and minor amounts of bone=osteoid matrix are found. Giant cell rich osteosarcoma contains multinucleated cells resembling osteoclasts. In the epithelioid type the tumor cells form large cohesive sheets. Malignant fibrous histiocytoma like and osteoblastoma like are also recognized histological patterns. The aforementioned are subtypes of conventional intramedullary osteosarcoma. Other varieties of intramedullary osteosarcoma are telangiectatic osteosarcoma which has characteristic blood-filled cystlike spaces, and well-differentiated intramedullary osteosarcoma. The microscopic findings may vary considerably among different lesions and in different areas of the same tumor. A four stage system based on histological findings can be used to grade osteosarcomas [17]. Osteosarcomas of the surface of bones have special features [3, 9]. Periosteal osteosarcoma arises from the inner layer of the periosteum and elevates it as it grows thereby causing periosteal new bone formation. It is of intermediate grade. Chondral

Keywords: Osteosarcoma; skull; epithelioid; surface high grade.

Introduction Two patients harboring primary skull osteosarcoma presented at the authors’ institution and gave rise to several diagnostic and therapeutic difficulties due to some unusual features of the lesions (Figs. 1 and 2). The cases prompted a review and analysis of the literature which disclosed several key points concerning the definition, classification, imaging, clinical series data and treatment options available for skull osteosarcoma. These will be highlighted.

Definition Osteosarcoma is a malignant neoplasm composed of cells that produce osteoid tissue or bone [1, 3]. Evidence of direct production of osteoid matrix by sarcomatous tumor cells is required to classify the lesion as an osteosarcoma.

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Fig. 1. 45 year old female with a ten year history of a slowly growing occipital mass. (A) Pre operative CT image showing features of osteolysis=osteosclerosis and dense cloudy areas of mineralization. (B) Pre operative T1 weighted MR image: the lesion shows enhancement after gadolinium injection. The patient was operated on and the lesion totally excised. The dura was intact. Histological examination showed an epithelioid osteosarcoma. Immunocytochemistry showed staining for vimentin, S-100 protein and epithelial membrane antigen (EMA), the EMA positivity confirming the epithelioid phenotype. S-100 immunostaining is seen in clearly chondroid areas in osteosarcoma and can be interpreted as implying chondroid differentiation as shown well in this case. (C) H&E stained section of the lesion at the present time: osteosarcoma with epithelioid tumor cells showing abundant pale cytoplasm, vesicular nuclei and prominent nucleoli, associated with scattered osteoclast like cells and osteoid formation. The patient had sought medical attention at another institution during the first year of evolution of the lesion. A biopsy had been performed under local anesthesia. Revision of the material biopsied ten years previously showed fibrofatty tissue, mature bone and a tiny representation of osteosarcoma similar to the present biopsy. (D) H&E stained section of the lesion ten years before: epithelioid tumor cells with osteoid deposits in the center. The patient at that time neglected her condition. Final diagnosis: conventional intramedullary osteosarcoma (epithelioid subtype) with 10 years of evolution

lobules with a perpendicular arrangement containing malignant osteoid tissue in the center and peripheral hypercellularity are typical. Para-osteal osteosarcoma originates in the outer layer of the periosteum. It is a low grade lesion containing well formed osteoid and a

spindle cell stroma. Para-osteal osteosarcoma can undergo dedifferentiation, i.e. transformation into a high grade sarcoma, not necessarily osteosarcoma. Unlike high grade surface osteosarcoma, concomitant areas of low grade tumor are found. High grade surface osteo-

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Skull osteosarcoma: illustrated review

Fig. 2. 20 year old female with a one year history of an exquisitely painful lump in the occipital region with rapid growth. (A) Pre-operative CT image showing a densely mineralized lesion with a spiculated outer border lying on the surface of the occipital squama; the outer table of the skull is intact. The patient was operated on. (B) Immediate post operative CT image: the lesion was excised and the outer table was drilled. Histological examination showed a high grade chondroblastic osteosarcoma. (C) H&E stained section of the lesion: lobules of malignant appearing cartilage with peripheral bone formation. Three months later, while on adjuvant radiotherapy but before programmed chemotherapy she presented with local pain and a slight bulging. (D) Contrast enhanced CT image: a soft tissue mass suggesting early relapse is seen. Reoperation was undertaken: tumor was again removed from the occipital squama at the same location as previously and a craniectomy was performed. Radiotherapy was continued and chemotherapy started. Final diagnosis: high grade surface osteosarcoma of the chondroblastic type

sarcoma is the rarest type and it is histologically similar to conventional intramedullary osteosarcoma. The chondroblastic subtype of high grade surface osteosarcoma lacks the pattern of organization described for periosteal osteosarcoma thereby allowing the differential diagnosis. Contrary to periosteal osteosarcoma, invasion of adjacent soft tissue is considerable in high grade surface osteosarcoma.

Imaging Radiologically osteosarcomas commonly have osteolytic and osteosclerotic features, a cloudy pattern of mineralization either diffuse or in clusters, and illdefined borders [1, 3, 9, 11]. Radiating striations (sunburst appearance) and Codman’s triangle are signs of periosteal reaction due to periosteal elevation. These

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can be seen in periosteal osteosarcomas and intramedullary osteosarcomas with cortical extension, but not in para-osteal osteosarcomas. High grade surface osteosarcomas tend to have a more immature and basal pattern of mineralization. Para-osteal osteosarcomas are usually dense sessile masses on the bone surface, with smooth or irregular margins. A thin radiolucent line may separate part of the tumor from the cortex. CT and MR scanning provide further details regarding tumor structure and extent, namely to adjacent soft tissue, bone itself and neurovascular structures. A chest CT scan and a bone scintigraphy can be used to evaluate the existence of lung and skeletal metastases respectively. Clinical series data Osteosarcomas arising from the skull are rare. In a survey of the literature 98 cases of primary osteosarcoma of the skull were found [14]. Three large series have been reported [6, 8, 13]. Skull osteosarcomas constituted 1.6–2% of osteosarcomas. Unlike osteosarcomas of the extremities, those of the skull showed a tendency to develop in the mature bone. They occurred in the third and fourth decades mainly. Both no sex predominance and a female predominance were noticed. The mean duration of complaints was less than a year. Skull osteosarcomas were more frequent in the vault than in the base. A lump with or without associated pain was the more common form of presentation. In approximately half the cases the histological subtype was osteoblastic. Other types reported were fibroblastic, small cell, malignant fibrous histiocytoma like, telangiectatic, chondroblastic and mixed. Skull osteosarcomas arise either de novo (primary type) or secondary to other disorders. The latter accounted for 27–47% of the total, appeared at a later age and had a worse prognosis. Paget’s disease of bone, fibrous dysplasia, chronic osteomyelitis, multiple osteochondromatosis and radiotherapy were found as associated conditions. Skull osteosarcomas can attain a huge size (12  7 cm) and relapse in a very short time after gross total resection (11  9 cm in three weeks) [2]. Subdural hematoma, intracerebral hematoma, invasion of the dura and subdural space may be associated features [14]. Although extremely rare, primary intracranial extraskeletal origins for this tumor are possible, namely the dura, and mesenchymal components in the subarachnoid cisterns and perivascular sheaths [19]. Osteosarcoma has been noticed to evolve from a fibrosarcoma in an intracranial location [5] and a skull osteoblastoma [4]. A series of para-osteal osteosarcomas [7], a case of a high grade

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surface osteosarcoma [18] and another of a periosteal osteosarcoma [12] arising from the skull have been reported as well. Treatment options Neoadjuvant chemotherapy (i.e. chemotherapy started before surgery) can be considered if a biopsy of the lesion is performed. Possible advantages of neoadjuvant chemotherapy include: decrease in tumor size and a better chance of total surgical removal; and evaluation of response to drugs and change if inadequate [15]. Surgery and chemotherapy have been recommended for the management of skull osteosarcoma [13, 16]. In a metaanalysis improved patient survival was seen using this strategy [15]. A recently proposed protocol includes: surgery aimed at obtaining negative surgical margins; neoadjuvant chemotherapy when this is not attainable and for high grade lesions; and adjuvant radiotherapy when only close or positive surgical margins are achieved [10]. Final remark The rarity of osteosarcomas of the skull makes it difficult to arrive at a definitive diagnosis and treatment plan. When dealing with skull lesions, even if the typical rapid painful growth pattern is lacking or the supposedly ‘‘benign surface lesion’’ entourage is found, the neurosurgeon should have in mind this uncommon entity as a possibility. References 1. Ayala AG, Ro JY, Raymond AK (1996) Bone tumors. In: Damjanov I, Linder J (eds) Anderson’s pathology, 10th edn. Mosby, St Louis, pp 2531–2573 2. Bose B (2002) Primary osteogenic sarcoma of the skull. Surg Neurol 58: 234–240 3. Dorfman HD, Czerniak B (1998) Bone Tumors. Mosby, St Louis, pp 128–252 4. Figarella Branger D, Perez Castillo M, Garbe L et al (1991) Malignant transformation of an osteoblastoma of the skull: an exceptional occurrence. Case report. J Neurosurg 75: 138–142 5. Gnanalingham KK, Chakraborty A, Galloway M et al (2002) Osteosarcoma and fibrosarcoma caused by postoperative radiotherapy for a pituitary adenoma. J Neurosurg 96: 960–963 6. Huvos AG, Sundaresan N, Bretsky SS et al (1985) Osteogenic sarcoma of the skull. A clinicopathologic study of 19 patients. Cancer 56: 1214–1221 7. Kumar R, Moser RP Jr, Madewell JE et al (1990) Parosteal osteogenic sarcoma arising in cranial bones: clinical and radiologic features in eight patients. AJR Am J Roentgenol 155: 113–117 8. Nora FE, Unni KK, Pritchard DJ et al (1983) Osteosarcoma of extragnathic craniofacial bones. Mayo Clin Proc 58: 268–272

Skull osteosarcoma: illustrated review 9. Okada K, Unni KK, Swee RG et al (1999) High grade surface osteosarcoma. A clinicopathologic study of 46 cases. Cancer 85: 1044–1054 10. Patel SG, Meyers P, Huvos AG et al (2002) Improved outcomes in patients with osteogenic sarcoma of the head and neck. Cancer 95: 1495–1503 11. Resnick D, Kyriakos M, Greenway GD (1995) Tumors and tumorlike lesions of bone: imaging and pathology of specific lesions. In: Resnick D (ed) Diagnosis of bone and joint disorders, 3rd edn. Saunders, Philadelphia, pp 3628–3938 12. Robertson NJ, Newman PL (2000) Periosteal osteosarcoma of the cranium. Ann Diagn Pathol 4: 300–302 13. Salvati M, Ciappetta P, Raco A (1993) Osteosarcomas of the skull. Clinical remarks on 19 cases. Cancer 71: 2210–2216 14. Shinoda J, Kimura T, Funakoshi T et al (1993) Primary osteosarcoma of the skull. A case report and review of the literature. J Neurooncol 17: 81–88 15. Smeele LE, Kostense PJ, van der Waal I et al (1997) Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients. J Clin Oncol 15: 363–367 16. Sundaresan N, Huvos AG, Rosen G et al (1985) Combinedmodality treatment of osteogenic sarcoma of the skull. J Neurosurg 63: 562–567 17. Unni KK, Dahlin DC (1984) Grading of bone tumors. Semin Diagn Pathol 1: 165–172 18. Ushigome S, Ushigome S, Moriseko K et al (1968) Case of osteogenic sarcoma of the frontal bone [in Japanese] Orthop Surg 19: 952–955 19. Walker MT, Toye LR, Coons SW et al (2001) Intradural primary chondroblastic osteosarcoma: case report. AJNR Am J Neuroradiol 22: 1960–1962

1239 and both patients are female. Other clinical features of both cases are different and do not permit generalising statements. I agree that skull osteosarcoma is a rare disease and its description in textbooks is based on multiple case reports found in the literature. Tomasz Trojanowski Lublin Primary skull osteosarcomas (PSOS) are exceedingly rare mesenchymal tumours, preferably affecting the adult population, and bearing a better prognosis than those located in skeletal long bones. Usually, they are locally aggressive, whereas distant metastases are infrequent. Differential diagnosis (mainly with more benign para-osteal sarcomas) may require an exhaustive synthesis of all the available data: clinical evolution, radiological pictures (neoplastic borders, mineralization, neovascularity), histological patterns. The Authors report two rather unusual cases of PSOS. The former characterized by an extremely rare cytological aspect (probably the first published epithelioid variety) as well as by an incredibly long clinical history (10 years). The latter described as an infrequent primary chondroblastic form of the occipital bone surface. In both cases, as expected, combined treatments gave excellent results. Indeed, during the last decade the combination of neo-adjuvant chemotherapy, surgery and radiotherapy have dramatically improved the outcomes of these patients. Given the limited literature in this field (a hundred reported cases) these specific contributions may be of some relevance to determine diagnostic criteria and treatment options. Massimo Gerosa Verona

Comments This is a case report of two cases of skull osteosarcoma. Their common feature besides pathology is location in the occipital bone

Correspondence: Lino Mascarenhas, Servic° o de Neurocirurgia, Hospital Pedro Hispano, Rua Dr. Eduardo Torres, 4454-509 Matosinhos, Portugal. e-mail: [email protected]