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Radiopathological evaluation of primary malignant skull tumors: A review
Clinical Neurology and Neurosurgery 114 (2012) 833–839
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Review
Radiopathological evaluation of primary malignant skull tumors: A review Kiran Gangadhar a,∗ , Deepa Santhosh b,∗∗ a b
Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
a r t i c l e
i n f o
Article history: Received 27 April 2012 Received in revised form 20 May 2012 Accepted 26 May 2012 Available online 19 June 2012
a b s t r a c t Skull tumors comprise a wide variety of entities, ranging from chronic inflammatory disease to primary and secondary neoplasms. There is no valid incidence or data about the incidence of skull tumors in general. Primary malignant skull tumors are rare, with most articles reporting single cases. We would discuss some of the frequent tumors in this group and review of the literature for the same. © 2012 Elsevier B.V. All rights reserved.
Keywords: Primary malignant skull tumors Osteosarcoma Skull Hemangiopericytoma Plasmacytoma Chordoma Chondrosarcoma
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Plasmacytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Chordoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Authors’ contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Metastatic carcinomas are the most common malignant tumor affecting the skeleton. Most metastases originate from common cancers namely breast, lung, prostate, kidney and thyroid gland,
Abbreviations: MDCT, multi detector computed tomography; NCCT, non contrast computed tomography; H&E, hematoxylin & eosin; SIP, Solitary intramedullary plasmacytoma; SPS, solitary plasmacytoma of the skull; CECT, contrast enhanced computed tomography; HPE, histopathological examination; MR, magnetic resonance; CNS, central nervous system; CT, computed tomography. ∗ Corresponding author at: Room No. 82, New Doctors Hostel, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. ∗∗ Corresponding author at: Room No. 62, Old Doctors Hostel, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. E-mail addresses: [email protected] (K. Gangadhar), [email protected] (D. Santhosh). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.05.041
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which account for 93% of all deposits. Out of 114 histologically evaluated lesions 44.3% involved axial skeleton, 28.8% the appendicular skeleton and 26.9% involved multiple bones [1]. Among the wide array of human neoplasms, primary tumors of bone are relatively uncommon. Not only has this contributed to the paucity of meaningful and useful data about the relative frequency and incidence rates of the various subtypes of bone tumors, but it also explains our rudimentary understanding of risk factors. In general, bone sarcomas account for only 0.2% of all neoplasms [2]. There is a wide variety of histopathological diagnosis in tumors of the skull. These neoplasms comprise tumors of bony, cartilaginous, fibrous, histiocytic or hematopological origin. The most common malignant skull tumors are osteogenic sarcoma and chondrosarcoma. The clinical presentation varies according to the site of tumor origin. However the most common symptom is painless, slowly growing epicranial mass, which may vary widely regarding size and rate of growth. Tumors of skull base may present with
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cranial nerve symptoms like diplopia, visual or hearing loss, olfactory sensations, or impaired swallowing function. [3]
2. Discussion 2.1. Osteosarcoma In a survey of the literature around 100 cases of primary osteosarcoma of the skull were found, including our cases. The occurrence of osteosarcoma in the craniofacial bones peaks in the third decade, where as that in the skeleton peaks in the second decade. The etiology of osteosarcoma is unknown, but the major risk factors for development of osteosarcoma in craniofacial bones may be similar to those of the long skeletal bones, consisting of exposure to radiation, retinoblastoma, Li–Fraumeni syndrome, and Paget’s disease. The skull is a favored site for osteosarcoma arising out of Paget’s disease. Other bone abnormalities, such as fibrous dysplasia, multiple osteochondromatosis, chronic osteomyelitis, myositis ossificans, and trauma, have also been proposed as risk factors [4]. Radiologically osteosarcomas commonly have osteolytic and osteosclerotic features, a cloudy pattern of mineralization either diffuse or in clusters, and illdefined borders. Radiating striations (sun-burst appearance) and Codman’s triangle are signs of periosteal reaction due to periosteal elevation [5]. These can be seen in periosteal osteosarcomas and intramedullary osteosarcomas with cortical extension, but not in paraosteal osteosarcomas. High grade surface osteosarcomas tend to have a more immature and basal pattern of mineralization. Paraosteal 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 [6]. The differential diagnosis of cranial osteosarcoma to be considered includes chondrosarcoma and osteochondroma. The CT findings of new bone formation in the soft tissue mass and the characteristic matrix strongly suggest osteogenic sarcoma, but differentiation from chondrosarcoma and osteochondroma cannot be made definitely without histology. Computed tomography in cases of chondrosarcoma of the base of skull shows similar changes, but once the calvarium undergoes membranous ossification, it becomes an unlikely site for cartilaginous tumors. Osteochondromas usually are sharply defined and homogenous indensity [7]. Pathologically the diagnosis of osteosarcoma is predicated on the accurate identification of osteoid. Histologically, osteoid is a dense, pink, amorphous intercellular material, which may appear somewhat refractile [8]. Surgery and chemotherapy have been recommended for the management of skull osteosarcoma [9]. The identification of prognostic factors has been an additive process in which factors have been investigated, identified and incorporated into an overall therapeutic strategy [10]. Traditionally, age, gender, location, tumor size, stage, and the results of various laboratory tests have been used in an effort to predict prognosis. However, response to pre-operative therapy is currently the most sensitive indicator of survival. At the same time, it is recognized that a single system does not apply to all cases. Unique biological aggressiveness, coupled with an inability to completely resect the tumor at certain sites (e.g., skull, spine) is one example (Figs. 1 and 2).
Fig. 1. (a) Coronal NCCT and (b) axial bone window settings of cranium showing a giant geographic sclerotic/lytic lesion involving parietal bone on left side with dense matrix mineralization (sunburst appearance) showing patchy central hypodense necrotic foci with gross mass effect over left cerebral hemisphere (parietal lobe) and large outer extracranial scalp portion. (c) H&E of chondroblastic osteosarcoma showing lobules of malignant-appearing cartilage with bone formation (arrow) in the center of the lobules.
2.2. Plasmacytoma Solitary intramedullary plasmacytoma (SIP), a sub-type of plasma cell tumors, is a malignant neoplasm that may occur as a primary focal entity or as the first presentation of systemic multiple myeloma. Plasma cell tumors are classified as either multiple myeloma (systemic), intramedullary plasmacytoma (involving bone), or extramedullary
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Fig. 2. (a) Axial CECT showing a large geographic sclerotic/lytic lesion involving occipital bone on right side with dense matrix mineralization (sunburst appearance) showing moderate contrast enhancement with gross mass effect over right cerebellar hemisphere. (b) Axial T2 weighted MR imaging showing hyperintense occipital bone mass with central hypointense linear sunburst pattern foci suggestive of calcifications associated with extra-axial signs like CSF cleft surrounding the mass and right cerebellar hemisphere gray white matter buckling. (c) Axial T1 weighted post contrast MR imaging showing intensely enhancing heterogenous occipital bone mass with central hypointense linear sunburst pattern foci suggestive of calcifications. (d) Sagittal CECT bone window settings showing a large geographic sclerotic/lytic lesion involving occipital bone on right side with dense matrix mineralization (sunburst appearance) with gross mass effect over right cerebellar hemisphere. (e) Saggital T1 weighted MR imaging revealed, with dense central linear calcific foci and a hemorrhagic focus (arrow). (f) H&E revealed high grade hyaline cartilage, which is intimately associated, and randomly mixed, with osteoid (arrow).
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Fig. 3. (a) Axial and (b) coronal CECT of brain showing a relatively well defined homogenously enhancing soft tissue density mass lesion with epicenter appearing to be involving greater wing of sphenoid and squamous part of temporal bone. Medially extension to extra conal part of lateral orbit with involvement of lateral rectus causing proptosis of right globe noted with optic canal extension and posterior ethmoidal sinus involvement noted. Extra-axial extension into middle/anterior cranial fossa and laterally into temporal fossa extension noted. (c) Axial CECT bone window settings revealed a large relatively well defined geographic lytic mass lesion with epicenter appeared to be involving greater wing of sphenoid and squamous part of temporal bone with medial sphenoid body extension. (d) FNA smear shows predominantly single cells (plasma cells) with round to oval eccentric nuclei and cartwheel chromatin appearance basophilic cytoplasm with perinuclear clear zone. Few binucleated cells are also seen (arrow) (May–Grunewald–Giemsa × Lp).
plasmacytoma (involving soft tissues). A significant percentage (up to 85%) of patients with solitary plasmacytoma will eventually develop disseminated multiple myeloma, if followed for a sufficient period of time [11]. Plasmacytomas are composed of a proliferation of abnormal plasma cells that exhibit monoclonal intracellular immunoglobulins with immunological staining techniques [12]. Solitary osseous plasmacytoma is characterized by osteolytic lesion and the presence of plasma cells in the biopsy [13]. On CT, SIPs have been reported as slightly high attenuation extra-axial masses that often demonstrate homogenous contrast enhancement, very similar to meningioma [14]. The MR appearance is either isointense, hyper-intense or heterogeneous intensity compared with the brain parenchyma on T1-weighted images and homogeneous enhancement by
intravenous administration of Gd DTPA [15]. Osteolytic lesion can usually be identified on X-ray film. The sharp borders, the lack of bony sclerosis and the paucity of periosteal reaction are characteristic findings of solitary plasmacytoma [16]. On angiography, SIPs are commonly hypervascular masses supplied by external carotid artery branches with prolonged capillary tumor stain that may also resemble meningioma [11]. Histologically, plasmacytomas are characterized by a diffuse or sheet-like proliferation of plasma cells with varying degrees of maturity and atypia. The nuclei are oval to round and eccentrically located with a dispersed (“clock-face”) nuclear chromatin pattern and a clear or halo area [17]. While meningiomas and hemangiopericytomas may resemble the imaging characteristics of plasmacytomas, the location of the tumor and the aggressive bone changes should raise other
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Fig. 4. Extra axial intra cranial extension of chordoma. (a) Saggital CECT and (b) saggital post contrast T1 weighted MR imaging shows ill defined geographic mass lesion diffusely involving clivus, showing intense enhancement on post contrast sequences, with extension to basilar artery cistern. (c) Low power view showing chords of tumor cells in a myxoid background with occasional cells displaying a bubbly cytoplasm. (d) High power view showing classic physaliphorous cell contain multiple intracytoplasmic bubbles [arrow].
possibilities such as plasmacytoma or metastatic disease. Other differential diagnosis list include Ewing sarcoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, bone langerhans cell histiocytosis, lymphoma leukemia, hyperparathyroidism/renal osteodystrophy, brown tumor and fibrosarcoma. Management of plasmacytoma of the skull base is complete removal of the tumor whenever possible, followed by radiation therapy [18] (Fig. 3). 2.3. Chordoma Chordoma is a low to intermediate grade malignant tumor that recapitulates notochord. Chordomas account for 1–4% of all primary malignant bone tumors. [19]. Chordoma occurs in the late middle age and most commonly arises in the sacrococcygeal (50–60%) or sphenooccipital regions (25–40%) [20]. The latter usually causes destruction of the clivus and spreads into the middle or posterior cranial fossa compressing the brainstem or the nasopharynx. CT demonstrates clearly the mass and the bony component of the tumor. MRI depicts better the extent of the lesion and its relation to the adjacent structures. On T1-weighted images
chordoma is iso- or hypointense and replaces the hyperintense clival fatty marrow. On T2-weighted images it is inhomogeneous and hyperintense. After the administration of contrast medium, chordoma shows heterogeneous enhancement. The differential diagnosis includes metastasis, craniopharyngioma, chondrosarcoma, pituitary tumors and nasopharyngeal carcinoma. Although they are similar in management, distinction between chordoma and chondrosarcoma is important due to different prognoses and outcomes. Chondroid chordoma has histological features of chondrosarcoma and chordoma [22]. Immunohistochemical study is helpful in which chordoma and chondroid chordoma are immunopositive for epithelial markers including cytokeratin and epithelial membrane antigen (EMA), where as chondrosarcoma is negative for both [26]. Chordomas are lobulated tumors, with individual lobules being separated by fibrous bands. The tumor cells are arranged in sheets, cords or float singly within an abundant myxoid stroma. They typically have an abundant pale vacuolated cytoplasm (the classic “physaliphorous cells”). They show mild to moderate nuclear atypia. In the chondroid variants, there are areas that may mimic hyaline or myxoid cartilage. Chordoma associated with a high grade
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is believed to provide some benefit, with a control rate of 60% in 5 years. Local recurrences are common, but systemic metastases are unusual [21] (Fig. 4).
2.4. Chondrosarcoma Chondrosarcoma of the skull base is rare and accounts for 6% of all skull base lesions and 0.1% of all head and neck tumors. Chondrosarcoma can be subclassified, in order of frequency, into the conventional (hyaline or myxoid), dedifferentiated, clear cell, and mesenchymal subtypes [22]. Radiologically they present as an area of lytic lesion with variably distributed punctate or ring-like matrix mineralization. MRI can be helpful in delineating the extent of the tumor and establishing the presence of soft tissue extension. CT scans aid in demonstrating matrix calcification. CHS shows abundant blue-gray cartilage matrix production. Irregularly shaped lobules of cartilage varying in size and shape are present. These lobules may be separated by fibrous bands or permeate bony trabeculae. The chondrocytes are atypical varying in size and shape and contain enlarged, hyperchromatic nuclei. Binucleation is frequently seen. The most important differential diagnosis for chondrosarcoma of the skull base is chordoma. Chordoma and chondrosarcoma have a similar radiological appearance. Typically, they are hypointense or isointense on T1 and hyperintense on T2, and frequently enhanced with gadolinium. Chondrosarcomas can periodically be distinguished from chordomas due to the occupation of a more lateral location along the petroclival fissure, while chordomas are typically located in the midline [26]. Treatment of chondrosarcoma includes careful pre-operative evaluation and surgical resection or radiotherapy, particularly carbon ion radiotherapy, which has been reported to achieve a better outcome than simple local control [23]. Other primary malignant skull tumors like Ewing’s sarcoma, malignant fibrous histiocytoma are extremely uncommon and these tumors represent very rare differential diagnosis of skull tumors. [3] While dealing with malignant skull tumors, metastatic tumors should be kept in mind. Most of these are calvarial circumscribed intraosseous tumors [24]. Source is hematogenous (most commonly breast, lung, prostate, kidney) or by direct extension (of squamous cell carcinoma) [25] (Fig. 5 and Table 1.).
Table 1 Radiological features of skull metastasis are [25].
Fig. 5. (a) Coronal T2 weighted MR imaging showing hyperintense bony mass involving sphenoid body predominantly with sella and extraaxial extension toward right medial temporal region with faint hypointense foci suggestive of calcification within the mass. (b) Moderate enhancement of the mass with bilateral internal carotid artery encasement (cavernous parts). Also showing perimesencephalic cisternal extension of the mass lesion at right side with mass effect over right side of mid brain. (c) High power view showing grade 2 chondrosarcoma characterized by hypercellularity, with pleomorphic cells, hyperchromasia and frequent binucleation [arrow].
sarcoma is called a “dedifferentiated” chordoma or sarcomatoid chordoma [19]. Treatment is primarily surgical. Incomplete resection is common due to adjacent vital structures and the infiltrative nature of the tumor. High-dose radiation therapy and photon-beam therapy
Imaging modality
Findings
Radiography
Focal lytic or blastic lesions lacking “benign” sclerotic border
CT
NCCT: May find hemorrhagic hyperdensity CECT: Enhancing mass centered in bone with osseous destruction, lacking ‘benign” sclerotic border. Most are lytic; a few sclerotic (e.g., prostate).
MR findings
TlWI: Hypointense marrow lesion. T2WI: Hyperintense marrow lesion; dura usually intact. T1 contrast: Lesion may enhance to “normal” T1 marrow signal; requires fat-saturation; with some dural thickening & enhancement.
K. Gangadhar, D. Santhosh / Clinical Neurology and Neurosurgery 114 (2012) 833–839
3. Conclusion In conclusion, primary malignant skull tumors are rare tumors, with very limited studies about its incidence and with varied presentation. With improvements in the diagnostic field, awareness will increase the knowledge about these tumors and can facilitate appropriate treatment planning, which may include a limited biopsy prior to considering more extensive skull surgery. Therefore, knowledge of the imaging spectrum is important because imaging plays a crucial role in the diagnosis and management of these patients. Authors’ contributions The author is involved in case collection and documentation. References [1] Desai S, Jambhekar N. Clinicopathological evaluation of metastatic carcinomas of bone: a retrospective analysis of 114 cases over 10 years. Indian Journal of Pathology and Microbiology 1995;38:49–54. [2] Ries LAG, Kosary CL, Hankey BF, et al. SEER cancer statistics review, 1973–1996. Bethesda, MD: National Cancer Institute; 1999. [3] Tonn J-C, Westphal M. Neuro-oncology of CNS tumors; 2006. Section 2, p. 75–7. [4] Ha PK, Eisele DW, Frassica FJ, et al. Osteosarcoma of the head and neck: a review of the Johns Hopkins experience. Laryngoscope 1999;109:964–9. [5] Ayala AG, Ro JY, Raymond AK. Bone tumors. In: Damjanov I, Linder J, editors. Anderson’s pathology. 10th ed. St. Louis: Mosby; 1996. p. 2531–73. [6] Mascarenhas L, Peteiro A, Ribeiro CA, et al. Skull osteosarcoma: illustrated review. Acta Neurochirurgica (Wien) 2004;146:1235–9. [7] Haque F, Fazal ST, Ahmad SA, et al. Primary osteosarcoma of the skull. Australasian Radiology 2006;50:63–5. [8] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 265 [Chapter 11]. [9] Okada K, Unni KK, Swee RG, et al. High grade surface osteosarcoma. A clinicopathologic study of 46 cases. Cancer 1999;85:1044–54.
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[10] Anon. Age and dose of chemotherapy as major prognostic factors in a trial of adjuvant therapy of osteosarcoma combining two alternating drug combinations and early prophylactic lung irradiation. French Bone Tumor Study Group. Cancer 1988;61:1304–11. [11] Meyer JR, Roychowdhury S, Cybulski G, et al. Solitary intramedullary plasmacytoma of the skull base mimicking aggressive meningioma. Skull Base Surgery 1997;7:101–5. [12] Ustuner Z, Basaran M, Bilgic B, et al. Skull base plasmacytoma in a patient with light chain myeloma. Skull Base 2003;13:161–71. [13] Rawlings NG, Browstein S, Robinson JW, et al. Solitary osseous plasmacytoma of the orbit with amyloidosis. Ophthalmic Plastic & Reconstructive Surgery 2007;23:79–80. [14] Marais J, Brookes GB, Lee CC. Solitary plasmacytoma of the skull base. The Annals of Otology, Rhinology, and Laryngology 1992;101:665–8. [15] Prasad ML, Mapapatra AK, Kumar L, et al. Solitary intracranial plasmacytoma of the skull base. Indian Journal of Cancer 1994;31:174–9. [16] Gross M, Eliashar R, Maly B, et al. Maxillary sinus plasmacytoma. Israel Medical Association Journal 2004:119–20. [17] Bindal AK, Bindal RK, van Loveren H, et al. Management of intracranial plasmacytoma. Journal of Neurosurgery 1995;83:218–21. [18] Woodruff RK, Malpas JS, White EE. Solitary plasmacytoma: II. Solitary plasmacytoma of bone. Cancer 1979;43:2344–7. [19] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 316–71 [Chapter 17]. [20] Murphy JM, Wallis F, Toland J, Toner M, Wilson JF. CT and MRI appearances of thoracic chordoma. European Radiology 1998;8:1677–9. [21] Vrionis FD, Kienstra MA, Rivera M, Padhya TA. Malignant tumors of the anterior skull base. Cancer Control 2004;11(May/June (3)). [22] Chu P-Y, Wei C-P, Tsai Y-F, Teng T-H, Lee C-C. Chondrosarcoma of the skull base – report of two cases. Tzu Chi Medical Journal 2006;18(3):229–31. [23] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 247–50 [Chapter 10]. [24] Mitsuya K, Nakasu Y, Horiguchi S, et al. Metastatic skull tumors: MRI features and a new conventional classification. Journal of Neuro-Oncology 2011;104:239–45. [25] Osborn AG, Blaser SI, Salzman LK, et al. Diagnostic imaging brain; 2004. Part 2, Section 4, p. 80–2. [26] Almefty K, Pravdenkova S, Colli BO, et al. Chordoma and chondrosarcoma similar, but quite different, skull base tumors. Cancer 2007;110 (December (11)).
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Review
Radiopathological evaluation of primary malignant skull tumors: A review Kiran Gangadhar a,∗ , Deepa Santhosh b,∗∗ a b
Department of Radiodiagnosis and Imaging, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
a r t i c l e
i n f o
Article history: Received 27 April 2012 Received in revised form 20 May 2012 Accepted 26 May 2012 Available online 19 June 2012
a b s t r a c t Skull tumors comprise a wide variety of entities, ranging from chronic inflammatory disease to primary and secondary neoplasms. There is no valid incidence or data about the incidence of skull tumors in general. Primary malignant skull tumors are rare, with most articles reporting single cases. We would discuss some of the frequent tumors in this group and review of the literature for the same. © 2012 Elsevier B.V. All rights reserved.
Keywords: Primary malignant skull tumors Osteosarcoma Skull Hemangiopericytoma Plasmacytoma Chordoma Chondrosarcoma
Contents 1. 2.
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Osteosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Plasmacytoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Chordoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Chondrosarcoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Authors’ contributions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1. Introduction Metastatic carcinomas are the most common malignant tumor affecting the skeleton. Most metastases originate from common cancers namely breast, lung, prostate, kidney and thyroid gland,
Abbreviations: MDCT, multi detector computed tomography; NCCT, non contrast computed tomography; H&E, hematoxylin & eosin; SIP, Solitary intramedullary plasmacytoma; SPS, solitary plasmacytoma of the skull; CECT, contrast enhanced computed tomography; HPE, histopathological examination; MR, magnetic resonance; CNS, central nervous system; CT, computed tomography. ∗ Corresponding author at: Room No. 82, New Doctors Hostel, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. ∗∗ Corresponding author at: Room No. 62, Old Doctors Hostel, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. E-mail addresses: [email protected] (K. Gangadhar), [email protected] (D. Santhosh). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.05.041
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which account for 93% of all deposits. Out of 114 histologically evaluated lesions 44.3% involved axial skeleton, 28.8% the appendicular skeleton and 26.9% involved multiple bones [1]. Among the wide array of human neoplasms, primary tumors of bone are relatively uncommon. Not only has this contributed to the paucity of meaningful and useful data about the relative frequency and incidence rates of the various subtypes of bone tumors, but it also explains our rudimentary understanding of risk factors. In general, bone sarcomas account for only 0.2% of all neoplasms [2]. There is a wide variety of histopathological diagnosis in tumors of the skull. These neoplasms comprise tumors of bony, cartilaginous, fibrous, histiocytic or hematopological origin. The most common malignant skull tumors are osteogenic sarcoma and chondrosarcoma. The clinical presentation varies according to the site of tumor origin. However the most common symptom is painless, slowly growing epicranial mass, which may vary widely regarding size and rate of growth. Tumors of skull base may present with
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cranial nerve symptoms like diplopia, visual or hearing loss, olfactory sensations, or impaired swallowing function. [3]
2. Discussion 2.1. Osteosarcoma In a survey of the literature around 100 cases of primary osteosarcoma of the skull were found, including our cases. The occurrence of osteosarcoma in the craniofacial bones peaks in the third decade, where as that in the skeleton peaks in the second decade. The etiology of osteosarcoma is unknown, but the major risk factors for development of osteosarcoma in craniofacial bones may be similar to those of the long skeletal bones, consisting of exposure to radiation, retinoblastoma, Li–Fraumeni syndrome, and Paget’s disease. The skull is a favored site for osteosarcoma arising out of Paget’s disease. Other bone abnormalities, such as fibrous dysplasia, multiple osteochondromatosis, chronic osteomyelitis, myositis ossificans, and trauma, have also been proposed as risk factors [4]. Radiologically osteosarcomas commonly have osteolytic and osteosclerotic features, a cloudy pattern of mineralization either diffuse or in clusters, and illdefined borders. Radiating striations (sun-burst appearance) and Codman’s triangle are signs of periosteal reaction due to periosteal elevation [5]. These can be seen in periosteal osteosarcomas and intramedullary osteosarcomas with cortical extension, but not in paraosteal osteosarcomas. High grade surface osteosarcomas tend to have a more immature and basal pattern of mineralization. Paraosteal 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 [6]. The differential diagnosis of cranial osteosarcoma to be considered includes chondrosarcoma and osteochondroma. The CT findings of new bone formation in the soft tissue mass and the characteristic matrix strongly suggest osteogenic sarcoma, but differentiation from chondrosarcoma and osteochondroma cannot be made definitely without histology. Computed tomography in cases of chondrosarcoma of the base of skull shows similar changes, but once the calvarium undergoes membranous ossification, it becomes an unlikely site for cartilaginous tumors. Osteochondromas usually are sharply defined and homogenous indensity [7]. Pathologically the diagnosis of osteosarcoma is predicated on the accurate identification of osteoid. Histologically, osteoid is a dense, pink, amorphous intercellular material, which may appear somewhat refractile [8]. Surgery and chemotherapy have been recommended for the management of skull osteosarcoma [9]. The identification of prognostic factors has been an additive process in which factors have been investigated, identified and incorporated into an overall therapeutic strategy [10]. Traditionally, age, gender, location, tumor size, stage, and the results of various laboratory tests have been used in an effort to predict prognosis. However, response to pre-operative therapy is currently the most sensitive indicator of survival. At the same time, it is recognized that a single system does not apply to all cases. Unique biological aggressiveness, coupled with an inability to completely resect the tumor at certain sites (e.g., skull, spine) is one example (Figs. 1 and 2).
Fig. 1. (a) Coronal NCCT and (b) axial bone window settings of cranium showing a giant geographic sclerotic/lytic lesion involving parietal bone on left side with dense matrix mineralization (sunburst appearance) showing patchy central hypodense necrotic foci with gross mass effect over left cerebral hemisphere (parietal lobe) and large outer extracranial scalp portion. (c) H&E of chondroblastic osteosarcoma showing lobules of malignant-appearing cartilage with bone formation (arrow) in the center of the lobules.
2.2. Plasmacytoma Solitary intramedullary plasmacytoma (SIP), a sub-type of plasma cell tumors, is a malignant neoplasm that may occur as a primary focal entity or as the first presentation of systemic multiple myeloma. Plasma cell tumors are classified as either multiple myeloma (systemic), intramedullary plasmacytoma (involving bone), or extramedullary
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Fig. 2. (a) Axial CECT showing a large geographic sclerotic/lytic lesion involving occipital bone on right side with dense matrix mineralization (sunburst appearance) showing moderate contrast enhancement with gross mass effect over right cerebellar hemisphere. (b) Axial T2 weighted MR imaging showing hyperintense occipital bone mass with central hypointense linear sunburst pattern foci suggestive of calcifications associated with extra-axial signs like CSF cleft surrounding the mass and right cerebellar hemisphere gray white matter buckling. (c) Axial T1 weighted post contrast MR imaging showing intensely enhancing heterogenous occipital bone mass with central hypointense linear sunburst pattern foci suggestive of calcifications. (d) Sagittal CECT bone window settings showing a large geographic sclerotic/lytic lesion involving occipital bone on right side with dense matrix mineralization (sunburst appearance) with gross mass effect over right cerebellar hemisphere. (e) Saggital T1 weighted MR imaging revealed, with dense central linear calcific foci and a hemorrhagic focus (arrow). (f) H&E revealed high grade hyaline cartilage, which is intimately associated, and randomly mixed, with osteoid (arrow).
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Fig. 3. (a) Axial and (b) coronal CECT of brain showing a relatively well defined homogenously enhancing soft tissue density mass lesion with epicenter appearing to be involving greater wing of sphenoid and squamous part of temporal bone. Medially extension to extra conal part of lateral orbit with involvement of lateral rectus causing proptosis of right globe noted with optic canal extension and posterior ethmoidal sinus involvement noted. Extra-axial extension into middle/anterior cranial fossa and laterally into temporal fossa extension noted. (c) Axial CECT bone window settings revealed a large relatively well defined geographic lytic mass lesion with epicenter appeared to be involving greater wing of sphenoid and squamous part of temporal bone with medial sphenoid body extension. (d) FNA smear shows predominantly single cells (plasma cells) with round to oval eccentric nuclei and cartwheel chromatin appearance basophilic cytoplasm with perinuclear clear zone. Few binucleated cells are also seen (arrow) (May–Grunewald–Giemsa × Lp).
plasmacytoma (involving soft tissues). A significant percentage (up to 85%) of patients with solitary plasmacytoma will eventually develop disseminated multiple myeloma, if followed for a sufficient period of time [11]. Plasmacytomas are composed of a proliferation of abnormal plasma cells that exhibit monoclonal intracellular immunoglobulins with immunological staining techniques [12]. Solitary osseous plasmacytoma is characterized by osteolytic lesion and the presence of plasma cells in the biopsy [13]. On CT, SIPs have been reported as slightly high attenuation extra-axial masses that often demonstrate homogenous contrast enhancement, very similar to meningioma [14]. The MR appearance is either isointense, hyper-intense or heterogeneous intensity compared with the brain parenchyma on T1-weighted images and homogeneous enhancement by
intravenous administration of Gd DTPA [15]. Osteolytic lesion can usually be identified on X-ray film. The sharp borders, the lack of bony sclerosis and the paucity of periosteal reaction are characteristic findings of solitary plasmacytoma [16]. On angiography, SIPs are commonly hypervascular masses supplied by external carotid artery branches with prolonged capillary tumor stain that may also resemble meningioma [11]. Histologically, plasmacytomas are characterized by a diffuse or sheet-like proliferation of plasma cells with varying degrees of maturity and atypia. The nuclei are oval to round and eccentrically located with a dispersed (“clock-face”) nuclear chromatin pattern and a clear or halo area [17]. While meningiomas and hemangiopericytomas may resemble the imaging characteristics of plasmacytomas, the location of the tumor and the aggressive bone changes should raise other
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Fig. 4. Extra axial intra cranial extension of chordoma. (a) Saggital CECT and (b) saggital post contrast T1 weighted MR imaging shows ill defined geographic mass lesion diffusely involving clivus, showing intense enhancement on post contrast sequences, with extension to basilar artery cistern. (c) Low power view showing chords of tumor cells in a myxoid background with occasional cells displaying a bubbly cytoplasm. (d) High power view showing classic physaliphorous cell contain multiple intracytoplasmic bubbles [arrow].
possibilities such as plasmacytoma or metastatic disease. Other differential diagnosis list include Ewing sarcoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, bone langerhans cell histiocytosis, lymphoma leukemia, hyperparathyroidism/renal osteodystrophy, brown tumor and fibrosarcoma. Management of plasmacytoma of the skull base is complete removal of the tumor whenever possible, followed by radiation therapy [18] (Fig. 3). 2.3. Chordoma Chordoma is a low to intermediate grade malignant tumor that recapitulates notochord. Chordomas account for 1–4% of all primary malignant bone tumors. [19]. Chordoma occurs in the late middle age and most commonly arises in the sacrococcygeal (50–60%) or sphenooccipital regions (25–40%) [20]. The latter usually causes destruction of the clivus and spreads into the middle or posterior cranial fossa compressing the brainstem or the nasopharynx. CT demonstrates clearly the mass and the bony component of the tumor. MRI depicts better the extent of the lesion and its relation to the adjacent structures. On T1-weighted images
chordoma is iso- or hypointense and replaces the hyperintense clival fatty marrow. On T2-weighted images it is inhomogeneous and hyperintense. After the administration of contrast medium, chordoma shows heterogeneous enhancement. The differential diagnosis includes metastasis, craniopharyngioma, chondrosarcoma, pituitary tumors and nasopharyngeal carcinoma. Although they are similar in management, distinction between chordoma and chondrosarcoma is important due to different prognoses and outcomes. Chondroid chordoma has histological features of chondrosarcoma and chordoma [22]. Immunohistochemical study is helpful in which chordoma and chondroid chordoma are immunopositive for epithelial markers including cytokeratin and epithelial membrane antigen (EMA), where as chondrosarcoma is negative for both [26]. Chordomas are lobulated tumors, with individual lobules being separated by fibrous bands. The tumor cells are arranged in sheets, cords or float singly within an abundant myxoid stroma. They typically have an abundant pale vacuolated cytoplasm (the classic “physaliphorous cells”). They show mild to moderate nuclear atypia. In the chondroid variants, there are areas that may mimic hyaline or myxoid cartilage. Chordoma associated with a high grade
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is believed to provide some benefit, with a control rate of 60% in 5 years. Local recurrences are common, but systemic metastases are unusual [21] (Fig. 4).
2.4. Chondrosarcoma Chondrosarcoma of the skull base is rare and accounts for 6% of all skull base lesions and 0.1% of all head and neck tumors. Chondrosarcoma can be subclassified, in order of frequency, into the conventional (hyaline or myxoid), dedifferentiated, clear cell, and mesenchymal subtypes [22]. Radiologically they present as an area of lytic lesion with variably distributed punctate or ring-like matrix mineralization. MRI can be helpful in delineating the extent of the tumor and establishing the presence of soft tissue extension. CT scans aid in demonstrating matrix calcification. CHS shows abundant blue-gray cartilage matrix production. Irregularly shaped lobules of cartilage varying in size and shape are present. These lobules may be separated by fibrous bands or permeate bony trabeculae. The chondrocytes are atypical varying in size and shape and contain enlarged, hyperchromatic nuclei. Binucleation is frequently seen. The most important differential diagnosis for chondrosarcoma of the skull base is chordoma. Chordoma and chondrosarcoma have a similar radiological appearance. Typically, they are hypointense or isointense on T1 and hyperintense on T2, and frequently enhanced with gadolinium. Chondrosarcomas can periodically be distinguished from chordomas due to the occupation of a more lateral location along the petroclival fissure, while chordomas are typically located in the midline [26]. Treatment of chondrosarcoma includes careful pre-operative evaluation and surgical resection or radiotherapy, particularly carbon ion radiotherapy, which has been reported to achieve a better outcome than simple local control [23]. Other primary malignant skull tumors like Ewing’s sarcoma, malignant fibrous histiocytoma are extremely uncommon and these tumors represent very rare differential diagnosis of skull tumors. [3] While dealing with malignant skull tumors, metastatic tumors should be kept in mind. Most of these are calvarial circumscribed intraosseous tumors [24]. Source is hematogenous (most commonly breast, lung, prostate, kidney) or by direct extension (of squamous cell carcinoma) [25] (Fig. 5 and Table 1.).
Table 1 Radiological features of skull metastasis are [25].
Fig. 5. (a) Coronal T2 weighted MR imaging showing hyperintense bony mass involving sphenoid body predominantly with sella and extraaxial extension toward right medial temporal region with faint hypointense foci suggestive of calcification within the mass. (b) Moderate enhancement of the mass with bilateral internal carotid artery encasement (cavernous parts). Also showing perimesencephalic cisternal extension of the mass lesion at right side with mass effect over right side of mid brain. (c) High power view showing grade 2 chondrosarcoma characterized by hypercellularity, with pleomorphic cells, hyperchromasia and frequent binucleation [arrow].
sarcoma is called a “dedifferentiated” chordoma or sarcomatoid chordoma [19]. Treatment is primarily surgical. Incomplete resection is common due to adjacent vital structures and the infiltrative nature of the tumor. High-dose radiation therapy and photon-beam therapy
Imaging modality
Findings
Radiography
Focal lytic or blastic lesions lacking “benign” sclerotic border
CT
NCCT: May find hemorrhagic hyperdensity CECT: Enhancing mass centered in bone with osseous destruction, lacking ‘benign” sclerotic border. Most are lytic; a few sclerotic (e.g., prostate).
MR findings
TlWI: Hypointense marrow lesion. T2WI: Hyperintense marrow lesion; dura usually intact. T1 contrast: Lesion may enhance to “normal” T1 marrow signal; requires fat-saturation; with some dural thickening & enhancement.
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3. Conclusion In conclusion, primary malignant skull tumors are rare tumors, with very limited studies about its incidence and with varied presentation. With improvements in the diagnostic field, awareness will increase the knowledge about these tumors and can facilitate appropriate treatment planning, which may include a limited biopsy prior to considering more extensive skull surgery. Therefore, knowledge of the imaging spectrum is important because imaging plays a crucial role in the diagnosis and management of these patients. Authors’ contributions The author is involved in case collection and documentation. References [1] Desai S, Jambhekar N. Clinicopathological evaluation of metastatic carcinomas of bone: a retrospective analysis of 114 cases over 10 years. Indian Journal of Pathology and Microbiology 1995;38:49–54. [2] Ries LAG, Kosary CL, Hankey BF, et al. SEER cancer statistics review, 1973–1996. Bethesda, MD: National Cancer Institute; 1999. [3] Tonn J-C, Westphal M. Neuro-oncology of CNS tumors; 2006. Section 2, p. 75–7. [4] Ha PK, Eisele DW, Frassica FJ, et al. Osteosarcoma of the head and neck: a review of the Johns Hopkins experience. Laryngoscope 1999;109:964–9. [5] Ayala AG, Ro JY, Raymond AK. Bone tumors. In: Damjanov I, Linder J, editors. Anderson’s pathology. 10th ed. St. Louis: Mosby; 1996. p. 2531–73. [6] Mascarenhas L, Peteiro A, Ribeiro CA, et al. Skull osteosarcoma: illustrated review. Acta Neurochirurgica (Wien) 2004;146:1235–9. [7] Haque F, Fazal ST, Ahmad SA, et al. Primary osteosarcoma of the skull. Australasian Radiology 2006;50:63–5. [8] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 265 [Chapter 11]. [9] Okada K, Unni KK, Swee RG, et al. High grade surface osteosarcoma. A clinicopathologic study of 46 cases. Cancer 1999;85:1044–54.
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[10] Anon. Age and dose of chemotherapy as major prognostic factors in a trial of adjuvant therapy of osteosarcoma combining two alternating drug combinations and early prophylactic lung irradiation. French Bone Tumor Study Group. Cancer 1988;61:1304–11. [11] Meyer JR, Roychowdhury S, Cybulski G, et al. Solitary intramedullary plasmacytoma of the skull base mimicking aggressive meningioma. Skull Base Surgery 1997;7:101–5. [12] Ustuner Z, Basaran M, Bilgic B, et al. Skull base plasmacytoma in a patient with light chain myeloma. Skull Base 2003;13:161–71. [13] Rawlings NG, Browstein S, Robinson JW, et al. Solitary osseous plasmacytoma of the orbit with amyloidosis. Ophthalmic Plastic & Reconstructive Surgery 2007;23:79–80. [14] Marais J, Brookes GB, Lee CC. Solitary plasmacytoma of the skull base. The Annals of Otology, Rhinology, and Laryngology 1992;101:665–8. [15] Prasad ML, Mapapatra AK, Kumar L, et al. Solitary intracranial plasmacytoma of the skull base. Indian Journal of Cancer 1994;31:174–9. [16] Gross M, Eliashar R, Maly B, et al. Maxillary sinus plasmacytoma. Israel Medical Association Journal 2004:119–20. [17] Bindal AK, Bindal RK, van Loveren H, et al. Management of intracranial plasmacytoma. Journal of Neurosurgery 1995;83:218–21. [18] Woodruff RK, Malpas JS, White EE. Solitary plasmacytoma: II. Solitary plasmacytoma of bone. Cancer 1979;43:2344–7. [19] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 316–71 [Chapter 17]. [20] Murphy JM, Wallis F, Toland J, Toner M, Wilson JF. CT and MRI appearances of thoracic chordoma. European Radiology 1998;8:1677–9. [21] Vrionis FD, Kienstra MA, Rivera M, Padhya TA. Malignant tumors of the anterior skull base. Cancer Control 2004;11(May/June (3)). [22] Chu P-Y, Wei C-P, Tsai Y-F, Teng T-H, Lee C-C. Chondrosarcoma of the skull base – report of two cases. Tzu Chi Medical Journal 2006;18(3):229–31. [23] Fletcher CDM, Krishnan Unni K, Mertens F. World Health Organization classification of tumours. In: Pathology and genetics of tumours of soft tissue and bone; 2002. p. 247–50 [Chapter 10]. [24] Mitsuya K, Nakasu Y, Horiguchi S, et al. Metastatic skull tumors: MRI features and a new conventional classification. Journal of Neuro-Oncology 2011;104:239–45. [25] Osborn AG, Blaser SI, Salzman LK, et al. Diagnostic imaging brain; 2004. Part 2, Section 4, p. 80–2. [26] Almefty K, Pravdenkova S, Colli BO, et al. Chordoma and chondrosarcoma similar, but quite different, skull base tumors. Cancer 2007;110 (December (11)).