- Email: [email protected]
Primary High-Grade Osteosarcoma of the Clivus: A Case Report and Literature Review
Case Report
Primary High-Grade Osteosarcoma of the Clivus: A Case Report and Literature Review Mansour Mathkour1,2, Juanita Garces1,2, Bryce Beard 2, Angela Bartholomew1, Olawale A.R. Sulaiman1, Marcus L. Ware1
Key words Clival osteosarcoma - Endonasal transphenoidal approach - Primary high-grade osteosarcoma - Sellar osteosarcoma - Skull base osteosarcoma -
Abbreviations and Acronyms CT: Computed tomography From the 1Department of Neurosurgery, Ochsner Health System, New Orleans; and 2Department of Neurosurgery, Tulane Medical Center, New Orleans, Louisiana, USA To whom correspondence should be addressed: Mansour Mathkour, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 89:730.e9-730.e13. http://dx.doi.org/10.1016/j.wneu.2016.01.054 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
INTRODUCTION Osteosarcoma is the second most common primary bone malignancy of the skeletal system behind multiple myeloma.1 Head and neck osteosarcomas are rare, comprising only 6%e10% of osteosarcomas.2,3 Usually, osteosarcoma occurs in the metaphysis of long bones and presents in teenagers. In contrast, osteosarcoma of the craniofacial region tends to present in the third and fourth decades of life. Although osteosarcoma of long bones shows a male preponderance, males and females are affected equally by this tumor in craniofacial region.4 Craniofacial osteosarcomas are frequently the result of previous radiation therapy to the region or an underlying bone condition such as Paget disease or fibrous dysplasia.5 These cases are referred to as secondary osteosarcoma, whereas primary osteosarcomas occur de novo and are less frequently encountered. Regarding craniofacial osteosarcomas, the mandible is the most common site of
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- BACKGROUND:
Osteosarcoma is the second most common primary tumor of the skeletal system and the most common primary bone tumor. Usually occurring at the metaphysis of long bones, osteosarcomas are highly aggressive lesions that comprise osteoid-producing spindle cells. Craniofacial osteosarcomas comprise <8% and are believed to be less aggressive and lower grade. Primary osteosarcomas of the skull and skull base comprise <2% of all skull tumors. Osteosarcomas originating from the clivus are rare. We present a case of a primar, high-grade clival osteosarcoma.
- CASE
DESCRIPTION: A 29-year-old man presented to our institution with a progressively worsening right frontal headache for 3 weeks. There were no sensory or cranial nerve deficits. Computed tomography revealed a destructive mass involving the clivus with extension into the left sphenoid sinus. Magnetic resonance imaging revealed a homogenously enhancing lesion measuring 2.7 3 2.5 3 3.2 cm. The patient underwent endonasal transphenoidal surgery for gross total resection. The histopathologic analysis revealed proliferation of malignantappearing spindled and epithelioid cells with associated osteoclast-like giant cells and a small area of osteoid production. The analysis was consistent with high-grade osteosarcoma. The patient did well and was discharged on postoperative day 2. He was referred for adjuvant radiation therapy and chemotherapy. Two-year follow-up showed postoperative changes and clival expansion caused by packing material.
- CONCLUSIONS:
Osteosarcoma is a highly malignant neoplasm. These lesions are usually found in the extremities; however, they may rarely present in the craniofacial region. Clival osteosarcomas are relatively infrequent. We present a case of a primary clival osteosarcoma with high-grade pathology.
occurrence followed by the maxilla then the skull.6,7 Primary osteosarcomas of the skull are uncommon and most occur more frequently in the calvaria than the skull base. The clivus, made up of the basisphenoid and basiocciput, is a rare site for these tumors; it forms the anterior margin of the foramen magnum and the posterior portion of the central skull base.8 The sella turcica, containing the pituitary, lies anterior and superior to the clivus. Lesions of the clivus, particularly those in the upper segment, can involve the sella.9 Inversely, lesions of the sella are likely to involve the clivus as they expand. Presentation depends on location, with osteosarcomas of the mandible, maxilla, and calvarium frequently presenting with
mass and swelling.6 Osteosarcomas of the skull base and the clivus particularly present with headache and cranial nerve palsies.2,6,10 Visual disturbance and endocrinopathy can also occur depending on involvement of adjacent structures. Radiographically, osteosarcoma is defined by poorly defined areas of bone formation and destruction.11,12 Classically, osteosarcoma of the long bones reveals a typical sunburst pattern on plain radiography; however, this pattern is typically absent in lesions of the head and neck.6 Histologically, osteosarcoma is characterized by osteoid-producing spindle cells with destruction of boney and medullary architecture. There are also commonly areas of necrosis throughout
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CASE REPORT MANSOUR MATHKOUR ET AL.
these lesions.10,13 These lesions are subcategorized by their predominant histologic differentiation as osteoblastic, chondroblastic, or fibroblastic. Also, these neoplasms are further divided into high-, intermediate-, and low-grade lesions based on degree of cellular atypia and architectural distortion.6 Because they are highly aggressive, surgery is the mainstay of treatment for all osteosarcomas. Although osteosarcomas of the long bones tend to be highly malignant, craniofacial osteosarcomas are often less aggressive.14,15 There is no consensus on optimal therapy, and treatment usually consists of a combination of surgery, chemotherapy, and radiation.6 Herein, we describe an exceedingly rare case of primary high-grade osteosarcoma of the middle clivus extending into the left sphenoidal sinus. We also review the literature on primary clival osteosarcomas along with primary sellar osteosarcomas because of their close relationship with the upper clivus. CASE DESCRIPTION A 29-year-old man presented to the emergency department at our institution complaining of a progressively worsening right frontal headache for the previous 3 weeks. The headache was initially intermittent and without associated symptoms; however, on presentation, the pain was constant, worsening in severity, and associated with dizziness. On physical examination, he was alert and oriented to person, place, and time with normal strength and reflexes. There were no sensory or cranial nerve deficits. Initial laboratory tests, including a complete blood count and basic metabolic panel, were unremarkable. A computed tomography (CT) scan without contrast revealed a destructive mass with focal calcifications involving the clivus with extension into the left sphenoid sinus and possibly extending into the nasopharynx (Figure 1A and B). Magnetic resonance imaging with and without gadolinium contrast was performed, and it showed a large, expansile, homogenously enhancing lesion within the clivus corresponding to the lesion seen on CT scan. Its maximum measurement was 2.7 2.5 3.2 cm in the anterioposterior, transverse, and
HIGH-GRADE OS OF THE CLIVUS
Figure 1. Computed tomography scan. (A, B) Preoperative sagittal and coronal view, respectively, showing destructive mass with focal calcifications involving the clivus with extension into the left sphenoid sinus. (C, D) Postoperative sagittal and coronal view, respectively, at 2 years showing postoperative changes and clival expansion caused by packing material.
craniocaudal dimensions, respectively (Figure 2). There was cortical thinning and questionable dehiscence of the posterior wall of the clivus, as well as the inferior aspect of the sella. On the basis of the imaging findings, differential diagnosis at this time included chordoma, chondrosarcoma, plasmocytoma, or clival metastasis. CT with contrast of the chest, abdomen, and pelvis, performed in search of a primary or metastatic tumor, was negative. The patient opted for surgery to remove the tumor and determine its diagnosis. Endonasal transphenoidal resection of the tumor was performed. The tumor, which was also seen in the sphenoidal sinus and was bloody, was removed. Histopathologic analysis revealed the tumor to be a highgrade osteosarcoma supported by proliferation of obviously malignant-appearing spindled and epithelioid cells. There were associated osteoclast-like giant cells and small areas of osteoid production (Figure 3). The patient recovered well from surgery and was discharged on postoperative day 2 with no deficits. He was referred to radiation oncology and hematology for further treatment. A CT scan performed 2 years postoperatively
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revealed postoperative changes and clival expansion caused by packing material (Figure 1C and D). DISCUSSION In this case, we present a patient with a primary osteosarcoma involving the clivus and extending into the sphenoid sinus and nasopharnyx, which is an extremely rare location for this type of neoplasm. Tumors commonly seen arising from the clivus include chordomas, chondrosarcomas, and metastasis.8 Traditionally, the clivus is classified into upper, middle, and lower segments to help characterize surgical approaches. The upper clivus extends from the dorsum sellae to the porus of the abducens nerve. Then, the middle clivus is superiorly defined by the porus of the abducens nerve and inferiorly by the glossopharyngeal meatus. The lower clivus extends from the glossopharyngeal meatus to the anterior border of the foramen magnum.16 Anteriorly and superiorly adjacent to the upper clivus lies the sella turcica, which contains the pituitary. Lesions originating from the clivus, especially the upper clivus, may involve the sellar structures and vice versa. Our patient had osteosarcoma originating from the
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HIGH-GRADE OS OF THE CLIVUS
Figure 2. Magnetic resonance imaging with (left) and without (right) gadolinium contrast showing a large, expansile, homogenously enhancing lesion within the clivus.
middle clivus and extending into the sphenoid sinus. Magnetic resonance imaging revealed early involvement of the floor of the sella. Typically, mass lesions of the clivus present like other skull base osteosarcomas with headaches or cranial nerve palsies.5,17 Diplopia caused by involvement of the abducens nerves, which pass through the Dorello canals on the posterior surface of the clivus is a common
presentation.8 Because of the proximity of the clivus to the sella turcica, endocrinopathy may occur if the lesion involves the pituitary.8 We searched the available literature and were able to find only 3 previously reported cases of primary clival osteosarcomas.10,18,19 We then broadened our search to include primary osteosarcomas involving the sella as a result of the proximity of the sella to the clivus and the likelihood that
Figure 3. Hematoxylin-eosin staining. (A) Low-power view showing a tumor with osteoid production (arrow), (B) high-power magnification showing numerous cytologically malignant spindle cells (arrows), and (C) numerous osteoclast-like giant cells (arrows).
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such tumors likely involved the clivus even if not explicitly stated in the report. After broadening our search, we were able to include an additional 5 cases of primary sellar lesions involving the clivus (Table 1).11,12,15,20,27 Of the cases we found reporting clival osteosarcoma, none specified which segment or segments of the clivus were involved. Of the 9 cases of primary osteosarcoma of the region in question, including our case, the average age of presentation was 29.8 years (range, 14e56 years), which is typical of other case series reporting on primary craniofacial osteosarcomas.2,3,21 Six of the patients were male (66%) and 3 were female (33%). The most common presenting symptoms were headache (33%) and visual disturbances (33%). Less common presentations included dysphagia,10 epistaxis,15 and obesity.11 Sixth cranial nerve deficits are common in clival tumors. Sixth cranial nerve deficits were reported in 71% of cases in which we were able to find an account of the physical examination.10,12,19,20 Our patient did not show signs of cranial nerve involvement on physical examination, although he did report dizziness. It is possible that this subjective finding was diplopia caused by a mild sixth cranial nerve deficit that was undetectable on physical examination. Poorly defined areas of bone formation and destruction as well as periosteal changes are commonly seen on plain radiographs of osteosarcomas.11,12 CT can reveal destructive boney changes. It also reveals the extent of cortical and soft tissue involvement of the tumor. In addition, focal areas of calcification may also be seen on CT, as in our patient. On magnetic resonance imaging, osteosarcomas of the skull base enhance with contrast and are isointense on T1-weighted imaging and hypointense on T2-weighted imaging.11 Histologically, osteosarcomas show osteoid-producing spindle cells with intermittent areas of necrosis.13 Disruption of the intramedullary architecture and destruction of normal bone can be seen.10 Osteosarcomas are further classified into osteoblastic, chondroblastic, and fibroblastic subtypes. In head and neck osteosarcomas, the chondroblastic subtype occurs most frequently.22 Degree of malignancy is classified as low,
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Table 1. Past Reports of Skull Base Osteosarcoma Histology Reference
Sex/age, years
History and Physical Examination
Location
Type
Follow-Up
Recurrence
F/48
ND
ND
ND
Death at 6 days
ND
Reichenthal et al., 198112
M/22
L frontal headache, and Floor and anterior Bx, CXT, and XRT ND diplopia/bilateral clinoid process of sella abducens nerve palsy turcica
ND
19 months
No further deficit
Park et al., 199519
F/56
Headache, and visual disturbance/L lateral gaze limitation
Low
Fibroblastic
ND
ND
Geetha et al., 199811
M/38
Diplopia and obesity/ Sellar-suprasellar mass STR and CXT decreased visual acuity involving sphenoid sinus
ND
ND
1 year
Remission at 1 year
Kachhara et al., 199920 M/38
Diplopia/CN VI palsy
ND
ND
ND
ND
Uysal et al., 200115
M/17
Epistaxis/L CN VII palsy Nasal cavity, paranasal Sx-NOS, and XRT ND sinuses, and extending to clivus
Chondroblastic 46 months
None
Chennupati et al., 200710
F/14
Diplopia. dysphagia, and Clivus-NOS voice change/CN VI, X, XI, and XII palsy
Bx, CXT, and XRT High
ND
1 year
Remission with XRT at 1 year
Mohindra et al., 201418 M/55
ND
ND
ND
ND
ND
ND
Present study
Headache and dizziness Middle clivus extending GTR, XRT, and through sphenoid sinus CXT into nasopharynx
High
NR
3.5 years
None
Clivus-NOS
Sella and sphenoid sinus region
Clivus-NOS
STR
Grade
Kleinsasser et al., 195727
M/29
Sella
Treatment
Sx-NOS
GTR, CXT, and XRT
F, female; ND, no data; STR, subtotal resection; M, male; L, left; Bx, biopsy; CXT, chemotherapy; XRT, radiation therapy; NOS, not otherwise specified; Sx, surgery; CN, cranial nerve; GTR, gross total resection; NR, not reported.
intermediate, or high grade and is determined by extent of cellular atypia and architectural distortion. In 1 case series of craniofacial osteosarcomas,22 52% were intermediate grade, 44% were high grade, and 4% were low grade. Lowgrade osteosarcomas are typically found in older patients, whereas high-grade osteosarcomas are more commonly found in younger patients.19 In the cases that we found, grade and histologic subtype were underreported. Including our study, only 3 cases reported grade. Nonetheless, our review is consistent with the aforementioned relationship between age and grade. Our patient, who was 29 years age, had a high-grade neoplasm. Of the 2 other cases, 1 reported a high-grade lesion in a 14-year-old girl presenting with multibulbar palsies11 and 1 reported a lowgrade lesion in an older patient of 56 years.19 Surgery, chemotherapy, and radiation therapy are used singularly or in
combination for treatment of osteosarcoma. The principles of treatment of craniofacial osteosarcomas are the same as those in the limbs, although no consensus exists regarding an optimal regimen. Complete surgical excision is the treatment of choice and wide surgical margins have been associated with improved survival.21,23,24 Skull base osteosarcomas, especially in the clival or sellar regions, can be challenging to resect and an aggressive surgical approach can result in poor cosmetic outcome.4 Thus, skull base tumors have a poorer prognosis than mandibular or maxillary tumors.21,24 Of the cases we reviewed that reported treatment, 25% (2/8) were deemed inoperable.10,19 In both cases, the patients went into remission with chemotherapy and radiation therapy. Overall, craniofacial osteosarcomas are considered less aggressive than osteosarcomas found elsewhere in the body. At diagnosis, pulmonary micrometastases are
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found in nearly 80% of patients with extremity osteosarcoma.25 In contrast, metastasis occurs in less than 20% of craniofacial osteosarcomas.23,26 Thus, local recurrence, which is particularly problematic for skull base tumors, is the main source of treatment failure in craniofacial osteosarcomas. Neoadjuvant and adjuvant chemotherapy in combination with surgery have been shown to decrease local recurrence and improve survival in all osteosarcomas.23 Of cases reporting treatment modality in our review, all but 2 patients received chemotherapy, radiation therapy, or a combination of the 2. One patient who did not receive multimodality therapy presented before the chemotherapy era and died 6 days after presentation.27 In the other patient, follow-up and recurrence were not reported.19 A wide variety of chemotherapeutic agents are used for osteosarcomas, including methotrexate with leucovorin rescue,
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adriamycin, cisplatin, isosfamide, and cyclophosphamide.6 For incomplete or uncertain resection, radiation therapy has been shown to improve outcome; however, the incidence of treatmentassociated side effects is high with this modality and must be weighed against the possibility of local recurrence.28 Two cases in our review10,12 reported good local control and sustained remission for unresectable tumors using chemotherapy and radiation therapy. CONCLUSIONS Osteosarcoma is a highly malignant neoplasm. It is usually found in the extremities; however, it may rarely present in the craniofacial region. Clival osteosarcomas are infrequent. We searched for reports of osteosarcomas of the clivus and the sellar region. To the best of our knowledge, there are 3 previously published reports of primary osteosarcomas of the clivus in the literature. We found an additional 5 reports of osteosarcomas in the sellar region immediately adjacent to the clivus. We present a case of a primary clival osteosarcoma with high-grade pathology. Our review supports the notion that primary osteosarcomas in this region are typically less aggressive than osteosarcomas found elsewhere in the body; and although complete surgical resection is optimal treatment, sustained remission with chemotherapy and radiation of unresectable tumors in this region have been reported. REFERENCES 1. Anil S, Krishnan AP, Rajendran R. Osteosarcoma of the mandible masquerading as a dental abscess: report of a case. Case Rep Dent. 2012;2012: 635062. 2. Caron AS, Hajdu SI, Strong EW. Osteogenic sarcoma of the facial and cranial bones. A review of forty-three cases. Am J Surg. 1971;122:719-725.
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the head and neck in children: the St Jude Children’s Research Hospital experience. Cancer. 2000;88:2172-2180. 5. Erdem E, Angtuaco EC, Van Hemert R, Park JS, Al-Mefty O. Comprehensive review of intracranial chordoma. Radiographics. 2003;23:995-1009.
20. Kachhara R, Nair S, Sandhyamani S, Bhattacharya RN. Primary osteogenic sarcoma involving sella-sphenoid sinusecase report. Neurol Med Chir (Tokyo). 1999;39:534-538.
7. Vege DS, Borges AM, Aggrawal K, Balasubramaniam G, Parikh DM, Bhaser B. Osteosarcoma of the craniofacial bones. A clinicopathological study. J Craniomaxillofac Surg. 1991;19: 90-93.
21. Gadwal SR, Gannon FH, Fanburg-Smith JC, Becoskie EM, Thompson LD. Primary osteosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 22 cases with a review of the literature. Cancer. 2001;91:598-605.
8. Neelakantan A, Rana AK. Benign and malignant diseases of the clivus. Clin Radiol. 2014;69: 1295-1303.
22. Junior AT, de Abreu Alves F, Pinto CA, Carvalho AL, Kowalski LP, Lopes MA. Clinicopathological and immunohistochemical analysis of twenty-five head and neck osteosarcomas. Oral Oncol. 2003;39:521-530.
9. Koksel T, Crockard HA. “Clivus”: through the eyes of the transoral surgeon. Turk Neurosurg. 1990; 1:146-150. 10. Chennupati SK, Norris R, Dunham B, Kazahaya K. Osteosarcoma of the skull base: case report and review of literature. Int J Pediatr Otorhinolaryngol. 2008;72:115-119. 11. Geetha N, Kumar A, Ramachandran K, Abraham E, Joseph F. Osteosarcoma of the sella. Australas Radiol. 1999;43:517-519. 12. Reichenthal E, Cohen ML, Manor CR, Marshak G, Matz S, Shalit MN. Primary osteogenic sarcoma of the sellar region. Case report. J Neurosurg. 1981;55: 299-302.
23. Ha PK, Eisele DW, Frassica FJ, Zahurak ML, McCarthy EF. Osteosarcoma of the head and neck: a review of the Johns Hopkins experience. Laryngoscope. 1999;109:964-969. 24. Oda D, Bavisotto LM, Schmidt RA, McNutt M, Bruckner JD, Conrad EU 3rd, et al. Head and neck osteosarcoma at the University of Washington. Head Neck. 1997;19:513-523. 25. Jaffe N. Osteosarcoma: review of the past, impact on the future. The American experience. Cancer Treat Res. 2009;152:239-262.
13. Gorlick R, Khanna C. Osteosarcoma. J Bone Miner Res. 2010;25:683-691.
26. Mark RJ, Sercarz JA, Tran L, Dodd LG, Selch M, Calcaterra TC. Osteogenic sarcoma of the head and neck. The UCLA experience. Arch Otolaryngol Head Neck Surg. 1991;117:761-766.
14. Smeele LE, Kostense PJ, van der Waal I, Snow GB. Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients. J Clin Oncol. 1997;15:363-367.
27. Kleinsasser O, Albrecht H. Zur Kenntnis der Osteosarkome des Stirn- und Keilbeines. Archiv für Ohren-, Nasen- und Kehlkopfheilkunde. 1957;170: 595-603 [in German].
15. Uysal KM, Koyuncuoglu M, Akman F, Guneri A, Sarialioglu F, Kargi A, et al. A rare tumor of craniofacial bones in children: a pediatric chondroblastic osteosarcoma case with diagnostic and therapeutic problems. Pediatr Hematol Oncol. 2001; 18:147-152.
28. Guadagnolo BA, Zagars GK, Raymond AK, Benjamin RS, Sturgis EM. Osteosarcoma of the jaw/craniofacial region: outcomes after multimodality treatment. Cancer. 2009;115:3262-3270.
16. Funaki T, Matsushima T, Peris-Celda M, Valentine RJ, Joo W, Rhoton AL Jr. Focal transnasal approach to the upper, middle, and lower clivus. Neurosurgery. 2013;73:ons155-ons190 [discussion: ons190-ons191]. 17. Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012;13:e69-e76.
4. Daw NC, Mahmoud HH, Meyer WH, Jenkins JJ, Kaste SC, Poquette CA, et al. Bone sarcomas of
18. Mohindra S, Savardekar A, Mahalingam SS, Mohindra S, Vashista RK. Primary osteosarcoma
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19. Park YK, Yang MH, Choi WS, Lim YJ. Welldifferentiated, low-grade osteosarcoma of the clivus. Skeletal Radiol. 1995;24:386-388.
6. O’Neill JP, Bilsky MH, Kraus D. Head and neck sarcomas: epidemiology, pathology, and management. Neurosurg Clin N Am. 2013;24:67-78.
3. Garrington GE, Scofield HH, Cornyn J, Hooker SP. Osteosarcoma of the jaws. Analysis of 56 cases. Cancer. 1967;20:377-391.
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of clivus: a short report. Br J Neurosurg. 2014;28: 531-533.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 1 November 2015; accepted 19 January 2016 Citation: World Neurosurg. (2016) 89:730.e9-730.e13. http://dx.doi.org/10.1016/j.wneu.2016.01.054 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
WORLD NEUROSURGERY, http://dx.doi.org/10.1016/j.wneu.2016.01.054
Primary High-Grade Osteosarcoma of the Clivus: A Case Report and Literature Review Mansour Mathkour1,2, Juanita Garces1,2, Bryce Beard 2, Angela Bartholomew1, Olawale A.R. Sulaiman1, Marcus L. Ware1
Key words Clival osteosarcoma - Endonasal transphenoidal approach - Primary high-grade osteosarcoma - Sellar osteosarcoma - Skull base osteosarcoma -
Abbreviations and Acronyms CT: Computed tomography From the 1Department of Neurosurgery, Ochsner Health System, New Orleans; and 2Department of Neurosurgery, Tulane Medical Center, New Orleans, Louisiana, USA To whom correspondence should be addressed: Mansour Mathkour, M.D. [E-mail: [email protected]] Citation: World Neurosurg. (2016) 89:730.e9-730.e13. http://dx.doi.org/10.1016/j.wneu.2016.01.054 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
INTRODUCTION Osteosarcoma is the second most common primary bone malignancy of the skeletal system behind multiple myeloma.1 Head and neck osteosarcomas are rare, comprising only 6%e10% of osteosarcomas.2,3 Usually, osteosarcoma occurs in the metaphysis of long bones and presents in teenagers. In contrast, osteosarcoma of the craniofacial region tends to present in the third and fourth decades of life. Although osteosarcoma of long bones shows a male preponderance, males and females are affected equally by this tumor in craniofacial region.4 Craniofacial osteosarcomas are frequently the result of previous radiation therapy to the region or an underlying bone condition such as Paget disease or fibrous dysplasia.5 These cases are referred to as secondary osteosarcoma, whereas primary osteosarcomas occur de novo and are less frequently encountered. Regarding craniofacial osteosarcomas, the mandible is the most common site of
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- BACKGROUND:
Osteosarcoma is the second most common primary tumor of the skeletal system and the most common primary bone tumor. Usually occurring at the metaphysis of long bones, osteosarcomas are highly aggressive lesions that comprise osteoid-producing spindle cells. Craniofacial osteosarcomas comprise <8% and are believed to be less aggressive and lower grade. Primary osteosarcomas of the skull and skull base comprise <2% of all skull tumors. Osteosarcomas originating from the clivus are rare. We present a case of a primar, high-grade clival osteosarcoma.
- CASE
DESCRIPTION: A 29-year-old man presented to our institution with a progressively worsening right frontal headache for 3 weeks. There were no sensory or cranial nerve deficits. Computed tomography revealed a destructive mass involving the clivus with extension into the left sphenoid sinus. Magnetic resonance imaging revealed a homogenously enhancing lesion measuring 2.7 3 2.5 3 3.2 cm. The patient underwent endonasal transphenoidal surgery for gross total resection. The histopathologic analysis revealed proliferation of malignantappearing spindled and epithelioid cells with associated osteoclast-like giant cells and a small area of osteoid production. The analysis was consistent with high-grade osteosarcoma. The patient did well and was discharged on postoperative day 2. He was referred for adjuvant radiation therapy and chemotherapy. Two-year follow-up showed postoperative changes and clival expansion caused by packing material.
- CONCLUSIONS:
Osteosarcoma is a highly malignant neoplasm. These lesions are usually found in the extremities; however, they may rarely present in the craniofacial region. Clival osteosarcomas are relatively infrequent. We present a case of a primary clival osteosarcoma with high-grade pathology.
occurrence followed by the maxilla then the skull.6,7 Primary osteosarcomas of the skull are uncommon and most occur more frequently in the calvaria than the skull base. The clivus, made up of the basisphenoid and basiocciput, is a rare site for these tumors; it forms the anterior margin of the foramen magnum and the posterior portion of the central skull base.8 The sella turcica, containing the pituitary, lies anterior and superior to the clivus. Lesions of the clivus, particularly those in the upper segment, can involve the sella.9 Inversely, lesions of the sella are likely to involve the clivus as they expand. Presentation depends on location, with osteosarcomas of the mandible, maxilla, and calvarium frequently presenting with
mass and swelling.6 Osteosarcomas of the skull base and the clivus particularly present with headache and cranial nerve palsies.2,6,10 Visual disturbance and endocrinopathy can also occur depending on involvement of adjacent structures. Radiographically, osteosarcoma is defined by poorly defined areas of bone formation and destruction.11,12 Classically, osteosarcoma of the long bones reveals a typical sunburst pattern on plain radiography; however, this pattern is typically absent in lesions of the head and neck.6 Histologically, osteosarcoma is characterized by osteoid-producing spindle cells with destruction of boney and medullary architecture. There are also commonly areas of necrosis throughout
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these lesions.10,13 These lesions are subcategorized by their predominant histologic differentiation as osteoblastic, chondroblastic, or fibroblastic. Also, these neoplasms are further divided into high-, intermediate-, and low-grade lesions based on degree of cellular atypia and architectural distortion.6 Because they are highly aggressive, surgery is the mainstay of treatment for all osteosarcomas. Although osteosarcomas of the long bones tend to be highly malignant, craniofacial osteosarcomas are often less aggressive.14,15 There is no consensus on optimal therapy, and treatment usually consists of a combination of surgery, chemotherapy, and radiation.6 Herein, we describe an exceedingly rare case of primary high-grade osteosarcoma of the middle clivus extending into the left sphenoidal sinus. We also review the literature on primary clival osteosarcomas along with primary sellar osteosarcomas because of their close relationship with the upper clivus. CASE DESCRIPTION A 29-year-old man presented to the emergency department at our institution complaining of a progressively worsening right frontal headache for the previous 3 weeks. The headache was initially intermittent and without associated symptoms; however, on presentation, the pain was constant, worsening in severity, and associated with dizziness. On physical examination, he was alert and oriented to person, place, and time with normal strength and reflexes. There were no sensory or cranial nerve deficits. Initial laboratory tests, including a complete blood count and basic metabolic panel, were unremarkable. A computed tomography (CT) scan without contrast revealed a destructive mass with focal calcifications involving the clivus with extension into the left sphenoid sinus and possibly extending into the nasopharynx (Figure 1A and B). Magnetic resonance imaging with and without gadolinium contrast was performed, and it showed a large, expansile, homogenously enhancing lesion within the clivus corresponding to the lesion seen on CT scan. Its maximum measurement was 2.7 2.5 3.2 cm in the anterioposterior, transverse, and
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Figure 1. Computed tomography scan. (A, B) Preoperative sagittal and coronal view, respectively, showing destructive mass with focal calcifications involving the clivus with extension into the left sphenoid sinus. (C, D) Postoperative sagittal and coronal view, respectively, at 2 years showing postoperative changes and clival expansion caused by packing material.
craniocaudal dimensions, respectively (Figure 2). There was cortical thinning and questionable dehiscence of the posterior wall of the clivus, as well as the inferior aspect of the sella. On the basis of the imaging findings, differential diagnosis at this time included chordoma, chondrosarcoma, plasmocytoma, or clival metastasis. CT with contrast of the chest, abdomen, and pelvis, performed in search of a primary or metastatic tumor, was negative. The patient opted for surgery to remove the tumor and determine its diagnosis. Endonasal transphenoidal resection of the tumor was performed. The tumor, which was also seen in the sphenoidal sinus and was bloody, was removed. Histopathologic analysis revealed the tumor to be a highgrade osteosarcoma supported by proliferation of obviously malignant-appearing spindled and epithelioid cells. There were associated osteoclast-like giant cells and small areas of osteoid production (Figure 3). The patient recovered well from surgery and was discharged on postoperative day 2 with no deficits. He was referred to radiation oncology and hematology for further treatment. A CT scan performed 2 years postoperatively
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revealed postoperative changes and clival expansion caused by packing material (Figure 1C and D). DISCUSSION In this case, we present a patient with a primary osteosarcoma involving the clivus and extending into the sphenoid sinus and nasopharnyx, which is an extremely rare location for this type of neoplasm. Tumors commonly seen arising from the clivus include chordomas, chondrosarcomas, and metastasis.8 Traditionally, the clivus is classified into upper, middle, and lower segments to help characterize surgical approaches. The upper clivus extends from the dorsum sellae to the porus of the abducens nerve. Then, the middle clivus is superiorly defined by the porus of the abducens nerve and inferiorly by the glossopharyngeal meatus. The lower clivus extends from the glossopharyngeal meatus to the anterior border of the foramen magnum.16 Anteriorly and superiorly adjacent to the upper clivus lies the sella turcica, which contains the pituitary. Lesions originating from the clivus, especially the upper clivus, may involve the sellar structures and vice versa. Our patient had osteosarcoma originating from the
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Figure 2. Magnetic resonance imaging with (left) and without (right) gadolinium contrast showing a large, expansile, homogenously enhancing lesion within the clivus.
middle clivus and extending into the sphenoid sinus. Magnetic resonance imaging revealed early involvement of the floor of the sella. Typically, mass lesions of the clivus present like other skull base osteosarcomas with headaches or cranial nerve palsies.5,17 Diplopia caused by involvement of the abducens nerves, which pass through the Dorello canals on the posterior surface of the clivus is a common
presentation.8 Because of the proximity of the clivus to the sella turcica, endocrinopathy may occur if the lesion involves the pituitary.8 We searched the available literature and were able to find only 3 previously reported cases of primary clival osteosarcomas.10,18,19 We then broadened our search to include primary osteosarcomas involving the sella as a result of the proximity of the sella to the clivus and the likelihood that
Figure 3. Hematoxylin-eosin staining. (A) Low-power view showing a tumor with osteoid production (arrow), (B) high-power magnification showing numerous cytologically malignant spindle cells (arrows), and (C) numerous osteoclast-like giant cells (arrows).
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such tumors likely involved the clivus even if not explicitly stated in the report. After broadening our search, we were able to include an additional 5 cases of primary sellar lesions involving the clivus (Table 1).11,12,15,20,27 Of the cases we found reporting clival osteosarcoma, none specified which segment or segments of the clivus were involved. Of the 9 cases of primary osteosarcoma of the region in question, including our case, the average age of presentation was 29.8 years (range, 14e56 years), which is typical of other case series reporting on primary craniofacial osteosarcomas.2,3,21 Six of the patients were male (66%) and 3 were female (33%). The most common presenting symptoms were headache (33%) and visual disturbances (33%). Less common presentations included dysphagia,10 epistaxis,15 and obesity.11 Sixth cranial nerve deficits are common in clival tumors. Sixth cranial nerve deficits were reported in 71% of cases in which we were able to find an account of the physical examination.10,12,19,20 Our patient did not show signs of cranial nerve involvement on physical examination, although he did report dizziness. It is possible that this subjective finding was diplopia caused by a mild sixth cranial nerve deficit that was undetectable on physical examination. Poorly defined areas of bone formation and destruction as well as periosteal changes are commonly seen on plain radiographs of osteosarcomas.11,12 CT can reveal destructive boney changes. It also reveals the extent of cortical and soft tissue involvement of the tumor. In addition, focal areas of calcification may also be seen on CT, as in our patient. On magnetic resonance imaging, osteosarcomas of the skull base enhance with contrast and are isointense on T1-weighted imaging and hypointense on T2-weighted imaging.11 Histologically, osteosarcomas show osteoid-producing spindle cells with intermittent areas of necrosis.13 Disruption of the intramedullary architecture and destruction of normal bone can be seen.10 Osteosarcomas are further classified into osteoblastic, chondroblastic, and fibroblastic subtypes. In head and neck osteosarcomas, the chondroblastic subtype occurs most frequently.22 Degree of malignancy is classified as low,
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Table 1. Past Reports of Skull Base Osteosarcoma Histology Reference
Sex/age, years
History and Physical Examination
Location
Type
Follow-Up
Recurrence
F/48
ND
ND
ND
Death at 6 days
ND
Reichenthal et al., 198112
M/22
L frontal headache, and Floor and anterior Bx, CXT, and XRT ND diplopia/bilateral clinoid process of sella abducens nerve palsy turcica
ND
19 months
No further deficit
Park et al., 199519
F/56
Headache, and visual disturbance/L lateral gaze limitation
Low
Fibroblastic
ND
ND
Geetha et al., 199811
M/38
Diplopia and obesity/ Sellar-suprasellar mass STR and CXT decreased visual acuity involving sphenoid sinus
ND
ND
1 year
Remission at 1 year
Kachhara et al., 199920 M/38
Diplopia/CN VI palsy
ND
ND
ND
ND
Uysal et al., 200115
M/17
Epistaxis/L CN VII palsy Nasal cavity, paranasal Sx-NOS, and XRT ND sinuses, and extending to clivus
Chondroblastic 46 months
None
Chennupati et al., 200710
F/14
Diplopia. dysphagia, and Clivus-NOS voice change/CN VI, X, XI, and XII palsy
Bx, CXT, and XRT High
ND
1 year
Remission with XRT at 1 year
Mohindra et al., 201418 M/55
ND
ND
ND
ND
ND
ND
Present study
Headache and dizziness Middle clivus extending GTR, XRT, and through sphenoid sinus CXT into nasopharynx
High
NR
3.5 years
None
Clivus-NOS
Sella and sphenoid sinus region
Clivus-NOS
STR
Grade
Kleinsasser et al., 195727
M/29
Sella
Treatment
Sx-NOS
GTR, CXT, and XRT
F, female; ND, no data; STR, subtotal resection; M, male; L, left; Bx, biopsy; CXT, chemotherapy; XRT, radiation therapy; NOS, not otherwise specified; Sx, surgery; CN, cranial nerve; GTR, gross total resection; NR, not reported.
intermediate, or high grade and is determined by extent of cellular atypia and architectural distortion. In 1 case series of craniofacial osteosarcomas,22 52% were intermediate grade, 44% were high grade, and 4% were low grade. Lowgrade osteosarcomas are typically found in older patients, whereas high-grade osteosarcomas are more commonly found in younger patients.19 In the cases that we found, grade and histologic subtype were underreported. Including our study, only 3 cases reported grade. Nonetheless, our review is consistent with the aforementioned relationship between age and grade. Our patient, who was 29 years age, had a high-grade neoplasm. Of the 2 other cases, 1 reported a high-grade lesion in a 14-year-old girl presenting with multibulbar palsies11 and 1 reported a lowgrade lesion in an older patient of 56 years.19 Surgery, chemotherapy, and radiation therapy are used singularly or in
combination for treatment of osteosarcoma. The principles of treatment of craniofacial osteosarcomas are the same as those in the limbs, although no consensus exists regarding an optimal regimen. Complete surgical excision is the treatment of choice and wide surgical margins have been associated with improved survival.21,23,24 Skull base osteosarcomas, especially in the clival or sellar regions, can be challenging to resect and an aggressive surgical approach can result in poor cosmetic outcome.4 Thus, skull base tumors have a poorer prognosis than mandibular or maxillary tumors.21,24 Of the cases we reviewed that reported treatment, 25% (2/8) were deemed inoperable.10,19 In both cases, the patients went into remission with chemotherapy and radiation therapy. Overall, craniofacial osteosarcomas are considered less aggressive than osteosarcomas found elsewhere in the body. At diagnosis, pulmonary micrometastases are
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found in nearly 80% of patients with extremity osteosarcoma.25 In contrast, metastasis occurs in less than 20% of craniofacial osteosarcomas.23,26 Thus, local recurrence, which is particularly problematic for skull base tumors, is the main source of treatment failure in craniofacial osteosarcomas. Neoadjuvant and adjuvant chemotherapy in combination with surgery have been shown to decrease local recurrence and improve survival in all osteosarcomas.23 Of cases reporting treatment modality in our review, all but 2 patients received chemotherapy, radiation therapy, or a combination of the 2. One patient who did not receive multimodality therapy presented before the chemotherapy era and died 6 days after presentation.27 In the other patient, follow-up and recurrence were not reported.19 A wide variety of chemotherapeutic agents are used for osteosarcomas, including methotrexate with leucovorin rescue,
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adriamycin, cisplatin, isosfamide, and cyclophosphamide.6 For incomplete or uncertain resection, radiation therapy has been shown to improve outcome; however, the incidence of treatmentassociated side effects is high with this modality and must be weighed against the possibility of local recurrence.28 Two cases in our review10,12 reported good local control and sustained remission for unresectable tumors using chemotherapy and radiation therapy. CONCLUSIONS Osteosarcoma is a highly malignant neoplasm. It is usually found in the extremities; however, it may rarely present in the craniofacial region. Clival osteosarcomas are infrequent. We searched for reports of osteosarcomas of the clivus and the sellar region. To the best of our knowledge, there are 3 previously published reports of primary osteosarcomas of the clivus in the literature. We found an additional 5 reports of osteosarcomas in the sellar region immediately adjacent to the clivus. We present a case of a primary clival osteosarcoma with high-grade pathology. Our review supports the notion that primary osteosarcomas in this region are typically less aggressive than osteosarcomas found elsewhere in the body; and although complete surgical resection is optimal treatment, sustained remission with chemotherapy and radiation of unresectable tumors in this region have been reported. REFERENCES 1. Anil S, Krishnan AP, Rajendran R. Osteosarcoma of the mandible masquerading as a dental abscess: report of a case. Case Rep Dent. 2012;2012: 635062. 2. Caron AS, Hajdu SI, Strong EW. Osteogenic sarcoma of the facial and cranial bones. A review of forty-three cases. Am J Surg. 1971;122:719-725.
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the head and neck in children: the St Jude Children’s Research Hospital experience. Cancer. 2000;88:2172-2180. 5. Erdem E, Angtuaco EC, Van Hemert R, Park JS, Al-Mefty O. Comprehensive review of intracranial chordoma. Radiographics. 2003;23:995-1009.
20. Kachhara R, Nair S, Sandhyamani S, Bhattacharya RN. Primary osteogenic sarcoma involving sella-sphenoid sinusecase report. Neurol Med Chir (Tokyo). 1999;39:534-538.
7. Vege DS, Borges AM, Aggrawal K, Balasubramaniam G, Parikh DM, Bhaser B. Osteosarcoma of the craniofacial bones. A clinicopathological study. J Craniomaxillofac Surg. 1991;19: 90-93.
21. Gadwal SR, Gannon FH, Fanburg-Smith JC, Becoskie EM, Thompson LD. Primary osteosarcoma of the head and neck in pediatric patients: a clinicopathologic study of 22 cases with a review of the literature. Cancer. 2001;91:598-605.
8. Neelakantan A, Rana AK. Benign and malignant diseases of the clivus. Clin Radiol. 2014;69: 1295-1303.
22. Junior AT, de Abreu Alves F, Pinto CA, Carvalho AL, Kowalski LP, Lopes MA. Clinicopathological and immunohistochemical analysis of twenty-five head and neck osteosarcomas. Oral Oncol. 2003;39:521-530.
9. Koksel T, Crockard HA. “Clivus”: through the eyes of the transoral surgeon. Turk Neurosurg. 1990; 1:146-150. 10. Chennupati SK, Norris R, Dunham B, Kazahaya K. Osteosarcoma of the skull base: case report and review of literature. Int J Pediatr Otorhinolaryngol. 2008;72:115-119. 11. Geetha N, Kumar A, Ramachandran K, Abraham E, Joseph F. Osteosarcoma of the sella. Australas Radiol. 1999;43:517-519. 12. Reichenthal E, Cohen ML, Manor CR, Marshak G, Matz S, Shalit MN. Primary osteogenic sarcoma of the sellar region. Case report. J Neurosurg. 1981;55: 299-302.
23. Ha PK, Eisele DW, Frassica FJ, Zahurak ML, McCarthy EF. Osteosarcoma of the head and neck: a review of the Johns Hopkins experience. Laryngoscope. 1999;109:964-969. 24. Oda D, Bavisotto LM, Schmidt RA, McNutt M, Bruckner JD, Conrad EU 3rd, et al. Head and neck osteosarcoma at the University of Washington. Head Neck. 1997;19:513-523. 25. Jaffe N. Osteosarcoma: review of the past, impact on the future. The American experience. Cancer Treat Res. 2009;152:239-262.
13. Gorlick R, Khanna C. Osteosarcoma. J Bone Miner Res. 2010;25:683-691.
26. Mark RJ, Sercarz JA, Tran L, Dodd LG, Selch M, Calcaterra TC. Osteogenic sarcoma of the head and neck. The UCLA experience. Arch Otolaryngol Head Neck Surg. 1991;117:761-766.
14. Smeele LE, Kostense PJ, van der Waal I, Snow GB. Effect of chemotherapy on survival of craniofacial osteosarcoma: a systematic review of 201 patients. J Clin Oncol. 1997;15:363-367.
27. Kleinsasser O, Albrecht H. Zur Kenntnis der Osteosarkome des Stirn- und Keilbeines. Archiv für Ohren-, Nasen- und Kehlkopfheilkunde. 1957;170: 595-603 [in German].
15. Uysal KM, Koyuncuoglu M, Akman F, Guneri A, Sarialioglu F, Kargi A, et al. A rare tumor of craniofacial bones in children: a pediatric chondroblastic osteosarcoma case with diagnostic and therapeutic problems. Pediatr Hematol Oncol. 2001; 18:147-152.
28. Guadagnolo BA, Zagars GK, Raymond AK, Benjamin RS, Sturgis EM. Osteosarcoma of the jaw/craniofacial region: outcomes after multimodality treatment. Cancer. 2009;115:3262-3270.
16. Funaki T, Matsushima T, Peris-Celda M, Valentine RJ, Joo W, Rhoton AL Jr. Focal transnasal approach to the upper, middle, and lower clivus. Neurosurgery. 2013;73:ons155-ons190 [discussion: ons190-ons191]. 17. Walcott BP, Nahed BV, Mohyeldin A, Coumans JV, Kahle KT, Ferreira MJ. Chordoma: current concepts, management, and future directions. Lancet Oncol. 2012;13:e69-e76.
4. Daw NC, Mahmoud HH, Meyer WH, Jenkins JJ, Kaste SC, Poquette CA, et al. Bone sarcomas of
18. Mohindra S, Savardekar A, Mahalingam SS, Mohindra S, Vashista RK. Primary osteosarcoma
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19. Park YK, Yang MH, Choi WS, Lim YJ. Welldifferentiated, low-grade osteosarcoma of the clivus. Skeletal Radiol. 1995;24:386-388.
6. O’Neill JP, Bilsky MH, Kraus D. Head and neck sarcomas: epidemiology, pathology, and management. Neurosurg Clin N Am. 2013;24:67-78.
3. Garrington GE, Scofield HH, Cornyn J, Hooker SP. Osteosarcoma of the jaws. Analysis of 56 cases. Cancer. 1967;20:377-391.
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of clivus: a short report. Br J Neurosurg. 2014;28: 531-533.
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Received 1 November 2015; accepted 19 January 2016 Citation: World Neurosurg. (2016) 89:730.e9-730.e13. http://dx.doi.org/10.1016/j.wneu.2016.01.054 Journal homepage: www.WORLDNEUROSURGERY.org Available online: www.sciencedirect.com 1878-8750/$ - see front matter ª 2016 Elsevier Inc. All rights reserved.
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