- Email: [email protected]
A Hemorrhagic Clival Chordoma with a Long Progression-Free Survival
Accepted Manuscript A hemorrhagic clival chordoma with a long progression free survival. Case report Marcelo D. Vilela, M.D., Hugo AS. Pedrosa, M.D., Marco Antonio Dias Filho, M.D. PII:
S1878-8750(17)31077-X
DOI:
10.1016/j.wneu.2017.06.169
Reference:
WNEU 6040
To appear in:
World Neurosurgery
Received Date: 25 May 2017 Revised Date:
24 June 2017
Accepted Date: 28 June 2017
Please cite this article as: Vilela MD, Pedrosa HA, Dias Filho MA, A hemorrhagic clival chordoma with a long progression free survival. Case report, World Neurosurgery (2017), doi: 10.1016/ j.wneu.2017.06.169. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT A hemorrhagic clival chordoma with a long progression free survival. Case report.
Marcelo D Vilela, M.D.1, 2, Hugo AS Pedrosa, M.D.1, Marco Antonio Dias Filho,
1
2
RI PT
M.D.3
Department of Neurosurgery, Mater Dei Hospital, Belo Horizonte, Brazil
Affiliate Assistant Professor, Department of Neurological Surgery, University of
3
SC
Washington, Seattle, WA
Neuropathologist, Laboratorio de Anatomia e Patologia Diagnostica, Belo Horizonte,
M AN U
Brazil
Corresponding author: Marcelo D Vilela, M.D
TE D
Department of Neurosurgery, Mater Dei Hospital, Belo Horizonte, Brazil Affiliate Assistant Professor, Department of Neurological Surgery, University of
Office address:
EP
Washington, Seattle, WA
AC C
Tenente Brito Melo 1215/5 andar. Belo Horizonte, MG, Brazil. 30180-070 Office phone number: 55-31-3568-6991 Email: [email protected] Keywords: Chordoma, Hemorrhage, Ecchordosis Physaliphora. Abbreviations: MRI – magnetic resonance imaging; CT – computerized tomography; EMA-Epithelial membrane antigen; EP- Ecchordosis physaliphora
ACCEPTED MANUSCRIPT Abstract Background: Chordomas and ecchordosis physaliphora may on rare occasions present with intracranial hemorrhage. Their distinction usually relies on the results of the Ki67 proliferative index, with a result lower than 1% favoring ecchordosis physaliphora. Intracranial hemorrhagic chordomas have been linked to unfavorable prognosis, due to
RI PT
acute neurological deterioration and death, or progression following treatment. To the best of our knowledge, this is the first report of an intracranial hemorrhagic chordoma who had a long progression free survival. Case description: A 67 year-old female presented with a large hemorrhagic clival tumor, which was resected through an
SC
endonasal endoscopic approach. Physallipharous cells interspersed in a myxoid matrix, positivity for S-100, Cytokeratin and Epithelial membrane antigen (EMA) were found,
M AN U
along with an extremely low Ki67 index. Imaging findings of bone erosion, a large size, and enhancement favored the diagnosis of chordoma. The patient received adjuvant stereotactic radiotherapy and has remained disease free after four years. Conclusions: Although hemorrhagic intracranial chordomas have been linked to unfavorable outcomes, our case demonstrates that they may have a low proliferative index and a
AC C
EP
TE D
long progression free survival may be seen.
ACCEPTED MANUSCRIPT Introduction
Chordomas and Ecchordosis physaliphora (EP) are lesions that arise from remnants of the notochord1 and both may rarely present with intracranial hemorrhage2,3. Clear cut
RI PT
differentiating features between these two entities are lacking and the diagnosis of ecchordosis is supported by a Ki67 index lower than 1% and lack of bone erosion and enhancement with Gadolinium, among other imaging features4.
Intracranial
hemorrhagic chordomas reported to date had a Ki67 index higher than 1%, due to their highly proliferative nature, and an unfavorable course either due to death or due to
SC
tumor progression following treatment3,5-10. Herein we present the case of a large clival hemorrhagic chordoma, with an extremely low Ki67 index, who had a long progression
M AN U
free survival, which we believe is the first report of such occurrence. Case report:
A 67 year old female presented with headache and dizziness after a minor fall. Her neurological examination was completely normal and there was no evidence of a CSF leak. A head CT scan demonstrated an erosive lesion arising from the clivus, with an
TE D
acute intratumoral hemorrhage (Figure 1). A head MRI demonstrated a clival lesion, hyperintense on T1 and T2-weighted images, with extension into the sphenoid sinus and the prepontine cistern, with enhancement (Figure 2). The lesion measured 2.7 x 2.1 x
EP
2.1 cm. Surgical removal was performed using an endonasal endoscopic approach, and the skull base defect was reconstructed with a vascularized nasoseptal flap. Histopathological examination demonstrated a lesion composed of cells with vacuolated
AC C
cytoplasm (physaliphorous cells) amid an abundant loose myxoid matrix. There was no necrosis and no hypercellularity.
Immunohistochemistry was positive for S100,
cytokeratin and EMA, and the MIB-1 labeling index was less than 1% (Figure 3). The neuropathologist confirmed a diagnosis of chordoma based on the combination of pathological and imaging findings. The patient was subsequently treated with conformational linac-based stereotactic radiotherapy. An MRI four years later demonstrated no evidence of recurrence (Figure 4).
Discussion
ACCEPTED MANUSCRIPT Chordomas and EP may rarely lead to intracranial hemorrhage
2,3,10,11
and their
distinction may become a challenge due to their pathological similarities, since both arise from remnants of the notochord. EP is usually a small (< 6cm3) gelatinous lesion, arising from a small, well delineated and midline clival bone defect
4,12
. No
enhancement and no major bony erosion are seen13. Occasionally, EP may rarely grow
RI PT
and become symptomatic14. Chordomas are seen as centrally located, expansive soft tissue masses, with lytic bone destruction and intratumoral calcification, and characteristically enhance with Gadolinium15.
Histologically, we observed in our patient the presence of physaliphorous cells along a
SC
myxoid matrix, findings that are usually seen in both chordomas and EP due to their same origin. Microscopically, chordomas may show destruction of bony trabeculae, from
field
to
field,
pleomorphism,
mitosis,
hypercellularity,
M AN U
variability
hyperchromatism, atypias and necrosis1. Tipically mitoses are absent in EP, indicating a low proliferative index and benign nature 1. In the immunohistochemistry panel, our case showed positivity for cytokeratins (e.g., AE1 and AE3), epithelial membrane antigen (EMA) and S-100, findings seen in chordomas as well as in EP 1,4. The MIB-1 index is characteristically less than 1% in EP4, while chordomas, due to their highly
TE D
proliferative nature, usually have a MIB-1 index higher than 1%16. Higher recurrence rates and growth potential have been linked to higher MIB-1 indexes in chordomas 16. In our case, while the immunohistochemical finding of a low Ki67 index would favor
EP
ecchordosis as the most likely diagnosis, but the radiological findings of large size, bone erosion, growth into the sphenoid sinus and enhancement with Gadolinium were more consistent with a chordoma. The diagnosis of chordoma, favored the addition of
AC C
postoperative stereotatic fractionated radiotherapy so as to achieve a better tumor control.
Intracranial hemorrhagic chordomas reported to date have had an unfavorable prognosis. While there are some reports of hemorrhagic chordomas without any detailed follow-up,
8,17,18
, many cases have evolved into fatal hemorrhages
cases reported had tumor progression following treatment
3,9,10,19
5-7
, and the other
. Only one case of
hemorrhagic chordoma with long term progression free survival has been reported, but the patient had a purely sphenoidal tumor, without any intracranial extension
20
. All
hemorrhagic intracranial chordomas reported to date, in which a Ki67 index was
ACCEPTED MANUSCRIPT measured, had a proliferative index above 1% 3,18. The finding of a low mitotic index in our case does not corroborate the theory that all hemorrhage cases may arise as a result of rapid tumor growth, as some have proposed
8,9,18
. Intratumoral hemorrhage in
chordomas has probably a distinct pathogenesis which leads to rupture of its vessels amid a loose tumoral matrix. Neovascularization, increased permeability, vessel
RI PT
fragility and spontaneous hemorrhage have been correlated with the overexpression of VEGF (vascular endothelial growth factor) in non-neoplastic as well as in neoplastic conditions such as animal glioblastoma models, metastatic brain tumors, pituitary adenomas and glioblastomas
21-26
vast majority of chordomas
27
. Adding the description that VEGF is found in the
SC
, we could speculate that its overexpression in some
tumors might be linked to intralesional hemorrhage due to an increased vessel fragility
M AN U
and permeability.
Conclusions: The mere presence of hemorrhage does not necessarily indicate aggressiveness in hemorrhagic chordomas, as they may have a very low Ki67
AC C
EP
TE D
proliferative index and a long term progression free survival may be seen.
ACCEPTED MANUSCRIPT Figure legends: Figure 1: A: Head CT scan showing a clival mass with evidence of acute intratumoral hemorrhage. B: head CT scan with bone windows showing erosion of the clivus. Figure 2: A: Axial T1 weighed image demonstrating a hyperintense/isointense lesion.
RI PT
B: Axial T1 weighed image with Gadolinium demonstrating enhancement of the isointense portion of the tumor.
Figure 3: A: H&E showing physaliphorous cells in a myxoid matrix. B:
SC
Immunostaining with Ki67 showing mitotic activity less than 1%.
Figure 4: A: Preoperative Sagittal T1-weighed image showing a large clival tumor. B: Postoperative Sagittal T1-weighed image showing absence of tumor four years after
AC C
EP
TE D
M AN U
surgery.
ACCEPTED MANUSCRIPT The authors state that they have no conflicts of interest.
RI PT
The patient has given consent for the submission of this case report.
References
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M AN U
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1. Macdonald RL, Deck JH. Immunohistochemistry of ecchordosis physaliphora and chordoma. Can J Neurol Sci 1990;17:420-3. 2. Alkan O, Yildirim T, Kizilkilic O, Tan M, Cekinmez M. A case of ecchordosis physaliphora presenting with an intratumoral hemorrhage. Turk Neurosurg 2009;19:293-6. 3. Vellutini Ede A, de Oliveira MF. Intradural chordoma presenting with intratumoral bleeding. J Clin Neurosci 2016;25:139-42. 4. Lagman C, Varshneya K, Sarmiento JM, Turtz AR, Chitale RV. Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora. Cureus 2016;8:e547. 5. Simonsen J. Fatal Subarachnoid Haemorrhage Originating in an Intracranial Chordoma. Acta Pathol Microbiol Scand 1963;59:13-20. 6. Koga N, Kadota Y, Hatashita S, et al. [A case of clivus chordoma showing hemorrhage in the posterior fossa]. No Shinkei Geka 1988;16:1417-21. 7. Franquemont DW, Katsetos CD, Ross GW. Fatal acute pontocerebellar hemorrhage due to an unsuspected spheno-occipital chordoma. Arch Pathol Lab Med 1989;113:1075-8. 8. Levi AD, Kucharczyk W, Lang AP, Schutz H. Clival chordoma presenting with acute brain stem hemorrhage. Can J Neurol Sci 1991;18:515-8. 9. Nakau R, Kamiyama H, Kazumata K, Andou M. Subarachnoid hemorrhage associated with clival chordoma--case report. Neurol Med Chir (Tokyo) 2003;43:605-7. 10. Uda T, Ohata K, Takami T, Hara M. An intradural skull base chordoma presenting with acute intratumoral hemorrhage. Neurol India 2006;54:306-7. 11. Fracasso T, Brinkmann B, Paulus W. Sudden death due to subarachnoid bleeding from ecchordosis physaliphora. Int J Legal Med 2008;122:225-7. 12. Park HH, Lee KS, Ahn SJ, Suh SH, Hong CK. Ecchordosis physaliphora: typical and atypical radiologic features. Neurosurg Rev 2017;40:87-94. 13. Toda H, Kondo A, Iwasaki K. Neuroradiological characteristics of ecchordosis physaliphora. Case report and review of the literature. J Neurosurg 1998;89:830-4. 14. Ling SS, Sader C, Robbins P, Rajan GP. A case of giant ecchordosis physaliphora: a case report and literature review. Otol Neurotol 2007;28:931-3. 15. Lanzino G, Dumont AS, Lopes MB, Laws ER, Jr. Skull base chordomas: overview of disease, management options, and outcome. Neurosurg Focus 2001;10:E12. 16. Matsuno A, Sasaki T, Nagashima T, et al. Immunohistochemical examination of proliferative potentials and the expression of cell cycle-related proteins of intracranial chordomas. Hum Pathol 1997;28:714-9. 17. Moore KA, Bohnstedt BN, Shah SU, et al. Intracranial chordoma presenting as acute hemorrhage in a child: Case report and literature review. Surg Neurol Int 2015;6:63. 18. Kim SK, Kim YH, Park CK, Kim MA, Park SH. Intracranial intradural chordoma presenting with intraventricular hemorrhage. Clin Neurol Neurosurg 2012;114:1189-92.
ACCEPTED MANUSCRIPT
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19. Warakaulle DR, Anslow P. A unique presentation of retroclival chordoma. J Postgrad Med 2002;48:285-7. 20. Kitai R, Yoshida K, Kubota T, et al. Clival chordoma manifesting as nasal bleeding. A case report. Neuroradiology 2005;47:368-71. 21. Jung S, Moon KS, Jung TY, et al. Possible pathophysiological role of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in metastatic brain tumorassociated intracerebral hemorrhage. J Neurooncol 2006;76:257-63. 22. Jin Kim Y, Hyun Kim C, Hwan Cheong J, Min Kim J. Relationship between expression of vascular endothelial growth factor and intratumoral hemorrhage in human pituitary adenomas. Tumori 2011;97:639-46. 23. Kaya B, Cicek O, Erdi F, et al. Intratumoral hemorrhage-related differences in the expression of vascular endothelial growth factor, basic fibroblast growth factor and thioredoxin reductase 1 in human glioblastoma. Mol Clin Oncol 2016;5:343-6. 24. Cheng SY, Nagane M, Huang HS, Cavenee WK. Intracerebral tumor-associated hemorrhage caused by overexpression of the vascular endothelial growth factor isoforms VEGF121 and VEGF165 but not VEGF189. Proc Natl Acad Sci U S A 1997;94:12081-7. 25. Cao R, Eriksson A, Kubo H, Alitalo K, Cao Y, Thyberg J. Comparative evaluation of FGF-2, VEGF-A-, and VEGF-C-induced angiogenesis, lymphangiogenesis, vascular fenestrations, and permeability. Circ Res 2004;94:664-70. 26. Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME. Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 2008;27:331-71. 27. Tauziede-Espariat A, Bresson D, Polivka M, et al. Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors. J Neuropathol Exp Neurol 2016;75:111-20.
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ACCEPTED MANUSCRIPT A large hemorrhagic clival chordoma with a long progression free survival. Case report
Highlights:
RI PT
Hemorrhagic chordomas are rare The distinction between hemorrhagic chordomas and hemorrhagic ecchordosis physaliphora may be challenging and has relied on the Ki67 index A low Ki67 index has not been reported previously in hemorrhagic chordomas
SC
Hemorrhagic chordomas have been linked to unfavorable prognosis
AC C
EP
TE D
M AN U
Our case is the first to document a low Ki67 index and a long progression free survival in a patient with a hemorrhagic chordoma
S1878-8750(17)31077-X
DOI:
10.1016/j.wneu.2017.06.169
Reference:
WNEU 6040
To appear in:
World Neurosurgery
Received Date: 25 May 2017 Revised Date:
24 June 2017
Accepted Date: 28 June 2017
Please cite this article as: Vilela MD, Pedrosa HA, Dias Filho MA, A hemorrhagic clival chordoma with a long progression free survival. Case report, World Neurosurgery (2017), doi: 10.1016/ j.wneu.2017.06.169. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT A hemorrhagic clival chordoma with a long progression free survival. Case report.
Marcelo D Vilela, M.D.1, 2, Hugo AS Pedrosa, M.D.1, Marco Antonio Dias Filho,
1
2
RI PT
M.D.3
Department of Neurosurgery, Mater Dei Hospital, Belo Horizonte, Brazil
Affiliate Assistant Professor, Department of Neurological Surgery, University of
3
SC
Washington, Seattle, WA
Neuropathologist, Laboratorio de Anatomia e Patologia Diagnostica, Belo Horizonte,
M AN U
Brazil
Corresponding author: Marcelo D Vilela, M.D
TE D
Department of Neurosurgery, Mater Dei Hospital, Belo Horizonte, Brazil Affiliate Assistant Professor, Department of Neurological Surgery, University of
Office address:
EP
Washington, Seattle, WA
AC C
Tenente Brito Melo 1215/5 andar. Belo Horizonte, MG, Brazil. 30180-070 Office phone number: 55-31-3568-6991 Email: [email protected] Keywords: Chordoma, Hemorrhage, Ecchordosis Physaliphora. Abbreviations: MRI – magnetic resonance imaging; CT – computerized tomography; EMA-Epithelial membrane antigen; EP- Ecchordosis physaliphora
ACCEPTED MANUSCRIPT Abstract Background: Chordomas and ecchordosis physaliphora may on rare occasions present with intracranial hemorrhage. Their distinction usually relies on the results of the Ki67 proliferative index, with a result lower than 1% favoring ecchordosis physaliphora. Intracranial hemorrhagic chordomas have been linked to unfavorable prognosis, due to
RI PT
acute neurological deterioration and death, or progression following treatment. To the best of our knowledge, this is the first report of an intracranial hemorrhagic chordoma who had a long progression free survival. Case description: A 67 year-old female presented with a large hemorrhagic clival tumor, which was resected through an
SC
endonasal endoscopic approach. Physallipharous cells interspersed in a myxoid matrix, positivity for S-100, Cytokeratin and Epithelial membrane antigen (EMA) were found,
M AN U
along with an extremely low Ki67 index. Imaging findings of bone erosion, a large size, and enhancement favored the diagnosis of chordoma. The patient received adjuvant stereotactic radiotherapy and has remained disease free after four years. Conclusions: Although hemorrhagic intracranial chordomas have been linked to unfavorable outcomes, our case demonstrates that they may have a low proliferative index and a
AC C
EP
TE D
long progression free survival may be seen.
ACCEPTED MANUSCRIPT Introduction
Chordomas and Ecchordosis physaliphora (EP) are lesions that arise from remnants of the notochord1 and both may rarely present with intracranial hemorrhage2,3. Clear cut
RI PT
differentiating features between these two entities are lacking and the diagnosis of ecchordosis is supported by a Ki67 index lower than 1% and lack of bone erosion and enhancement with Gadolinium, among other imaging features4.
Intracranial
hemorrhagic chordomas reported to date had a Ki67 index higher than 1%, due to their highly proliferative nature, and an unfavorable course either due to death or due to
SC
tumor progression following treatment3,5-10. Herein we present the case of a large clival hemorrhagic chordoma, with an extremely low Ki67 index, who had a long progression
M AN U
free survival, which we believe is the first report of such occurrence. Case report:
A 67 year old female presented with headache and dizziness after a minor fall. Her neurological examination was completely normal and there was no evidence of a CSF leak. A head CT scan demonstrated an erosive lesion arising from the clivus, with an
TE D
acute intratumoral hemorrhage (Figure 1). A head MRI demonstrated a clival lesion, hyperintense on T1 and T2-weighted images, with extension into the sphenoid sinus and the prepontine cistern, with enhancement (Figure 2). The lesion measured 2.7 x 2.1 x
EP
2.1 cm. Surgical removal was performed using an endonasal endoscopic approach, and the skull base defect was reconstructed with a vascularized nasoseptal flap. Histopathological examination demonstrated a lesion composed of cells with vacuolated
AC C
cytoplasm (physaliphorous cells) amid an abundant loose myxoid matrix. There was no necrosis and no hypercellularity.
Immunohistochemistry was positive for S100,
cytokeratin and EMA, and the MIB-1 labeling index was less than 1% (Figure 3). The neuropathologist confirmed a diagnosis of chordoma based on the combination of pathological and imaging findings. The patient was subsequently treated with conformational linac-based stereotactic radiotherapy. An MRI four years later demonstrated no evidence of recurrence (Figure 4).
Discussion
ACCEPTED MANUSCRIPT Chordomas and EP may rarely lead to intracranial hemorrhage
2,3,10,11
and their
distinction may become a challenge due to their pathological similarities, since both arise from remnants of the notochord. EP is usually a small (< 6cm3) gelatinous lesion, arising from a small, well delineated and midline clival bone defect
4,12
. No
enhancement and no major bony erosion are seen13. Occasionally, EP may rarely grow
RI PT
and become symptomatic14. Chordomas are seen as centrally located, expansive soft tissue masses, with lytic bone destruction and intratumoral calcification, and characteristically enhance with Gadolinium15.
Histologically, we observed in our patient the presence of physaliphorous cells along a
SC
myxoid matrix, findings that are usually seen in both chordomas and EP due to their same origin. Microscopically, chordomas may show destruction of bony trabeculae, from
field
to
field,
pleomorphism,
mitosis,
hypercellularity,
M AN U
variability
hyperchromatism, atypias and necrosis1. Tipically mitoses are absent in EP, indicating a low proliferative index and benign nature 1. In the immunohistochemistry panel, our case showed positivity for cytokeratins (e.g., AE1 and AE3), epithelial membrane antigen (EMA) and S-100, findings seen in chordomas as well as in EP 1,4. The MIB-1 index is characteristically less than 1% in EP4, while chordomas, due to their highly
TE D
proliferative nature, usually have a MIB-1 index higher than 1%16. Higher recurrence rates and growth potential have been linked to higher MIB-1 indexes in chordomas 16. In our case, while the immunohistochemical finding of a low Ki67 index would favor
EP
ecchordosis as the most likely diagnosis, but the radiological findings of large size, bone erosion, growth into the sphenoid sinus and enhancement with Gadolinium were more consistent with a chordoma. The diagnosis of chordoma, favored the addition of
AC C
postoperative stereotatic fractionated radiotherapy so as to achieve a better tumor control.
Intracranial hemorrhagic chordomas reported to date have had an unfavorable prognosis. While there are some reports of hemorrhagic chordomas without any detailed follow-up,
8,17,18
, many cases have evolved into fatal hemorrhages
cases reported had tumor progression following treatment
3,9,10,19
5-7
, and the other
. Only one case of
hemorrhagic chordoma with long term progression free survival has been reported, but the patient had a purely sphenoidal tumor, without any intracranial extension
20
. All
hemorrhagic intracranial chordomas reported to date, in which a Ki67 index was
ACCEPTED MANUSCRIPT measured, had a proliferative index above 1% 3,18. The finding of a low mitotic index in our case does not corroborate the theory that all hemorrhage cases may arise as a result of rapid tumor growth, as some have proposed
8,9,18
. Intratumoral hemorrhage in
chordomas has probably a distinct pathogenesis which leads to rupture of its vessels amid a loose tumoral matrix. Neovascularization, increased permeability, vessel
RI PT
fragility and spontaneous hemorrhage have been correlated with the overexpression of VEGF (vascular endothelial growth factor) in non-neoplastic as well as in neoplastic conditions such as animal glioblastoma models, metastatic brain tumors, pituitary adenomas and glioblastomas
21-26
vast majority of chordomas
27
. Adding the description that VEGF is found in the
SC
, we could speculate that its overexpression in some
tumors might be linked to intralesional hemorrhage due to an increased vessel fragility
M AN U
and permeability.
Conclusions: The mere presence of hemorrhage does not necessarily indicate aggressiveness in hemorrhagic chordomas, as they may have a very low Ki67
AC C
EP
TE D
proliferative index and a long term progression free survival may be seen.
ACCEPTED MANUSCRIPT Figure legends: Figure 1: A: Head CT scan showing a clival mass with evidence of acute intratumoral hemorrhage. B: head CT scan with bone windows showing erosion of the clivus. Figure 2: A: Axial T1 weighed image demonstrating a hyperintense/isointense lesion.
RI PT
B: Axial T1 weighed image with Gadolinium demonstrating enhancement of the isointense portion of the tumor.
Figure 3: A: H&E showing physaliphorous cells in a myxoid matrix. B:
SC
Immunostaining with Ki67 showing mitotic activity less than 1%.
Figure 4: A: Preoperative Sagittal T1-weighed image showing a large clival tumor. B: Postoperative Sagittal T1-weighed image showing absence of tumor four years after
AC C
EP
TE D
M AN U
surgery.
ACCEPTED MANUSCRIPT The authors state that they have no conflicts of interest.
RI PT
The patient has given consent for the submission of this case report.
References
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EP
TE D
M AN U
SC
1. Macdonald RL, Deck JH. Immunohistochemistry of ecchordosis physaliphora and chordoma. Can J Neurol Sci 1990;17:420-3. 2. Alkan O, Yildirim T, Kizilkilic O, Tan M, Cekinmez M. A case of ecchordosis physaliphora presenting with an intratumoral hemorrhage. Turk Neurosurg 2009;19:293-6. 3. Vellutini Ede A, de Oliveira MF. Intradural chordoma presenting with intratumoral bleeding. J Clin Neurosci 2016;25:139-42. 4. Lagman C, Varshneya K, Sarmiento JM, Turtz AR, Chitale RV. Proposed Diagnostic Criteria, Classification Schema, and Review of Literature of Notochord-Derived Ecchordosis Physaliphora. Cureus 2016;8:e547. 5. Simonsen J. Fatal Subarachnoid Haemorrhage Originating in an Intracranial Chordoma. Acta Pathol Microbiol Scand 1963;59:13-20. 6. Koga N, Kadota Y, Hatashita S, et al. [A case of clivus chordoma showing hemorrhage in the posterior fossa]. No Shinkei Geka 1988;16:1417-21. 7. Franquemont DW, Katsetos CD, Ross GW. Fatal acute pontocerebellar hemorrhage due to an unsuspected spheno-occipital chordoma. Arch Pathol Lab Med 1989;113:1075-8. 8. Levi AD, Kucharczyk W, Lang AP, Schutz H. Clival chordoma presenting with acute brain stem hemorrhage. Can J Neurol Sci 1991;18:515-8. 9. Nakau R, Kamiyama H, Kazumata K, Andou M. Subarachnoid hemorrhage associated with clival chordoma--case report. Neurol Med Chir (Tokyo) 2003;43:605-7. 10. Uda T, Ohata K, Takami T, Hara M. An intradural skull base chordoma presenting with acute intratumoral hemorrhage. Neurol India 2006;54:306-7. 11. Fracasso T, Brinkmann B, Paulus W. Sudden death due to subarachnoid bleeding from ecchordosis physaliphora. Int J Legal Med 2008;122:225-7. 12. Park HH, Lee KS, Ahn SJ, Suh SH, Hong CK. Ecchordosis physaliphora: typical and atypical radiologic features. Neurosurg Rev 2017;40:87-94. 13. Toda H, Kondo A, Iwasaki K. Neuroradiological characteristics of ecchordosis physaliphora. Case report and review of the literature. J Neurosurg 1998;89:830-4. 14. Ling SS, Sader C, Robbins P, Rajan GP. A case of giant ecchordosis physaliphora: a case report and literature review. Otol Neurotol 2007;28:931-3. 15. Lanzino G, Dumont AS, Lopes MB, Laws ER, Jr. Skull base chordomas: overview of disease, management options, and outcome. Neurosurg Focus 2001;10:E12. 16. Matsuno A, Sasaki T, Nagashima T, et al. Immunohistochemical examination of proliferative potentials and the expression of cell cycle-related proteins of intracranial chordomas. Hum Pathol 1997;28:714-9. 17. Moore KA, Bohnstedt BN, Shah SU, et al. Intracranial chordoma presenting as acute hemorrhage in a child: Case report and literature review. Surg Neurol Int 2015;6:63. 18. Kim SK, Kim YH, Park CK, Kim MA, Park SH. Intracranial intradural chordoma presenting with intraventricular hemorrhage. Clin Neurol Neurosurg 2012;114:1189-92.
ACCEPTED MANUSCRIPT
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ACCEPTED MANUSCRIPT A large hemorrhagic clival chordoma with a long progression free survival. Case report
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Hemorrhagic chordomas are rare The distinction between hemorrhagic chordomas and hemorrhagic ecchordosis physaliphora may be challenging and has relied on the Ki67 index A low Ki67 index has not been reported previously in hemorrhagic chordomas
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Hemorrhagic chordomas have been linked to unfavorable prognosis
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Our case is the first to document a low Ki67 index and a long progression free survival in a patient with a hemorrhagic chordoma