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Hemangiopericytomas in the central nervous system
Journal of Clinical Neuroscience 16 (2009) 519–523
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Hemangiopericytomas in the central nervous system Wei Wu a, Ji-xin Shi a,*, Hui-lin Cheng a, Han-dong Wang a, Chun-hua Hang a, Qun-Li Shi b, Hong-xia Yin a a b
Department of Neurosurgery, Jinling Hospital, 305 East Zhongshan Road, Second Military Medical University, Nanjing 210002, Jiangsu Province, China Department of Pathology, Jinling Hospital, Second Military Medical University, Nanjing, Jiangsu Province, China
a r t i c l e
i n f o
Article history: Received 23 January 2008 Accepted 24 June 2008
Keywords: Hemangiopericytoma Meningioma Clinical features Pathology Radiology Treatment
a b s t r a c t Hemangiopericytomas, which are more aggressive than meningiomas, are rare in the central nervous system (CNS). We analyzed the clinical, radiological and histological features and treatment of 26 patients with hemangiopericytomas in the CNS. The ratio of male to female patients was 1:1. Most tumors were located in the parasagittal and falx regions. The tumors were dense or mixed as assessed by CT scans, and most were homogeneously enhanced. Most tumors were isointense on T1-weighted MRI, and high or mixed intensity on T2-weighted MRI; they were homogeneously or heterogeneously enhanced. Histological examination indicated numerous small vascular spaces in the tumor. All tumors were immunohistochemically positive for vimentin. All patients were treated with surgery, and some of them underwent subsequent radiotherapy. The recurrence rate for hemangiopericytoma in this study was high. Our observations suggest that the biological behavior of hemangiopericytoma differs markedly from that of meningioma. Surgical removal and post-operative radiotherapy are thus critical for the treatment of this tumor. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Hemangiopericytomas are rare tumors thought to be derived from pericytes, the cells surrounding capillaries and postcapillary venules. They can occur anywhere in the human body because pericytes are ubiquitous in all types of mesenchymal tissue. However, most hemangiopericytomas are found in the musculoskeletal system and skin.1,2 Hemangiopericytomas in the central nervous system (CNS) are rare, and they account for less than 1% of all CNS tumors.3,4 The histogenesis of CNS hemangiopericytoma has been a matter of controversy. These tumors were once thought to be either soft tissue tumors2 or an aggressive variant of angioblastic meningioma.5 According to the current World Health Organization (WHO) classification of CNS tumors, hemangiopericytoma has its own entity within the ‘‘mesenchymal, non-meningothelial tumor” group. It exhibits different clinical behaviors, immunohistochemical characteristics, and ultrastructural features than meningioma.6 However, hemangiopericytomas resemble meningomas on imaging, and this leads to frequent misdiagnosis. Because hemangiopericytomas are believed to be more aggressive than meningomas and to have a propensity for both local recurrence and extraneural metastases, correct diagnosis and treatments are critical.
* Corresponding author. Tel.: +86 25 80860071; fax: +86 25 84817581. E-mail address: [email protected] (J.-x. Shi). 0967-5868/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2008.06.011
We analyzed the clinicopathological features, clinicoradiological features, and therapeutic outcomes of 26 patients with hemangiopericytomas in the CNS.
2. Patients and methods A total of 32 patients with hemangiopericytomas in the CNS were treated in our department between 1984 and 2005, but only 26 patients were included in this study because the data were incomplete for the rest. Biopsy tumor specimens from all patients were re-examined by an experienced neuropathologist. We also carried out immunohistochemical staining for vimentin (Vim), epithelial membrane antigen (EMA), CD34, and glial fibrillary acidic protein (GFAP). Tumor specimens from four patients were further examined by electron microscopy. All available clinical, surgical, and radiological data (including CT scans, MRI, and angiograms) were reviewed from the patients’ hospital records, in particular the surgical notes to determine the extent of the tumor removal.7 Plain and post-contrast CT scans were performed, and 23 patients had MRI examinations (T1-weighted, T2-weighted, and contrastenhanced T1-weighted studies). Only four patients underwent pre-operative cerebral angiography. Tumors were said to have reoccurred after surgical removal if: (i) CT scans or MRI examinations had detected a new tumor; or (ii) the tumor had increased in size (if the surgery had removed only part of the tumor), regardless of the presence or absence of symptoms or signs.
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W. Wu et al. / Journal of Clinical Neuroscience 16 (2009) 519–523
Three patients were lost to follow-up. The median follow-up time for the remaining 23 patients was 12 years (range 1–23 years).
3. Results Patient characteristics, including epidemiological, clinical, and radiological data, operative findings, additional treatments, and follow-up, are summarized in Table 1. 3.1. Clinical data The group of 26 patients with hemangiopericytoma in the CNS was composed of 13 men (50.0%) and 13 women (50.0%). The age at diagnosis ranged from 28 to 71 years, with an average of 46 years. 3.2. Tumor location Among the 26 patients, 23 had intracranial meningeal hemangiopericytomas, and three had spinal meningeal hemangiopericy-
tomas. Most intracranial meningeal hemangiopericytomas were supratentorial and located in the frontoparietal region. Three tumors were located at the tentorium and extended to both the supratentorial and infratentorial compartments. There were four tumors located in the middle cranial base and one in the paracavernous sinus. In three patients the lesions were located in the sellar, suprasellar or parasellar areas. 3.3. Clinical symptoms The most frequent symptoms in these patients were headache and dizziness. Most patients had symptoms of intracranial hypertension and suffered from visual deficits. Other frequent symptoms included focal motor deficits, and patients with tumors in the spinal cord frequently presented with paralysis. 3.4. Radiological studies The tumors were hyperdense or mixed-density on plain CT scans and enhanced homogeneously or heterogeneously following intravenous contrast injection. No calcification was observed. The tumors were mainly isointense on T1-weighted MRI and isointense
Table 1 Patient clinical data, treatment, and final outcomes No.
Age (y)
Sex
Tumor localization
Presenting symptoms
Symptoms at diagnosis
Degree of resection
Radiotherapy
Followup (y)
Recurrence
Metastasis
Survival
1 2 3
40 33 71
F F M
Dizziness Headaches Headaches
Hemiparesis Monoparesis Hemiparesis
CR CR SR
Yes Yes Unknown
3 6
No No Unknown
No No Unknown
Alive Alive Unavailable
4
52
M
Parasagittal Tentorium Falxtentorium Tentorium
Visual deficit
SR
No
9
Alive
38 55 33 65
M M F F
CR SR CR SR
No Yes No No
4 4 4 4
No No No No
Alive Alive Alive Alive
9 10
41 28
F M
Dizziness Headaches
Monoparesis, dysaudia Hemiparesis Intracranial hypertension Visual deficit and intracranial hypertension Hemiparesis Intracranial hypertension
SR SR
Yes No
5 8
No No
Alive Alive
11
46
F
Headaches
Visual deficit
SR
Yes
4
Yes (after 5 y, S+Rad) No No No Yes (after 2 y, S+Rad) No Yes (after 5 y, S+Rad) No
No
5 6 7 8
Dizziness and headaches Headaches Headaches Headaches Headaches
No
Alive
12 13
38 48
M F
Unknown No
Unknown No
Unavailable Alive
14
38
3 y,
No
Dead
15
2 y,
No
Alive
10
No
Alive
5 y,
No
Alive Dead
Headaches Headaches
Hemiparesis Visual deficit
CR CR
Unknown Yes
3
F
Tentorium Parasagittal Falx Sellar and suprasellar Parasagittal Falxtentorium Middle fossa base Falx Sellar and suprasellar Falx
Headaches
Monoparesis
SR
No
8
44
F
Falx
Headaches
Intracranial hypertension
SR
Yes
3
16
34
M
Falx
Headaches
Coma
SR
No
14
17
42
M
SR
No
6
56
F
Dizziness and headaches Headaches
Hemiparesis
18
Visual deficit
SR
Yes
22
19 20 21
59 62 38
M M F
22
34
F
23
53
M
Falxtentorium Middle fossa base Parasellar Parasagittal Middle fossa base Middle fossa base Paracavernous
Yes (after S+Rad) Yes (after S+Rad) Yes (after y, S+Rad) Yes (after S+Rad) Yesa
24 25
60 48
M F
C6 to T2 T10
26
42
M
C4-5
Epilepsy Dizziness Dizziness and headaches Headaches
Epilepsy Hemiparesis Intracranial hypertension
CR SR CR
No Yes No
4 5 3
No No No
Yes (after 19 y) No No No
Numbness in face
SR
Yes
3
No
No
Alive
Headaches
Visual deficit
SR
No
17
No
Alive
Pain in the leg Numbness in limbs Numbness in limbs
Paralysis Hemiparesis
SR SR
No Unknown
23
Yes (after 12 y, S+Rad) Yesb Unknown
No Unknown
Alive Unavailable
Paralysis
SR
No
5
Yes (after 3 y, S)
No
Alive
Alive Alive Alive
C = cervical segment, CR = complete resection, F = female, M = male, Rad = radiotherapy, S = surgical treatment, SR = subtotal resection, T = thoracic segment, y = years. a This patient had two recurrences, the first 17 y after surgery and radiotherapy, and the second 2 y after radiotherapy. b This patient had three recurrences, the first 8 y after surgery, the second 8 y after a second surgery, and the third 1 y after a third surgery and radiotherapy.
W. Wu et al. / Journal of Clinical Neuroscience 16 (2009) 519–523
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(or showed slightly higher signals) on T2-weighted MRI. No ‘‘dural tail” sign was observed (Figs 1 and 2). Four patients underwent pre-operative cerebral angiography. Radiological examinations showed that these tumors had both a meningeal-dural and a cortical-pial blood supply. Only one of the 26 patients was diagnosed as having a meningeal hemangiopericytoma by pre-operative imaging studies. The other 25 patients were all diagnosed as having meningomas. Thus, the misdiagnosis rate from imaging techniques was 96.2%. 3.5. Surgical treatments Radical excision was performed in 26 patients (as Simpson grades I and II). In each patient, no tumor was detectable in an imaging examination immediately after surgery. Most tumors had clear margins with the peripheral tissues, and some appeared to have capsules. The tumors were slightly soft with an abundant blood supply. In 13 patients, excision of the tumor caused brisk bleeding, including 3000 mL of blood in one patient. The tumors had apparent dural attachments in most cases. All patients survived surgery; thus, the operative mortality rate was zero. 3.6. Pathological studies Macroscopically, the excised tumors appeared grayish-pink in color and were prominently vascular. Some tumors had capsules, which looked like fish meat and had a tenacious texture. Microscopic examination revealed numerous small vascular spaces in the tumors. Characteristic ‘‘staghorn” vascular channels were also seen. These channels were distributed radially and were surrounded by haphazardly arranged round and oval tumor cells (Supplementary Fig. 1) that showed indistinct cytoplasmic borders
Fig. 2. CT and MRI of a 65-y-old female (patient 8). (A) The brain CT scan showed a mass in the sellar and suprasellar areas. (B) The coronal T1-weighted MRI showed an isointense mass in the sellar and suprasellar areas with (D) homogeneous enhancement. (C) The coronal T2-weighted MRI showed a mixed-intensity mass.
and had fusiform nuclei. Staining for argyrophilic fibers showed that they surrounded single tumor cells and were distributed radially around the vessels. Immunohistochemical staining revealed that all tumors were negative for S-100 protein, EMA, and GFAP but were positive for Vim (Supplementary Fig. 1). Only one tumor stained positive for CD34. Electron microscopy revealed many bundles of 10 nm intermediate filaments in the tumor cells, which contained electron-lucent cytoplasm with few organelles, numerous micropinocytotic vesicles, and subplasmalemmal linear densities. Poorly developed intercellular junctions were present between interdigitating cytoplasmic processes. The tumor cells surrounding the vascular units displayed a continuous basement membrane as well as all the features of well-differentiated pericytes. Some tumor cells that were distant from vascular structures showed focally discontinuous basement membranes. 3.7. Follow-up Of the 26 patients, 10 were treated with external radiotherapy after surgery, and of the 23 patients followed after surgery, 11 developed local recurrences after the initial surgery at an average interval of 6.5 years (range 2–17 years). Thus, the recurrence rate was 47.8%. The one-year survival rate was 100%.
4. Discussion
Fig. 1. CT and MRI scans of a 34-year-old male (patient 16). (A) The brain CT scan showed a large lobulated parieto-occipital mass. (B) The coronal T1-weighted MRI showed a midline and mixed-intensity mass with an irregular border. (C) The axial T2-weighted MRI showed a mixed-intensity mass. (D) The axial contrast-enhanced T1-weighted MRI showed that the mass was heterogeneously enhanced.
Hemangiopericytomas in the CNS were once regarded as a type of meningioma because (i) their initial clinical and radiological presentations do not differ substantially from various types of meningioma, and (ii) their surgical management resembles that of meningiomas.8 However, the current WHO classification of CNS
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tumors distinguishes hemangiopericytomas as an entity in the group of ‘‘mesenchymal, non-meningothelial tumors” that may have special histological origins. It is now widely accepted that these tumors arise from meningeal capillary pericytes. Their high recurrence rates and tendency to metastasize also distinguish their clinical course from that of most meningioma patients and make the management of hemangiopericytomas a challenging multidisciplinary task. Epidemiologically, some characteristics differ between hemangiopericytoma and meningioma. Unlike meningiomas, hemangiopericytomas may be more common in males than in females. A male to female ratio of 1.1:1 to 1.5:1 is reported.9–12 The ratio in the present study (1:1) is slightly lower. In addition, the mean age of diagnosis of hemangiopericytoma is younger than that of meningiomas.9–11 In our study, the mean age at diagnosis was 46, which falls within the previously reported range. Although about 10% of hemangiopericytomas occur in childhood, no children were diagnosed with hemangiopericytomas in our department during this study. Meningeal hemangiopericytomas and meningiomas occur in similar regions of the brain, such as the orbit,13–17 lateral ventricles,18–21 third ventricles,22 sellar and suprasellar areas,23,24 the optic nerve sheath,25 and the skull base.26,27 In addition to those supratentorial locations, the tumor may also localize to infratentorial regions such as the cerebellopontine angle and spinal meninges.28–36 In the present study, the most common location for hemangiopericytoma was the frontoparietal region. It is extremely difficult to differentially diagnose hemangiopericytomas and meningiomas on the basis of their clinical symptoms and radiological examinations. Patients with hemangiopericytomas may have many unusual symptoms.37–45 Consistent with our observations, the CT scans reveal these tumors to be generally heterogeneous, dense, and dural-based lesions.10,11,40,41 They are usually misdiagnosed as meningiomas before surgery. Hence, histological examination is essential for reliable diagnosis. In the present study, only 1 out of 26 patients was diagnosed correctly as having a hemangiopericytoma on the basis of clinical symptoms and brain imaging. Our low diagnosis rate is consistent with previous observations.9,12,42–45 Our histological diagnosis of hemangiopericytoma was further confirmed by immunohistochemical staining with a Vim antibody, which is specific to mesenchymal tissue. These tumors could be distinguished by Vim immunostaining because hemangiopericytomas, but not meningiomas, are derived from the mesenchymal tissue of the external layer of the basement membrane of blood vessels.1–4 Some features may help differentiate hemangiopericytomas from meningiomas: (i) the former do not commonly calcify; (ii) the former tend to show irregular or lobulated borders, apparent parenchymal invasion, and more heterogeneous contrast enhancement than meningiomas, consistent with their aggressive behavior; (iii) bone erosion can sometimes be found in patients with hemangiopericytomas; and (iv) a narrow dural attachment suggests a diagnosis of hemangiopericytoma rather than meningioma. Surgical removal is the major effective treatment for hemangiopericytoma. The excision should be as complete as possible to reduce the chances of recurrence or metastasis. Because the tumors exhibit high vascularity, however, the excision of hemangiopericytomas is very challenging since it may lead to substantial blood loss. The average amount of blood lost during surgery is reported to be as high as 1000 mL.11,12 Some authors report the use of pre-operative embolization to reduce blood loss during surgery.12,46 However, the use of microsurgical techniques can reduce operative mortality and morbidity. In the present study, there were no deaths during surgery. Radiotherapy is believed necessary for hemangiopericytoma patients after surgery. Stereotactic radiosurgery has been used as a
major treatment for patients with a high surgical risk.3,47 However, despite the beneficial effects of radiotherapy, hemangiopericytomas tend to recur locally. In the present study, we treated 10 patients with external radiotherapy after surgery. Radiotherapy seemed to reduce the recurrence rate of hemangiopericytomas after surgery. Further analyses are underway to evaluate the efficacy of radiotherapy in the management of hemangiopericytoma and meningioma patients. The one-year survival rate of the patients in our cohort was 100%, and the overall recurrence rate was 47.8%; both values are consistent with previous reports.10,12 The high recurrence rate reflects the aggressive behavior of hemangiopericytomas. The survival rates were not statistically analysed because there were too few patients at any specific follow-up time. In conclusion, although hemangiopericytomas are difficult to distinguish from meningiomas on the basis of clinical expression and brain imaging, they are more aggressive and require different management. Appropriate treatments include surgical excision of the tumor and post-operative radiotherapy. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2008.06.011.
References 1. Horten BC, Urich H, Rubinstein LJ, et al. The angioblastic meningioma: a reappraisal of the nosological problem. Light-, electron-microscopic, tissue, and organ culture observations. J Neurol Sci 1977;31:387–410. 2. Stout AP, Murray MR. Hemangiopericytoma: a vascular tumor featuring Zimmerman’s pericytes. Ann Surg 1942;116:26–33. 3. Bastin KT, Mehta MP. Meningeal hemangiopericytoma: defining the role for radiation therapy. J Neurooncol 1992;14:277–87. 4. Goellner JR, Laws Jr ER, Soule EH, et al. Hemangiopericytoma of the meninges. Mayo clinic experience. Am J Clin Pathol 1978;70:375–80. 5. Begg CF, Garret R. Hemangiopericytoma occurring in the meninges: case report. Cancer 1954;7:602–6. 6. Kleihues P, Burger PC, Scheithauer BW. World Health Organization International Histological Classification of Tumours: Histological Typing of Tumours of the Central Nervous System. Tokyo: Springer; 1991. 7. Simpson D. The recurrence of intracranial meningiomas after surgical treatment. J Neurol Neurosurg Psychiatry 1957;20:22–39. 8. Combs SE, Thilmann C, Debus J, et al. Precision radiotherapy for hemangiopericytomas of the central nervous system. Cancer 2005;104:2457–65. 9. Brunori A, Delitala A, Oddi G, et al. Recent experience in the management of meningeal hemangiopericytomas. Tumori 1997;83:856–61. 10. Guthrie BL, Ebersold MJ, Scheithauer BW, et al. Meningeal hemangiopericytoma: histopathological features, treatment, and long-term follow-up of 44 cases. Neurosurgery 1989;25:514–22. 11. Jaaskelainen J, Servo A, Haltia M, et al. Intracranial hemangiopericytoma: radiology, surgery, radiotherapy, and outcome in 21 patients. Surg Neurol 1985;23:227–36. 12. Fountas KN, Kapsalaki E, Kassam M, et al. Management of intracranial meningeal hemangiopericytomas: Outcome and experience. Neurosurg Rev 2006;29:145–53. 13. McGarity T. Ultrasound findings in a patient with primary orbital hemangiopericytoma. J Ark Med Soc 2002;98:412–3. 14. Tsai CC, Kau HC, Chen SJ, et al. Primary orbital hemangiopericytoma: a case report. Zhonghua Yi Xue Za Zhi (Taipei) 1997;59:382–5. 15. Fu ER, Goh SH, Fong CM. Case report of primary orbital hemangiopericytoma. Ann Acad Med Singapore 1993;22:966–8. 16. Abe M, Hara Y, Ohnishi Y, et al. Case of primary orbital hemangiopericytoma. Jpn J Ophthalmol 1983;27:90–5. 17. Henderson JW, Farrow GM. Primary orbital hemangiopericytoma. An aggressive and potentially malignant neoplasm. Arch Ophthalmol 1978;96:666–73. 18. Hattingen E, Pilatus U, Good C, et al. An unusual intraventricular haemangiopericytoma: MRI and spectroscopy. Neuroradiology 2003;45:386–9. 19. Al-Brahim N, Devilliers R, Provias J. Intraventricular hemangiopericytoma. Ann Diagn Pathol 2004;8:347–51. 20. McDonald JV. Intraventricular hemangiopericytoma. J Neurosurg 1999;91:167. 21. Muttaqin Z, Uozumi T, Kuwabara S, et al. Intraventricular hemangiopericytoma - case report. Neurol Med Chir (Tokyo) 1991;31:662–5. 22. Abrahams JM, Forman MS, Lavi E, et al. Hemangiopericytoma of the third ventricle. Case report. J Neurosurg 1999;90:359–62.
W. Wu et al. / Journal of Clinical Neuroscience 16 (2009) 519–523 23. Mena H, Ribas JL, Pezeshkpour GH, et al. Hemangiopericytoma of the central nervous system: a review of 94 cases. Hum Pathol 1991;22:84–91. 24. Morrison DA, Bibby K. Sellar and suprasellar hemangiopericytoma mimicking pituitary adenoma. Arch Ophthalmol 1997;115:1201–3. 25. Boniuk M, Messmer EP, Font RL. Hemangiopericytoma of the meninges of the optic nerve. A clinicopathologic report including electron microscopic observations. Ophthalmology 1985;92:1780–7. 26. Comacchio F, D’Eredita R, Poletto E, et al. Hemangiopericytoma of the skull base and collet-sicard syndrome: a case report. Ear Nose Throat J 1995;74:845–7. 27. Abdel-Fattah HM, Adams GL, Wick MR. Hemangiopericytoma of the maxillary sinus and skull base. Head Neck 1990;12:77–83. 28. Brass SD, Guiot MC, Albrecht S, et al. Metastatic hemangiopericytoma presenting as an epidural spinal cord lesion. Can J Neurol Sci 2004;31:550–3. 29. Mohammadianpanah M, Torabinejad S, Bagheri MH, et al. Primary epidural malignant hemangiopericytoma of thoracic spinal column causing cord compression: Case report. Sao Paulo Med J 2004;122:220–2. 30. Woitzik J, Sommer C, Krauss JK. Delayed manifestation of spinal metastasis: a special feature of hemangiopericytoma. Clin Neurol Neurosurg 2003;105:159–66. 31. Radley MG, McDonald JV. Meningeal hemangiopericytoma of the posterior fossa and thoracic spinal epidural space. Case report. Neurosurgery 1992;30:446–52. 32. Cappabianca P, Maiuri F, Pettinato G, et al. Hemangiopericytoma of the spinal canal. Surg Neurol 1981;15:298–302. 33. Harris DJ, Fornasier VL, Livingston KE. Hemangiopericytoma of the spinal canal. Report of three cases. J Neurosurg 1978;49:914–20. 34. Pitlyk PJ, Dockery MB, Miller RH. Hemangiopericytoma of the spinal cord: report of three cases. Neurology 1965;15:649–53. 35. Bikmaz K, Cosar M, Kurtkaya-Yapicier O, et al. Recurrent solitary fibrous tumour in the cerebellopontine angle. J Clin Neurosci 2005;12:829–32.
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36. Chang C, Kuwana N, Tanabe Y, et al. Haemangiopericytoma of occipital bone with invasion of the transverse sinus. J Clin Neurosci 1999;6:515–8. 37. Pillai A, Kumar S, Kumar A, et al. An unusual parasagittal tumour with acute blindness and response to cerebrospinal fluid shunting. J Clin Neurosci 2007;14:1112–6. 38. Matsushige T, Nakaoka M, Yahara K, et al. Single-stage operation for a giant haemangiopericytoma following intracranial feeder embolization. J Clin Neurosci 2007;14:162–7. 39. Hunn M, Stoodley M, Blumbergs P, et al. Haemangiopericytoma presenting as recurrent intracranial haemorrhage. J Clin Neurosci 1997;4:262–6. 40. Alen JF, Lobato RD, Gomez PA, et al. Intracranial hemangiopericytoma: study of 12 cases. Acta Neurochir (Wien) 2001;143:575–86. 41. Akiyama M, Sakai H, Onoue H, et al. Imaging intracranial haemangiopericytomas: study of seven cases. Neuroradiology 2004;46: 194–7. 42. Herzog CE, Leeds NE, Bruner JM, et al. Intracranial hemangiopericytomas in children. Pediatr Neurosurg 1995;22:274–9. 43. Iwaki T, Fukui M, Takeshita I, et al. Hemangiopericytoma of the meninges: a clinicopathologic and immunohistochemical study. Clin Neuropathol 1988;7:93–9. 44. Kanazawa T, Nishino H, Miyata M, et al. Haemangiopericytoma of infratemporal fossa. J Laryngol Otol 2001;115:77–9. 45. Pena CE. Intracranial hemangiopericytoma: Ultrastructural evidence of its leiomyoblastic differentiation. Acta Neuropathol (Berl) 1975;33: 279–84. 46. George B, Casasco A, Deffrennes D, et al. Intratumoral embolization of intracranial and extracranial tumors: Technical note. Neurosurgery 1994;35:771–3. 47. Payne BR, Prasad D, Steiner M, et al. Gamma surgery for hemangiopericytomas. Acta Neurochir (Wien) 2000;142:527–36.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
Hemangiopericytomas in the central nervous system Wei Wu a, Ji-xin Shi a,*, Hui-lin Cheng a, Han-dong Wang a, Chun-hua Hang a, Qun-Li Shi b, Hong-xia Yin a a b
Department of Neurosurgery, Jinling Hospital, 305 East Zhongshan Road, Second Military Medical University, Nanjing 210002, Jiangsu Province, China Department of Pathology, Jinling Hospital, Second Military Medical University, Nanjing, Jiangsu Province, China
a r t i c l e
i n f o
Article history: Received 23 January 2008 Accepted 24 June 2008
Keywords: Hemangiopericytoma Meningioma Clinical features Pathology Radiology Treatment
a b s t r a c t Hemangiopericytomas, which are more aggressive than meningiomas, are rare in the central nervous system (CNS). We analyzed the clinical, radiological and histological features and treatment of 26 patients with hemangiopericytomas in the CNS. The ratio of male to female patients was 1:1. Most tumors were located in the parasagittal and falx regions. The tumors were dense or mixed as assessed by CT scans, and most were homogeneously enhanced. Most tumors were isointense on T1-weighted MRI, and high or mixed intensity on T2-weighted MRI; they were homogeneously or heterogeneously enhanced. Histological examination indicated numerous small vascular spaces in the tumor. All tumors were immunohistochemically positive for vimentin. All patients were treated with surgery, and some of them underwent subsequent radiotherapy. The recurrence rate for hemangiopericytoma in this study was high. Our observations suggest that the biological behavior of hemangiopericytoma differs markedly from that of meningioma. Surgical removal and post-operative radiotherapy are thus critical for the treatment of this tumor. Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction Hemangiopericytomas are rare tumors thought to be derived from pericytes, the cells surrounding capillaries and postcapillary venules. They can occur anywhere in the human body because pericytes are ubiquitous in all types of mesenchymal tissue. However, most hemangiopericytomas are found in the musculoskeletal system and skin.1,2 Hemangiopericytomas in the central nervous system (CNS) are rare, and they account for less than 1% of all CNS tumors.3,4 The histogenesis of CNS hemangiopericytoma has been a matter of controversy. These tumors were once thought to be either soft tissue tumors2 or an aggressive variant of angioblastic meningioma.5 According to the current World Health Organization (WHO) classification of CNS tumors, hemangiopericytoma has its own entity within the ‘‘mesenchymal, non-meningothelial tumor” group. It exhibits different clinical behaviors, immunohistochemical characteristics, and ultrastructural features than meningioma.6 However, hemangiopericytomas resemble meningomas on imaging, and this leads to frequent misdiagnosis. Because hemangiopericytomas are believed to be more aggressive than meningomas and to have a propensity for both local recurrence and extraneural metastases, correct diagnosis and treatments are critical.
* Corresponding author. Tel.: +86 25 80860071; fax: +86 25 84817581. E-mail address: [email protected] (J.-x. Shi). 0967-5868/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2008.06.011
We analyzed the clinicopathological features, clinicoradiological features, and therapeutic outcomes of 26 patients with hemangiopericytomas in the CNS.
2. Patients and methods A total of 32 patients with hemangiopericytomas in the CNS were treated in our department between 1984 and 2005, but only 26 patients were included in this study because the data were incomplete for the rest. Biopsy tumor specimens from all patients were re-examined by an experienced neuropathologist. We also carried out immunohistochemical staining for vimentin (Vim), epithelial membrane antigen (EMA), CD34, and glial fibrillary acidic protein (GFAP). Tumor specimens from four patients were further examined by electron microscopy. All available clinical, surgical, and radiological data (including CT scans, MRI, and angiograms) were reviewed from the patients’ hospital records, in particular the surgical notes to determine the extent of the tumor removal.7 Plain and post-contrast CT scans were performed, and 23 patients had MRI examinations (T1-weighted, T2-weighted, and contrastenhanced T1-weighted studies). Only four patients underwent pre-operative cerebral angiography. Tumors were said to have reoccurred after surgical removal if: (i) CT scans or MRI examinations had detected a new tumor; or (ii) the tumor had increased in size (if the surgery had removed only part of the tumor), regardless of the presence or absence of symptoms or signs.
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W. Wu et al. / Journal of Clinical Neuroscience 16 (2009) 519–523
Three patients were lost to follow-up. The median follow-up time for the remaining 23 patients was 12 years (range 1–23 years).
3. Results Patient characteristics, including epidemiological, clinical, and radiological data, operative findings, additional treatments, and follow-up, are summarized in Table 1. 3.1. Clinical data The group of 26 patients with hemangiopericytoma in the CNS was composed of 13 men (50.0%) and 13 women (50.0%). The age at diagnosis ranged from 28 to 71 years, with an average of 46 years. 3.2. Tumor location Among the 26 patients, 23 had intracranial meningeal hemangiopericytomas, and three had spinal meningeal hemangiopericy-
tomas. Most intracranial meningeal hemangiopericytomas were supratentorial and located in the frontoparietal region. Three tumors were located at the tentorium and extended to both the supratentorial and infratentorial compartments. There were four tumors located in the middle cranial base and one in the paracavernous sinus. In three patients the lesions were located in the sellar, suprasellar or parasellar areas. 3.3. Clinical symptoms The most frequent symptoms in these patients were headache and dizziness. Most patients had symptoms of intracranial hypertension and suffered from visual deficits. Other frequent symptoms included focal motor deficits, and patients with tumors in the spinal cord frequently presented with paralysis. 3.4. Radiological studies The tumors were hyperdense or mixed-density on plain CT scans and enhanced homogeneously or heterogeneously following intravenous contrast injection. No calcification was observed. The tumors were mainly isointense on T1-weighted MRI and isointense
Table 1 Patient clinical data, treatment, and final outcomes No.
Age (y)
Sex
Tumor localization
Presenting symptoms
Symptoms at diagnosis
Degree of resection
Radiotherapy
Followup (y)
Recurrence
Metastasis
Survival
1 2 3
40 33 71
F F M
Dizziness Headaches Headaches
Hemiparesis Monoparesis Hemiparesis
CR CR SR
Yes Yes Unknown
3 6
No No Unknown
No No Unknown
Alive Alive Unavailable
4
52
M
Parasagittal Tentorium Falxtentorium Tentorium
Visual deficit
SR
No
9
Alive
38 55 33 65
M M F F
CR SR CR SR
No Yes No No
4 4 4 4
No No No No
Alive Alive Alive Alive
9 10
41 28
F M
Dizziness Headaches
Monoparesis, dysaudia Hemiparesis Intracranial hypertension Visual deficit and intracranial hypertension Hemiparesis Intracranial hypertension
SR SR
Yes No
5 8
No No
Alive Alive
11
46
F
Headaches
Visual deficit
SR
Yes
4
Yes (after 5 y, S+Rad) No No No Yes (after 2 y, S+Rad) No Yes (after 5 y, S+Rad) No
No
5 6 7 8
Dizziness and headaches Headaches Headaches Headaches Headaches
No
Alive
12 13
38 48
M F
Unknown No
Unknown No
Unavailable Alive
14
38
3 y,
No
Dead
15
2 y,
No
Alive
10
No
Alive
5 y,
No
Alive Dead
Headaches Headaches
Hemiparesis Visual deficit
CR CR
Unknown Yes
3
F
Tentorium Parasagittal Falx Sellar and suprasellar Parasagittal Falxtentorium Middle fossa base Falx Sellar and suprasellar Falx
Headaches
Monoparesis
SR
No
8
44
F
Falx
Headaches
Intracranial hypertension
SR
Yes
3
16
34
M
Falx
Headaches
Coma
SR
No
14
17
42
M
SR
No
6
56
F
Dizziness and headaches Headaches
Hemiparesis
18
Visual deficit
SR
Yes
22
19 20 21
59 62 38
M M F
22
34
F
23
53
M
Falxtentorium Middle fossa base Parasellar Parasagittal Middle fossa base Middle fossa base Paracavernous
Yes (after S+Rad) Yes (after S+Rad) Yes (after y, S+Rad) Yes (after S+Rad) Yesa
24 25
60 48
M F
C6 to T2 T10
26
42
M
C4-5
Epilepsy Dizziness Dizziness and headaches Headaches
Epilepsy Hemiparesis Intracranial hypertension
CR SR CR
No Yes No
4 5 3
No No No
Yes (after 19 y) No No No
Numbness in face
SR
Yes
3
No
No
Alive
Headaches
Visual deficit
SR
No
17
No
Alive
Pain in the leg Numbness in limbs Numbness in limbs
Paralysis Hemiparesis
SR SR
No Unknown
23
Yes (after 12 y, S+Rad) Yesb Unknown
No Unknown
Alive Unavailable
Paralysis
SR
No
5
Yes (after 3 y, S)
No
Alive
Alive Alive Alive
C = cervical segment, CR = complete resection, F = female, M = male, Rad = radiotherapy, S = surgical treatment, SR = subtotal resection, T = thoracic segment, y = years. a This patient had two recurrences, the first 17 y after surgery and radiotherapy, and the second 2 y after radiotherapy. b This patient had three recurrences, the first 8 y after surgery, the second 8 y after a second surgery, and the third 1 y after a third surgery and radiotherapy.
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(or showed slightly higher signals) on T2-weighted MRI. No ‘‘dural tail” sign was observed (Figs 1 and 2). Four patients underwent pre-operative cerebral angiography. Radiological examinations showed that these tumors had both a meningeal-dural and a cortical-pial blood supply. Only one of the 26 patients was diagnosed as having a meningeal hemangiopericytoma by pre-operative imaging studies. The other 25 patients were all diagnosed as having meningomas. Thus, the misdiagnosis rate from imaging techniques was 96.2%. 3.5. Surgical treatments Radical excision was performed in 26 patients (as Simpson grades I and II). In each patient, no tumor was detectable in an imaging examination immediately after surgery. Most tumors had clear margins with the peripheral tissues, and some appeared to have capsules. The tumors were slightly soft with an abundant blood supply. In 13 patients, excision of the tumor caused brisk bleeding, including 3000 mL of blood in one patient. The tumors had apparent dural attachments in most cases. All patients survived surgery; thus, the operative mortality rate was zero. 3.6. Pathological studies Macroscopically, the excised tumors appeared grayish-pink in color and were prominently vascular. Some tumors had capsules, which looked like fish meat and had a tenacious texture. Microscopic examination revealed numerous small vascular spaces in the tumors. Characteristic ‘‘staghorn” vascular channels were also seen. These channels were distributed radially and were surrounded by haphazardly arranged round and oval tumor cells (Supplementary Fig. 1) that showed indistinct cytoplasmic borders
Fig. 2. CT and MRI of a 65-y-old female (patient 8). (A) The brain CT scan showed a mass in the sellar and suprasellar areas. (B) The coronal T1-weighted MRI showed an isointense mass in the sellar and suprasellar areas with (D) homogeneous enhancement. (C) The coronal T2-weighted MRI showed a mixed-intensity mass.
and had fusiform nuclei. Staining for argyrophilic fibers showed that they surrounded single tumor cells and were distributed radially around the vessels. Immunohistochemical staining revealed that all tumors were negative for S-100 protein, EMA, and GFAP but were positive for Vim (Supplementary Fig. 1). Only one tumor stained positive for CD34. Electron microscopy revealed many bundles of 10 nm intermediate filaments in the tumor cells, which contained electron-lucent cytoplasm with few organelles, numerous micropinocytotic vesicles, and subplasmalemmal linear densities. Poorly developed intercellular junctions were present between interdigitating cytoplasmic processes. The tumor cells surrounding the vascular units displayed a continuous basement membrane as well as all the features of well-differentiated pericytes. Some tumor cells that were distant from vascular structures showed focally discontinuous basement membranes. 3.7. Follow-up Of the 26 patients, 10 were treated with external radiotherapy after surgery, and of the 23 patients followed after surgery, 11 developed local recurrences after the initial surgery at an average interval of 6.5 years (range 2–17 years). Thus, the recurrence rate was 47.8%. The one-year survival rate was 100%.
4. Discussion
Fig. 1. CT and MRI scans of a 34-year-old male (patient 16). (A) The brain CT scan showed a large lobulated parieto-occipital mass. (B) The coronal T1-weighted MRI showed a midline and mixed-intensity mass with an irregular border. (C) The axial T2-weighted MRI showed a mixed-intensity mass. (D) The axial contrast-enhanced T1-weighted MRI showed that the mass was heterogeneously enhanced.
Hemangiopericytomas in the CNS were once regarded as a type of meningioma because (i) their initial clinical and radiological presentations do not differ substantially from various types of meningioma, and (ii) their surgical management resembles that of meningiomas.8 However, the current WHO classification of CNS
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tumors distinguishes hemangiopericytomas as an entity in the group of ‘‘mesenchymal, non-meningothelial tumors” that may have special histological origins. It is now widely accepted that these tumors arise from meningeal capillary pericytes. Their high recurrence rates and tendency to metastasize also distinguish their clinical course from that of most meningioma patients and make the management of hemangiopericytomas a challenging multidisciplinary task. Epidemiologically, some characteristics differ between hemangiopericytoma and meningioma. Unlike meningiomas, hemangiopericytomas may be more common in males than in females. A male to female ratio of 1.1:1 to 1.5:1 is reported.9–12 The ratio in the present study (1:1) is slightly lower. In addition, the mean age of diagnosis of hemangiopericytoma is younger than that of meningiomas.9–11 In our study, the mean age at diagnosis was 46, which falls within the previously reported range. Although about 10% of hemangiopericytomas occur in childhood, no children were diagnosed with hemangiopericytomas in our department during this study. Meningeal hemangiopericytomas and meningiomas occur in similar regions of the brain, such as the orbit,13–17 lateral ventricles,18–21 third ventricles,22 sellar and suprasellar areas,23,24 the optic nerve sheath,25 and the skull base.26,27 In addition to those supratentorial locations, the tumor may also localize to infratentorial regions such as the cerebellopontine angle and spinal meninges.28–36 In the present study, the most common location for hemangiopericytoma was the frontoparietal region. It is extremely difficult to differentially diagnose hemangiopericytomas and meningiomas on the basis of their clinical symptoms and radiological examinations. Patients with hemangiopericytomas may have many unusual symptoms.37–45 Consistent with our observations, the CT scans reveal these tumors to be generally heterogeneous, dense, and dural-based lesions.10,11,40,41 They are usually misdiagnosed as meningiomas before surgery. Hence, histological examination is essential for reliable diagnosis. In the present study, only 1 out of 26 patients was diagnosed correctly as having a hemangiopericytoma on the basis of clinical symptoms and brain imaging. Our low diagnosis rate is consistent with previous observations.9,12,42–45 Our histological diagnosis of hemangiopericytoma was further confirmed by immunohistochemical staining with a Vim antibody, which is specific to mesenchymal tissue. These tumors could be distinguished by Vim immunostaining because hemangiopericytomas, but not meningiomas, are derived from the mesenchymal tissue of the external layer of the basement membrane of blood vessels.1–4 Some features may help differentiate hemangiopericytomas from meningiomas: (i) the former do not commonly calcify; (ii) the former tend to show irregular or lobulated borders, apparent parenchymal invasion, and more heterogeneous contrast enhancement than meningiomas, consistent with their aggressive behavior; (iii) bone erosion can sometimes be found in patients with hemangiopericytomas; and (iv) a narrow dural attachment suggests a diagnosis of hemangiopericytoma rather than meningioma. Surgical removal is the major effective treatment for hemangiopericytoma. The excision should be as complete as possible to reduce the chances of recurrence or metastasis. Because the tumors exhibit high vascularity, however, the excision of hemangiopericytomas is very challenging since it may lead to substantial blood loss. The average amount of blood lost during surgery is reported to be as high as 1000 mL.11,12 Some authors report the use of pre-operative embolization to reduce blood loss during surgery.12,46 However, the use of microsurgical techniques can reduce operative mortality and morbidity. In the present study, there were no deaths during surgery. Radiotherapy is believed necessary for hemangiopericytoma patients after surgery. Stereotactic radiosurgery has been used as a
major treatment for patients with a high surgical risk.3,47 However, despite the beneficial effects of radiotherapy, hemangiopericytomas tend to recur locally. In the present study, we treated 10 patients with external radiotherapy after surgery. Radiotherapy seemed to reduce the recurrence rate of hemangiopericytomas after surgery. Further analyses are underway to evaluate the efficacy of radiotherapy in the management of hemangiopericytoma and meningioma patients. The one-year survival rate of the patients in our cohort was 100%, and the overall recurrence rate was 47.8%; both values are consistent with previous reports.10,12 The high recurrence rate reflects the aggressive behavior of hemangiopericytomas. The survival rates were not statistically analysed because there were too few patients at any specific follow-up time. In conclusion, although hemangiopericytomas are difficult to distinguish from meningiomas on the basis of clinical expression and brain imaging, they are more aggressive and require different management. Appropriate treatments include surgical excision of the tumor and post-operative radiotherapy. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2008.06.011.
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