- Email: [email protected]
A clinicopathological and immunohistochemical study of central nervous system hemangiopericytomas
Journal of Clinical Neuroscience 17 (2010) 469–472
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
A clinicopathological and immunohistochemical study of central nervous system hemangiopericytomas Challa Sundaram a,*, Shantveer G. Uppin a, Megha S. Uppin a, J. Sree Rekha a, Manas Kumar Panigrahi b, A.K. Purohit b, S. Rammurti c a b c
Department of Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad 500082, Andhra Pradesh, India Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India Department of Radiology and Imageology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India
a r t i c l e
i n f o
Article history: Received 25 June 2009 Accepted 23 August 2009
Keywords: CD34 Central nervous system tumors Hemangiopericytoma Immunohistochemistry Ki-67
a b s t r a c t Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. Because there are few reports about these tumors from India, we aimed to study the clinico-pathological and immunohistochemical features of CNS HPC. During 2000 to 2008 all 23 patients diagnosed with HPC of CNS at our Institution were reviewed in the study (11 males and 12 females, mean age of 46 years). Clinical, radiological and histopathological features were reviewed. There were 14 patients with grade II and nine with grade III tumors. Immunohistochemistry with antibodies to epithelial membrane antigen (EMA), vimentin, S-100, CD34 and Ki67 was done on routinely processed, paraffin-embedded sections of 20 tumors. All patients were EMA and S-100 negative, and vimentin positive. CD34 was positive in only five out of 20 patients. The mean Ki-67 labeling index was 4.25% in grade II tumors and 7.8% in grade III tumors. We concluded that HPC are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior, although they resemble each other clinically and radiologically, HPCs need to be differentiated from meningiomas. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. The histogenesis and terminology of these tumors has been debated. Stout and Murray described HPC in the soft tissues as perivascular tumor.1 An earlier report of an HPC from the meninges described it as an angioblastic meningioma.2 The current World Health Organization (WHO) classification differentiates HPC from meningioma.3 Awareness and diagnosis of CNS HPC as a distinct clinicopathologic entity is important because of its high tendency to recur and metastasize.3 There are few reports of CNS HPC from India,4–12 and in view of its rarity, we present our patients with CNS HPC seen over 9 years. 2. Material and methods The medical records of all 23 patients diagnosed with CNS HPC during 2000 to 2008 were examined. The details recorded
* Corresponding author. Tel.: +91 40 23489051; fax: +91 40 23310076. E-mail address: [email protected] (C. Sundaram). 0967-5868/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2009.08.018
were: patient age, gender, and clinical presentation; tumor location and radiological features on CT scans or MRI; and the surgery performed. The hematoxylin and eosin (H&E) and reticulin-stained slides of all patients were reviewed and the tumors were placed into grades II and III according to the WHO 2007 criteria.3 2.1. Immunohistochemistry Sections 4 lm thick were prepared from formalin-fixed paraffin-embedded tissue and mounted on poly-L-lysine coated slides. After deparaffinization and hydration through a graded alcohol series, endogenous peroxidase was quenched by incubation with 3% peroxide in methanol for 10 minutes. Antigen retrieval was carried out by autoclaving sections at 121 °C for 10 minutes in 0.01 mol/L citrate buffer, pH 6.0. The horseradish peroxidase polymer staining technique was used. Sections were incubated for 1 hour at room temperature with primary antibodies. An epithelial membrane antigen (EMA) antibody (1:75), vimentin antibody (1:200), and Ki-67 antibody (1:20) (Biogenex; San Ramon, CA, USA) were used in this study. To calculate the Ki-67 labeling index (LI), 1000 tumor cell nuclei were counted. The follow-up data were examined for recurrence and metastases.
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3. Results During the study, we diagnosed 23 HPC, 673 meningiomas and two solitary fibrous tumors (SFT), constituting an approximately 1:30 ratio of HPC to meningiomas. Of 23 patients diagnosed with HPC, there were 11 males and 12 females aged from 10 years to 70 years old (mean 46 years). The age, gender, clinical features, radiological features, surgery performed, tumor grade and immunohistochemical features are given in Supplementary Table 1. 3.1. Clinical features of patients with hemangiopericytoma Of 23 patients with HPC, 10 presented with headache, eight of whom also had vomiting; two had both visual and memory disturbances; one had ataxia; six had focal neurologic deficits; two had seizures; one had low mood; and one had limb pain (Supplementary Table 1). 3.2. Radiological features On CT scan, the HPC tumors were iso- to hyperdense an displayed contrast enhancement. On MRI, which was available in 10 patients in addition to CT scans, the tumors were iso- to hypointense on T1-weighted MRI. Contrast enhancement was present in 15 tumors, perifocal edema in six, and mass effect in eight (Figs. 1 and 2). The tumors were dural based and dural attachment was seen in 10. Cystic change was noted in five tumors. Lytic lesions in bone were seen in two. Hyperostosis and calcification were absent. Angiographic studies were not performed. Of 23 patients, 20 had a pre-operative diagnosis of meningioma; and one patient each was thought to have glioblastoma multiforme primitive neuroectodermal tumor; and schwannoma. 3.3. Surgery Craniotomy and complete surgical excision was performed in 15 patients and a subtotal excision in seven. A subtotal excision only was performed on tumors that were: adherent to the falx, had infiltrated the dura and sinuses, were near the motor cortex, were close to the internal carotid artery or involved the skull base or orbit. In 11 patients the tumors were moderate to highly vascu-
Fig. 1. Axial contrast-enhanced brain MRI showing a well-circumscribed, homogenously enhancing extra-axial dural-based lesion involving the right temporal region. A small non-enhancing cystic component is noted within the lesion. There is minimal perilesional edema and mass effect.
lar, and these tumors had infiltrated the adjacent dural sinuses and brain parenchyma. One patient died post-operatively due to sepsis. The remaining 21 patients recovered with minor deficits. A lumbar laminectomy and complete tumour resection was performed for one patient with a spinal tumor. All patients received radiotherapy post-operatively. 3.4. Histopathology On H&E stained sections, the tumors were cellular, and were composed of plump spindle-shaped cells with scant cytoplasm and oval nuclei. The mitotic activity was 2 to 3 per 10 high-power fields (HPF) in grade II tumors. The cells were arranged around thin-walled vascular spaces with a characteristic staghorn pattern (Fig. 3a,b). There were no whorls, pseudoinclusions or calcifications. A reticulin stain showed a characteristic pattern of reticulin around individual cells (Fig. 3c). In grade III or anaplastic tumors, mitotic activity of more than 5 per 10 HPF, necrosis, hemorrhage, nuclear pleomorphism, and increased cellularity were seen (Fig. 4). There were 14 grade II and nine grade III HPC. 3.5. Immunohistochemistry Immunohistochemistry with EMA, vimentin, CD34, S-100 and Ki-67 was performed in 20 tumors only. EMA and S-100 staining were negative, and vimentin was positive, in all tumors. Blood vessels stained CD34 positive in all tumors, but tumor cells stained CD34 positive in the tumour cells of only five tumors (25%) (Supplementary Fig. 1a,b). The Ki-67 LI ranged from 2 to 7 (mean 4.25) in grade II (Supplementary Fig. 1c) and from 3 to 12 in grade III (mean 7.8) (Supplementary Fig. 1d). There were five (21.7%) recurrences – 3 grade II tumors and 2 grade III tumors. One tumor, initially diagnosed as grade II, was upgraded to grade III on recurrence. The time from initial surgery to recurrence of symptoms ranged from 2 months to 9 years and the Ki-67 LI in these tumors ranged from 3 to 7 (Table 1). 4. Discussion Hemangiopericytomas constitute 2% to 4% of meningiomas and occur more commonly in males. They are similar to meningiomas in location and clinical features.13–15 In our study, HPC constituted 3.42% of mengiomas with no significant gender predilection. Posterior fossa and spinal location occurred in one tumor each and there were no multiple HPC in our series. Multifocal HPC has been rarely reported.6 All tumors in our series were dural based and none of them showed calcification or hyperostosis. Perifocal edema, mass effect and infiltration into adjacent structures were seen despite gross lobularity and circumscription. A pre-operative diagnosis was not made in any of our patients. Chiechi et al. described the CT scan and MRI features of intracranial hemangiopericytoma.16 They emphasize that lack of calcification, hyperostosis and narrow base with prominent lobularity help in differentiating HPC from meningiomas on CT scans and MRI.16 Dural-based tumors like HPC derive their blood supply from the external carotid system, whereas intraparenchymal tumors derive their blood supply either from the internal carotid or the vertebrobasilar system, thus angiography may differentiate them.17 Angiographic studies were not done in our patients. The histology of HPC is characteristic. However, it needs to be differentiated from fibroblastic meningiomas and SFT. Unlike meningiomas, which often show nuclear pseudoinclusions and mild nuclear pleomorphism, grade II HPC lack whorls and pseudoinclusions. They are characterized by reticulin around individual
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Fig. 2. Axial CT brain scans showing on plain scans (B, C, D) a large, lobulated hyperdense lesion with hypodense areas involving the right frontal parasagittal region. On postcontrast images (G,H), the hypodense areas show enhancement with midline shift and extensive perilesional white matter edema. (A, E) A few smaller ring-enhancing lesions can be seen adjacent to the lesion. This figure is available in colour at www.sciencedirect.com.
Fig. 3. (a, b) Hematoxylin and eosin stained sections showing (a) a cellular tumor with dilated staghorn vascular channels (100) and (b) haphazardly arranged plump, spindle-shaped cells with scant cytoplasm and oval nuclei (200). (c) Reticulin-stained section showing prominent reticulin fibers within the tumor surrounding the vessels and wrapping around individual cells (reticulin stain, 200). This figure is available in colour at www.sciencedirect.com.
cells. SFT is composed of fascicles of elongated cells in a collagenrich stroma, and lacks whorls, storiform pattern, mitoses and psammoma bodies. The immunoreactivity of HPC is diverse and several antibodies, which include EMA, CD34, glial fibrillary acidic protein, vimentin, factor XIIIa, Leu 7 and S-100, are sometimes positive in HPC. In our study we used EMA, CD34 and S-100 to differentiate HPC from meningioma. Both EMA and S-100 were negative in all our patients, and only five tumors (25%) stained positive for CD34. Although no single marker is 100% sensitive or specific, the immunoprofile of HPC is sufficiently distinct to differentiate it from meningioma and SFT.18–21 The immunoprofile of meningioma shows positivity for EMA and vimentin and variable positivity for S-100, whereas HPC are usually negative for EMA and S-100 and positive for vimentin. CD34 is positive in SFT whereas only 25%
to 30% of CNS HPC show CD34 positivity.18–21 CNS HPC might represent the cellular form of SFT, which tends to express CD34 less frequently.18–20 The CNS HPC grows more rapidly than meningioma and the mitotic activity is prominent even in grade II tumors.22 In our series the Ki-67 LI was 4.3% for grade II tumors and 7.8% for grade III tumors. In the present series, the mean Ki-67 LI in recurrent tumors was 5.16%: in recurrent grade II tumors, the mean Ki-67 LI was 4.33%; and in recurrent grade III HPC tumors was 6.4%. However, the number of patients was too small to draw any conclusion. Probst-Cousin et al. and Vuorinen et al. found that the group with a Ki-67 LI of <5% tended to survive longer but this feature did not increase the accuracy of predicting the clinical outcome.22,23 Chacko et al. used the proliferation marker topoisomerase IIa expression in meningeal HPC and correlated it with biologic behavior. They concluded
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In conclusion, HPCs are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior. Hence, although HPC and meningioma are clinically and radiologically similar, they need to be differentiated. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2009.08.018. References
Fig. 4. Hematoxylin and eosin stained sections of an anaplastic hemangiopericytoma showing (a) increased cellularity and mitotic activity (black arrows) (400) and (b) foci of necrosis (200). This figure is available in colour at www. sciencedirect.com.
Table 1 Recurrent hemangiopericytomas (HPC): tumor grade, surgery extent, time from surgery to recurrence and the labeling index (LI) of Ki-67 Patient no.
Time to recurrence
Extent of excision
Tumor grade
Ki-67 LI
1 2 3 4 5
5 6 6 5 2
Total Total Subtotal Subtotal Subtotal
II–III II II III II
7 3 5 5.8 5
yrs yrs yrs yrs mon
Recurrent grade II HPC, mean Ki-67 LI – 4.33%; recurrent grade III HPC, mean Ki-67 LI – 6.4%; recurrent HPC (all), mean Ki-67 LI – 5.16%, mon = months, yrs = years. World Health Organization classification grade.
that the relative risk of recurrence was 2.9 times greater in patients with topoisomerase index (TPI) of 5% or greater compared to those with a TPI of less than 5%.7 The behavior of CNS HPC is more aggressive than meningioma, with high recurrence rates and extracranial metastases. This may be related to incomplete surgical excision due to the location of the tumor.19,20 Ecker et al. concluded that the 5-year survival rate of CNS HPC has improved in the last 10 years and that high-grade tumors recurred earlier than low grade tumors, with chemotherapy being ineffective.24 Chacko et al. concluded that intracranial HPC recurred despite radical excision and adjuvant radiation and suggested a role for adjuvant chemotherapy using antitopoisomerase IIa agents in tumors expressing high levels of topoisomerase IIa.7 In our series, five of the 23 tumors recurred (21.7%), three of which had been excised subtotally at initial surgery. The time to recurrence varied from 2 months to 9 years and there was not much difference between grade II and III tumors. In contrast, meningeal SFTs have a benign course after complete resection. The histogenesis of HPC is uncertain. Initially it was considered pericytic in origin by Stout and Murray.1 The working group of the new WHO classification of Tumors of Soft Tissue and Bone stated that HPCs show no evidence of pericytic differentiation and are instead fibroblastic and further suggested that HPCs form a morphological continuum with SFT.25 According to Gengler and Guillou, the same concept may also hold true for meningeal HPC.26
1. Stout AP, Murray MR. Hemangiopericytoma. A vascular tumor featuring Zimmermann’s pericytes. Ann Surg 1942;116:26–33. 2. Cushing H, Eisenhardt L. Meningiomas: their classification, regional behaviour, life history, and surgical results. Springfield IL: Charles C. Thomas; 1938.. p. 4–47. 3. Giannini C, Rushing EJ, Hainfellner JA. Haemangiopericytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, editors. WHO classification of tumours of the central nervous system. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2007. p. 178–80. 4. Ganapathy K. Hemangiopericytoma. CT scan differentiation. Neurol India 1987;35:123. 5. Goel A, Muzumdar D, Desai K, et al. Retroorbital hemangiopericytoma and cavernous sinus schwannoma. Neurol Med Chir (Tokyo) 2003;43:47–50. 6. Desai K, Nadkarni T, Fattepurker S, et al. Hemangiopericytoma in the trigone of lateral ventricle – case report. Neurol Med Chir (Tokyo) 2004;44:484–8. 7. Chacko G, Chacko AG, Rajshekhar V, et al. Intracranial hemangiopericytomas: correlation of topoisomerase II alpha expression with biologic behavior. Surg Neurol 2006;65:11–7. 8. Bahl A, Sharma DN, Eesa M, et al. Multifocal hemangiopericytoma. Ind J Med Paediatric Oncol 2007;28:84–91. 9. Gill SS, Bharadwaj R. Cytomorphologic findings of haemangiopericytoma of the meninges: a case report. Indian J Pathol Microbiol 2007;50:425. 10. Goel D, Balu S, Prayaga AK, et al. Pulmonary metastases of recurrent intracranial hemangiopericytoma diagnosed on fine needle aspiration cytology – a case report. Acta Cytologica 2008;52:344–6. 11. Jalali R, Srinivas C, Nadkarni T, et al. Suprasellar hemangiopericytoma – challenges in diagnosis and treatment. Acta Neurochir. 2008;150:67–71. 12. Bonde VR, Goel A. Two patients with intracranial hemangiopericytoma. J Clin Neurosci 2009;16:330–3. 13. Jaaskelainen J, Servo A, Haltia M, et al. Intracranial hemangiopericytoma: radiology, surgery, radiotherapy, and outcome in 21 patients. Surg Neurol 1985;23:227–36. 14. 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. 15. 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. 16. Chiechi M, Surirmotopoulos J, Mena H. Intracranial hemangiopericytomas: MR and CT features. Am J Neuroradiol 1996;17:1365–71. 17. Burger PC, Scheithauer BW. Tumors of the central nervous system. AFIP Atlas of Tumor Pathology. 4th series. Washington, DC: ARP; 2007. 18. Renshaw AA, Paulus W, Joseph JT. CD34 and epithelial membrane antigen distinguish dural hemangiopericytoma and meningiomas. Appl Immunohistochem 1995;3:108–14. 19. Perry A, Scheithauer BW, Nascimento AG. The immunophenotypic spectrum of meningeal hemangiopericytoma: a comparison with fibrous meningiomas and solitary fibrous tumor of meninges. Am J Surg Pathol 1997;21:1354–60. 20. Tihan T, Viglione M, Rosenblum MK, et al. Solitary fibrous tumors in the central nervous system. A clinicopathologic review of 18 cases and comparison to meningeal hemangiopericytomas. Arch Pathol Lab Med 2003;127:432–9. 21. Rajaram V, Brat DJ, Perry A. Anaplastic meningiomas versus meningeal hemangiopericytoms: immunohistochemical and genetic markers. Hum Pathol 2004;35:1413–8. 22. Probst-Cousin S, Bergmann M, Schorder R, et al. Ki-67 and biological behaviour in meningeal haemangiopericytomas. Histopathology 1996;29:57–61. 23. Vuorinen V, Sallinen P, Haapsalo H, et al. Outcome of 31 intracranial hemangiopericytomas: poor predictive value of cell proliferation indices. Acta Neurochir 1996;138:1399–408. 24. Ecker RD, Marsh WR, Pollock BE, et al. Hemangiopericytoma in the central nervous system: treatment, pathological features, and long-term follow-up in 38 patients. J Neurosurg 2003;98:1182–7. 25. Fletcher CD. The evolving classification of soft tissue tumors: an update based on the new WHO classification. Histopathology 2006;48:3–12. 26. Gengler C, Guillou L. Solitary fibrous tumour and haemangiopericytoma: evolution of a concept. Histopathology 2006;48:63–74.
Contents lists available at ScienceDirect
Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn
Clinical Study
A clinicopathological and immunohistochemical study of central nervous system hemangiopericytomas Challa Sundaram a,*, Shantveer G. Uppin a, Megha S. Uppin a, J. Sree Rekha a, Manas Kumar Panigrahi b, A.K. Purohit b, S. Rammurti c a b c
Department of Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad 500082, Andhra Pradesh, India Department of Neurosurgery, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India Department of Radiology and Imageology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad, Andhra Pradesh, India
a r t i c l e
i n f o
Article history: Received 25 June 2009 Accepted 23 August 2009
Keywords: CD34 Central nervous system tumors Hemangiopericytoma Immunohistochemistry Ki-67
a b s t r a c t Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. Because there are few reports about these tumors from India, we aimed to study the clinico-pathological and immunohistochemical features of CNS HPC. During 2000 to 2008 all 23 patients diagnosed with HPC of CNS at our Institution were reviewed in the study (11 males and 12 females, mean age of 46 years). Clinical, radiological and histopathological features were reviewed. There were 14 patients with grade II and nine with grade III tumors. Immunohistochemistry with antibodies to epithelial membrane antigen (EMA), vimentin, S-100, CD34 and Ki67 was done on routinely processed, paraffin-embedded sections of 20 tumors. All patients were EMA and S-100 negative, and vimentin positive. CD34 was positive in only five out of 20 patients. The mean Ki-67 labeling index was 4.25% in grade II tumors and 7.8% in grade III tumors. We concluded that HPC are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior, although they resemble each other clinically and radiologically, HPCs need to be differentiated from meningiomas. Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction Hemangiopericytomas (HPC) of the central nervous system (CNS) are uncommon dural-based tumors that mimic meningiomas clinically and radiologically. The histogenesis and terminology of these tumors has been debated. Stout and Murray described HPC in the soft tissues as perivascular tumor.1 An earlier report of an HPC from the meninges described it as an angioblastic meningioma.2 The current World Health Organization (WHO) classification differentiates HPC from meningioma.3 Awareness and diagnosis of CNS HPC as a distinct clinicopathologic entity is important because of its high tendency to recur and metastasize.3 There are few reports of CNS HPC from India,4–12 and in view of its rarity, we present our patients with CNS HPC seen over 9 years. 2. Material and methods The medical records of all 23 patients diagnosed with CNS HPC during 2000 to 2008 were examined. The details recorded
* Corresponding author. Tel.: +91 40 23489051; fax: +91 40 23310076. E-mail address: [email protected] (C. Sundaram). 0967-5868/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.jocn.2009.08.018
were: patient age, gender, and clinical presentation; tumor location and radiological features on CT scans or MRI; and the surgery performed. The hematoxylin and eosin (H&E) and reticulin-stained slides of all patients were reviewed and the tumors were placed into grades II and III according to the WHO 2007 criteria.3 2.1. Immunohistochemistry Sections 4 lm thick were prepared from formalin-fixed paraffin-embedded tissue and mounted on poly-L-lysine coated slides. After deparaffinization and hydration through a graded alcohol series, endogenous peroxidase was quenched by incubation with 3% peroxide in methanol for 10 minutes. Antigen retrieval was carried out by autoclaving sections at 121 °C for 10 minutes in 0.01 mol/L citrate buffer, pH 6.0. The horseradish peroxidase polymer staining technique was used. Sections were incubated for 1 hour at room temperature with primary antibodies. An epithelial membrane antigen (EMA) antibody (1:75), vimentin antibody (1:200), and Ki-67 antibody (1:20) (Biogenex; San Ramon, CA, USA) were used in this study. To calculate the Ki-67 labeling index (LI), 1000 tumor cell nuclei were counted. The follow-up data were examined for recurrence and metastases.
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3. Results During the study, we diagnosed 23 HPC, 673 meningiomas and two solitary fibrous tumors (SFT), constituting an approximately 1:30 ratio of HPC to meningiomas. Of 23 patients diagnosed with HPC, there were 11 males and 12 females aged from 10 years to 70 years old (mean 46 years). The age, gender, clinical features, radiological features, surgery performed, tumor grade and immunohistochemical features are given in Supplementary Table 1. 3.1. Clinical features of patients with hemangiopericytoma Of 23 patients with HPC, 10 presented with headache, eight of whom also had vomiting; two had both visual and memory disturbances; one had ataxia; six had focal neurologic deficits; two had seizures; one had low mood; and one had limb pain (Supplementary Table 1). 3.2. Radiological features On CT scan, the HPC tumors were iso- to hyperdense an displayed contrast enhancement. On MRI, which was available in 10 patients in addition to CT scans, the tumors were iso- to hypointense on T1-weighted MRI. Contrast enhancement was present in 15 tumors, perifocal edema in six, and mass effect in eight (Figs. 1 and 2). The tumors were dural based and dural attachment was seen in 10. Cystic change was noted in five tumors. Lytic lesions in bone were seen in two. Hyperostosis and calcification were absent. Angiographic studies were not performed. Of 23 patients, 20 had a pre-operative diagnosis of meningioma; and one patient each was thought to have glioblastoma multiforme primitive neuroectodermal tumor; and schwannoma. 3.3. Surgery Craniotomy and complete surgical excision was performed in 15 patients and a subtotal excision in seven. A subtotal excision only was performed on tumors that were: adherent to the falx, had infiltrated the dura and sinuses, were near the motor cortex, were close to the internal carotid artery or involved the skull base or orbit. In 11 patients the tumors were moderate to highly vascu-
Fig. 1. Axial contrast-enhanced brain MRI showing a well-circumscribed, homogenously enhancing extra-axial dural-based lesion involving the right temporal region. A small non-enhancing cystic component is noted within the lesion. There is minimal perilesional edema and mass effect.
lar, and these tumors had infiltrated the adjacent dural sinuses and brain parenchyma. One patient died post-operatively due to sepsis. The remaining 21 patients recovered with minor deficits. A lumbar laminectomy and complete tumour resection was performed for one patient with a spinal tumor. All patients received radiotherapy post-operatively. 3.4. Histopathology On H&E stained sections, the tumors were cellular, and were composed of plump spindle-shaped cells with scant cytoplasm and oval nuclei. The mitotic activity was 2 to 3 per 10 high-power fields (HPF) in grade II tumors. The cells were arranged around thin-walled vascular spaces with a characteristic staghorn pattern (Fig. 3a,b). There were no whorls, pseudoinclusions or calcifications. A reticulin stain showed a characteristic pattern of reticulin around individual cells (Fig. 3c). In grade III or anaplastic tumors, mitotic activity of more than 5 per 10 HPF, necrosis, hemorrhage, nuclear pleomorphism, and increased cellularity were seen (Fig. 4). There were 14 grade II and nine grade III HPC. 3.5. Immunohistochemistry Immunohistochemistry with EMA, vimentin, CD34, S-100 and Ki-67 was performed in 20 tumors only. EMA and S-100 staining were negative, and vimentin was positive, in all tumors. Blood vessels stained CD34 positive in all tumors, but tumor cells stained CD34 positive in the tumour cells of only five tumors (25%) (Supplementary Fig. 1a,b). The Ki-67 LI ranged from 2 to 7 (mean 4.25) in grade II (Supplementary Fig. 1c) and from 3 to 12 in grade III (mean 7.8) (Supplementary Fig. 1d). There were five (21.7%) recurrences – 3 grade II tumors and 2 grade III tumors. One tumor, initially diagnosed as grade II, was upgraded to grade III on recurrence. The time from initial surgery to recurrence of symptoms ranged from 2 months to 9 years and the Ki-67 LI in these tumors ranged from 3 to 7 (Table 1). 4. Discussion Hemangiopericytomas constitute 2% to 4% of meningiomas and occur more commonly in males. They are similar to meningiomas in location and clinical features.13–15 In our study, HPC constituted 3.42% of mengiomas with no significant gender predilection. Posterior fossa and spinal location occurred in one tumor each and there were no multiple HPC in our series. Multifocal HPC has been rarely reported.6 All tumors in our series were dural based and none of them showed calcification or hyperostosis. Perifocal edema, mass effect and infiltration into adjacent structures were seen despite gross lobularity and circumscription. A pre-operative diagnosis was not made in any of our patients. Chiechi et al. described the CT scan and MRI features of intracranial hemangiopericytoma.16 They emphasize that lack of calcification, hyperostosis and narrow base with prominent lobularity help in differentiating HPC from meningiomas on CT scans and MRI.16 Dural-based tumors like HPC derive their blood supply from the external carotid system, whereas intraparenchymal tumors derive their blood supply either from the internal carotid or the vertebrobasilar system, thus angiography may differentiate them.17 Angiographic studies were not done in our patients. The histology of HPC is characteristic. However, it needs to be differentiated from fibroblastic meningiomas and SFT. Unlike meningiomas, which often show nuclear pseudoinclusions and mild nuclear pleomorphism, grade II HPC lack whorls and pseudoinclusions. They are characterized by reticulin around individual
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Fig. 2. Axial CT brain scans showing on plain scans (B, C, D) a large, lobulated hyperdense lesion with hypodense areas involving the right frontal parasagittal region. On postcontrast images (G,H), the hypodense areas show enhancement with midline shift and extensive perilesional white matter edema. (A, E) A few smaller ring-enhancing lesions can be seen adjacent to the lesion. This figure is available in colour at www.sciencedirect.com.
Fig. 3. (a, b) Hematoxylin and eosin stained sections showing (a) a cellular tumor with dilated staghorn vascular channels (100) and (b) haphazardly arranged plump, spindle-shaped cells with scant cytoplasm and oval nuclei (200). (c) Reticulin-stained section showing prominent reticulin fibers within the tumor surrounding the vessels and wrapping around individual cells (reticulin stain, 200). This figure is available in colour at www.sciencedirect.com.
cells. SFT is composed of fascicles of elongated cells in a collagenrich stroma, and lacks whorls, storiform pattern, mitoses and psammoma bodies. The immunoreactivity of HPC is diverse and several antibodies, which include EMA, CD34, glial fibrillary acidic protein, vimentin, factor XIIIa, Leu 7 and S-100, are sometimes positive in HPC. In our study we used EMA, CD34 and S-100 to differentiate HPC from meningioma. Both EMA and S-100 were negative in all our patients, and only five tumors (25%) stained positive for CD34. Although no single marker is 100% sensitive or specific, the immunoprofile of HPC is sufficiently distinct to differentiate it from meningioma and SFT.18–21 The immunoprofile of meningioma shows positivity for EMA and vimentin and variable positivity for S-100, whereas HPC are usually negative for EMA and S-100 and positive for vimentin. CD34 is positive in SFT whereas only 25%
to 30% of CNS HPC show CD34 positivity.18–21 CNS HPC might represent the cellular form of SFT, which tends to express CD34 less frequently.18–20 The CNS HPC grows more rapidly than meningioma and the mitotic activity is prominent even in grade II tumors.22 In our series the Ki-67 LI was 4.3% for grade II tumors and 7.8% for grade III tumors. In the present series, the mean Ki-67 LI in recurrent tumors was 5.16%: in recurrent grade II tumors, the mean Ki-67 LI was 4.33%; and in recurrent grade III HPC tumors was 6.4%. However, the number of patients was too small to draw any conclusion. Probst-Cousin et al. and Vuorinen et al. found that the group with a Ki-67 LI of <5% tended to survive longer but this feature did not increase the accuracy of predicting the clinical outcome.22,23 Chacko et al. used the proliferation marker topoisomerase IIa expression in meningeal HPC and correlated it with biologic behavior. They concluded
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In conclusion, HPCs are distinct from meningiomas in morphology, immunohistochemistry and biologic behavior. Hence, although HPC and meningioma are clinically and radiologically similar, they need to be differentiated. Appendix A. Supplementary material Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.jocn.2009.08.018. References
Fig. 4. Hematoxylin and eosin stained sections of an anaplastic hemangiopericytoma showing (a) increased cellularity and mitotic activity (black arrows) (400) and (b) foci of necrosis (200). This figure is available in colour at www. sciencedirect.com.
Table 1 Recurrent hemangiopericytomas (HPC): tumor grade, surgery extent, time from surgery to recurrence and the labeling index (LI) of Ki-67 Patient no.
Time to recurrence
Extent of excision
Tumor grade
Ki-67 LI
1 2 3 4 5
5 6 6 5 2
Total Total Subtotal Subtotal Subtotal
II–III II II III II
7 3 5 5.8 5
yrs yrs yrs yrs mon
Recurrent grade II HPC, mean Ki-67 LI – 4.33%; recurrent grade III HPC, mean Ki-67 LI – 6.4%; recurrent HPC (all), mean Ki-67 LI – 5.16%, mon = months, yrs = years. World Health Organization classification grade.
that the relative risk of recurrence was 2.9 times greater in patients with topoisomerase index (TPI) of 5% or greater compared to those with a TPI of less than 5%.7 The behavior of CNS HPC is more aggressive than meningioma, with high recurrence rates and extracranial metastases. This may be related to incomplete surgical excision due to the location of the tumor.19,20 Ecker et al. concluded that the 5-year survival rate of CNS HPC has improved in the last 10 years and that high-grade tumors recurred earlier than low grade tumors, with chemotherapy being ineffective.24 Chacko et al. concluded that intracranial HPC recurred despite radical excision and adjuvant radiation and suggested a role for adjuvant chemotherapy using antitopoisomerase IIa agents in tumors expressing high levels of topoisomerase IIa.7 In our series, five of the 23 tumors recurred (21.7%), three of which had been excised subtotally at initial surgery. The time to recurrence varied from 2 months to 9 years and there was not much difference between grade II and III tumors. In contrast, meningeal SFTs have a benign course after complete resection. The histogenesis of HPC is uncertain. Initially it was considered pericytic in origin by Stout and Murray.1 The working group of the new WHO classification of Tumors of Soft Tissue and Bone stated that HPCs show no evidence of pericytic differentiation and are instead fibroblastic and further suggested that HPCs form a morphological continuum with SFT.25 According to Gengler and Guillou, the same concept may also hold true for meningeal HPC.26
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