Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 


 
 Table of Contents  
CORRESPONDENCE
Year : 2014  |  Volume : 10  |  Issue : 2  |  Page : 377-380

Primary Ewing's sarcoma of the cranium: Case series and review of literature


1 Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad, India
2 Department of Pathology, Nizam's Institute of Medical Sciences, Hyderabad, India

Date of Web Publication14-Jul-2014

Correspondence Address:
Kalpathi Krishnamani
Department of Medical Oncology, Nizam's Institute of Medical Sciences, Hyderabad - 500 082
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.136663

Rights and Permissions
 > Abstract 

Primary Ewing's sarcoma (EWS) of the cranium is extremely rare. It accounts for <1% of cases. We retrospectively analyzed our EWS cases to determine those which had a primary cranial involvement. Out of a total of 332 cases of EWS registered between the years 2000 and 2011, 7 were of the primary cranial involvement. Treatment modalities included surgery, chemotherapy, and radiotherapy (RT), as indicated. The follow-up ranged from 8 months to 7.5 years. In our study, parieto-occipital region was the commonest site. Most patients presented with localized disease and swelling of the scalp. Excision followed by chemotherapy or RT appears to have good survival rates. At a median follow-up of 32.2 months, only one patient had a recurrence, and was successfully salvaged with second line chemotherapy. These cases illustrate that a multi-disciplinary approach in patients with EWS of the cranium results in a good outcome.

 > Abstract in Chinese 

颅骨原发性尤文氏肉瘤病例及文献回顾
摘要
头骨的原发性尤文氏肉瘤(EWS)是极为罕见的。它占<1%的病例。本文回顾性分析了我们的原发于颅骨的EWS病例。2000和2011年间登记的EWS共332例,7例原发颅骨受累。治疗方式包括手术,化疗,放疗(RT)。随访8个月~7.5年。在我们的研究中,顶枕区是最常见的部位。绝大多数患者表现为局部病灶和头皮肿胀。化疗或放疗后切除似乎有良好的生存率。中位随访32.2月,只有一个病人复发,并被二线化疗成功挽救。这些情况说明,多学科联合治疗有助于颅骨EWS患者治疗。
关键词:化疗,颅骨,尤文氏肉瘤


Keywords: Chemotherapy, cranium, Ewing′s sarcoma


How to cite this article:
Krishnamani K, Kumar TN, Gandhi LV, Raghunadharao D, Sadashivudu G, Megha U. Primary Ewing's sarcoma of the cranium: Case series and review of literature. J Can Res Ther 2014;10:377-80

How to cite this URL:
Krishnamani K, Kumar TN, Gandhi LV, Raghunadharao D, Sadashivudu G, Megha U. Primary Ewing's sarcoma of the cranium: Case series and review of literature. J Can Res Ther [serial online] 2014 [cited 2019 Nov 12];10:377-80. Available from: http://www.cancerjournal.net/text.asp?2014/10/2/377/136663


 > Introduction Top


Primary Ewing's sarcoma (EWS) of the cranium is rare. Most of the available literature is from case reports. Paulus et al. [1] in their study on 2500 biopsy proven brain tumors encountered only one case of primary EWS of the skull. In this retrospective analysis over an 11-year period, seven cases of primary EWS of the skull were identified. There are only eight case reports of intracranial extension of primary cranial EWS. In our series, two children had an intracranial extension.


 > Case report Top


Of a total of 332 patients with a diagnosis of ESFT between 2000 and 2011, there were six children with primary cranial involvement. The male to female ratio was 1.3:1. The age of the children ranged between 1 and 17 years. Parieto-occipital region was the commonest site of involvement, occurring in four children. One child each had involvement of the cavernous sinus, sphenoid bone, and baso-frontal region. Three children presented with a scalp swelling [Figure 1] and [Figure 2]. Proptosis was the presenting feature in two children. Of the remaining two, one each presented with squint and symptoms of raised intracranial pressure and facial nerve palsy. Squint as a presenting feature has not been reported till date. To the best of our knowledge this is the first report of a child presenting with squint. In our series, two children had an intracranial extension [Figure 3].
Figure 1: Lateral radiograph of skull showing ill-defined lytic lesion in posterior parietal bone with spiculated periosteal reaction and soft tissue component

Click here to view
Figure 2: (a, b) Sagittal computed tomography images showing large lesion in parieto-occipital region causing destruction of skull bone with large extra-dural and extra-cranial soft tissue component

Click here to view
Figure 3: Large intensely enhancing soft tissue lesion involving all the paranasal sinuses (a) with intracranial extension (b) causing extensive bone destruction (c)

Click here to view


Localized presentation was seen in six children. Excision of the tumor was performed in six children. Histopathology was suggestive of small round cells exhibiting CD99 positivity [Figure 4],[Figure 5] and [Figure 6]. Post-operative radiotherapy (RT) was given in two children. Six children received adjuvant chemotherapy. Vincristine, doxorubicin, cyclophosphamide/ifosfamide, etoposide VAC/IE regimen was the common protocol used in our patients. Lomustine CCNU/vincristine and cis-platinum was used in one patient who had a local recurrence. The schedule of the agents used is as follows: VAC alternating with IE q 3 weekly; vincristine - 1.4 mg/m 2 D1, doxorubicin - 75 mg/m 2 D1, cyclophosphamide - 1200 mg/m 2 D1, ifosfamide - 1.8 g/m 2 D1-5, and etoposide - 100 mg/m 2 D1-5. CCNU - 75 mg/m 2 D1, cisplatin - 60 mg/m 2 D1, and vincristine - 1.4 mg/m 2 D1 and D8 q 4 weekly.
Figure 4: Uniform small round cells with rosette formation (H and E, ×100)

Click here to view
Figure 5: Cells show scant cytoplasm and round to oval nuclei with finely granular chromatin (H and E, ×400)

Click here to view
Figure 6: Immunohistochemistry with CD 99 shows positivity in tumor cells (×100) (a, b)

Click here to view


The median follow-up in our study is 32.2 months. Six children are under regular follow-up ranging from 8 months to 7.5 years. One child expired before initiation of therapy. One child had a recurrence at 6 years after initial presentation and was successfully treated with second-line chemotherapy [Table 1].
Table 1: Clinical characteristics

Click here to view



 > Discussion Top


First described by James Ewing in 1921, EWS comprises 11% of all bone tumors. The peak incidence is between the age groups of 5 and 15 years. [2] The male to female ratio is 1.6:1. [3] Diaphysis is the commonest site of involvement although metaphyses may be involved in 25% of the cases.

Primary EWS of the cranium is rare accounting for <1% of cases. [4] In tumors of the skull vault, frontal, parietal, and temporal bones are the commonest sites of occurrence accounting for 28%, 22%, and 11%, respectively. Vohra recorded eight cases of EWS involving the skull bone while describing the radiologic manifestations in 156 cases of EWS. [5] Pritchard and Coley reported three cases each among 234 and 149 cases of EWS respectively. [2],[6]

Case reports describing the clinical characteristics, radiologic manifestations and treatment modalities are the largest source of available literature on this subject. Syed has reported a case of EWS of the calvarium that presented with mass effect. [7]

Headache and localized swelling are the common modes of presentation. Features of raised intracranial tension is seen in cases of intracranial involvement. [8],[9] Involvement or extension into orbit and nasopharynx leads to proptosis and nasal stuffiness respectively. Non-specific symptoms include fever, weight loss and decreased appetite, usually in advanced disease. Abnormal laboratory findings may include elevated Lactate dehydrogenase (LDH) and Alkaline phosphatase (ALP). LDH is a surrogate of tumor burden and usually falls with effective treatment.

Primary EWS of the skull presents with osteolytic lesion with soft tissue component on X-ray. [10] Similar osteolytic lesions are seen in eosinophilic granuloma, fibrous dysplasia, aneurysmal bone cyst, osteoclastoma and metastases.

Imaging with computed tomography (CT) scan and magnetic resonance imaging (MRI) provide information regarding the size, extent and involvement of dura and parenchyma. On an MRI, the mass is hypo- to iso-intense on T1W and iso- or hyper-intense on T2W with heterogeneous enhancement on contrast. CT scan is useful to delineate bone involvement. CT scan reveals an iso-hyperdense mass which enhances with contrast. Chest X-rays and CT scans of chest are useful in detecting pulmonary metastases. Radioisotope bone scan is necessary to rule out metastases. Bone scans also help in detecting early recurrence as reported in one study. [11]

Histological examination reveals a homogenous population of small cells with fibro vascular stroma with scant cytoplasm and round to oval vesicular nuclei. The cytoplasm contains glycogen. These cells are positive for vimentin, CD99, and negative for desmin, Leucocyte common antigen (LCA) and synaptophysin differentiating it from other small round cell tumors like rhabdomyosarcoma, lymphoma and neuroblastoma. More than 95% tumors of EWS family express the adhesion receptor CD99 on the cell membranes. Identification of EWS rearrangements using Flourosence in situ hybridization (FISH) or Reverse transcriptase polymerase chain reaction or RT-PCR is useful in differentiating EWS from other round cell tumors. [12] Most cases have a balanced translocation between chromosomes 11 and 22 which fuses portions of EWS gene on chromosome 22q12 with FLI1 gene on 11q24. Other translocations observed are t (21;22) which results in the fusion between EWS and ERG gene and t (7;22) which is due to fusion between EWS and ETV1 located on chromosome 7p22. [13]

Good prognostic factors include longer duration of symptoms (>6 months), female gender, absence of systemic symptoms, absence of metastases at diagnosis, peripheral location of tumor, tumor <8 cm, small cell histology, initial LDH <170 IU/L, White blood count (WBC) <7000/cu mm, lymphocyte count <2000, and platelet <400,000/cu mm. [14]

Multimodal therapy is the treatment of choice in cranial EWS. Total or subtotal excision of the mass followed by post-operative RT and chemotherapy gives good results with a 2-5 year disease-free survival of 50-80%. [5],[14] Most studies suggest radical excision of the lesion, but this may not be possible when there is involvement of technically difficult areas like the petrous region and clivus. When the tumor affects the cranial bone, surgical resection is necessary. This helps to decompress vital neural structures and decrease the primary tumor mass. Post-operative chemotherapy with a four-drug regimen using vincristine, cyclophosphamide, actinomycin D, and doxorubicin is considered superior to the three-drug regimen of vincristine, cyclophosphamide, and doxorubicin. [15],[16] RT as the sole treatment is indicated in inoperable cases of skull, spine, and sacrum. EWS of the calvarium generally has a good prognosis following multi-modal treatment. RT is indicated to reduce or prevent loco regional recurrences. It is used as an adjuvant after incomplete excision or positive microscopic margins. Most of our cases had parietal bone involvement. Complete excision with negative margins was possible in these cases, hence RT was not employed. In the one case, the patient's relatives refused RT, hence RT was not given. Pre-operative chemotherapy followed by surgery followed by post-operative chemotherapy and RT gives good results in extra-cranial EWS. This helps to downstage the tumor and obviates the need for large surgical fields and closure of large defects. Primary EWS of the cranium rarely metastasizes. Development of metastases is the main factor in treatment failure.

Peripheral PNETs differ from central PNETs in that the former have a better prognosis. [17] CD99 positivity is seen in cranial EWS and not in central PNET's. Translocation studies may be used to differentiate between the two. The chromosomal translocation t (11;22) is observed in peripheral PNETs and is quite characteristic. It is not seen in central PNETs. In contrast to medulloblastoma the occurrence of isochromosome 17q is very rare in peripheral PNETs. Treatment protocols used in these two entities are different.

Cranial EWS behaves differently when compared to their peripheral counterparts. They differ in clinical presentation, radiological picture, low incidence of metastases, propensity to involve dura often, treatment, and outcome. The reason may be due to the putative cell of origin or may lie at the molecular level. The mesenchymal stem cell is proposed as the cell of origin for this family of tumors, but there could be other cell types which may give rise to this tumor based on its ability to occur at multiple sites. [18] Differences are observed even within cranial EWS in that the calvarial and meningeal variety do better than the skull base lesions.

In our study, parieto-occipital region was the commonest site of involvement. Most patients presented with localized disease and swelling of the scalp. Excision followed by chemotherapy or RT appears to have good survival rates. At a median follow-up in our study of 32.2 months, only one patient had a recurrence, and was successfully salvaged with second line chemotherapy.

 
 > References Top

1.Paulus W, Slowik F, Jellinger K. Primary intracranial sarcomas: Histopathological features of 19 cases. Histopathology 1991;18:395-402.  Back to cited text no. 1
    
2.Pritchard DJ, Dahlin DC, Dauphine RT, Taylor WF, Beabout JW. Ewing′s sarcoma. A clinicopathological and statistical analysis of patients surviving five years or longer. J Bone Joint Surg Am 1975;57:10-6.  Back to cited text no. 2
[PUBMED]    
3.Dahlin D. Ewing′s tumor Bone Tumours: General Aspects and Data on 6221 Cases. 3 rd ed. Springfield, IL: Charles C. Thomas; 1978. p. 278.  Back to cited text no. 3
    
4.Desai KI, Nadkarni TD, Goel A, Muzumdar DP, Naresh KN, Nair CN. Primary Ewing′s sarcoma of the cranium. Neurosurgery 2000;46:62-8.  Back to cited text no. 4
    
5.Vohra VG. Roentgen manifestations in Ewing′s sarcoma. A study of 156 cases. Cancer 1967;20:727-33.  Back to cited text no. 5
[PUBMED]    
6.Coley BL.: Neoplasms of Bone and related Conditions. New York: Paul B Hoeber 1949. p. 297-318.  Back to cited text no. 6
    
7.BA Syed. Primary intracranial ewings sarcoma of calvarium presenting as acute neurosurgical emergency. Case report and literature review. Pan Arab J Neurosurg 1999;3:1.  Back to cited text no. 7
    
8.Agrawal A, Dulani R, Mahadevan A, Vagaha SJ, Vagha J, Shankar SK. Primary Ewing′s sarcoma of the frontal bone with intracranial extension. J Cancer Res Ther 2009;5:208-9.  Back to cited text no. 8
    
9.Kuzeyli K, Aktürk F, Reis A, Cakir E, Baykal S, Pekínce A, et al. Primary Ewing′s sarcoma of the temporal bone with intracranial, extracranial and intraorbital extension. Case report. Neurosurg Rev 1997;20:132-4.  Back to cited text no. 9
    
10.Steinbok P, Flodmark O, Norman MG, Chan KW, Fryer CJ. Primary Ewing′s sarcoma of the base of the skull. Neurosurgery 1986;19:104-7.  Back to cited text no. 10
[PUBMED]    
11.Yildizhan A, Gezen F. Primary Ewing′s sarcoma of the skull: Follow-up with bone scanning. Neurosurg Rev 1992;15:225-9.  Back to cited text no. 11
    
12.Lam DS, Li CK, Cheng LL, Teo JG, Chik KW, Kwan WH, et al. Primary orbital Ewing′s sarcoma: Report of a case and review of the literature. Eye (Lond) 1999;13:38-42.  Back to cited text no. 12
    
13.Salunke PS, Gupta K, Malik V, Kumar N, Henke LE, Cai C, et al. Primary Ewing′s sarcoma of cranial bones: Analysis of ten patients. Acta Neurochir (Wien) 2011;153:1477-85.  Back to cited text no. 13
    
14.Alvarez-Berdecia A, Schut L, Bruce DA. Localized primary intracranial Ewing′s sarcoma of the orbital roof. Case report. J Neurosurg 1979;50:811-3.  Back to cited text no. 14
[PUBMED]    
15.Dunst J, Sauer R. Therapy of Ewing′s sarcoma. Strahlenther Onkol 1993;169:695-708.  Back to cited text no. 15
    
16.Bhatoe HS, Deshpande GU. Primary cranial Ewing′s sarcoma. Br J Neurosurg 1998;12:165-9.  Back to cited text no. 16
    
17.Dedeurwaerdere F, Giannini C, Sciot R, Rubin BP, Perilongo G, Borghi L, et al. Primary peripheral PNET/Ewing′s sarcoma of the dura: A clinicopathologic entity distinct from central PNET. Mod Pathol 2002;15:673-8.  Back to cited text no. 17
    
18.Salunke PS, Gupta K, Pfeifer JD. The cell of origin of cranial Ewings sarcoma: The dilemma persists. Acta Neurochir (Wein) 2012;154:567-8.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Case report>Discussion>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed2629    
    Printed44    
    Emailed0    
    PDF Downloaded167    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]