Epidemiologic Evaluation of Central Nervous System Sarcomas in Iran: A 2009-2014 Survey

  

    
Region of Iran
    
Number of affected patients (Percentage)
  
  

    
Central parts
    
115 (38.59%)
  
  

    
Southern parts
    
58 (19.46%)
  
  

    
Eastern parts
    
53 (17.78%)
  
  

    
Western parts
    
42 (14.09%)
  
  

    
Northern parts
    
30 (10.06%)
  
  

    
Total
    
298 (100%)
  

Table 6: CNS sarcomas distribution based on country’s territories.

Discussion

Based on histopathological classifications, subtypes of bone sarcomas are osteosarcoma, chondroblastoma, poorly differentiated round or spindle cell tumors, chordoma and neural sheet tumors [15]. Also, soft tissue sarcoma subtypes include liposarcoma, fibrosarcoma, leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, gastrointestinal stromal tumor and undifferentiated sarcomas, along with other less frequent subtypes [16]. Although no exact mechanism or etiology is found to be responsible for development of sarcomas, several environmental and genetic mutations risk factors are considered to play important role in transformation of mesenchymal cells to different sarcoma subtypes. To give an instance, chromosomal translocation of chromosome 11 and chromosome 22 which results in EWS gene is associated with Ewing sarcoma [17]. Also, duplication of a part of chromosome 12 and resultant CDK4 gene and MDM2 gene play a significant role in development liposarcoma [18]. Furthermore, CSF1 gene which follows chromosomal translocation between chromosome 1 and chromosome 2, is related to increased risk of development of giant cell tumors of soft tissue [19]. Primary CNS sarcomas are primitive non-meningothelial tumors which represent about 0.2% of all intracranial malignancies, with equal trend to affect both sexes at any age [20-22]. Despite the trivial risk, sarcoma’s burden on affected patients demands our fortified understanding of its natural history and pathogenesis to reach acceptable standards towards appropriate management of sarcomas individually. As stated above, mesenchymal origin of sarcomas provides emersion of wide variety of subtypes of both bone and soft tissue sarcomas [23]. Although rare, wide variety of presentation and subtypes have made Soft Tissue Sarcomas (STSs) a challenging malignancy with somehow unknown etiologic background.

In a report on 13 Children, Adolescent and Young Adults (CAYA) from 1990 to 2015, it is found that the affected patients with primary IS have mean age of 7 years, while another report on CAYA patient groups from 1990 to 2001, revealed the mean age of diagnosis of primary IS as 16.9 years [24,25]. In addition to the mentioned data of former report from United States of mean age of diagnosis, this 25-year observation stated unclassified sarcoma, followed by chondrosarcoma and rhabdomyosarcoma [24]. Also, Benesch et al conducted a cooperative study in Austria from 1988 to 2009 on 19 CAYA age group cases diagnosed with CNS sarcomas with mean age of 9.7 age with unspecified sarcoma was the most encountered histological type, followed by embryonal rhabdomyosarcoma, chondrosarcoma and malignant mesenchymal tumor [25]. Moreover, Al Ghahtany performed a similar study on 16 CAYA age group patients with CNS sarcoma with mean age of 4.8 and found 14 patients with intracranial sarcoma followed by the rest as spinal sarcomas in Canada [26]. Given the above results of mentioned researches, this study includes a considerable greater population of patients with age group 1 (0-14) which is comparable to CAYA age group (0-19), with similar first major subtype as unspecified sarcoma (22.5%) to other two studies, followed by desmoplastic small round cell and gliosarcoma (12.9% each) which demonstrated different sequence compared to previous surveys. Away from CAYA age group, Tihan et al reported a 20-year survey on 43 cases diagnosed with primary CNS sarcomas with mean age of 40.3 years (3-75 years). In this study which was performed in United States and published in 2007, 16 cases were diagnosed with hemangiopericytoma, followed by 15 cases with chondrosarcoma and 3 with solitary fibrous tumor [27]. In addition, another 40-year report on 18 cases aged between 3-63 years (mean age 28) affected with primary IS revealed 15 cases with cerebral sarcoma, 2 with cerebellum involvement and one with spinal sarcoma [28]. Their histopathological evaluation exhibit fibrosarcoma, malignant fibrous histiocytoma and undifferentiated sarcoma as the most common tumor types in descending manner. Although Oliveira et al did not report detailed subtypes based on patient’s age group, regarding their mean age of 28 years, our age group 2 (15-64) most common sarcoma types exhibit different sequence, as gliosarcoma (18.9%) chordoma 11.8% and desmoplastic small round cell tumor (11%). Although former surveys that were conducted on developed countries, demonstrates different sequence of common CNS sarcoma types based on their histopathologic features, authors believe that our results may act as a considerable representative of epidemiological and histopathological features of developing countries with different values compared to developed ones.

Despite scant available data on tumorigenesis of primary IS, studies suggest activation of receptor tyrosine kinase and angiogenesis pathways in most of the pediatric ISs [29,30]. Also, overexpression of platelet-derived growth factor receptor was found to be associated with osteosarcoma, rhabdomyosarcoma and Ewing sarcoma [31]. Beside special molecular and genetic processes responsible for development of this cancer, sarcomas are linked to multiple environmental offenders, such as ionizing radiation, alkylating agents and vinyl chloride and arsenic exposure. Moreover, sarcomas are associated with certain syndromes, including Li-fraumeni and neurofibromatosis type 1 [32,33]. Regarding primary IS, similar to other space occupying lesions, its clinical and neurological manifestation is consistent with tumor’s location. Despite its natural tendency to originate from various cells in different locations, existing evidence suggest primary IS’s predilection towards supra-tentorial regions, mostly affecting temporal and parietal lobes [34]. Neurological symptoms range from asymptomatic and mild headache, to significant neurological deficit and altered level of consciousness. However, multiple histopathological subtypes were found in previous conducted studies, being mostly reported as undifferentiated sarcomas, followed by chordoma, chondrosarcoma and rhabdomyosarcoma, as well as other less frequent subtypes [35-37]. Our analysis revealed obvious male to female dominance regarding prevalence of CNS sarcomas, with three quarters of the patients being in second age group category from 15- 64 years (76.17%), followed by age group III (13.42%) and I (10.4%), showing higher tendency of CNS sarcomas to affect people away from their extremes of their ages. Our ASIR analysis revealed lower ASIR of CNS Sarcomas than expected number of cases compared to standard world population by WHO’s ASIR as 0.035 person per 100000-years. Also, our evidence suggests CNS sarcoma’s trend to affect brain roughly 2 times more than spinal cord and isolated meningeal layers of less than 5%. Also, WHO classification of CNS sarcomas of our studied patients revealed significant grade 9 or tumors of uncertain differentiation compared to other subtypes. Gliosarcoma represents the most frequent detected CNS sarcoma, followed by desmoplastic small round cell tumor, chordoma, malignant peripheral nerve sheet tumor and hemangiopericytoma malignant as top 5 lesions based on frequency. Moreover, our detailed report of patient’s geographical distribution pattern may provide potential fields for environmental and public health activist to use this data as a primary reference in their future plans.

Conclusion

Coherent with various subtypes, multiple medical and surgical approaches have been suggested for patients diagnosed with primary IS. However, due to lack of unified viewpoint of its natural history and existence of criteria for selection of appropriate management approach, insufficiency of an optimal strategy towards primary IS, is perceived. This is the first report of epidemiological assessment of CNS sarcomas in Iran, which can act as a foundation for better understanding the underlying pathophysiological mechanism and selection of optimal treatment strategies based on improved understanding of these neoplasms.

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