Introduction
============

Hemangioblastoma refers to a benign vascular neoplasm that comprises stromal and capillary cells ([@B1]). Based on the classification of nervous system tumors proposed by the WHO, hemangioblastomas are classified as Grade I meningeal tumors of uncertain origin ([@B2], [@B3]). These tumors are found almost exclusively in the central nervous system (CNS) and rarely occur in the peripheral nervous system. They can occur sporadically in 60%-75% of cases or in association with von Hippel-Lindau (VHL) disease in 20%-40% of cases ([@B4], [@B5]). Sporadic lesions have a later onset (40-50 yr) compared to VHL-associated tumors (30-40 yr) ([@B6]). Hemangioblastomas account for 0.9% to 2.1% of all primary CNS tumors and most commonly affect the cerebellum (63%), followed by spinal cord (32%) ([@B7], [@B8]) and medulla (5%) ([@B9]). The tumor has also been rarely reported in other locations including supratentorial compartment ([@B10]-[@B12]), sella turcica ([@B13]), optic nerve ([@B14], [@B15]), ventricular system ([@B16], [@B17]) peripheral nerves ([@B18], [@B19]) or soft tissues ([@B20]). Males are 1.5 to 2 times more frequently affected by hemangioblastomas compared to females.

On neuroimaging studies, the lesions appear as either small contrast-enhancing mural nodules with associated pseudocysts in 30% to 80% of cases, or solid tumors ([@B21]). The clinical presentation of hemangioblastoma is caused by the mass effect of the tumor or impairment of cerebrospinal fluid and depends on the anatomical location and growth pattern of the lesion ([@B22]-[@B24]). Generally, intracranial lesions present with a long history of minor neurological symptoms followed by an abrupt exacerbation. Ataxia, discoordination or increased intracranial pressure can be seen in cerebellar hemangioblastomas and spinal cord lesions can be associated with pain and signs of spinal cord compression.

Considering the low incidence of hemangioblastoma and the consequent lack of information on this entity particularly in Iran, hereby we present basic demographic characteristics of hemangioblastoma tumors diagnosed in the patients referring to Shohada-e-Tajrish Hospital, Tehran, Iran during 2004-2014.

Materials & Methods
===================

In this descriptive retrospective study, the archives of pathology reports were reviewed in the Department of Pathology of Shohada-e-Tajrish Hospital and patients with definite diagnosis of hemangioblastoma made through histopathological examinations during 2004-2014 were identified. Age, gender and the location of tumor were extracted from the medical records and entered into SPSS statistical software v.22 ([@B25]) for analysis.

The study was approved by Ethics Committee of the hospital.

Results
=======

Thirty patients including 16 males (53.3%) and 14 females (46.7%) were identified. The mean age of the patients was calculated to be 41.2±13.47 yr, ranging from 19 to 62 yr old. The mean age of male subjects was slightly higher than that of females (41.75 vs. 40.57 yr). The majority of lesions had been found in the cerebellum of the patients (93.3%); only one had occurred in the cerebrum (3.3%) and another in the fourth ventricle (3.3%) ([Table 1](#T1){ref-type="table"}). Overall, 28 lesions found in the cerebellum, 3 (10.0%) were reported in the right hemisphere, 7 (23.3%) in the left hemisphere and the remaining 18 (60.0%) were just reported to be in the cerebellum and their exact location was not recorded. [Table 2](#T2){ref-type="table"} presents age- gender and site-wise distribution of the 30 cases included in this study.

Discussion
==========

Overall, 30 patients with definite diagnosis of hemangioblastoma were identified in the pathology archives of Shohada-e-Tajrish Hospital. The mean age of the patients was found to be 41.2±13.47 yr, ranging from 19 to 62 yr old, which was quite compatible with the results of previous reports ([@B4], [@B6], [@B7], [@B26], [@B27]). Cerebellum was the most commonly affected location by the tumors accounting for 93.3% of cases. This figure was slightly higher than the reports of previous studies. Overall, 63% of cerebellum involvement was reported in patients with CNS hemangioblastomas ([@B6]). The second most common affected site has been reported by multiple studies to be the spinal cord ([@B2], [@B4], [@B6], [@B23], [@B27]) while none of the cases included in our study had tumors of this location. Instead the two sites affected by hemangioblastomas other than cerebellum were found to be cerebrum in one patient and the fourth ventricle in another. A male preponderance was observed in the present case series with a ratio of 1.14. Some of the previous studies had shown equal risk in both genders ([@B28]) while other surveys have reported the same male preponderance as found in the present study ([@B4], [@B6], [@B7],[@B29]).

Hemangioblastomas are adherent to the pia mater and have a well-defined border. They usually are bright red or red-orange due to the extreme vascularity from the pial vessels ([@B30]). The tumor consists of yellow areas of the lipid-laden stromal cells with a spongy and hemorrhagic cut surface. The majority of its vascular components consists comprise small capillaries that may lead to larger vessels. The lesion might also have peritumoral cysts fluid filled and surrounded by Rosenthal fibers and reactive gliosis ([@B6]).

###### 

Demographic characteristics of the patients

  Age (yr)                                                          41.2±13.47
  ------------------------------- --------------------------------- ------------
  Gender                          Male                              16 (53.3%)
  Female                          14 (46.7%)                        
  Site                            Cerebellum (Side not specified)   18 (60.0%)
  Cerebellum (Right hemisphere)   3 (10.0%)                         
  Cerebellum (Left hemisphere)    7 (23.3%)                         
  Fourth ventricle                1 (3.3%)                          
  Cerebrum                        1 (3.3%)                          

###### 

Age-gender- and site-wise distribution of hemangioblastoma cases

  **Year**   **Age(yr)**   **Gender**                      **Site**
  ---------- ------------- ------------------------------- -------------------------------
  2004       52            Female                          Cerebellum
  2005       59            Female                          Cerebellum
  62         Female        Cerebellum                      
  2006       50            Male                            Cerebellum (Right hemisphere)
  48         Male          Cerebellum (Left hemisphere)    
  62         Female        Cerebellum (Left hemisphere)    
  2007       23            Male                            Cerebellum
  31         Male          Cerebellum                      
  19         Female        Fourth ventricle                
  28         Female        Cerebellum (Right hemisphere)   
  2008       49            Male                            Cerebellum
  24         Female        Cerebellum                      
  53         Female        Cerebellum                      
  2009       48            Male                            Cerebellum
  61         Male          Cerebellum                      
  23         Male          Cerebellum                      
  38         Female        Cerebellum (Left hemisphere)    
  20         Female        Cerebellum                      
  39         Female        Cerebellum                      
  41         Female        Cerebellum (Left hemisphere)    
  27         Female        Cerebellum                      
  2010       45            Male                            Cerebellum
  34         Male          Cerebellum                      
  2011       42            Male                            Cerebellum (Right hemisphere)
  27         Male          Cerebellum (Left hemisphere)    
  2012       43            Male                            Cerebellum (Left hemisphere)
  58         Male          Cerebellum                      
  32         Male          Cerebrum                        
  2013       44            Female                          Cerebellum (Left hemisphere)
  2014       54            Male                            Cerebellum

As highly vascular tumors, hemangioblastomas can consist of variable proportions of capillary-sized thin walled vessels interweaved with pericytes and inhibin-expressing, round or polygonal, vacuolated stromal cells of uncertain origin ([@B31]). These stromal cells are lightly periodic acid-Schiff (PAS) positive and have a lipid-rich, pale eosinophilic cytoplasm. The nuclei of these cells are round or oval and centrally located and might show considerable pleomorphism such as karyomegaly, irregularities of the nuclear membrane and hyperchromasia. Specific organelles or intracellular attachments might lack in these stromal cells but various lipid droplets and glycogen particles might be found in their cytoplasm ([@B32]). Weibel-Palade-like bodies and neurosecretory granule-like structures have also been described by some studies. Uncommonly, mitotic figures do not affect the clinical characteristics of the lesion. A second somatic mutation of the VHL allele is present in these stromal cells and so they are considered as the neoplastic element in hemangioblastomas. In the reticular variant of the lesion, vascular components are predominant while the stromal components predominate in the cellular variant ([@B6]).

The treatment of choice for hemangioblastomas is surgical excision and radiotherapy is reserved for non-resectable or recurrent lesions ([@B33]). Tumor regrowth might be associated with solid lesions and paucity of stromal cells within the tumor ([@B34]). VHL disease has been shown to be accompanied by an increased risk for multifocal hemangioblastomas and extracerebellar lesion ([@B9]).

**In conclusion,**cerebellum is the most commonly affected location in patients with CNS hemangioblastomas, and a male preponderance is observed in these cases.

The authors would like to thank all the staff of Shohada-e-Tajrish Hospital, who helped us in conducting this study.

Authors' Contribution
=====================

Mahsa Ahadi, Mahsa Ahadi, Azadeh Rakhshan, Afshin

Moradi: Study concepts

Mahsa Ahadi, Mitra Rafizadeh, Davood Talebi Bayazi:

Study design

Mahsa Ahadi, Mahsa Ahadi, Mitra Rafizadeh, Afshin

Moradi: Data acquisition

Davood Talebi Bayazi, Masoud Baikpour, Afshin

Moradi: Data analysis and interpretation

Mitra Rafizadeh, Masoud Baikpour, Afshin Moradi:

Manuscript preparation

Mahsa Ahadi, Mahsa Ahadi, Azadeh Rakhshan,

Afshin Moradi: Manuscript editing

All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Conflict of interest
====================

The authors declare that there is no conflict of interests.
