Inflammation as a cause of headache in patients with pituitary adenomas

Introduction: Headache is a common clinical finding in patients with space-occupying lesions in the sellar region. Irritation of pain-sensitive structures (e.g. dura mater and blood vessel walls) caused by tumor growth but also the personality structure of the individual patient are implicated in this process, but reliable data are missing. To evaluate a possible role of inflammation in the pathophysiology of headache, we analyzed the existence of lymphocytic infiltrations in tissue samples collected from patients (n = 104) who underwent surgical removal mainly of pituitary adenomas but also other sellar lesions. Methods: Headache prevalence was assessed using the MIDAS Questionnaire. Lymphocytic infiltrations were uncovered by immunohistochemistry with antibodies directed against CD3, CD20 and CD45. The extent of inflammation was scored in three different anatomical regions separately (i.e. perinasal mucosa, parasellar dura and tumor bulk). Depending on the extent of lymphocytic infiltrations we defined three different groups: A = no staining to single cells; B = small scattered cell groups; C = moderate to massive tissue infiltration by lymphocytes forming follicle-like structures. Results: We were able to show, that the extent of inflammation within pituitary adenomas is associated with the presence of headache (Mann-Whitney-U-Test: p = 0.028 for CD 45, p = 0.031 for CD3). Additionally, there is a strong correlation between headache and gender (70% in women compared to 34.7% in men) confirming pre-existing findings i.e. in primary headache. In contrast, there was no correlation between headache and lymphocytic infiltrations in tumor surrounding structures or the other space occupying lesions under study. Conclusion: Our results strongly suggest that inflammatory events within sellar tumors are more frequent than expected and could be involved in the pathogenesis of headache.