Comparison of infectious and noninfectious intracranial caseating granulomas

Although caseating granulomas are classically associated with infectious processes, a subgroup of intracranial caseating granulomas without identifiable infectious pathology (ICGN) is described. We aimed to identify clinical, laboratory, radiological and histological markers with potential to distinguish patients with ICGN from those with intracranial caseating granulomas with infectious etiology (ICGI) on tissue microbiological examinations. In a referral hospital setting, we identified 11 patients with ICGNs and 6 patients with ICGI over an 11-year period. The two groups had similar demographics (other than higher infection risk factors in ICGIs), clinical presentation, serology, location of lesions and cellular composition of the inflammatory infiltrate. Significant differences were the homogenous vs. ring pattern of enhancement on neuroimaging and small (<1 mm) vs. large (>1 mm) area of necrosis on histological examination, in ICGNs and ICGIs, respectively. The dichotomy was best reflected in the response of ICGNs to immunomodulatory and not antimicrobial treatment and the reverse pattern in ICGIs. Based on these findings, we suggest a scheme for the diagnosis of ICGN: (i) caseating granulomas with areas of necrosis predominantly <1 mm in diameter; (ii) absence of an identifiable infectious agent in extensive tissue examinations; and (iii) no clinical and radiological response within 2 months of appropriate antimicrobial treatment.