If PET is positive, what confirmatory test should come next?

A positive PET does not confirm neurosarcoidosis. The next step is tissue: a biopsy showing non-caseating granulomas.

FDG-PET lights up inflammation, not a specific disease. In the case reports here, PET showed FDG-avid areas in neck, chest, pelvis and groin [1], and symmetric diffuse uptake read as sarcoid myositis [1]. Neither scan made the diagnosis. The diagnosis came from biopsy: EBUS biopsy showing multiple non-caseating granulomas [1]. The same pattern in the second case, where EBUS biopsy found non-caseating granulomas [1].

So the confirmatory test is a biopsy of the most accessible PET-positive site, ideally guided by the PET itself. The review record lists non-caseating granulomas on biopsy as the histologic finding for neurosarcoidosis [3]. Where the lesion is in the brain or meninges, that means a targeted brain or meningeal biopsy, which is invasive and can miss the lesion.

The honest limit: nothing in these records tells you how often a PET-guided biopsy of a specific site confirms neurosarcoidosis, or what to do when the biopsy is negative. One case here was diagnosed as "possible neurosarcoidosis" without pathological confirmation at all, on MRI dural enhancement plus CSF lymphocytic pleocytosis with elevated β2-microglobulin, neopterin and IL-2R, and a normal ACE [2]. That is a real fallback when biopsy is not safe, but it is a weaker diagnosis, not a confirmed one.

My call: biopsy the hottest accessible PET site before aHSCT, and treat a negative biopsy as unresolved, not as clearance. Confidence: moderate, because the biopsy-first logic is consistent across these records but no study here measured how well PET-guided biopsy confirms neurosarcoidosis before transplant.