A Review of Neuropathological Features of Familial and Adult Hemophagocytic Lymphohistiocytosis.

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is a hematological disorder that can be due to genetic (primary HLH) causes or excessive activation of the immune system in association with infection, malignancy, rheumatologic disorders, or immune suppression (secondary HLH). Hemophagocytic lymphohistiocytosis remains an under-recognized condition among neuropathologists, especially the secondary forms, where it may be diagnosed only at brain biopsy or autopsy due to confounding comorbidities. The CNS is frequently affected, but neuropathological features are underappreciated. We place our own experience with HLH in context with review of neuropathological features from the literature. A 10-year database search for cases from our pediatric and adult hospitals with re-review of neuropathological features revealed 1 biopsy and 5 autopsies. Literature that reported neuropathological features was tabulated and 8 adult and 12 pediatric cases were identified. Children had predominantly secondary HLH 5/12 co-associated with Epstein Barr (or dual) viral infections, 3/12 with malignancy. One biopsy showed florid lymphohistiocytic infiltrates and hemophagocytosis and served as first diagnosis; 2/5 CNS autopsies had originally been reported as negative for HLH, but on re-review had subtle lymphohistiocytic infiltrates with hemophagocytosis confined to leptomeninges. In conclusion, the neuropathological features are highly variable in HLH; features such as focal erythrophagocytosis may be histologically subtle in early phases, but should be sought.