Characterizing Histiocytosis With 68Ga-FAPI PET/CT

Histiocytic disorders are rare diseases that are characterized by tissue infiltration of histiocytes (dendritic cells) and other inflammatory white blood cells. The archaic term "histiocyte" refers to large white blood cells resident in tissues and includes Langerhans cells, monocytes/macrophages, and dermal/interstitial dendritic cells. The Histiocytic Society classification divides histiocytic disorders into five categories, based on clinical, histologic, immunophenotypic, and molecular features. They are langerhans (L) group, cutaneous and mucocutaneous (C) group, Rosai-Dorfman disease (R) group, malignant histiocytosis (M) group and hemophagocytic lymphohistiocytosis (H) group. Langerhans cell histiocytosis is the most common histiocytic disorder. Less common types include Erdheim-Chester disease, Rosai-Dorfman disease, adult and juvenile xanthogranuloma. Diagnosis, which relies on a multidisciplinary approach, is challenging and often delayed because clinical findings are nonspecific and may mimic malignant processes at radiologic evaluation. Compared with conventional imaging, PET/CT allows detection of the increased metabolic activity in histiocytes and provides a comprehensive whole-body evaluation of their potential involvement with multiple organ systems and allows monitoring of therapeutic response. However, one drawback is that the uptake of FDG is nonspecific because histiocytic lesions may mimic neoplastic processes at PET/CT. And the physiological FDG metabolism in brain, liver and gastrointestinal tract, et al. hampers the detection rate of lesions located in these organs.68Ga-FAPI has been developed as a tumor-targeting agent as fibroblast activation protein is overexpressed in cancer-associated fibroblasts and it might be a pan-tumor PET agent. Although the pathogenesis of histiocytosis may be attributable to mutations in the oncogenic driver, recent discoveries have shown that inflammation and fibrosis secondary to mutated histiocytes, rather than a proliferative cell mechanism, result in manifestation of the disease. Considering 68Ga-FAPI revealing cancer-associated fibroblasts, the investigators aim to carry out this prospective study to investigate the role of 68Ga-FAPI PET/CT in the diagnosis, therapy response assessment and follow-up of histiocytosis.