Erdheim-Chester Disease: Cytomorphologic Clues for a Rare Histiocytic Neoplasm Including a Distinct Tigroid Background Pattern on Smears

We present the cytomorphologic features of Erdheim-Chester disease (ECD) from 7 patients who have a confirmed diagnosis of ECD, including correlation with the histology on the needle core biopsies. ECD is a rare multi-organ neoplastic histiocytic disorder. The most common locations of involvement are long bones, retroperitoneum, and vasculature. Cytologic preparations often show scant cellularity. Even when neoplastic histiocytes are present on smears, they may be readily overlooked as they are not typically monomorphic, and instead exhibit a variety of morphologies from epithelioid to spindled, with multinucleated giant cells variably present. To our knowledge, ours is the first description of a distinct reticular or tigroid background on smears that is variably present due to rupture of the foamy neoplastic cells. Typically, smears from a targeted mass lesion from any site showing scant polymorphous histiocytes would be regarded as non-diagnostic. A diagnosis of ECD in all cases was based on the needle core biopsy with corresponding immunohistochemical (IHC) stains and BRAF mutational analysis, except for one case in which molecular analysis was not able to be performed. We present these cases to alert practicing cytopathologists to the pitfalls related to the highly variable location, smear cellularity, and cytomorphology of ECD, which should prompt the request of dedicated tissue cores at the time of rapid on-site evaluation and trigger careful clinical-radiologic correlation, as well as consultation with hematopathology colleagues.