An 8-y-old, spayed female Bernese Mountain Dog was presented to a referral center for evaluation of right thoracic limb lameness and previously suspected Evans syndrome that had been poorly responsive to immunosuppressive therapy. Based on review of examination findings and laboratory data, Evans syndrome was deemed unlikely and hemophagocytic histiocytic sarcoma (HHS) was strongly suspected. On blood smear evaluation, atypical, histiocytic cells were noted, some of which exhibited siderophagia. Considering that circulating cells are not typically observed in dogs with HHS, additional diagnostic investigation was performed. Autopsy and histopathology revealed that the dog had a mixed form of HS (dendritic-cell origin HS in the lung, and HHS in the spleen, liver, and bone marrow), and immunocytochemical characterization of cultured cells derived from blood suggested that the cells were of dendritic HS origin, rather than HHS origin, as originally suspected. Whole-exome sequencing revealed genetic similarity between cell lines derived from lung tissue and blood, providing additional evidence of the relatedness of these 2 cell populations. Our case highlights the rare entity of mixed HS and typifies the inherent challenges in classifying rare, atypical, circulating neoplastic cells.
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