Histiocytic sarcoma (HS)—an aggressive hematopoietic malignancy originating from dendritic cells or cells of the macrophage lineage with gross and histologic features that overlap with other neoplasms in laboratory rodents—is a diagnostic challenge in exotic species. HS has not been reported previously in the Brazilian red-rumped agouti (Dasyprocta leporina), to our knowledge. Here, we describe a case of an agouti in which the primary differential diagnosis, based on its location and gross appearance, was chemodectoma. Although the mass grossly resembled a neuroendocrine tumor, histologic and immunohistochemical findings confirmed HS, with variable immunoreactivity for IBA1, CD204, MHC II, and CD163, and no immunolabeling by neuroendocrine and endothelial cell markers. Our case highlights the diagnostic challenges of cranial mediastinal tumors in exotic animals—emphasizing the value of integrating gross, histologic, and immunohistochemical data in the evaluation of thoracic neoplasia and the utility of comparative pathology in exotic species with minimal data available.
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