Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment

<jats:title>Abstract</jats:title><jats:p>Histiocytic sarcoma (<jats:styled-content style="fixed-case">HS</jats:styled-content>) is an extremely rare non‐Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary <jats:styled-content style="fixed-case">HS</jats:styled-content>. Deriving conclusions from previously reported cases of <jats:styled-content style="fixed-case">HS</jats:styled-content> arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72‐year‐old man with a diagnosis of chronic myeloid leukemia (<jats:styled-content style="fixed-case">CML</jats:styled-content>), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of <jats:styled-content style="fixed-case">HS</jats:styled-content>. The liver mass showed a retained <jats:styled-content style="fixed-case">BCR</jats:styled-content>‐<jats:styled-content style="fixed-case">ABL</jats:styled-content>1 translocation suggesting clonality between the <jats:styled-content style="fixed-case">CML</jats:styled-content> and <jats:styled-content style="fixed-case">HS</jats:styled-content>. As seen in our case and other reported cases of <jats:styled-content style="fixed-case">HS</jats:styled-content> derived secondarily, the concurrent expression of immunoglobulin heavy (<jats:styled-content style="fixed-case">IGH</jats:styled-content>)‐/light‐chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.</jats:p>