Histiocytic sarcoma with a common clonal origin emerged after 33 years from B-cell precursor acute lymphoblastic leukemia.

Histiocytic sarcoma (HS) is a rare, aggressive malignant neoplasm characterized by histiocytic features, frequently presenting in advanced clinical stages and associated with a poor prognosis. Although HS can occur sporadically or secondary to other hematological malignancies, cases with a long latency period have been rarely reported. This case report presents a unique case of secondary HS diagnosed 33 years and seven months after the initial diagnosis of B-cell precursor acute lymphoblastic leukemia. Both neoplasms shared identical immunoglobulin heavy chain and T-cell receptor gene rearrangements, confirming a clonal relationship. To the best of our knowledge, this case represents the longest reported interval between primary leukemia and secondary HS, highlighting the potential for lineage switching and transformation over extended periods. These findings underscore the need for ongoing research on the mechanisms underlying "transdifferentiation", including the roles of transcription factors, cytokine signaling, and epigenetic modifications.