Genomic and clinicopathologic analysis of conventional dendritic cell sarcomas coexisting with myeloid neoplasms

Langerhans cell sarcoma (LCS), malignant indeterminate dendritic cell tumor (IDCT), and interdigitating dendritic cell sarcoma (IDCS) are rare malignant neoplasms that originate from antigen-presenting conventional dendritic cells (cDCs). These tumors, collectively termed cDC sarcoma in this study, have been reported only rarely in association with myeloid malignancies. We collected five cases of cDC sarcoma coexisting with acute myeloid leukemia (AML) or myelodysplastic neoplasm with increased blasts (MDS-IB), conducted clinicopathologic and genetic analyses, and compared these with four reported cases. Among the nine cases, histological subtypes included LCS (n = 6), malignant IDCT (n = 2), and IDCS (n = 1), whereas associated myeloid neoplasms comprised AML (n = 8) and MDS-IB2 (n = 1). Clinically, five patients developed cDC sarcoma and AML/MDS-IB nearly simultaneously, whereas four developed AML after cDC sarcoma. Six patients died or required palliative care within 2 years, whereas three achieved complete remission or long-term survival. Nodal involvement predominated (8/9 cases). Immunohistochemically, cDC sarcomas frequently expressed myeloid markers (CD33 5/5; CD34 2/8). Conversely, myeloid blasts expressed histiocytic/monocytic-associated markers including CD68 and lysozyme in 3/5 cases, whereas S-100 and CD1a were focally expressed in only one case. Genetically, next-generation sequencing revealed shared mutations-including those in the RAS-MAPK pathway-in four of five paired cases. Further, one case harbored a shared KMT2A rearrangement, which supports a common clonal origin. These results indicate a close biological relationship between cDC sarcoma and myeloid neoplasms and highlight the importance of recognizing concomitant myeloid disease in patients with cDC sarcoma.