86. Diagnostic challenges of high-grade myeloid malignancies with partial plasmacytoid dendritic cell differentiation

Aly Abdelkareem

Karen Nahmod

Dr. Karen Nahmod obtained her Medical degree (MD) and a Ph.D. in Immunology from the University of Buenos Aires, Argentina, where she graduated with Honors. Since very early, she has been actively involved in teaching, including Biochemistry, Pharmacology, Histopathology, and Immunology, which significantly contributed to building her academic background. Dr. Nahmod completed a research postdoctoral fellowship at the Laboratory of Immunology, National Academy of Medicine, Buenos Aires, and in 2013, she joined the Texas Children’s Hospital Center for Human Immunobiology, Baylor College of Medicine, as a Postdoctoral Associate. In 2021 she graduated from Anatomical and Clinical Pathology Residency at the University of Texas, Medical Branch. In 2023 she completed a 2-year fellowship training in Hematopathology at The University of Texas MD Anderson Cancer Center, Department of Pathology and Laboratory Medicine and she will complete a one-year Fellowship in GI/pancreas/Liver at MD Anderson Cancer Center. Dr. Nahmod is interested in immune-mediated disorders and lymphoproliferative disorders involving the gastrointestinal tract, liver, and pancreas.


Karen Nahmod, Roberto Miranda, Francisco Vega, Beenu Thakral, Naveen Pemmaraju, Sanam Loghavi, Fatima Jelloul, Wei Wang, Sa Wang, Tariq Muzzafar, Keyur Patel, Carlos Bueso-Ramos, L. Jeffrey Medeiros, Rashmi Kanagal-Shamanna

MD Anderson Cancer Center, Houston, TX, United States

We describe a rare case of chronic myelomonocytic leukemia (CMML) showing an unusual pattern of progression to myeloid sarcoma with partial plasmacytoid dendritic cell (pDC) differentiation which is previously not been well-described in literature. A 71-year-old man, diagnosed with CMML five years back, developed progressive lymphadenopathy. Lymph node (LN) biopsy confirmed myeloid sarcoma with prominent (~40%) pDC differentiation [dual TCF4/CD123 positivity by immunohistochemistry (IHC) and flow cytometry (FC) analysis (CD123bright/HLA-DR+/CD303+/CD2partial/CD7partial)]. In contrast, bone marrow (BM) showed CMML, 9% blasts with sparsely scattered pDCs with mature immunophenotype. During therapy, he developed a concurrent non-germinal center diffuse large B-cell lymphoma (DLBCL) of supraglottis, with scattered CD33+/CD11c+ monocytes without a significant pDC infiltrate.

Targeted NGS studies were performed at baseline and progression (on BM, LN and supraglottic mass). The mutational profile of CMML remained the same at baseline and progression in both BM and LN [ASXL1, JAK2, KRAS, SRSF2, TET2, MAP2K1]. DLBCL showed MYD88 and IGLL5 mutations (~70% VAF), admixed with low-level (VAFs, 5-11%) mutations involving the same genes as CMML, indicating lymphoid and myeloid neoplasms to be clonally unrelated. Importantly, prominent pDC differentiation seen only in LN, which expanded the therapeutic opportunities with CD123-targeting drugs, was identifiable only by IHC or FC.

The case highlights the persistent need for comprehensive evaluation of myeloid neoplasms using all modalities (morphology, IHC, FC) along with NGS for application of precision medicine. The non-parallel expansion of pDCs exclusively seen in LN (versus BM) suggests a critical role of microenvironment and need for novel single-cell spatial transcriptomics.