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Background: Idiopathic multicentric Castleman disease (iMCD) is a rare inflammatory disorder mediated by excessive proinflammatory cytokine signaling, most notably by interleukin 6 (IL‐6). IL‐6‐induced extramedullary hematopoiesis (EMH) has been reported in murine models of iMCD. Herein we present four cases of iMCD with EMH in humans. Case Series: The index case is a 24‐year‐old white woman who presented with pancytopenia, hepatosplenomegaly, and diffuse lymphadenopathy (LAD) with EMH in core lymph node biopsies. We then searched ACCELERATE, a Castleman disease (CD) natural history registry, and identified three additional CD cases with EMH reported in biopsies: A 23‐year‐old Asian man with fatigue, edema, LAD, and splenomegaly; a 20‐year‐old white man with fever, dyspnea, LAD, and hepatosplenomegaly; and a 50‐year‐old white man with constitutional symptoms, LAD, and myelodysplastic syndrome in bone marrow with a KRAS mutation. Results: All four patients presented with thrombocytopenia and fever and/or markedly elevated C‐reactive protein. Patient 1 had iMCD‐NOS (not otherwise specified) with severe thrombocytopenia, reticulin fibrosis in bone marrow, small volume LAD and organomegaly but no anasarca. The other three patients had iMCD‐TAFRO (thrombocytopenia, anasarca, reticulin fibrosis, renal dysfunction, organomegaly). Two had mixed CD and two had hypervascular CD in lymph nodes. All four had bone marrow hypercellularity and megakaryocyte hyperplasia and two had reticulin fibrosis. Conclusions: This case series demonstrates that EMH can be seen in CD, particularly in iMCD‐TAFRO. Given the similarity of this finding to previous murine models of IL‐6‐induced marrow and lymph node changes we hypothesize that this is an IL‐6‐mediated phenomenon. [ABSTRACT FROM AUTHOR]

Background: The vertebrate retina is an organized laminar structure comprised of distinct cell types populating three nuclear layers. During development, each retinal cell type follows a stereotypical temporal order of genesis, differentiation, and migration, giving rise to its stratified organization. Once born, the precise positioning of cells along the apico‐basal (radial) axis of the retina is critical for subsequent connections to form, relying on highly orchestrated migratory processes. While these processes are critical for visual function to arise, the regulators of cellular migration and retinal lamination remain largely unexplored. Results: We report a role for a microtubule‐interacting protein, Mllt11 (myeloid/lymphoid or mixed‐lineage leukemia; translocated to chromosome 11/All1 fused gene from chromosome 1q) in mammalian retinal cell migration during retinogenesis. We show that Mllt11 loss‐of‐function in mouse retinal neuroblasts affected the migration of ganglion and amacrine cells into the ganglion cell layer and led to their aberrant accumulation in the inner nuclear and plexiform layers. Conclusions: We demonstrate a role for Mllt11 in neuroblast migration and formation of the ganglion cell layer of the retina. Key Findings: Mllt11 plays a role in mammalian retinal lamination during development.Mllt11 regulates neuroblast morphology important for migration into the ganglion cell layer.Mllt11 loss of function leads to aberrant accumulation of retinal ganglion cells and displaced amacrine cells in the inner plexiform layer. [ABSTRACT FROM AUTHOR]