Detection of unique cell communities and evidence of focally increased lymphocytes. (A) A 75 μm region was used for community detection (top right). Six unique cellular/structural communities were detected, differentiated based on proportions of constituent hematopoietic and NHEs, and relative contributions from bone trabeculae, CD34⁺ vasculature, and fat (left). Schematic respresentation of paired hematoxylin and eosin–stained section, MxIF preparation, and topographic communities map (case WCM66), with a highlighted juxtatrabecular focus enriched for immature myeloid elements including myeloblasts and promyelocytes, with distal progression toward MMCs. (B) HSPCs are relatively enriched in clusters 1 (0.0282 ± 0.1 vs 0.0178 ± 0.006) and 5 (0.0315 ± 0.095 vs 0.0178 ± 0.006), and next most abundant in cluster 4 (bottom right). Cluster 1 exhibits a relative depletion of promyelocytes (0.0038 ± 0.0036 vs 0.0098 ± 0.009; P < .005) and proerythroblasts (0.0026 ± 0.0023 vs 0.0059 ± 0.0045; P < .001) compared with cluster 5. (C) Clusters 0 (0.232 ± 0.157 vs 0.136 ± 0.155; P < .005) and 3 (0.265 ± 0.071 vs 0.175±0.068; P < .005) are relatively enriched in ≤20 year marrows as compared with >60 year marrows. Clusters 1 (0.067 ± 0.043 vs 0.187 ± 0.123; P < .005) and 4 (0.085 ± 0.043 vs 0.161 ± 0.072; P < .005) are relatively enriched in >60 year marrows as compared with ≤20 year marrows. (D) Mapping of cluster 1 foci back to hematoxylin and eosin–stained WSI reveals conspicuous mature lymphocytes by histomorphologic assessment. Box plot showing significantly higher percentage of mature lymphocytes in cluster 1 compared to all other clusters. See supplemental Methods for experimental details. (E) Hypothetical model of increased mature lymphocytes comprising the NHEs (light blue cells) enriched in cluster 1. ∗0.01 < P ≤ .05; ∗∗.001 < P ≤ .01; ∗∗∗.0001 < P ≤ .001; ∗∗∗∗P < .0001. H&E, hematoxylin and eosin.