Supplementary figure legends Supplementary Fig. 1 (Related to Fig. 1). Gallery of pancreatic tissue maps showing peri-lobular islet aggregation and duct lesion (PanIN) -islet complex in human donor pancreases. Magenta: glucagon. Green: CK7. White: nuclei. Tile scanning and overlay of fluorescence and transmitted light signals are used to detect and identify the lesion-islet complex. Supplementary Fig. 2 (Related to Fig. 2). Intra-islet ducts in human pancreas. This unique structure is identified in the PanIN-islet complex via quadruple staining of glucagon (magenta, a-cells), insulin (blue, b-cells), CK7 (green, ductal epithelium), and nuclei (white). Supplementary tables Supplementary Table 1 (Related to Materials and Methods). Summary of primary antibodies used in illustrations. Supplementary Table 2 (Related to Materials and Methods). Summary of color codes presented in illustrations. Supplementary video legends Supplementary Video 1 (Related to Fig. 1). High-definition presentation of PanIN in PanIN-islet complex. This video uses a side-by-side illustration to compare the lesion in the H&E micrograph (left) and the 3-D image stack (right, in-depth recording of fluorescence and transmitted light signals). The H&E micrograph provides the ground-truth tissue information to identify this PanIN-1B lesion. Its feature is truthfully presented in the recording (right), confirming our 3-D imaging approach. Magenta: glucagon. Green: CK7. White: nuclei. Supplementary Video 2 (Related to Fig. 2). In-depth recording of islet aggregation and intra-islet duct in PanIN-islet complex. Left: PanIN-1A lesion and its islet association. Right: islet aggregation and formation of intra-islet duct (00:05-00:12). Blue: insulin. Magenta: glucagon. Green: CK7. White: nuclei. Supplementary Video 3 (Related to Fig. 3). In-depth recording of stromal accumulation in PanIN-islet complex. Left: map of pancreas and projection of lesion-islet complex (arrow, zoom-in area). Right: zoom-in examination of stromal accumulation in lesion-islet complex. Blue: insulin. Yellow: a-SMA. Green: CK7. White: nuclei. Supplementary Video 4 (Related to Fig. 4). Lymphangiogenesis associated with PanIN-islet complex. Left: in-depth recording of lymphatic vessels (green, D2-40) around duct lesions and aggregated islets (magenta, glucagon). Right: 3-D projection of lymphatic vessels in the microenvironment. White: nuclei. Supplementary Video 5 (Related to Fig. 5). Peri- and intra-islet cell proliferation in PanIN-islet microenvironment. Left: gross view of aggregated islets (3-D projection and 2-D image). Right: zoom-in examination of Ki-67+ nuclei. The Ki-67+ nuclei are identified inside and around the islet but not enclosed by the glucagon (magenta) or insulin (blue) signals. Blue: insulin. Magenta: glucagon. Green: nuclei. Yellow: Ki-67. In the first half of the video (00:00-00:10), the overlap of yellow (Ki-67) and green (nuclear staining) signals is used to detect and confirm the cell proliferation. In the second half (00:11-00:21), the same microenvironment is displayed without the green signals to emphasize the locations of Ki-67+ nuclei. Supplementary Video 6 (Related to Fig. 5). Second example of cell proliferation in PanIN-islet microenvironment. Upper panel: in-depth recording of Ki-67+ nuclei. Lower panel: projection of Ki-67+ signals to register their locations. Blue: insulin. Magenta: glucagon. Green: nuclei. Yellow: Ki-67. Sixteen Ki-67+ nuclei are identified in this view. The numbers at the lower panel indicate their order of appearance in the video. In particular, number 1, 2, 4, 5, 6, 13, and 14 are adjacent to the glucagon+ (magenta) or insulin+ (blue) cells but not enclosed by the two endocrine markers.