Figure 1.

Tissue-like organization in paraganglioma. (a) Dark brown immunohistochemical staining for S100, a glial marker, highlights the sustentacular cell component surrounding the alveolar nests (“zellballen”) of neuroepithelial (“chief”) cells (avidin-biotin immunoperoxidase counterstained with hematoxylin and eosin, bar = 10 µm). (b) Immunofluorescence highlights thin sustentacular cells at the edges of neuroepithelial “zellballen,” identified by labeling with antibody to S100 (green). The endothelial lining of the capillaries in the surrounding stroma is labeled in red with CD34 (double immunofluorescence on semithin frozen section, bar = 10 µm). (c) Transmission electron micrograph showing the cytological features and topological relationships of the four main cell types that organize the paraganglioma microenvironment (endothelial cells, EC; pericytes, PC; sustentacular cells, SC; neuroepithelial cells, NE). Note the nuclear pleomorphism and similarities between chromatin patterns (bar = 2 µm). (d) Dark brown cytoplasmic staining for chromogranin A (CGA), a marker for neuroendocrine neoplasia, highlights neuroepithelial cell nests (“zellballen”) (avidin-biotin immunoperoxidase counterstained with hematoxylin and eosin, bar = 10 µm). (e) Immunofluorescence highlights the pericytic/mural cell component of the paraganglioma vasculature, identified by red labeling with antibody to smooth muscle actin (SMA, immunofluorescence on semithin frozen section, bar = 10 µm). (f) Ultrastructural cross section of a paraganglioma capillary showing the atypical cytological features of endothelial cells (EC) and pericytes (PC), two cell types whose roles in paragangliar tumorigenesis have been thus far scarcely considered (bar = 2 µm).