Piecemeal degranulation in human tumour pheochromocytes

Abstract

Piecemeal degranulation (PMD) has been recognized in two cases of human pheochromocytoma from the adrenal medulla, which were studied by transmission electron microscopy. Tumour pheochromocytes presented a highly characteristic cytoplasmic admixture of normal resting granules, swollen granules with eroded matrices and enlarged empty containers. Chromaffin granules that appeared to be normal and altered granules maintained their individual structure, and did not fuse with each other or with the plasma membrane. In accordance with the currently accepted model for granule discharge during PMD, electron-dense or clear vesicles 30-150 nm in diameter were seen either attached to the surface of chromaffin granules and the plasma membrane or free in the cytosol. This is the first description of PMD in human adrenal chromaffin cells and, in addition, is the first report of PMD in tumour secretory cells. These findings add further to the concept that PMD may have a broader spectrum of expression than hitherto recognized.

Figs 1 and 2

Electron micrographs showing features suggestive of piecemeal degranulation in human tumour pheochromocytes. A characteristic admixture of resting granules (large arrows), haloed granules with ‘piecemealed’ or dissolved matrices (small arrows) and empty containers (asterisks) is observable. Numerous electron-dense and electron-lucent vesicles (arrowheads in Fig. 2) are free in the cytoplasm or attached to the plasma membrane. Some granules present irregular, budding projections of their limiting membranes (curved arrows in Fig. 2). Scale bars, 0.2 µm.

Figs 3 and 4

Chromaffin granules exhibit a highly characteristic polymorphism and are not fused with each other. Resting, normal granules (large arrows) are mixed with empty containers (asterisks) and dilated granules with evidence of reduced or mobilized components (small arrows). Curved arrows in Fig. 3 point to perigranule membrane budding. A rich population of membrane-bound, clear or electron-dense vesicles 30–150 nm in diameter is visible close to granules (arrowheads). Scale bars, 0.2 µm.

Figs 5 and 6

At higher magnification, small electron-lucent vesicles (straight arrows) or vesicles containing pieces of dense material (curved arrows) are seen attached to chromaffin granules or free in the cytosol. Scale bars, 0.1 µm.

Fig. 7

Electron micrograph of a normal pheochromocyte. The population of secretory granules is less pleomorphic and consists mostly of electron-dense structures with closely adhering limiting membranes. A haloed granule with ‘piecemealed’ matrix (arrow) and two empty containers (asterisk) are visible. Scale bar, 0.3 µm.

Fig. 8

Graph highlighting the differences in granule features between tumour (shaded columns) and normal (open columns) pheochromocytes. (A) Resting granules, (B) altered ‘haloed’ granules and (C) empty containers. Each column represents the mean ± SD. Each value in tumour pheochromocytes is significantly different from control (P < 0.01).