AN ELECTRON MICROSCOPIC STUDY OF THE HUMAN ADRENAL MEDULLA AND PHEOCHROMOCYTOMA

Abstract

Fine structure of five cases of pheochromocytoma and that of normal adrenal medulla were studied, considering its endocrinological aspect.
Adrenal tumors in all five cases of pheochromocytoma were removed by surgery and human adrenal biopsy specimens were taken mainly at the time of renal operation of young adults. Tissue specimens were fixed in cold buffered osmium tetroxide, dehydrated in a series of ethanol and embedded in Epon. They were submitted to electron microscopy thereafter.
Human medullary cells appeared to be almost uniform in shape and contain numerous round, membrane-limited, cored, osmiophilic granules in the cytoplasm, which were already known as catecholamine (CA) granules. Mitochondria were scattered among them, while smooth or rough surfaced endoplasmic reticula developed poorly. Small vesicles and vacuoles were also scarcely seen. (Fig. 1-8)
Pheochromocytema cells, however, gave such variable findings that two major cell types were distinguished by the existence of CA granules-Type I with CA granules in the cytoplasm and Type II without them. The former were divided into three sub-groups according to their cytoplasmic CA granules and vacuoles, which could be observed in the same cytoplasm. This could be interpreted as the expression of cellular activities. (Fig. 9-13)
Features of each cell type are as follows.
Type I: Nucleus and nucleolus are round or oval. Cytoplasmic CA granules and vacuoles are more or less present. Mitochondria are scattered and endoplasmic reticula are quite scanty in cytoplasm.
Type Ia: CA granules are scanty and small in size. The entire cytoplasm is occupied by numerous vacuoles of same size. (Fig. 9-11)
Type Ib: There are more CA granules and less vacuoles in this type. The size of granules is larger than that of type Ia. (Fig. 11, 15, 19-22)
Type Ic: CA granules are abundant in cytoplasm. They are larger than any other cell types and even those of normal medullary cells, while vacuoles are vice versa. (Fig. 9, 10, 13, 14)
Type II: Nucleus exhibits polymorphism, being composed of dense nuclear chromatins, and cytoplasm shows high electron density, in which well developed smooth surfaced endoplasmic reticula, a few granules apparently different from CA granules are seen, but mitochondria are not observed. (Fig. 11-12)
These cell types were seen in the same section.
In order to compare these cell types and its CA granules, the number of CA granule and vacuole were counted along with measuring their sizes. Then, the ratio, G/(G+V) was calculated and distribution curve of granular size was made, calculating their mean diameter in each cell type. The value of G/(G+V) was summarized in the Table 2. (Fig. 25) T-test as to the mean value of G/(G+V) showed significant difference among these four cell types. On the CA granular sizes, Ic>>N>>Ib was ascertained by t test. Distribution curves had one peak on granular sizes of normal medullary cells, while two peaks were shown in type Ib and Ic. Results are summarized in the table 3.
From these findings, it is possible to make the concept of cellular functional cycle of Ia-Ib-Ic-Ia in the secretooy cell of the pheochromocytoma, which should be closely related to its CA biosynthesis, storage and secretion mechanism.
Experimental studies on the action of reserpine to adrenal medulla seem to support this hypothesis. According to them the cytoplasmic CA granules disappeared and vacuoles appeared after reserpine administration. This is reversed in a few days. In these works the ultrastructural changes progress uniformly in the course of the experiment.
In pheochromocytoma, however, these cell types can be observed simultaneously in the same section. of the tumors in our cases. Therefore, it is concluded that the co-existece of these cell types in pheochromocytoma might be morphological evidence for the abnormality of CA metabolism and that different patterns of the granular distribution