ULTRASTRUCTURE O F CHROMOPHOBE ADENOMA O F THE HUMAN PITUITARY GLAND
S. ROY Department of Pathology, All India Institute of Medical Sciences, New Delhi 110016,India
PLATES CX-CXIII THEpituitary adenomas are traditionally divided into three types, namely acidophil, basophil and chromophobe adenoma on the basis of light microscopic examination (Russell and Rubinstein, 1971), although the concept that the tumours containing cells with secretory granules (the chromophils) are functionally active and the ones with cells containing no stainable granules (the chromophobes) are functionally inactive is no longer accepted (Lewis and Van Noorden, 1972; 1974). Electron-microscopic studies of normal pituitary (Farquhar, 1961; Barnes, 1962; Bergland and Torack, 1969; Lawzewitsch et al., 1972) have established different types of secretory granules in different cells and ultrastructural studies of pituitary adenomas (Schelin, 1962; Zambrano et al., 1968; Schechter, 1973; Lewis and Van Noorden, 1972; 1974) have indicated that secretory granules are not only present in the chromophils but also in the chromophobes. The results of ultrastructural studies of chromophobe adenoma (Schelin ; Zambrano et al. ; Schechter; Tomiyasu, Hirano and Zimmerman, 1973; Lewis and Van Noorden, 1974) have not been uniform and in only an occasional study the ultrastructure of chromophobes in non-functioning adenoma has been compared with that of chromophobes found in acromegaly (Schechter). The present study was undertaken to analyse the ultrastructure of light microscopically diagnosed chromophobe adenomas with a view to recording the fine structural morphology of chromophobes and to compare the ultrastructure of chromophobes present in non-functioning pituitary adenomas with that of chromophobes found in the tumours associated with acromegaly. "
"
MATERIALS AND METHODS Material for this study was collected at the time of surgery from 16 cases of pituitary adenomas. Twelve of these cases, seven males and five females, presented with symptoms, lasting for a period of 6 mth to 6 yr, related mainly to the spread of the tumour outside the sella resulting in compression of the adjacent structure. Common clinical presentation was gradual loss of vision, headache with or without other features of raised intracranial tension. There was no clinical evidence of hyper- or hypo-pituitarism in eight of these cases while in four others there was hypofunction in the form of amenorrhoea or loss of libido. All the tumours appeared as chromophobe adenoma at light microscopy. Tissue was also obtained Received 23 Sept. 1976; accepted 12 Dec. 1976 J. PATH.-VOL.
122 (1977)
2 19
P'
220
S. ROY
from four cases of pituitary adenoma, three males and one female, associated with acromegaly but with the light-microscopic appearance of chromophobe adenoma. Part of the tissue was fixed in buffered neutral formalin for light microscopic examination. Paraffin sections were stained routinely with haematoxylin and eosin stain and by PAS method counter-stained with orange G (Pearse, 1960). The other part of the tissue was cut into 1 mm blocks and immediately dropped into 4 per cent. gluteraldehyde solution in phosphate buffer for fixation for electron microscopy. The tissues were post-fixed in 1 per cent. cold osmium tetroxide, further processed in ascending grades of alcohol and embedded in epoxy resin. Thin sections were stained with uranyl acetate and lead citrate and examined with a Philips 300 electron microscope.
RESULTS Light microscopic examination Tumour cells in all the 16 cases showed the typical appearance of chromophobe adenomas (Russell and Rubinstein). They exhibited a characteristic sinusoidal or diffuse pattern. Both patterns could be seen in the same tumour in some of the cases. On haematoxylin and eosin staining, the tumour cells showed pale cytoplasm which did not show any granules on staining with PAS orange G technique. Electron microscopic study " Non-functioning " adenoma (12 cases). Varying numbers of secretory granules were present in the cytoplasm of the majority of the tumour cells in all the cases. In five cases most of the tumour cells were sparsely granular while in five others there was a mixed population of sparsely granular and moderately and heavily granular cells and in two cases a majority of the cells showed abundant secretory granules. Not infrequently sparsely granular cells could be seen lying adjacent to those containing moderate amounts or abundant granules (fig. 1). The granules were membrane bound and were spherical, containing uniform or finely granular electron-dense material and the majority of them were small, measuring from 100 to 150 nm in diameter. In the cells with moderate or abundant granularity, the granules were more or less uniformly distributed (fig. 1) while in the sparsely granulated cells they often showed preferential location close to the cell membrane (fig. 2). Mitochondria were present in large numbers (figs. 1 and 2) in many cells in several cases. They were variable in size and shape andmorphologically they were similar to those seen in cells of many other tissues but in a few cells mitochondria appeared swollen or irregular with irregular cristae (fig. 1). Prominentrough endoplasmic reticulum (RER) with many free ribosomes and with or without well developed Golgi apparatus (fig. 3) was observed in four cases. All these cases had tumours composed mostly of sparsely granular or agranular cells. In some agranular cells elaborate RER was seen with cisternae arranged in parallel manner or as concentric whorls (fig. 4), similar to those described by Tomiyasu et al. In some cells a prominent Golgi complex was present with no elaborate RER. Although in some cases many sparsely granular cells showed poorly developed RER and Golgi apparatus (fig. 2), the cells with abundant
CHROMOPHOBE A DENOMA
221
secretory granules (figs. 1 and 5) almost always showed poorly developed RER and Golgi apparatus. Inclusion bodies showing variable structure were frequently seen. The majority of these were not membrane bound and appeared to be complex lipid droplets (fig. 5 ) while others seemed to be lysosomal in nature. In three cases large numbers of cytoplasmic vacuoles of uncertain nature were present and all of these had tumours with sparsely granular cells. Variation in nuclear size and shape was a common feature and in many cells the nuclei showed deep irregular indentation (fig. 2). Occasional cells showed basal bodies but no cilia were observed. Adenomas in acromegalics (four cases). In three out of four cases of pituitary adenoma with acromegaly, most of the tumour cells were either agranular or sparsely granular (fig. 6). In one case in addition to many agranular or sparsely granular cells, many cells with a large number of secretory granules were also present (fig. 7). The secretory granules were mostly spherical and uniformly electron dense but were generally larger than those in the previous group and many of them measured between 250 to 350 nm. In all these cases, the tumour cells, especially those with sparsely granular and agranular cytoplasm, were richly endowed with RER, free ribosomes and Golgi apparatus (fig. 6) but were generally poor in mitochondria1 content. Here, again, the cells containing large numbers of secretory granules did not show prominent RER or Golgi complex. In all the four cases complex lipid inclusions, similar to those seen in the previous group, were frequently found and many cells also showed large numbers of cytoplasmic vacuoles. The nuclei in the majority of the cells were irregular in size and shape and as in the previous group they often showed deep irregular indentation andin an occasional cell basal bodies with no cilia were present.
DISCUSSION The ultrastructure of " non-functioning " adenoma has been described by other workers (Schelin; Zambrano et al.; Doniach, 1972; Tomiyasu et al.; and Lewis and Van Noorden, 1974) and the present investigation is an extension of these earlier observations. It has been established that a pituitary tumour, associated with hyper, hypo- or normal functional status may appear as chromophobe adenoma at light-microscopic examination. Ultrastructurally, varying amounts of secretory granules are usually observed in most of the chromophobe adenomas, irrespective of the functional status of the patient. However, the results of various studies have not been uniform. Thus, Schelin observed sparse granularity in most of the tumour cells in cases of nonfunctioning chromophobe adenomas and reported that the cells were poor in RER and Golgi apparatus, suggesting lack of secretory activity, while in Doniach's study of non-functioning chromophobe adenoma he noted many secretory granules in the tumour cells associated with poorly developed RER and Golgi apparatus. Zambrano et al. found varying amounts of secretory granules along with prominent RER and Golgi complex in chromophobe adenomas associated with hypofunction and in Schechter's study he did not
222
S. ROY
find any difference between the structure of chromophobes found in nonfunctioning tumours and those in acromegaly. In the present investigations varying degrees of secretory granules were found in the tumour cells in all the chromophobe adenomas, irrespective of whether they were non-functioning or were associated with acromegaly. However, ultrastructurally, chromophobes could be divided into two distinct morphological types. The common type contained many secretory granules but was poor in RER and Golgi apparatus, the organelles associated with active secretion (Palade, 1961). This type of cell predominated in the majority of the non-functioning tumours and can be considered a storage cell. The other type of cell was sparsely granular or agranular but was rich in RER and Golgi apparatus. It appears that this type of cell is involved in active secretion with rapid turnover, and therefore the secretion does not accumulate in the form of cytoplasmic secretory granules. This type of cell dominated the picture in all the four cases of acromegaly. It is considered likely, therefore, that even in acidophil adenomas, manifestation of hyperfunction depends on the poorly granulated but actively secretory cells rather than the well-granulated cells. This contention is supported by the observations of Lewis and Van Noorden (1972) who found that the serum growth hormone level was much greater in cases with poorly granulated tumour than in those with wellgranulated tumour. However, it is interesting to note that the evidence of secretory activity with poor granularity was not only present in the tumours of four acromegalics but similar morphological features were also prominent in four cases of “ non-functioning ” adenoma. The significance of morphological evidence of secretory activity in “ non-functioning ” chromophobe adenomas is not clear. It is possible that they secrete some proteins not related to the functional activity of the normal pituitary gland. Zambrano et aE. found active secretory cells in tumours associated with hypofunction and suggested that the secretion by these cells in some cases of chromophobe adenoma night be responsible for the severe insufficiency that was present in their cases. Another type of cell, seen in some cases, contained neither many secretory granules nor prominent RER or Golgi apparatus. They are also considered to be secretorily inactive cells. SUMMARY
Sixteen specimens of pituitary adenoma were studied by electron microscopy. Twelve of them were “ non-functioning ” tumours and four were associated with acromegaly. All the tumours showed the light-microscopic appearance of classical chromophobe adenoma. Though electron microscopy revealed varying degrees of granularity in the majority of the cells in all the tumours, two distinct morphological types of chromophobe tumours were observed. In one type, secretory granules were frequently seen in moderate or large numbers and the cells were poor in RER and Golgi apparatus. These cells are considered to be secretorily inactive storage cells and they were the predominant cells in eight cases of “nonfunctioning ” adenomas.
PLATECX
ROY
CHROMOPHOBE ADENOMA
FIG. 1.-Electron micrograph showing two tumour cells. The upper one contains many secretory granules while the lower one is agranular. Both the cells have many mitochondria, a few showing morphological irregularities (arrow) but poorly developed rough endoplasmic reticulum and Golgi apparatus. x 16,800.
FIG. 2.-Electron micrograph showing sparsely granular tumour cells. The granules are mostly located near the plasma membranes and there are many mitochondria inside the cytoplasm. Note deep irregular indentation in the nuclei (N). x 10,000.
PLATECXI
ROY
CHROMOPHOBE ADENOMA
FIG.3.-Sparsely granular tumour cells with well-developed Golgi apparatus and rough endoplasmic reticulum. Note the presence of a complex lipid inclusion (I). x 13,600.
FIG. 4a.-Tumour
cell with prominent rough endoplasmic reticulum arranged in parallel manner. x 30,000
PLATE CXII
ROY
CHROMOPHORE ADENOMA
FIG.4b.-Tumour
cell with prominent rough endoplasmic reticulum arranged in concentric whorls. x 20,000.
FIG. 5.--A tuniour cell with many secretory granules and poorly developed rough endoplasmic reticulum and Golgi apparatus. Note the presence of a complex lipid inclusion (I). x 20,000.
PLATECXIII
ROY CHROMOPHOBE ADENOMA
FIG. 6.-Tumour
cells showing prominent rough endoplasmic reticulum and Golgi apparatus. x 12,000.
FIG.7.-Electron
micrograph showing turnour cells with many secretory granules and an intercellular space (S). x 11,500.
CHROMOPHOBE ADENOMA
223
The other type was noted in four cases of " non-functioning " adenomas and in all the four cases of adenoma with acromegaly. In this type, the tumour cells were generally poor in secretory granules but were rich in RER and Golgi apparatus, suggesting secretory activity. In acromegaly these features appear to indicate active hormone synthesis and its discharge into the circulation but the reason for the morphological evidence of active secretion in the four cases of " non-functioning " adenoma is not clearly understood. I am indebted to my colleagues in the department of neurosurgery for help in collecting the specimens and for providing the clinical data. I am grateful to Mr Achar Singh for his technical assistance. REFERENCES BARNES, B. G. 1962. Electron microscopic study on the secretory cytopathology of the mouse anterior pituitary. Endocrinology, 71, 618. BERGLAND, R. M., AND TORACK, R. M. 1969. An ultrastructural study of follicular cells in the human anterior pituitary. Amer. J. Path., 57, 273. DONIACH, I. 1972. Cytology of pituitary adenomas. J. Roy. Coll. Physcns., Lond., 6 , 299. FARQUHAR, M. G. 1961. Origin and fate of the secretory granules in the anterior pituitary gland. Trans. N. Y. Acad. Sci., 23, 346. LEWIS,P. D., AND VAN NOORDEN, S. 1972. Pituitary abnormalities in acromegaly. Arch. Pathol., 94, 119. LEWIS,P. D., AND VAN NOORDEN, S. 1974. " Nonfunctioning " pituitary tumours. Arch. Pathol., 97, 178. PALADE, G. E. 1961. In Electron microscopy in anatomy, edited by J. D. Boyd, F. R. Johnson, and J. D. Lever, London, p. 176. PEARSE, A. G. E. 1960. Histochemistry, 2nd ed., London, p. 831. RUSSELL, D. S., AND RUBINSTEIN, L. G. 1971. Pathology of tumours of the nervous system, 3rd ed., London, p. 233. SCHECHTER, J. 1973. Electron microscopic studies of human pituitary tumours. 1. Chromophobe adenomas. Am. J. Anat., 138, 371. SCHELIN, U. 1962. Chromophobe and acidophil adenomas of the human pituitary gland. Acta Path. Microbiol. Scand., Suppl. 158, 1. TOMIYASU, U., HIRANO, A., AND ZIMMERMAN, H. M. 1973. Fine structure of human pituitary adenoma. Arch. Pathol., 95, 287. VON LAWZEWITSCH, I., DICKMANN, G . H., AMEZUA, L., AND PARDAL, c. 1972. Cytological and ultrastructural characterisation of the human pituitary. Acta Anat., 81, 286. ZAMBRANO, D., h z u a , L., DICKMANN, G., AND FRANKE, E. 1968. Ultrastructure of human pituitary adenoma. Acta Neurochirurgica, 18, 78.
S. ROY Department of Pathology, All India Institute of Medical Sciences, New Delhi 110016,India
PLATES CX-CXIII THEpituitary adenomas are traditionally divided into three types, namely acidophil, basophil and chromophobe adenoma on the basis of light microscopic examination (Russell and Rubinstein, 1971), although the concept that the tumours containing cells with secretory granules (the chromophils) are functionally active and the ones with cells containing no stainable granules (the chromophobes) are functionally inactive is no longer accepted (Lewis and Van Noorden, 1972; 1974). Electron-microscopic studies of normal pituitary (Farquhar, 1961; Barnes, 1962; Bergland and Torack, 1969; Lawzewitsch et al., 1972) have established different types of secretory granules in different cells and ultrastructural studies of pituitary adenomas (Schelin, 1962; Zambrano et al., 1968; Schechter, 1973; Lewis and Van Noorden, 1972; 1974) have indicated that secretory granules are not only present in the chromophils but also in the chromophobes. The results of ultrastructural studies of chromophobe adenoma (Schelin ; Zambrano et al. ; Schechter; Tomiyasu, Hirano and Zimmerman, 1973; Lewis and Van Noorden, 1974) have not been uniform and in only an occasional study the ultrastructure of chromophobes in non-functioning adenoma has been compared with that of chromophobes found in acromegaly (Schechter). The present study was undertaken to analyse the ultrastructure of light microscopically diagnosed chromophobe adenomas with a view to recording the fine structural morphology of chromophobes and to compare the ultrastructure of chromophobes present in non-functioning pituitary adenomas with that of chromophobes found in the tumours associated with acromegaly. "
"
MATERIALS AND METHODS Material for this study was collected at the time of surgery from 16 cases of pituitary adenomas. Twelve of these cases, seven males and five females, presented with symptoms, lasting for a period of 6 mth to 6 yr, related mainly to the spread of the tumour outside the sella resulting in compression of the adjacent structure. Common clinical presentation was gradual loss of vision, headache with or without other features of raised intracranial tension. There was no clinical evidence of hyper- or hypo-pituitarism in eight of these cases while in four others there was hypofunction in the form of amenorrhoea or loss of libido. All the tumours appeared as chromophobe adenoma at light microscopy. Tissue was also obtained Received 23 Sept. 1976; accepted 12 Dec. 1976 J. PATH.-VOL.
122 (1977)
2 19
P'
220
S. ROY
from four cases of pituitary adenoma, three males and one female, associated with acromegaly but with the light-microscopic appearance of chromophobe adenoma. Part of the tissue was fixed in buffered neutral formalin for light microscopic examination. Paraffin sections were stained routinely with haematoxylin and eosin stain and by PAS method counter-stained with orange G (Pearse, 1960). The other part of the tissue was cut into 1 mm blocks and immediately dropped into 4 per cent. gluteraldehyde solution in phosphate buffer for fixation for electron microscopy. The tissues were post-fixed in 1 per cent. cold osmium tetroxide, further processed in ascending grades of alcohol and embedded in epoxy resin. Thin sections were stained with uranyl acetate and lead citrate and examined with a Philips 300 electron microscope.
RESULTS Light microscopic examination Tumour cells in all the 16 cases showed the typical appearance of chromophobe adenomas (Russell and Rubinstein). They exhibited a characteristic sinusoidal or diffuse pattern. Both patterns could be seen in the same tumour in some of the cases. On haematoxylin and eosin staining, the tumour cells showed pale cytoplasm which did not show any granules on staining with PAS orange G technique. Electron microscopic study " Non-functioning " adenoma (12 cases). Varying numbers of secretory granules were present in the cytoplasm of the majority of the tumour cells in all the cases. In five cases most of the tumour cells were sparsely granular while in five others there was a mixed population of sparsely granular and moderately and heavily granular cells and in two cases a majority of the cells showed abundant secretory granules. Not infrequently sparsely granular cells could be seen lying adjacent to those containing moderate amounts or abundant granules (fig. 1). The granules were membrane bound and were spherical, containing uniform or finely granular electron-dense material and the majority of them were small, measuring from 100 to 150 nm in diameter. In the cells with moderate or abundant granularity, the granules were more or less uniformly distributed (fig. 1) while in the sparsely granulated cells they often showed preferential location close to the cell membrane (fig. 2). Mitochondria were present in large numbers (figs. 1 and 2) in many cells in several cases. They were variable in size and shape andmorphologically they were similar to those seen in cells of many other tissues but in a few cells mitochondria appeared swollen or irregular with irregular cristae (fig. 1). Prominentrough endoplasmic reticulum (RER) with many free ribosomes and with or without well developed Golgi apparatus (fig. 3) was observed in four cases. All these cases had tumours composed mostly of sparsely granular or agranular cells. In some agranular cells elaborate RER was seen with cisternae arranged in parallel manner or as concentric whorls (fig. 4), similar to those described by Tomiyasu et al. In some cells a prominent Golgi complex was present with no elaborate RER. Although in some cases many sparsely granular cells showed poorly developed RER and Golgi apparatus (fig. 2), the cells with abundant
CHROMOPHOBE A DENOMA
221
secretory granules (figs. 1 and 5) almost always showed poorly developed RER and Golgi apparatus. Inclusion bodies showing variable structure were frequently seen. The majority of these were not membrane bound and appeared to be complex lipid droplets (fig. 5 ) while others seemed to be lysosomal in nature. In three cases large numbers of cytoplasmic vacuoles of uncertain nature were present and all of these had tumours with sparsely granular cells. Variation in nuclear size and shape was a common feature and in many cells the nuclei showed deep irregular indentation (fig. 2). Occasional cells showed basal bodies but no cilia were observed. Adenomas in acromegalics (four cases). In three out of four cases of pituitary adenoma with acromegaly, most of the tumour cells were either agranular or sparsely granular (fig. 6). In one case in addition to many agranular or sparsely granular cells, many cells with a large number of secretory granules were also present (fig. 7). The secretory granules were mostly spherical and uniformly electron dense but were generally larger than those in the previous group and many of them measured between 250 to 350 nm. In all these cases, the tumour cells, especially those with sparsely granular and agranular cytoplasm, were richly endowed with RER, free ribosomes and Golgi apparatus (fig. 6) but were generally poor in mitochondria1 content. Here, again, the cells containing large numbers of secretory granules did not show prominent RER or Golgi complex. In all the four cases complex lipid inclusions, similar to those seen in the previous group, were frequently found and many cells also showed large numbers of cytoplasmic vacuoles. The nuclei in the majority of the cells were irregular in size and shape and as in the previous group they often showed deep irregular indentation andin an occasional cell basal bodies with no cilia were present.
DISCUSSION The ultrastructure of " non-functioning " adenoma has been described by other workers (Schelin; Zambrano et al.; Doniach, 1972; Tomiyasu et al.; and Lewis and Van Noorden, 1974) and the present investigation is an extension of these earlier observations. It has been established that a pituitary tumour, associated with hyper, hypo- or normal functional status may appear as chromophobe adenoma at light-microscopic examination. Ultrastructurally, varying amounts of secretory granules are usually observed in most of the chromophobe adenomas, irrespective of the functional status of the patient. However, the results of various studies have not been uniform. Thus, Schelin observed sparse granularity in most of the tumour cells in cases of nonfunctioning chromophobe adenomas and reported that the cells were poor in RER and Golgi apparatus, suggesting lack of secretory activity, while in Doniach's study of non-functioning chromophobe adenoma he noted many secretory granules in the tumour cells associated with poorly developed RER and Golgi apparatus. Zambrano et al. found varying amounts of secretory granules along with prominent RER and Golgi complex in chromophobe adenomas associated with hypofunction and in Schechter's study he did not
222
S. ROY
find any difference between the structure of chromophobes found in nonfunctioning tumours and those in acromegaly. In the present investigations varying degrees of secretory granules were found in the tumour cells in all the chromophobe adenomas, irrespective of whether they were non-functioning or were associated with acromegaly. However, ultrastructurally, chromophobes could be divided into two distinct morphological types. The common type contained many secretory granules but was poor in RER and Golgi apparatus, the organelles associated with active secretion (Palade, 1961). This type of cell predominated in the majority of the non-functioning tumours and can be considered a storage cell. The other type of cell was sparsely granular or agranular but was rich in RER and Golgi apparatus. It appears that this type of cell is involved in active secretion with rapid turnover, and therefore the secretion does not accumulate in the form of cytoplasmic secretory granules. This type of cell dominated the picture in all the four cases of acromegaly. It is considered likely, therefore, that even in acidophil adenomas, manifestation of hyperfunction depends on the poorly granulated but actively secretory cells rather than the well-granulated cells. This contention is supported by the observations of Lewis and Van Noorden (1972) who found that the serum growth hormone level was much greater in cases with poorly granulated tumour than in those with wellgranulated tumour. However, it is interesting to note that the evidence of secretory activity with poor granularity was not only present in the tumours of four acromegalics but similar morphological features were also prominent in four cases of “ non-functioning ” adenoma. The significance of morphological evidence of secretory activity in “ non-functioning ” chromophobe adenomas is not clear. It is possible that they secrete some proteins not related to the functional activity of the normal pituitary gland. Zambrano et aE. found active secretory cells in tumours associated with hypofunction and suggested that the secretion by these cells in some cases of chromophobe adenoma night be responsible for the severe insufficiency that was present in their cases. Another type of cell, seen in some cases, contained neither many secretory granules nor prominent RER or Golgi apparatus. They are also considered to be secretorily inactive cells. SUMMARY
Sixteen specimens of pituitary adenoma were studied by electron microscopy. Twelve of them were “ non-functioning ” tumours and four were associated with acromegaly. All the tumours showed the light-microscopic appearance of classical chromophobe adenoma. Though electron microscopy revealed varying degrees of granularity in the majority of the cells in all the tumours, two distinct morphological types of chromophobe tumours were observed. In one type, secretory granules were frequently seen in moderate or large numbers and the cells were poor in RER and Golgi apparatus. These cells are considered to be secretorily inactive storage cells and they were the predominant cells in eight cases of “nonfunctioning ” adenomas.
PLATECX
ROY
CHROMOPHOBE ADENOMA
FIG. 1.-Electron micrograph showing two tumour cells. The upper one contains many secretory granules while the lower one is agranular. Both the cells have many mitochondria, a few showing morphological irregularities (arrow) but poorly developed rough endoplasmic reticulum and Golgi apparatus. x 16,800.
FIG. 2.-Electron micrograph showing sparsely granular tumour cells. The granules are mostly located near the plasma membranes and there are many mitochondria inside the cytoplasm. Note deep irregular indentation in the nuclei (N). x 10,000.
PLATECXI
ROY
CHROMOPHOBE ADENOMA
FIG.3.-Sparsely granular tumour cells with well-developed Golgi apparatus and rough endoplasmic reticulum. Note the presence of a complex lipid inclusion (I). x 13,600.
FIG. 4a.-Tumour
cell with prominent rough endoplasmic reticulum arranged in parallel manner. x 30,000
PLATE CXII
ROY
CHROMOPHORE ADENOMA
FIG.4b.-Tumour
cell with prominent rough endoplasmic reticulum arranged in concentric whorls. x 20,000.
FIG. 5.--A tuniour cell with many secretory granules and poorly developed rough endoplasmic reticulum and Golgi apparatus. Note the presence of a complex lipid inclusion (I). x 20,000.
PLATECXIII
ROY CHROMOPHOBE ADENOMA
FIG. 6.-Tumour
cells showing prominent rough endoplasmic reticulum and Golgi apparatus. x 12,000.
FIG.7.-Electron
micrograph showing turnour cells with many secretory granules and an intercellular space (S). x 11,500.
CHROMOPHOBE ADENOMA
223
The other type was noted in four cases of " non-functioning " adenomas and in all the four cases of adenoma with acromegaly. In this type, the tumour cells were generally poor in secretory granules but were rich in RER and Golgi apparatus, suggesting secretory activity. In acromegaly these features appear to indicate active hormone synthesis and its discharge into the circulation but the reason for the morphological evidence of active secretion in the four cases of " non-functioning " adenoma is not clearly understood. I am indebted to my colleagues in the department of neurosurgery for help in collecting the specimens and for providing the clinical data. I am grateful to Mr Achar Singh for his technical assistance. REFERENCES BARNES, B. G. 1962. Electron microscopic study on the secretory cytopathology of the mouse anterior pituitary. Endocrinology, 71, 618. BERGLAND, R. M., AND TORACK, R. M. 1969. An ultrastructural study of follicular cells in the human anterior pituitary. Amer. J. Path., 57, 273. DONIACH, I. 1972. Cytology of pituitary adenomas. J. Roy. Coll. Physcns., Lond., 6 , 299. FARQUHAR, M. G. 1961. Origin and fate of the secretory granules in the anterior pituitary gland. Trans. N. Y. Acad. Sci., 23, 346. LEWIS,P. D., AND VAN NOORDEN, S. 1972. Pituitary abnormalities in acromegaly. Arch. Pathol., 94, 119. LEWIS,P. D., AND VAN NOORDEN, S. 1974. " Nonfunctioning " pituitary tumours. Arch. Pathol., 97, 178. PALADE, G. E. 1961. In Electron microscopy in anatomy, edited by J. D. Boyd, F. R. Johnson, and J. D. Lever, London, p. 176. PEARSE, A. G. E. 1960. Histochemistry, 2nd ed., London, p. 831. RUSSELL, D. S., AND RUBINSTEIN, L. G. 1971. Pathology of tumours of the nervous system, 3rd ed., London, p. 233. SCHECHTER, J. 1973. Electron microscopic studies of human pituitary tumours. 1. Chromophobe adenomas. Am. J. Anat., 138, 371. SCHELIN, U. 1962. Chromophobe and acidophil adenomas of the human pituitary gland. Acta Path. Microbiol. Scand., Suppl. 158, 1. TOMIYASU, U., HIRANO, A., AND ZIMMERMAN, H. M. 1973. Fine structure of human pituitary adenoma. Arch. Pathol., 95, 287. VON LAWZEWITSCH, I., DICKMANN, G . H., AMEZUA, L., AND PARDAL, c. 1972. Cytological and ultrastructural characterisation of the human pituitary. Acta Anat., 81, 286. ZAMBRANO, D., h z u a , L., DICKMANN, G., AND FRANKE, E. 1968. Ultrastructure of human pituitary adenoma. Acta Neurochirurgica, 18, 78.
